ИНГИБИТОРЫ ГЛИКОЛАТОКСИДАЗЫ ДЛЯ ЛЕЧЕНИЯ ЗАБОЛЕВАНИЙ

Изобретение относится к новым химическим соединениям, которые могут найти применение для лечения или профилактики заболеваний или нарушений, связанных с ферментом гликолатоксидазой. Предложено соединение формулы (I), где кольцо С выбрано из структур (Ia) и (Ib), где волнистые линии ( ) указывают на точки присоединения углерода C1 к карбонилу C(O)-OR1 и углерода C2 к L; L представляет собой NRL, S, C(=O), CH2-Q или Q-CH2; где Q представляет собой O, NRL или S; RL представляет собой водород, C1-2 алкил или бензил; кольцо A представляет собой C4-8 циклоалкил, C8-11 спироциклоалкил, 5-8-членный гетероциклоалкил, содержащий 1-2 атома азота, имидазолил, триазолил, тиазолил, тиенил, бензотиазолил, индолинил или изоиндолинил; кольцо B присутствует или отсутствует; при этом: когда кольцо B присутствует, тогда кольцо A необязательно замещено метилом; когда кольцо B отсутствует, тогда (i) кольцо A замещено одной группой RAB; или (ii) кольцо A не замещено, когда кольцо A представляет собой незамещенный ...

НОВЫЕ ПРОИЗВОДНЫЕ ТЕТРАЗОЛА И ИХ ПРИМЕНЕНИЕ В ЛЕЧЕНИИ ТУБЕРКУЛЕЗА

Изобретение относится к соединению формулы (I) или его фармацевтически приемлемой соли, где Х является СН или N; n равно 0, 1 или 2; R1 представляет метил, этил, цианометил, С-связанный ацетамидо, метилацетат, 2-гидроксиэтил, 2-гидрокси-1-пропил, 1,3-дигидрокси-2-пропил или 1,2-дигидрокси-3-пропил; R2 независимо выбран из атома галогена, C1-2 алкила или C1-2 алкокси; R3 представляет фенил, пиридил, пиримидинил, пиразинил или пиридазинил, где каждая из этих групп может быть необязательно замещена одним или двумя заместителями, выбранными из атома галогена, циано, C1-2 алкила, необязательно замещенного не более чем тремя атомами фтора, и C1-2 алкокси, необязательно замещенного не более чем тремя атомами фтора, где заместители могут быть одинаковыми или различными; или R3 представляет циклогексил, который может быть необязательно замещен одним или двумя атомами фтора или хлора, где каждый заместитель может быть присоединен к одному и тому же атому углерода и каждый заместитель может быть одинаковым ...

ФЕНИКОЛОВЫЕ ПРОТИВОБАКТЕРИАЛЬНЫЕ СРЕДСТВА

Изобретение относится к соединению формулы I или его фармацевтически приемлемым солям, где группировка Het представляет собой пиридинил или тиазолил; каждый из Rи Rпредставляет собой Н; каждый из Rи Rнезависимо представляет собой Н, -Салкил или Rи R, взятые вместе, образуют Сциклоакил; W представляет собой -Н, -РО(ОН)или -СНОРО(ОН); каждый из X и Y представляет собой хлор или каждый из X и Y представляет собой фтор, и Z представляет собой Н. Соединения формулы I используют в способе контролирования или лечения инфекций у домашнего скота, включающем введение нуждающемуся в этом животному терапевтически эффективного количества соединения формулы I или его фармацевтически приемлемой соли. 2 н. и 6 з.п. ф-лы, 3 табл., 161 пр.

АНИЛИДЫ АМИНОКИСЛОТ В КАЧЕСТВЕ НИЗКОМОЛЕКУЛЯРНЫХ МОДУЛЯТОРОВ IL-17

Изобретение относится к соединению формулы (I) или его фармацевтически приемлемым солям, которые обладают ингибирующей активностью в отношении IL-17. В формуле (I) R1 выбирают из группы, состоящей из 5-членного гетероарила, который содержит от 2 до 3 гетероатомов, выбранных из N, O и S, 9- или 10-членного бициклического гетероарила, который содержит от 2 до 3 гетероатомов, выбранных из N, O и S, фенила, (C1-C6)алкокси, (C3-C7)циклоалкокси, (C1-C6)алкила, фенил-(C1-C4)алкила, (C3-C7)циклоалкила и -NRcRd, где указанный 5-членный гетероарил, 9- или 10-членный бициклический гетероарил, фенил, (C1-C6)алкокси, (C3-C7)циклоалкокси, (C1-C6)алкил, фенил-(C1-C4)алкил и (C3-C7)циклоалкил необязательно замещен одним или более заместителями, независимо выбранными из Ra; Ra представляет собой галоген, гидрокси, -NRcRd, (C1-C6)алкил, (C3-C7)циклоалкил, фенил, 5- или 6-членный гетероарил, который содержит от 1 до 3 гетероатомов, выбранных из N, O и S, или 4-6-членный гетероциклоалкил, который содержит ...

ПРОИЗВОДНЫЕ АМИДА, СПОСОБ ИХ ПОЛУЧЕНИЯ И ФАРМАЦЕВТИЧЕСКАЯ КОМПОЗИЦИЯ НА ИХ ОСНОВЕ

Изобретение относится к производным амида формулы I где R3 представляет собой (1-6С)алкил или галоген; m равно 0, 1, 2 или 3; R1 представляет собой гидрокси, галоген, трифторметил, нитро, амино, (1-6С)алкил, (2-6С)алкенил, (2-6С)алкинил, (1-6С)алкокси, (1-6С)алкиламино, ди-[(1-6С)алкил] амино, амино-(2-6С)алкиламино, (1-6С)алкиламино-(2-6С)алкиламино и т.д. или R1 представляет собой арил, арил-(1-6С)алкил, гетероарил, гетероарил-(1-6С)алкил, гетероарилокси, гетероарил-(1-6С)алкокси, гетероциклил, гетероциклил-(1-6С)алкил или гетероциклилокси, р равно 0, 1 или 2; R2 представляет собой гидрокси, галоген, трифторметил, (1-6С)алкил или (1-6С)алкокси; R4 представляет собой амино, (1-6С)алкиламино, ди-[(1-6С)алкил] амино, амино-(1-6С)алкил, (1-6С)алкиламино-(1-6С)алкил и т.д. или R4 представляет собой гетероарил, гетероарил-(1-6С)алкил, гетероарилокси, гетероарил-(1-6С)алкокси, гетероциклил и т.д., q равно 0, 1, 2, 3 или 4 и Q2 представляет собой гетероарил, гетероарилокси или гетероарил-(1-6С ...

КОНДЕНСИРОВАННЫЕ БИЦИКЛИЧЕСКИЕ КАРБОКСАМИДНЫЕ ПРОИЗВОДНЫЕ, ИСПОЛЬЗУЕМЫЕ В КАЧЕСТВЕ ИНГИБИТОРОВ СХСR2 ДЛЯ ЛЕЧЕНИЯ ВОСПАЛЕНИЙ

Настоящее изобретение относится к соединениям формулы I и к их фармацевтически приемлемым солям. Соединения настоящего изобретения могут быть использованы в качестве лекарственного средства, обладающего свойствами ингибитора CXCR2. В формуле I ! ! Х представляет собой -CR3=CR4-, -CR5=N-, -N=CR6-, -NR7- или -S-; R3, R4, R5 и R6 независимо представляют собой водород, F, Cl, Br, I; R7 представляет собой водород; Y1, Y2, Y3 и Y4 независимо представляют собой -CR8- или азот, при условии, что по меньшей мере два из Y1, Y2, Y3 и Y4 представляют собой -CR8-; где R8 представляет собой водород, F, Cl, Br, I; A представляет собой циклоалкил, имеющий 3, 4, 5, 6, 7 или 8 атомов углерода; бициклический частично насыщенный 9-членный циклоалкил; бициклический частично насыщенный 9-10-членный гетероцикл, в котором два атома на кольце представляют собой атомы кислорода; фенил; нафтил; 5-6-членный гетероарил, в котором один-три атома на кольце представляют собой атомы кислорода, серы и азота; 9-10-членный ...

1Н-ХИНАЗОЛИН-2,4-ДИОНЫ

... 1. Соединения формулы (I) ! ! где R1 означает CF3, CHF2, CH2F, СН3CHF-, СН3CF3-, этил или изопропил, а ! R2 означает алкил, замещенный одним или более заместителями, выбранными из группы, включающей галоген, нитро, циано, ацил, гидрокси, оксо (=O), алкокси, циклоалкокси, ацилокси, алкоксикарбонилокси, амино, алкиламино, диалкиламино, формил, ациламино, алкоксикарбониламино, или ! R2 означает гетероциклилалкил, замещенный одним или более заместителями, выбранными из группы, включающей галоген, нитро, циано, гидрокси, алкокси, алкилкарбонилокси, алкоксикарбонилокси, амино, алкиламино, диалкиламино, алкоксикарбониламино, или ! R2 означает фенил, замещенный одним или более заместителями, выбранными из группы, включающей циано, гидрокси, алкандиил, алкендиил, алкокси, гидроксиалкил, формил, алкилкарбонил, алкоксикарбонил, алкилкарбонилокси, алкоксикарбонилокси, амино, алкиламино, диалкиламино, аминоалкил, алкиламиноалкил, диалкиламиноалкил, алкоксикарбониламино, или ! R2 означает гетероциклил ...

ТРИАЗОЛЗАМЕЩЕННЫЕ АМИНОБЕНЗОФЕНОНОВЫЕ СОЕДИНЕНИЯ

... 1. Соединение общей формулы Ia или Ib где R1 - это метил, хлор, бром или метокси; R2 - это хлор или метил; R3 представляет собой С1-6алкил, С2-6алкенил, С2-6алкинил, С1-6гидроксиалкил, С1-6галогеналкил, С1-6алкокси, С1-6алкоксикарбонил, С1-6амино, уреидо, тиоуреидо, С1-6алкилкарбонилокси, С1-6алкилкарбонил, С1-6алкоксикарбонилокси, С1-6алкоксисульфонилокси, С1-6алкоксикарбамоил или С1-6аминокарбонил, каждый из которых необязательно замещен одним или более, одинаковыми или различными заместителями, выбранными из группы, состоящей из галогена, гидрокси, меркапто, трифторметила, циано, карбокси, CONH2, нитро, оксо, -S(O)2NH2, С1-4алкила, С2-4алкенила, С2-4алкинила, С1-4гидроксиалкила, С1-6галогеналкила, С1-4алкокси, С1-4алкоксикарбонила, уреидо, тиоуреидо, С1-4алкилкарбонилокси, С1-4алкоксикарбонилокси, С1-4алкоксисульфонилокси, С1-4алкоксикарбамоила, С1-4аминокарбонила, С1-4алкилтио, С3-6циклоалкила, С3-6циклоалкенила, амино, имино, С1-4аминосульфонила, С1-4аминокарбонилокси, С1-4алкилсульфониламино ...

АЦИЛАМИНОЗАМЕЩЕННЫЕ ПРОИЗВОДНЫЕ КОНДЕНСИРОВАННЫХ ЦИКЛОПЕНТАНКАРБОНОВЫХ КИСЛОТ И ИХ ПРИМЕНЕНИЕ В КАЧЕСТВЕ ФАРМАЦЕВТИЧЕСКИХ СРЕДСТВ

... 1. Соединение формулы I в любой из его стереоизомерных форм или сочетании стереоизомерных форм в любом соотношении, или его физиологически приемлемая соль, или физиологически приемлемый сольват любого из них ! ! где кольцо A является циклоалкановым кольцом с числом членов от 3 до 7, бензольным кольцом или моноциклическим 5-членным или 6-членным ароматическим гетероциклическим кольцом, содержащим 1 или 2 одинаковых или разных гетерочленов кольца, выбранных из группы, содержащей N, N(R0), O и S, причем циклоалкановое кольцо может необязательно иметь один или более одинаковых или разных заместителей, выбранных из группы, содержащей фтор и (C1-C4)-алкил, а бензольное и гетероциклическое кольца могут необязательно иметь один или более одинаковых или разных заместителей, выбранных из группы, содержащей галоген, R1, HO-, R1-O-, R1-C(O)-O-, R1-S(O)2-O-, R1-S(O)m-, H2N-, R1-NH-, R1-N(R1)-, R1-C(O)-NH-, R1-C(O)-N(R71)-, R1-S(O)2-NH-, R1-S(O)2-N(R71)-, R1-C(O)-, HO-C(O)-, R1-O-C(O)-, H2N-C(O)-, R1 ...

ПРОИЗВОДНЫЕ ПИПЕРАЗИНА, ХАРАКТЕРИЗУЮЩИЕСЯ МУЛЬТИМОДАЛЬНОЙ АКТИВНОСТЬЮ В ОТНОШЕНИИ БОЛИ

ФУНГИЦИДЫ НА ОСНОВЕ ЗАМЕЩЕННОГО ТОЛИЛА

... 1. Соединение, выбранное из формулы 1, его N-оксиды и соли,гдеA представляет собой радикал, выбранный из группы, состоящей изгде связь, расположенная с левой стороны группы A, соединена с фенильной группой, включающей CHO(C=O)NHCH, а связь, расположенная с правой стороны от группы A, соединена с фенильной группой, содержащей заместители Rи Rв формуле 1;Q представляет собой CH или N;Rпредставляет собой галоген, циано, гидрокси, нитро, амино, C-Cалкил, C-Cциклоалкил, C-Cциклоалкилалкил, C-Cалкенил, C-Cалкинил, C-Cгалогеналкил, C-Cалкокси, C-Cгалогеналкокси, C-Cциклоалкокси, C-Cгалогенциклоалкокси, C-Cциклоалкилалкокси, C-Cалкенилокси, C-Cгалогеналкенилокси, C-Cалкинилокси, C-Cгалогеналкинилокси, C-Cалкоксиалкокси, C-Cалкоксиалкил, C-Cцианоалкил, C-Cцианоалкокси, C-Cалкилтио, C-Cгалогеналкилтио, C-Cалкилсульфинил, C-Cгалогеналкилсульфинил, C-Cалкилсульфонил или C-Cгалогеналкилсульфонил;Rпредставляет собой галоген, циано, гидрокси, нитро,амино, C-Cалкил, C-Cциклоалкил, C-Cциклоалкилалкил, C-Cалкенил ...

ЗАМЕЩЕННОЕ ПРОИЗВОДНОЕ ФЕНИЛАЗОЛА

... 1. Соединение, представленное общей формулой (I):,где кольцо А представляет собой* обозначает положение связывания с бензольным кольцом,X представляет собой СН или N,Rпредставляет собой -C(=O)-NH-R, -NH-C(=O)-NH-Rили -S(=O)-R,Rпредставляет собой -F или -Н,Rпредставляет собой -СНили -СН,Rпредставляет собой,Rпредставляет собой -H или представляет собой C1-C6 алкильную группу, C3-C6 циклоалкильную группу или,каждая из которых может быть замещена 1-3 группами -OH;или его фармацевтически приемлемая соль.2. Соединение по п. 1, где кольцо А представляет собой,Rпредставляет собой -C(=O)-NH-Rили -NH-C(=O)-NH-R,Rпредставляет собой -F, иRпредставляет собой;или его фармацевтически приемлемая соль.3. Соединение по п. 1, где кольцо А представляет собой,Rпредставляет собой -С(=O)-NH-R,Rпредставляет собой -F,Rпредставляет собой,иRпредставляет собой гидроксиизопропильную группу или циклопропильную группу;или его фармацевтически приемлемая соль.4. Соединение по п. 1, где кольцо А представляет собой,Rпредставляет ...

Способ получения ациламинопроизводных гетероциклических соединений

4-STILBENYL-1,2,3-TRIAZOLE, VERFAHREN ZU DEREN HERSTELLUNG UND IHRE VERWENDUNG ALS OPTISCHE AUFHELLER

2-Equiv. coupler prodn. from 4-equiv. coupler - by introducing leaving gp. using selenium or tellurium cpd. for preliminary electrophilic reaction

Prodn. of a 2-equiv. coupler Cp-Nu (I) involves reacting a 4-equiv. coupler Cp-H (II) or a corresp. coupler with a COOH, CHO or SO3H gp. in the coupling position with either (a) a cpd. (IV) contg. positive Se or Te and (the anion) of a cpd. Nu-H (III) or (b) a prim. prod. formed from (III) and (IV) and eliminating Se or Te or a Se or Te cpd. of low valency. Nu = the gp. of a cpd. (III) released during colour development, the H atom of (III) being attached to O or N. (I) is useful in colour photographic materials, e.g. negative and reversal film and colour paper. Introduction of Se or Te in the coupling position by electrophilic reaction makes it possible then to introduce O- or N-fugitive gps. by addn. of nucleophilic exchange. In an example, a soln. of 25 g. 1-trichlorophenyl-3-(2-chloro -5- tetradecanoylamino)-anilinopyrazol-5-one in 400 ml. i-PrOH was treated with 2.8 g. fine SeO2 powder and stirred 10 hrs. at room temp. 300 ml. toluene at 50 deg.C were added then the dark suspension ...

NEUE BENZOXAZOL-STYRYLE

6-(SUBSTITUIERTE) METHYLEN-PENICILLANSAEURE UND 6-(SUBSTITUIERTE) HYDROXYMETHYL-PENICILLANSAEURE UND DEREN DERIVATE.

INDANESSIGSÄURE-DERIVATE UND IHRE VERWENDUNG ALS PHARMAZEUTISCHE MITTEL SOWIE ZWISCHENPRODUKTE UND METHODEN ZU IHRER HERSTELLUNG

VERFAHREN ZUM OPTISCHEN AUFHELLEN VON ORGANISCHEN MATERIALIEN

VERBINDUNGEN, VERFAHREN UND FORMULIERUNGEN ZUR ORALEN VERABREICHUNG EINER GLUCAGONARTIGEN PEPTID (GLP)-1-VERBINDUNG ODER EINES MELANOCORTIN-4-REZEPTOR-(MC4-)AGONISTSCHEN PEPTIDS

1,5-DIPHENYLTRIAZOLE DERIVATIVE FOR USE IN HERBICIDAL PREPARA TIONS AND METHODS FOR CONTROLLING WEEDS THEREBY

... 1459060 1 - (3 - Trifluoromethylphenyl) 5- phenyl - 1,2,3 - triazole SOC ITALIANA RESINE SIR SpA 17 April 1975 [19 April 1974] 15943/75 Heading C2C 1 - (3 - Trifluoromethylphenyl) - 5 - phenyl- 1,2,3-triazole is prepared by decarboxylation of 1 - (3 - trifluoromethylphenyl) - 4 - carboxyl - 5- phenyl - 1,2,3 - triazole. 1 - (3 - Trifluoromethylphenyl) - 4 - carboxyl - 5 - phenyl - 1,2,3- triazole is prepared by the reaction of m-trifluoromethylphenyl azide with ethyl benzoyl acetate. Herbicidal compositions contain as active ingredient 1-(3 -trifluoromethylphenyl)-5-phenyl-1,2,3-triazole together with an inert diluent or filler.

PROCESS FOR THE MANUFACTURE OF 2-ARYL-V-TRIAZOLES

... 1381063 2-Aryl-v-triazoles BAYER AG 2 March 1973 [3 March 1972] 10241/73 Heading C2C A process for preparing v-triazoles of the general formula wherein Ar is a mono- or divalent optionally substituted carbocyclic or heterocyclic radical; R 1 is an optionally substituted alkyl or aryl radical or a nitro group; R 2 is a hydrogen atom or an optionally substituted alkyl or aryl radical and n is 1 or 2, by reacting an -oximinoaryl-hydrazone of the formula with either (a) at least 2 equivalents of an isocyanate or carbamic acid halide or (b) at least 1 equivalent of a pyrocarbonic acid ester. The reaction is suitably carried out at a temperature of from 20‹ to 100‹ C. in the presence of a solvent, e.g. dimethylformamide or a water/alcohol mixture, and/or a basic catalyst. The isocyanate is suitably of the formula Q.NCO wherein Q is hydrogen, (C 1 -C 6 ) alkyl or (C 5 -C 7 ) cycloalkyl optionally substituted by halogen, (C 1 -C 4 ) alkyl, (C 1 -C 4 ) alkoxy or nitro, or a phenyl, phenylcarbonyl ...

Improvements in and relating to addition reactions between aminoacetylene compounds and compounds containing at least one non-aromatic unsaturated site

Addition products are obtained by contacting, at a sufficient temperature, an aminoacetylenic compound wherein at least one of the acetylenic carbon atoms has a secondary amino group bonded thereto, and a compound having at least one non-aromatic unsaturated site; the addition product contains a new ring consisting of the originally acetylenic carbon atoms and at least two atoms which were part of the originally unsaturated site. In particular, the following addition products are claimed per se, and are obtained from YC ­ CNR2 and RCON3, ROOC.C ­ COOR, RN3, RCNO, ONC.R11. CNO, RC ­ N = N-R, RR1C = O and RR1C = NR respectively (R is C1- 18 monovalent hydrocarbon; Y is hydrogen, R or NR2 (where the two R groups may form an alkylene chain); R1 is hydrogen or R; and R11 is C1- 10 divalent hydrocarbon) Подробнее

Substituted aminoalkylazoles as malarial aspartic protease inhibitors

The present invention relates to novel aminoalkylazoles acting as inhibitors of malarial protease plasmepsin II. These can be used as medicines or as constituent of medicines for the treatment of malaria infection.

G-quadruplex stabilising agent

Novel insecticides

Compounds

OX1 Antagonists

Novel compounds, methods for their manufacture, and uses thereof

Synthetic cannabinoid analogue compounds of formula (I), wherein X is a group as defined herein. Also provided is a pharmaceutical composition of compounds of formula (I). Also provided is a compound of formula (I), or pharmaceutical composition, for use in a method of treatment, or for use as a medicament; which may be for use in the treatment of, or for use as a medicament for treating, epilepsy, generalised seizure, tonic-clonic seizure. Also provided is a method of preparing a compound of formula (I), comprising reacting a compound of formula (II) with a compound of formula (III), both defined herein. The method may use a palladium catalyst. Also provided is a method of preparing compounds of formula (I), comprising reacting a compound of formula (II) with bis(pinacolato)diboron (B2pin2), and reacting the product of that with a compound of formula (IV). The steps of the method may use a palladium catalyst. Also provided is an intermediate compound of formula (II), for use in the preparation ...

Biaryl ether derivatives useful as monomine reuptake inhibitors

Glucagon receptor modulator

Triazole insecticides.

Benzanilide derivatives as 5-HT 1D antaginists.

This invention relates to novel benzanilide derivatives, to processes for their preparation, and to pharmaceutical compositions containing them.

Prevention of loss and restoration of bone mass by certain prostaglandin agonists.

Prostaglandin agonists of formula (1), in which, for example, A is a sulphonyl or acyl group, B is N or CH, M contains a ring and K and Q are linking groups, methods of using such prostaglandin agonists, pharmaceutical compositions containing such prostaglandin _ . agonists and kits useful for the treatment of bone disorders including osteoporosis.

Triazole insecticides

Compounds of ...

Substituted N-({Aminoiminomethyl or aminomethyl} phenyl] propyl amides.

The compounds according to the invention are substituted N-[ (aminoiminomethyl or aminomethyl) phenyl]propyl amides of formula (I) herein which exhibit useful pharmacological activity and accordingly are incorporated into pharmaceutical compositions and used in the treatment of patients suffering from certain medical disorders. More especially, they are Factor Xa inhibitors. The present invention is directed to compounds of formula (I), compositions containing compounds of formula (I), methods for their preparation and their use, which are for treating a patient suffering from, or subject to, conditions which can be ameliorated by the administration of an inhibitor of Factor"' Xa.

Substituted N-[(Aminoiminomethyl or aminomethyl) Phenyl] Propyl amides.

This invention relates to compounds of formula (I) which inhibit Factor Xa, to pharmaceutical compositions containing the compounds, and to the use of the compounds for the treatment of patients suffering from conditions which can be ameliorated by the administration of an inhibitor of Factor Xa.

Diphenyl ether compounds useful in therapy.

A compound of general formula (1), or pharmaceutically acceptable salts, solvates or polymorphs thereof, wherein R3 is independently CF3, OCF3, C1-C4alkylthio or C1-C4alkoxy, N is 1,2 or 3; and the other valuables are as defined in the claims. These compounds inhibit monoamine re-uptake inhibitors. They are useful in disorders such as depression, attention deficit hyperactivity disorder, obsessive-compulsive disorder, post-traumatic stress disorder, substances abuse disorders and sexual dysfunction including premature ejaculation.

Diphenyl ether compound as useful in therpay

Prevention of loss and restoration of bone mass by certain prostaglandin

1-heterocycle substituted diarylamines.

... 1-heterocycle substituted diarylamines, methods of making and using them, and compositions containing them.

Subs itute n-Ú( minoi inome hyl or aminomethyl)phenyl¾propyl amides

Substituted n-[(aminoiminomethyl or aminomethyl) phenyl]propyl amides

Compounds for the treatment of ischemia.

Nhe-1 inhibitors, methods of using such nhe-1 inhibitors and pharmaceutical compositions containing such nhe-1 inhibitors. The nhe-1 inhibitors are useful for the reduction of tissue damage resulting from tissue ischemia ...

Biaryl ether derivatives useful as monoamine reuptake inhibitors.

The present invention relates to compounds of formula (I) and to their pharmaceutically acceptable salts. Compounds of formula (I) exhibit activity as serotonin, norepinephrine, and dopanine reuptake inhibitors and can be used in the treatment of central nervous system and other disorders.

TRIOAZOLE INSECTICIDE

BENZANILIDE DERIVATIVES

Substituted aryl acylthioureas and related compounds; inhibitors of viral replication

N,N' -substituted-1,3-diamino -2-hydroxypropane derivatives.

Disclosed are compounds of the formula (0, wherein the variables RN, RC, R1, R25, R2, and R3 are as defined herein. These compounds have activity as inhibitors of betasec-retase and are therefore useful in treating a variety of discorders such as Alzheimer's Disease.

Alpha substituted carboxylic acids as ppar modulators.

Substituted aryl thioureas and related compounds; inhibitors of viral replication

Glucagon receptor modulator

Glucagon receptor modulator

Biaryl ether derivatives useful as monoamine reuptake inhibitors.

Substituted n-Ä(aminoiminomethyl or aminomethyl)p henylÜpropyl amides

N-Ä(substituted five-membered di-or triaza diunsaturated ring)carbonylÜ guanidine derivatives for the treatment of ischemia.

N,N'-substituted-1,3-diamino-2-hydroxypropane derivatives.

1-Heterocycle substituted diarylamines.

Diphenyl ether compounds useful in therapy.

Benzanilide derivatives

Heterocyclic herbicides.

Substituted aryl thioureas and related compounds, inhibitors of viral replication.

Alpha substituted carboxylic as PPAR modulators.

Prevention of loss and restoration of bone mass bycertain prostaglandin agonists

Substituted N-[(aminoiminomethyl or aminomethyl) phenyl]propyl amides

Substituted aryl thioureas and related compounds; inhibitors of viral replication

Alpha substituted carboxylic acids as ppar modulators.

Substituted n-[(aminoiminomethyl or aminomethyl) phenyl]propyl amides

Prevention of loss and restoration of bone mass by certain prostaglandin

Diphenyl ether compound as useful in therpay

BENZANILIDE DERIVATIVES

Substituted aryl thioureas and related compounds; inhibitors of viral replication

Subs itute n-Ú( minoi inome hyl or aminomethyl)phenyl¾propyl amides

Alpha substituted carboxylic acids as ppar modulators.

TRIOAZOLE INSECTICIDE

Glucagon receptor modulator

Substituted aryl acylthioureas and related compounds; inhibitors of viral replication

Diphenyl ether compound as useful in therpay

PROCEDURE FOR THE PRODUCTION OF NEW ONE 1.2.3 - TRIAZOLDERIVATEN

CONNECTIONS, PROCEDURES AND FORMULATIONS FOR the ORAL ADMINISTRATION of a GLUCAGON LIKE of PEPTIDE (GLP) - 1-VERBINDUNG OR TO MELANOCORTIN-4 RECEPTOR (MC4) AS AGONIST a WORKING PEPTIDS

HERBIZID

DIPEPTIDE NITRILES

NIACIN REZEPTORAGONISTEN, COMPOSITIONS WITH SUCH CONNECTIONS AND TREATMENT PROCEDURES

ARYL-SULFONE-AMIDE-SUBSTITUTED HYDROXAMIC ACID DERIVATIVES

ARYLSULFONYLNAPHTHALINDERIVATE AS 5HT2A ANTAGONISTS

VERFAHREN ZUR HERSTELLUNG NEUER PYRAZOL-TRIAZOL -ODER TETRAZOLDERIVATE

AS CETP HEMMER SUITABLE HOMOUND HETERO-CYCLIC CONNECTIONS

Procedure for the Hochveredlung of natural or synthetic synthetic materials under simultaneous optical clarification

CONNECTIONS THE VLA-4 OBTAINED ADHESION OF LEUKOCYTES INHIBIEREN

BENZEN, PYRIDIN, PYRIMIDINDERIVAT

ALPHA AMINOPHENYLESSIGSAEUREDERIVATE ONE FOR USE WITH THE TREATMENT OF INFLAMMATIONS AS WELL AS NEW ONE ALPHA AMINOPHENYLESSIGSAEUREDERIVATE ONE.

BENZAMIDINDERIVATE AS ANTAGONISTS OF OREXINREZEPTOREN

Procedure for the production of new Triazol derivatives

BENZAMID DERIVATIVES AND YOUR USE AS CYTOKINE INHIBITORS

Procedure for the production of new Triazolderivaten

SULPHONYL AMINOCARBONIC ACIDS

N-ALKANOYLPHENYLALANINDERIVATE ONE

Novel tetrazole compounds and their use in the treatment of tuberculosis

The invention relates to a compound of Formula (I) or a pharmaceutically acceptable salt thereof and their use in therapy, for example in the treatment of mycobacterial infections or in the treatment of diseases caused by mycobacterium, such as tuberculosis.

Benzamide derivatives and their use as cytokine inhibitors

HIV reverse transcriptase inhibitors

Pharmaceutical product

An agent for suppressing the production of various cytokines (IL-8 and the like) and inflammatory mediators, an agent for suppressing the expression of COX-II and the like, or an inhibitor of various phosphorylation enzymes (ATF2 and the like), which contains a TLR signaling inhibitory substance, preferably a compound represented by the formula (I) or the formula (II) wherein each symbol is as defined in the specification, or a salt thereof or a prodrug thereof.

Compounds, Compositions and Methods for Modulating Uric Acid Levels

Described herein are compounds useful in the reduction of blood uric acid levels, formulations containing them and methods of making and using them. In some embodiments, the compounds described herein are used in the treatment or prevention of disorders related to aberrant levels of uric acid.

Substituted Esters as Cannabinoid-1 Receptor Modulators

Novel compounds of the structural formula (I) are antagonists and/or inverse agonists of the Cannabinoid-1 (CB1) receptor and are useful in the treatment, prevention and suppression of diseases mediated by the CB1 receptor. The compounds of the present invention are useful as centrally acting drugs in the treatment of psychosis, memory deficits, cognitive disorders, Alzheimer's disease, migraine, neuropathy, neuro-inflammatory disorders including multiple sclerosis and Guillain-Barre syndrome and the inflammatory sequelae of viral encephalitis, cerebral vascular accidents, and head trauma, anxiety disorders, stress, epilepsy, Parkinson's disease, movement disorders, and schizophrenia. The compounds are also useful for the treatment of substance abuse disorders, the treatment of obesity or eating disorders, as well as the treatment of asthma, constipation, chronic intestinal pseudo-obstruction, cirrhosis of the liver, non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH), and the promotion of wakefulness.

Iodine radiolabelling method

The present invention provides a novel method of labelling biological targeting molecules (BTMs) of interest with radioiodine. Also provided are novel radioiodinated BTMs prepared using the method, as well as radiopharmaceutical compositions comprising such radioiodinated BTMs. The invention also provides radioiodinated intermediates useful in the method, as well as in vivo imaging methods using the radioiodinated BTMs.

COMPOUNDS AND METHODS FOR MODULATING G PROTEIN-COUPLED RECEPTORS

The invention provides compounds, pharmaceutical compositions comprising such compounds and methods of using such compounds to treat or prevent diseases or disorders associated with or mediated by G protein-coupled receptors, in particular G protein-coupled receptor 120. 2. (canceled)3. The compound of claim 1 , wherein Ris H or Calkyl.4. The compound of claim 3 , wherein each Ris independently a halo.5. The compound of claim 4 , wherein each Ris independently selected from fluoro and bromo.6. (canceled)8. The compound of selected from:3-(4-p-tolyl-1H-1,2,3-triazol-1-yl)benzoic acid,3-(4-(4-(trifluoromethyl)phenyl)-1H-1,2,3-triazol-1-yl)benzoic acid,3-(4-(4-chlorophenyl)-1H-1,2,3-triazol-1-yl)benzoic acid,3-(4-(2-fluorophenyl)-1H-1,2,3-triazol-1-yl)benzoic acid,3-(4-(4-ethylphenyl)-1H-1,2,3-triazol-1-yl)benzoic acid,3-(4-(2,4-difluorophenyl)-1H-1,2,3-triazol-1-yl)benzoic acid,3-(4-(4-bromophenyl)-1H-1,2,3-triazol-1-yl)benzoic acid,3-(1-(4-isopropylphenyl)-1H-1,2,3-triazol-4-yl)benzoic acid,3-(4-(4-ethylphenyl)-1H-1,2,3-triazol-1-yl)-5-methoxybenzoic acid,3-(4-(4-ethylphenyl)-1H-1,2,3-triazol-1-yl)-5-fluorobenzoic acid,3-(1-(2-fluoro-4-methylphenyl)-1H-1,2,3-triazol-4-yl)benzoic acid,5-(4-(4-ethylphenyl)-1H-1,2,3-triazol-1-yl)-2-fluorobenzoic acid and3-(4-(4-ethylphenyl)-1H-1,2,3-triazol-1-yl)-4-fluorobenzoic acid.9. A pharmaceutical composition comprising a therapeutically effective amount of a compound of Formula (I) of claim 1 , and a pharmaceutically acceptable carrier.10. (canceled)11. (canceled)12. (canceled)13. (canceled)14. (canceled)15. (canceled)16. A method for treating a disease or disorder where modulation of GPR120 is implicated claim 1 , comprising administering to a system or subject in need of such treatment an effective amount of a compound of Formula (I) of claim 1 , or pharmaceutically acceptable salts or pharmaceutical compositions thereof claim 1 , thereby treating the disease or disorder claim 1 , wherein the disease or disorder is selected ...

TRYPTOPHAN HYDROXYLASE INHIBITORS FOR THE TREATMENT OF METASTATIC BONE DISEASE

This invention relates to tryptophan hydroxylase inhibitors, compositions comprising them, and methods of their use for the treatment, management and/or prevention of metastatic bone disease. 2. The use of claim 1 , wherein the metastatic bone disease is osteosclerotic (osteoblastic).3. The use of claim 2 , wherein the metastatic bone disease is bone metastases of prostate cancer.4. The use of claim 3 , wherein the compound is used in combination with a therapeutically or prophylactically effective amount of a second drug.5. The use of claim 4 , wherein the second drug is a luteinizing hormone-releasing hormone agonist (e.g. claim 4 , leuprolide claim 4 , goserelin claim 4 , buserelin); an antiandrogen (e.g. claim 4 , flutamide claim 4 , nilutamide); or an adrenal gland inhibitor (e.g. claim 4 , ketoconazole claim 4 , aminoglutethimide).6. The use of claim 5 , wherein the second drug is mitoxantrone claim 5 , estramustine claim 5 , doxorubicin claim 5 , etoposide claim 5 , vinblastine claim 5 , paclitaxel claim 5 , carboplatin claim 5 , or vinorelbine.11. The pharmaceutical composition of claim 10 , wherein the second drug is mitoxantrone claim 10 , estramustine claim 10 , doxorubicin claim 10 , etoposide claim 10 , vinblastine claim 10 , paclitaxel claim 10 , carboplatin claim 10 , or vinorelbine. This invention relates to tryptophan hydroxylase inhibitors, compositions comprising them, and methods of their use for the treatment, management and/or prevention of metastatic bone disease.The neurotransmitter serotonin [5-hydroxytryptamine (5-HT)] is involved in multiple central nervous facets of mood control and in regulating sleep, anxiety, alcoholism, drug abuse, food intake, and sexual behavior. In peripheral tissues, serotonin is implicated in the regulation of vascular tone, gut motility, primary hemostasis, and cell-mediated immune responses. Walther, D. J., et al., 299:76 (2003). Some evidence also suggests that serotonin can affect bone growth. See, e.g., ...

PROCESS FOR PREPARATION OF RUFINAMIDE

The invention relates to a novel, industrially viable, cost effective process for the preparation of 1-(2,6-difluorobenzyl)-1H-1,2,3-triazole-4-carboxamide commonly known as Rufinamide and intermediates thereof. 2. The process according to claim 1 , wherein R is hydrogen claim 1 , methyl or ethyl.3. The process according to claim 1 , wherein formula V is selected from 2-bromoacrylic acid claim 1 , methyl 2-bromoacrylate and ethyl 2-bromo acrylate.4. The process according to claim 1 , wherein the compound of formula VI prepared in step (b) is methyl 1-(2 claim 1 ,6-difluorobenzyI)-1H-1 claim 1 ,2 claim 1 ,3-triazole-4-carboxylate.6. The process according to claim 5 , wherein the compound of formula V is selected from 2-bromoacrylic acid claim 5 , methyl 2-bromoacrylate and ethyl 2-bromo acrylate.7. The process according to claim 5 , wherein the compound prepared is methyl 1-(2 claim 5 ,6-difluorobenzyl)-1H-1 claim 5 ,2 claim 5 ,3-triazole-4-carboxylate.9. The process according to claim 8 , wherein R is hydrogen claim 8 , methyl or ethyl.10. The process according to claim 9 , wherein R is methyl.11. The process according to claim 8 , wherein the brominating agent is selected from the group consisting of phosphorus tribromide claim 8 , aluminum tribromide and bromine.12. The process according to claim 11 , wherein the brominating agent is bromine.13. The process according to claim 8 , wherein the base is selected from the group consisting of sodium carbonate claim 8 , sodium bicarbonate claim 8 , potassium carbonate claim 8 , potassium bicarbonate claim 8 , potassium t-butoxide and triethylamine.14. The process according to claim 13 , wherein sodium carbonate and triethylamine is used as base.15. The process according to claim 8 , wherein the compound prepared is methyl 2-bromoacrylate. The invention provides a novel, industrially viable, cost effective process for manufacturing methyl 1-(2,6-difluorobenzyl)-1H-1,2,3-triazole-4-carboxylate a key intermediate in the ...

CRYSTALLINE 1H-1,2,3-TRIAZOL-5-YLIDENES

The present invention provides novel and stable crystalline 1H-1,2,3 triazolium carbenes and metal complexes of 1H-1,2,3 triazolium carbenes. The present invention also provides methods of making 1H-1,2,3 triazolium carbenes and metal complexes of 1H-1,2,3 triazolium carbenes. The present invention also provides methods of using 1H-1,2,3 triazolium carbenes and metal complexes of 1H-1,2,3 triazolium carbenes in catalytic reactions. 84. The compound of any one of - claims 2 , wherein Rand Rare claims 2 , in each instance claims 2 , independently selected from the group consisting of hydrogen claims 2 , methyl claims 2 , ethyl claims 2 , propyl claims 2 , isopropyl claims 2 , butyl claims 2 , isobutyl claims 2 , halogen claims 2 , and hydroxyl.9. The compound of claim 8 , wherein Rand Rare both isopropyl and subscripts m and n are both 2.10. The compound of claim 8 , wherein Ris isopropyl and subscript m is 2.11. The compound of claim 8 , wherein Ris isopropyl and subscript n is 2.12. The compound of claim 8 , wherein Rand Rare both methyl and subscripts m and n are both 3.13. The compound of claim 8 , wherein Ris methyl and subscript m is 3.14. The compound of claim 8 , wherein Ris methyl and subscript n is 3.15. The compound of claim 8 , wherein m and n are both 0.16. The compound of claim 8 , wherein m is 0.17. The compound of claim 8 , wherein n is 0.18. The compound of claim 5 , wherein Rand Rare both isopropyl and subscripts m and p are both 2.19. The compound of claim 5 , wherein Ris isopropyl and subscript m is 2.20. The compound of claim 5 , wherein Ris isopropyl and subscript p is 2.21. The compound of claim 5 , wherein Rand Rare both methyl and subscripts m and p are both 3.22. The compound of claim 5 , wherein Ris methyl and subscript m is 3.23. The compound of claim 5 , wherein Ris methyl and subscript p is 3.24. The compound of claim 5 , wherein m and p are both 0.25. The compound of claim 5 , wherein m is 0.26. The compound of claim 5 , wherein p is 0. ...

Compounds And Methods For Treating Candidiasis And Aspergillus Infections

The present disclosure provides compounds, or pharmaceutically acceptable salts thereof, for killing or inhibiting the growth of a or species or preventing or treating a mammal having candidiasis (oral and/or disseminated) or an infection. 2. The method of wherein each X is S.3. The method of wherein each Ris claim 1 , independently claim 1 , —CH claim 1 , —(CH)—NH claim 1 , —(CH)—NH—C(═NH)NH claim 1 , or —(CH)—NH—C(═O)—R claim 1 , where each n is claim 1 , independently claim 1 , 1 or 2 claim 1 , and each Ris claim 1 , independently claim 1 , H or methyl.49-. (canceled)10. The method of wherein each Ris CF.11. The method of wherein each Vis H and each Vis claim 1 , independently claim 1 , —N—C(═O)—R claim 1 , where each Ris claim 1 , independently claim 1 , —(CH)—NHor —(CH)—NH—C(═NH)NH claim 1 , where each n is claim 1 , independently claim 1 , 1 to 4.1218-. (canceled)19. The method of wherein each Vis H and each Vis —S—R claim 1 , where each Ris —(CH)—NHwhere each n is 2.20. The method of wherein each Ris H claim 1 , —S—(CH)—NH claim 1 , or —S—(CH)—NH—C(═NH)NH claim 1 , where each m is claim 1 , independently claim 1 , 1 to 4.2123-. (canceled)24. The method of wherein:each X is S;{'sup': '1', 'sub': 2', 'n', '2', '2', 'n', '2, 'each Ris, independently, —(CH)—NHor —(CH)—NH—C(═NH)NH, where each n is, independently, 1 to 4;'}{'sup': '2', 'sub': 3', '3', '3, 'each Ris, independently, halo, CF, or C(CH); and'}{'sup': 1', '2', '5', '5, 'sub': 2', 'n', '2, 'each Vis H and each Vis, independently, —S—R, where each Ris, independently, —(CH)—NH, where each n is, independently, 1 to 4.'}2532-. (canceled)3553-. (canceled)5576-. (canceled)7880-. (canceled)82122-. (canceled)124159-. (canceled)161179-. (canceled)181198-. (canceled)200218-. (canceled)220237-. (canceled)239243-. (canceled)245252-. (canceled) The present disclosure was supported by funds from the U.S. Government (NIH/NIDCR Grant No. 2R44DE018371-02) and the U.S. Government may therefore have certain rights in the ...

AZOLE COMPOUNDS USED AS TUBERCULOSTATIC AND LEISHMANICIDE AGENTS

This invention refers to new 1,2,3-triazole and imidazole compounds included in the families of compounds represented by general formula VIII. This invention also refers to a pharmaceutical composition comprising at least one of the azole compounds represented by the general formula VIII, to the use of such compositions and to methods of treatment or inhibition of tuberculosis and leishmaniasis. 2. The method according to claim 1 , wherein the pharmaceutical composition is employed in the pharmaceutical form of solution claim 1 , suspension claim 1 , emulsion claim 1 , ointment claim 1 , cream claim 1 , gel claim 1 , tablet and/or capsule.3. The method according to claim 2 , wherein the pharmaceutical composition is employed in the pharmaceutical form for oral claim 2 , topical and/or injectable use.4. The method of claim 1 , wherein the azole compound is selected from the group consisting of:1-(3-chlorophenyl)-4-difluoromethyl-1H-1,2,3-triazole,1-(3,5-dichlorophenyl)-4-difluoromethyl-1H-1,2,3-triazole, andone of their salts.5. The method of claim 1 , wherein the azole compound is selected from the group consisting of:(AND)-4-chloride-N-((1-(4-chlorophenyl)-1H-1,2,3-triazole-4-il)methylene)benzenamine,(AND)-4-bromo-N-((1-(4-bromophenyl)-1H-1,2,3-triazole-4-il)methylene)benzenamine, andone of their salts. This is a divisional of co-pending U.S. patent application Ser. No. 12/981,315, filed Dec. 29, 2010, which is a continuation of U.S. application Ser. No. 12/064,241, filed Jun. 16, 2008, now abandoned, which is the U.S. National Stage of International Application No. PCT/BR2006/000169, filed Aug. 21, 2006, which was published in English under PCT Article 21(2), and which claims benefit of priority of Brazilian Patent Application No. PI 0503681-0, filed Aug. 19, 2005, all of which are incorporated herein in their entirety.This invention refers to azole compounds pertaining to the 1,2,3-triazole and imidazole classes that can be used to treat tuberculosis and ...

TRIAZOLIDE BASED IONIC LIQUIDS

A method of synthesizing an ionic liquid, includes reacting a 1,2,3-triazole including at least one of a 4-substituent or a 5-substituent with a hydroxide compound having the formula ROH in a dehydration reaction, wherein R is an ionic liquid cation. R is a five-membered heterocyclic cation, an aromatic cation, a sulfonium cation, an ammonium cation, or a phosphonium cation. In a number of embodiments, R is a pyridinium cation, a bipyridinium cation, an amino pyridinium cation, a pyridazinium cation, an ozaxolium cation, a pyrazolium cation, an imidazolium cation, a pyramidinium cation, a triazolium cation, a thiazolium cation, an acridinium cation, a quinolinium cation, an isoquinolinium cation, an orange-acridinium cation, a benzotriazolium cation, a methimzolium cation, a sulfonium cation, an ammonium cation, or a phosphonium cation. 1. A method of synthesizing an ionic liquid , comprising: reacting a 1 ,2 ,3-triazole comprising at least one of a 4-substituent or a 5-substituent with a hydroxide compound having the formula ROH in a dehydration reaction , wherein R is an ionic liquid cation.2. The method of wherein R is a five-membered heterocyclic cation claim 1 , an aromatic cation claim 1 , a sulfonium cation claim 1 , an ammonium cation claim 1 , or a phosphonium cation.3. The method of wherein R is a pyridinium cation claim 1 , a bipyridinium cation claim 1 , an amino pyridinium cation claim 1 , a pyridazinium cation claim 1 , an ozaxolium cation claim 1 , a pyrazolium cation claim 1 , an imidazolium cation claim 1 , a pyramidinium cation claim 1 , a triazolium cation claim 1 , a thiazolium cation claim 1 , an acridinium cation claim 1 , a quinolinium cation claim 1 , an isoquinolinium cation claim 1 , an orange-acridinium cation claim 1 , a benzotriazolium cation claim 1 , a methimzolium cation claim 1 , a sulfonium cation claim 1 , an ammonium cation claim 1 , or a phosphonium cation.5. The method of wherein R is an imidazolium cation claim 1 , an ammonium ...

FUNCTIONALIZED NAPHTHALENE FLUOROPHORES

Methods for the synthesis and use of functionalized, substituted naphthalenes are described. The functionalized, substituted naphthalenes display useful properties including liquid crystals and fluorescence properties, such as solvatochromatic fluorescence, with high quantum yields, Stoke's shift, and show emission maxima that are significantly red-shifted. 1. A functionalized naphthalene fluorophore having a structure:a) 1-(5-(dimethylamino)-2′,2′-dimethyl-1,3-dihydrospiro[cyclopenta[b]naphthalene-2,5′-[1,3]dioxan]-9-yl)ethanone;b) 1-(5-(dimethylamino)-2′,2′-dimethyl-1,3-dihydrospiro[cyclopenta[b]naphthalene-2,5′-[1,3]dioxan]-9-yl)-2,2-dimethylpropan-1-one;c) 1-(2,2-bis(((tert-butyldimethylsilyl)oxy)methyl)-8-(dimethylamino)-2,3-dihydro-1H-cyclo-penta[b]naphthalen-4-yl)ethanone;d) 1-(2′,2′-dimethyl-5-(pyrrolidin-1-yl)-1,3-dihydrospiro[cyclopenta[b]naphthalene-2,5′-[1,3]dioxan]-9-yl)ethanone;e) 1-(8-(dimethylamino)-2,2-bis(hydroxymethyl)-2,3-dihydro-1H-cyclopenta[b]naphthalen-4-yl)ethanone;f) 1-(8-(dimethylamino)-2,2-bis(hydroxymethyl)-2,3-dihydro-1H-cyclopenta[b]naphthalen-4-yl)-2,2-dimethylpropan-1-one;g) 1-(2,2-bis(hydroxymethyl)-8-(pyrrolidin-1-yl)-2,3-dihydro-1H-cyclopenta[b]naphthalen-4-yl)ethanone;h) (8-(dimethylamino)-4-pivaloyl-2,3-dihydro-1H-cyclopenta[b]naphthalene-2,2-diyl)bis(methylene)bis(undec-10-enoate);i) 6-((tert-butyldimethylsilyl)oxy)-1-(8-(dimethylamino)-2,3-dihydro-1H-cyclopenta[b]naphthalen-4-yl)hexan-1-one;j) 1-(8-(dimethylamino)-2,3-dihydro-1H-cyclopenta[b]naphthalen-4-yl)-6-hydroxyhexan-1-one;k) 9-(4-(2-((tert-butyldimethylsilyl)oxy)ethoxy)phenyl)-7-(dimethylamino)-2,3-dihydro-1H-cyclopenta[b]naphthalen-1-one;1) 7-(dimethylamino)-9-(4-(2-hydroxyethoxy)phenyl)-2,3-dihydro-1H-cyclopenta[b]naphthalen-1-one;m) 9-(4-(((tert-butyldimethylsilyl)oxy)methyl)phenyl)-7-(dimethylamino)-2,3-dihydro-1H-cyclopenta[b]naphthalen-1-one;n) 7-(dimethylamino)-9-(4-(hydroxymethyl)phenyl)-2,3-dihydro-1H-cyclopenta[b]naphthalen-1-one;o) 2-(4-(6-dimethylamino)-3- ...

Compounds for the treatment of proliferative disorders

The invention relates to compounds of structural formula (I): or a pharmaceutically acceptable salt, solvate, clathrate, and prodrug thereof, wherein R a , R b , and R 2 are defined herein. These compounds inhibit tubulin polymerization and/or target vasculature and are useful for treating proliferative disorders, such as cancer.

Compounds for the treatment of neurodegenerative diseases

Compounds and their pharmaceutically acceptable salts for treatment of synucleinopathies, such as Parkinson's disease and tauopathies.

N1- and N2-CARBAMOYL-1,2,3-TRIAZOLE SERINE HYDROLASE INHIBITORS AND METHODS

The present invention provides inhibitors of a wide variety of serine hydrolase enzymes. The inhibitors of the present invention are N1- and N2-carbamoyl-1,2,3-triazole compounds such as those of Formula (I): 3. The triazole compound of claim 2 , wherein Xis CH.4. The triazole compound of claim 2 , wherein Ris benzyl.5. The triazole compound of claim 1 , wherein Ror Ris diphenylmethanolyl.6. The triazole compound of claim 1 , wherein Ror Ris 4-phenyloxyphenyl.7. The triazole compound of claim 1 , wherein Ror Ris phenyl or naphthyl optionally substituted by a moiety selected from the group consisting of halo claim 1 , hydroxyl claim 1 , carboxyl claim 1 , NO claim 1 , Calkyl (optionally substituted by one claim 1 , two claim 1 , or three substituents each independently selected from hydroxyl claim 1 , cyano claim 1 , or halo) claim 1 , and Calkoxy (optionally substituted by one claim 1 , two claim 1 , or three substituents each independently selected from hydroxyl claim 1 , cyano claim 1 , and halo).9. The triazole compound of claim 1 , wherein Ris H.10. The triazole compound of claim 1 , wherein Ris H.15. The triazole compound of wherein w is 1 claim 14 , and Ris H.16. The triazole compound of wherein Ris phenyl or biphenyl claim 14 , optionally substituted with one claim 14 , two claim 14 , or three substituents each independently selected from the group consisting of: Calkyl claim 14 , Chydroxyalky claim 14 , Calkoxy claim 14 , Cperfluoroalkoxy claim 14 , halogen claim 14 , and hydroxyl.19. A pharmaceutical composition comprising a compound of and a pharmaceutically acceptable carrier.20. A method of inhibiting a serine hydrolase enzyme comprising contacting the serine hydrolase enzyme with a compound of .21. A method of inhibiting diacylglycerol lipase β (DAGLB) comprising contacting DAGLB with a compound of .24. (canceled)25. A method of treating pain claim 1 , comprising administering to a patient in need thereof an effective amount of a compound of .26. A ...

Imidazole, Pyrazole, and Triazole Derivatives Useful As Antibacterial Agents

The present invention is directed to a new class of hydroxamic acid derivatives, their use as LpxC inhibitors and, more specifically, their use to treat bacterial infections. 2. The compound according to claim 1 , or a pharmaceutically acceptable salt thereof; [{'sup': '1', 'sub': 1', '3, 'Ris (C-C)alkyl;'}, {'sup': '2', 'sub': 1', '3, 'Ris (C-C)alkyl;'}, {'sup': '3', 'sub': 1', '3, 'Ris hydrogen or (C-C)alkyl;'}, 'X is N;', {'sup': '4', 'Y is N or CR;'}, {'sup': '4', 'sub': 1', '3, 'Ris hydrogen or (C-C)alkyl;'}, {'sub': 2', '6', '2', 'n', '2', 'p', '2', 'n', '2', 'p, 'L is a bond, (C-C)alkynylene, —(CH)O—(CH)—, or —(CH)S(CH)—;'}, 'n is 0, 1, or 2;', 'p is 0, 1, or 2;', {'sup': '7', 'sub': 1', '6', '6', '12', '5', '8', '3', '8', '5', '12', '3', '13, 'Ris (C-C)alkyl, (C-C)aryl, cyano, (C-C)cycloalkenyl, (C-C)cycloalkyl, (C-C)heteroaryl, or (C-C)heterocycle; and'}, {'sup': '8', 'sub': 6', '12', '6', '12', '1', '6', '3', '8', '5', '12, 'Ris absent, (C-C)aryl, (C-C)aryl(C-C)alkyl, (C-C)cycloalkyl, or (C-C)heteroaryl.'}], 'wherein3. The compound according to claim 1 , or a pharmaceutically acceptable salt thereof; [{'sup': '1', 'Ris methyl;'}, {'sup': '2', 'Ris methyl;'}, {'sup': '3', 'Ris hydrogen or methyl;'}, 'X is N;', {'sup': '4', 'Y is N or CR;'}, {'sup': '4', 'Ris hydrogen or methyl;'}, {'sub': 2', '6', '2', 'n', '2', 'p', '2', 'n', '2', 'p, 'L is a bond, (C-C)alkynylene, —(CH)O—(CH)—, or —(CH)S(CH)—;'}, 'n is 0, 1, or 2;', 'p is 0, 1, or 2;', {'sup': '7', 'sub': 6', '12', '6', '12', '1', '6', '1', '6', '1', '6', '1', '6', '1', '6, 'Ris (C-C)aryl, wherein the (C-C)aryl is dihydroindenyl, naphthyl, phenyl, or tetrahydronaphthalenyl, wherein each is optionally substituted with 1, 2, or 3 substituents that are independently (C-C)alkoxy, (C-C)alkyl, (C-C)alkylthio, cyano, ethylenedioxy, halo(C-C)alkoxy, halo(C-C)alkyl, halogen, hydroxy, or oxo; and'}, {'sup': '8', 'sub': 3', '8', '5', '12, 'Ris absent, (C-C)cycloalkyl, or (C-C)heteroaryl.'}], 'wherein4. The compound ...

Near-ir glucose sensors

Glucose-sensing luminescent dyes, polymers, and sensors are provided. Additionally, systems including the sensors and methods of using these sensors and systems are provided.

Piperazine derivatives having multimodal activity against pain

The present invention relates to compounds having dual pharmacological activity towards both the sigma (σ) receptor, and the μ-opioid receptor and more particularly to piperazine compounds having this pharmacological activity, to processes of preparation of such compounds, to pharmaceutical compositions comprising them, and to their use in therapy, in particular for the treatment of pain.

COMPOUNDS FOR THE TREATMENT OF NEURODEGENERATIVE DISEASES

Compounds and their pharmaceutically acceptable salts for treatment of tauopathies, such as Alzheimer's disease, Pick's disease, progressive supranuclear palsy, corticobasal degeneration, familial frontotemporal dementia/Parkinsonism linked to chromosome 17, amyotrophic lateral sclerosis/Parkinsonism-dementia complex, argyrophilic grain dementia, dementia pugilistic, diffuse neurofibrillary tangles with calcification, progressive subcortical gliosis and tangle only dementia. 2. A method of disrupting or inhibiting the formation claim 1 , deposition claim 1 , accumulation claim 1 , or persistence of tau fibrils and/or aggregates claim 1 , comprising administering a therapeutically effective amount of the compounds of .3. The method of claim 2 , where the compound administered is in an amount between 0.1 mg/Kg/day and 1000 mg/Kg/day.4. The method of claim 2 , where the compound is administered in an amount between 1 mg/Kg/day and 100 mg/Kg/day.5. The method of claim 2 , where amount of compound administered is in an amount between 10 mg/Kg/day and 100 mg/Kg/day.6. A method resulting in neuroprotection from a tauopathy in a mammal comprising the step of administrating a therapeutically effective amount of a compound of .7. The method of where the tauopathy is one selected from; Alzheimer's disease claim 6 , Pick's disease claim 6 , progressive supranuclear palsy claim 6 , corticobasal degeneration claim 6 , familial frontotemporal dementia/Parkinsonism linked to chromosome 17 claim 6 , amyotrophic lateral sclerosis/Parkinsonism-dementia complex claim 6 , argyrophilic grain dementia claim 6 , dementia pugilistic claim 6 , diffuse neurofibrillary tangles with calcification claim 6 , progressive subcortical gliosis and tangle only dementia.8. An article of manufacture claim 1 , comprising packaging material claim 1 , the compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , contained within packaging material claim 1 , which is used for treating ...

ARYLAZOLE COMPOUND AND PEST CONTROL AGENT

A compound represented by Formula (I), or a salt or N-oxide compound thereof is provided. 3. A pest control agent comprising at least one compound according to claim 1 , a salt thereof claim 1 , or an N-oxide compound thereof as an active ingredient and a carrier.4. A method for controlling a pest or mite on or in a subject comprising the step of administrating to the subject an effective amount of at least one compound according to claim 1 , a salt thereof claim 1 , or an N-oxide compound thereof claim 1 ,{'i': 'Polyphaga', 'wherein the pest or mite is one or more selected from the group consisting of: butterflies and moths of the order Lepidoptera; pests of the order Thysanoptera; pests of the order Hemiptera; pests of the order ; pests of the order Diptera; pests of the order Orthoptera; and mites of the subclass Acari.'}5. A method for controlling an insect or acarus on or in a subject comprising the step of administrating to the subject an effective amount of at least one compound according to claim 1 , a salt thereof claim 1 , or an N-oxide compound thereof.6. A method for controlling an ectoparasite on or in a subject comprising the step of administrating to the subject an effective amount of at least one compound according to claim 1 , a salt thereof claim 1 , or an N-oxide compound thereof.7. A method for controlling or expelling an endoparasite in a subject comprising the step of administrating to the subject an effective amount of at least one compound according to claim 1 , a salt thereof claim 1 , or an N-oxide compound thereof. This application is a Divisional of U.S. application Ser. No. 16/061,783, which is the U.S. National Stage application of PCT/JP2016/087358, filed Dec. 15, 2016, which claims priority from Japanese Patent Application No. 2015-245712, filed on Dec. 16, 2015, Japanese Patent Application No. 2016-060605, filed on Mar. 24, 2016, and Japanese Patent Application No. 2016-198677, filed on Oct. 7, 2016, the contents of which are ...

SMALL MOLECULE INHIBITION OF SULFOTRANSFERASE SULT1A3

Provided herein are small molecule compounds and methods inhibiting human sulfotransferase 1A3 (SULT1A3) using these small molecule compounds. Methods of manufacturing and treatment are also disclosed. 4. The compound of claim 1 , wherein X is a C-Calkyl chain.5. The compound of claim 1 , wherein Y is —CONR′or —COOR′ or optionally substituted triazole.6. The compound of claim 1 , wherein Z is a C-Calkyl claim 1 , alkenyl or alkynyl chain.7. The compound of claim 1 , wherein two Zs together form a substituted cyclohexanone claim 1 , cyclohexene claim 1 , or cyclohexanone.8. The compound of claim 1 , wherein Z is —X—Y.9. The compound of claim 1 , wherein a is 1 or 2.10. The compound of claim 1 , wherein the binding to the allosteric pocket of SULT1A3 is signified by enzymatic activity in a 1-hydroxypyrene (1-HP) assay.12. The compound of claim 11 , wherein X is a C-Calkylene.13. The compound of claim 11 , wherein:{'sub': '2', '(a) Y is —CONR′; or'}(b) Y is —COOR′; or(c) Y is an optionally substituted triazole.14. The compound of claim 11 , wherein:{'sub': 1', '2', '3', '6, '(a) Zis H and Zis a C-Calkyl; or'}{'sub': 1', '2, '(b) Zand Ztogether form a substituted cyclohexanone.'}17. The compound of claim 16 , wherein:{'sub': 1', '2', '1', '6, '(a) Zis H and Zis a —C-Calkyl; and/or'}{'sub': 2', '1', '4, '(b) Zis a —C-Calkyl.'}19. The compound of claim 16 , wherein:(a) A is N and B is CH; or(b) A is CH and B is N; or(c) A and B are each N.21. A pharmaceutical composition comprising a compound of claim 1 , and a pharmaceutically acceptable carrier.22. A method of inhibiting SULT1A3 in a subject in need thereof claim 1 , comprising administering a compound of claim 1 , or a composition comprising a compound of in combination with a pharmaceutically acceptable carrier to the subject.23. The method of claim 22 , wherein the subject is a human.24. A method inhibiting SULT1A3 in a cell claim 1 , comprising contacting a cell with a compound of .25. The method of claim 24 , ...

RADIOLABELED AMINO ACIDS FOR DIAGNOSTIC IMAGING

This invention relates to novel compounds suitable for labeling by F and to the corresponding F labeled compounds themselves, F-fluorinated analogues thereof and their use as reference standards, methods of preparing such compounds, compositions comprising such compounds, kits comprising such compounds or compositions and uses of such compounds, compositions or kits for diagnostic imaging by Positron Emission Tomography (PET). 2. The compound according to wherein independently from each other{'sup': '1', 'Ris a carboxyl-protecting group selected from methyl, ethyl, propyl, butyl, tert-butyl, allyl, benzyl, 4-methoxybenzyl and 4-methoxyphenyl,'}{'sup': '2', 'Ris a carboxyl-protecting group selected from methyl, ethyl, propyl, butyl, tert-butyl, allyl, benzyl, 4-methoxybenzyl and 4-methoxyphenyl,'}{'sup': '3', 'Ris hydrogen,'}{'sup': '4', 'Ris tert-butyloxycarbonyl (Boc) or triphenylmethyl (Trityl),'}Q is phenylene or pyridylene, [{'sub': '2', 'a) CH, and'}, {'sub': 2', '2, 'b) CH—CH,'}], 'X is selected from a) sulfonate leaving group, and', 'b) halogen., 'LG is selected from5. The compound according to wherein Q is phenylene or pyridylene.8. The compound according to wherein independently from each other{'sup': '1', 'Ris a carboxyl-protecting group selected from methyl, ethyl, propyl, butyl, tert-butyl, allyl, benzyl, 4-methoxybenzyl and 4-methoxyphenyl,'}{'sup': '2', 'Ris a carboxyl-protecting group selected from methyl, ethyl, propyl, butyl, tert-butyl, allyl, benzyl, 4-methoxybenzyl and 4-methoxyphenyl,'}{'sup': '3', 'Ris hydrogen,'}{'sup': '4', 'Ris tert-butyloxycarbonyl (Boc) or triphenylmethyl (Trityl),'}Q is phenylene or pyridylene, and [{'sub': '2', 'a) CH, and'}, {'sub': 2', '2, 'b) CH—CH.'}], 'X is selected from11. The compound according to wherein Q is phenylene or pyridylene.14. The compound according to wherein Q is phenylene or pyridylene.17. The compound according to wherein independently from each other{'sup': '1', 'Ris hydrogen or a carboxyl- ...

DISUBSTITUTED TRIAZOLE ANALOGS

The present invention relates to disubstituted triazoles, their synthesis, and their use as anti-cancer compounds. In particular, compounds of Formula (I) are provided. 2. The compound of claim 1 , wherein Rand Rare hydrogen.3. The compound of claim 1 , wherein Ris hydrogen.4. The compound of claim 1 , wherein R claim 1 , R claim 1 , and Rare independently chosen from hydrogen claim 1 , methoxy claim 1 , ethoxy claim 1 , benzyloxy claim 1 , substituted benzyloxy claim 1 , hydroxyl claim 1 , and lower alkyl groups.5. The compound of claim 1 , wherein R claim 1 , R claim 1 , and Rare independently chosen from hydrogen claim 1 , hydroxyl claim 1 , and methoxy.6. The compound of claim 1 , wherein R claim 1 , Rand Rare hydrogen and R claim 1 , R claim 1 , and Rare independently chosen from hydrogen claim 1 , methoxy claim 1 , and hydroxyl.7. The compound of claim 1 , wherein Ar is chosen from phenyl claim 1 , benzyl claim 1 , substituted benzyl claim 1 , benzoyl claim 1 , substituted benzoyl claim 1 , naphthyl claim 1 , substituted naphthyl claim 1 , naphthoyl claim 1 , substituted naphthoyl claim 1 , benzenesulphonyl claim 1 , substituted benzenesulphonyl claim 1 , heteroaryl; substituted heteroaryl claim 1 , aroyl claim 1 , heteroaroyl.15. The pharmaceutical formulation of claim 14 , wherein the compound of Formula (I) is chosen from a compound comprising Formula (I)(a) claim 14 , (I)(b) claim 14 , (I)(c) claim 14 , (I)(d) claim 14 , (I)(e) claim 14 , and (I)(f).17. The process of claim 16 , wherein the proton donor is hydrochloric acid.18. The process of claim 16 , wherein the proton acceptor is ammonium chloride.19. The process of claim 16 , wherein the contacting is conducted in a solvent that is a DMF/water mixture.20. The process of claim 19 , wherein the DMF/water mixture is in volumetric proportions of about 1:4. This application is a continuation-in part of PCT Application PCT/US2015/023628, filed Mar. 31, 2015, which claims the benefit of U.S. provisional ...

Selective androgen receptor degrader (sard) ligands and methods of use thereof

This invention is directed to pyrrole, pyrazole, imidazole, triazole, and morpholine based selective androgen receptor degrader (SARD) compounds including heterocyclic anilide rings and their synthetic precursors, R-isomers, and non-hydroxylated and/or non-chiral propanamides, and pharmaceutical compositions and uses thereof in treating prostate cancer, advanced prostate cancer, castration resistant prostate cancer, triple negative breast cancer, other cancers expressing the androgen receptor, androgenic alopecia or other hyperandrogenic dermal diseases, Kennedy's disease, amyotrophic lateral sclerosis (ALS), abdominal aortic aneurysm (AAA), and uterine fibroids, and to methods for reducing the levels of androgen receptor-full length (AR-FL) including pathogenic or resistance mutations, AR-splice variants (AR-SV), and pathogenic polyglutamine (polyQ) polymorphisms of AR in a subject.

HUMAN HELICASE DDX3 INHIBITORS AS THERAPEUTIC AGENTS

The present invention refers to compounds endowed with RNA helicase DDX3 inhibitory activity of formula I and II and their therapeutic use, in particular for the treatment of viral diseases. 2. The compound according to wherein X and Y are C.3. The compound according to or wherein A is substituted aryl.4. The compound according to wherein the substituted aryl is phenyl.5. The compound according to wherein the phenyl is substituted by one claim 4 , two or more groups independently selected from methyl claim 4 , isopropyl claim 4 , CF claim 4 , F claim 4 , Cl claim 4 , OH claim 4 , OMe.6. The compound according to or wherein A is unsubstituted or substituted heteroaryl.7. The compound according to wherein the substituted heteroaryl is pyridinyl or isoquinolinyl.10. The compound or pharmaceutical acceptable salt claim 6 , solvate claim 6 , stereoisomer thereof according to any one of previous claim being an inhibitor of DDX3.11. The compound or pharmaceutical acceptable salt claim 6 , solvate claim 6 , stereoisomer thereof according to any one of previous claim for medical use.12. The compound or pharmaceutical acceptable salt claim 11 , solvate claim 11 , stereoisomer thereof according to for use in the treatment of a viral disease.13. The compound for use according to wherein the viral disease is modulated by DDX3.14. The compound for use according to or wherein the viral disease is caused by a virus that is resistant to at least one compound selected from the group consisting of: protease inhibitor; nucleoside reverse transcriptase inhibitor claim 12 , non-nucleoside reverse transcriptase inhibitor or integrase inhibitor.15. The compound according to to for use in the treatment of a viral disease is caused by a virus selected from the group consisting of: Human Immunodeficiency Virus 1 (HIV-1) claim 12 , Hepatitis C Virus claim 12 , Hepatitis B Virus claim 12 , Eastern Equine Encephalitis Virus claim 12 , Western Equine Encephalitis Virus claim 12 , Venezuelan ...

N-(2-(HETARYL)ARYL)ARYLSULFONAMIDES AND N-(2-(HETARYL)HETARYL)ARYLSULFONAMIDES

Compounds are provided that act as potent antagonists of the CCR9 receptor. Animal testing demonstrates that these compounds are useful for treating inflammation, a hallmark disease for CCR9. The compounds are generally aryl sulfonamide derivatives and are useful in pharmaceutical compositions, methods for the treatment of CCR9-mediated diseases, and as controls in assays for the identification of CCR9 antagonists. 138-. (canceled)45. The compound of claim 44 , or a salt thereof.52. The compound of claim 39 , wherein said compound is selected from the group consisting of:N-(2-(1H-[1,2,3]triazolo[4,5-b]pyridin-1-yl)-4-chlorophenyl)-4-(1-(methoxyimino)ethyl)benzenesulfonamide;N-(2-(1H-[1,2,3]triazolo[4,5-b]pyridin-1-yl)-4-chlorophenyl)-4-(1-aminoethyl)benzenesulfonamide;N-(2-(1H-[1,2,3]triazolo[4,5-b]pyridin-1-yl)-4-chlorophenyl)-4-(1-(methylamino)ethyl)benzenesulfonamide;N-(2-(1H-[1,2,3]triazolo[4,5-b]pyridin-1-yl)-4-chlorophenyl)-4-(1-(dimethylamino)ethyl)benzenesulfonamide;N-(2-(1H-[1,2,3]triazolo[4,5-b]pyridin-1-yl)-4-chlorophenyl)-4-(1-morpholinoethyl)benzenesulfonamide;N-(4-Chloro-2[1,2,3]triazolo[4,5-b]pyridin-1-yl-phenyl)-4-(1-hydroxy-1-methyl-ethyl)-benzene-sulfonamide;N-(2-(1H-[1,2,3]triazolo[4,5-b]pyridin-1-yl)-4-chlorophenyl)-4-(1-(ethoxyimino)ethyl)benzenesulfonamide;N-(2-(1H-[1,2,3]triazolo[4,5-b]pyridin-1-yl)-4-chlorophenyl)-4-(1-(allyloxyimino)ethyl)benzenesulfonamide;N-(2-(1H-[1,2,3]triazolo[4,5-b]pyridin-1-yl)-4-chlorophenyl)-4-(1-(tert-butoxyimina)ethyl)benzenesulfonamide;2-(1-(4-(N-(2-(1H-[1,2,3]triazolo[4,5-b]pyridin-1-yl)-4-chlorophenyl)sulfamoyl)phenyl)ethylideneaminooxy)acetic acid;N-(2-(1H-[1,2,3]triazolo[4,5-b]pyridin-1-yl)-4-chlorophenyl)-4-(1-hydroxy-2-methylpropan-2-yl)benzenesulfonamide;methyl 2-(4-(N-(2-(1H-[1,2,3]triazolo[4,5-b]pyridin-1-yl)-4-chlorophenyl)sulfamoyl)phenyl)-2-methylpropanoate;N-(2-(1H-[1,2,3]triazolo[4,5-b]pyridin-1-yl)-4-chlorophenyl)-4-isopropylbenzenesulfonamide;N-(2-(1H-[1,2,3]triazolo[4,5-b]pyridin-1-yl)-4- ...

HETEROCYCLIC COMPOUNDS AS PESTICIDES

The present application relates to the use of heterocyclic compounds for controlling animal pests including arthropods, insects and nematodes, to novel heterocyclic compounds, to processes for their preparation and to intermediates for preparing the heterocyclic compounds. 1. 1-(2 ,6-difluorophenyl)-1H-pyrazole-3-amine.2. N-[1-[(2 ,6-difluorophenyl)-1H-pyrazol-3-yl]acetamide. This application is a divisional of U.S. patent application Ser. No. 16/536,902, filed 9 Aug. 2019, which is a divisional of U.S. patent application Ser. No. 15/645,814, filed 10 Jul. 2017 (now U.S. Pat. No. 10,435,374, issued 8 Oct. 2019), which is a continuation of U.S. patent application Ser. No. 14/432,501, filed 31 Mar. 2015 (now U.S. Pat. No. 9,802,899, issued 31 Oct. 2017), which is a § 371 National Stage Application of PCT/EP2013/070371, filed 30 Sep. 2013, which claims priority to EP 12186946.5, filed 2 Oct. 2012 and EP 13170565.9, filed 5 Jun. 2013, the contents of each are incorporated by reference herein in their entireties.The present application relates to the use of heterocyclic compounds for controlling animal pests including arthropods, insects and nematodes, to novel heterocyclic compounds, to processes for their preparation and to intermediates for preparing the heterocyclic compounds.The heterocyclic compounds of the formulae (W) and (W2) are known (cf. for the compounds of the formula (W) Registry Numbers 1189645-25-7, 1189474-83-6, 1193202-69-5, 1172407-07-6, 1185158-40-0, 1185036-12-7, 1170986-74-9, 1193179-17-7, 1189458-68-1, 1189956-23-7, 1189915-26-1, 1170047-96-7). A use of these compounds has not been described.Derivatives of pyrazole-4-carboxamides are known from JP 2010-202649. The compounds described therein have bactericidal action against plant-damaging bacteria. Intermediates for their preparation are described in JP2010-202648.Crop protection compositions, which also include pesticides, have to meet many demands, for example in relation to efficacy, ...

G-QUADRUPLEX STABILISING AGENT

A compound of formula I 2. A compound according to claim 1 , wherein Aris a naphthalene ring.3. A compound according to claim 2 , wherein X and Y are substituted 2 claim 2 ,7 on the naphthalene ring.4. A compound according to wherein X is identical to Y.6. A compound according to claim 1 , wherein n is 1 or 2.7. A compound according to claim 1 , wherein each Aris triazole.8. A compound according to claim 1 , wherein each Aris phenyl.9. A compound according to claim 1 , wherein each Lis a bond and/or each Lis a bond.10. A compound according to claim 1 , wherein Rand Rare each independently Calkyl claim 1 , which is optionally substituted claim 1 , wherein each —NRRis independently selected from —N(Me) claim 1 , —N(Et) claim 1 , —N(nPr) claim 1 , —N(iPr) claim 1 , —N(nBu) claim 1 , or —N(tBu) claim 1 , or wherein in each group NRRRand R claim 1 , taken together with the nitrogen atom to which they are attached claim 1 , form a heterocyclic ring having from 3 to 8 ring atoms claim 1 , which heterocyclic ring may saturated claim 1 , partially unsaturated claim 1 , or fully unsaturated claim 1 , and is optionally substituted claim 1 , wherein Rand R claim 1 , taken together with the nitrogen atom to which they are attached claim 1 , form a saturated heterocyclic ring having from 3 to 8 ring atoms claim 1 , wherein only one of said ring atoms is nitrogen claim 1 , and all others are carbon claim 1 , and which heterocyclic ring is optionally substituted.12. A compound according to claim 11 , wherein said cyclic amino group is substituted with one or more substituents selected from Calkyl claim 11 , Caryl claim 11 , hydroxy claim 11 , and Chydroxyalkyl.15. A pharmaceutical composition comprising a compound according to claim 1 , or a pharmaceutically acceptable salt claim 1 , ester claim 1 , amide claim 1 , solvate claim 1 , hydrate or protected form thereof claim 1 , and a pharmaceutically acceptable diluent or carrier.16. (canceled)17. (canceled)18. A method of inhibiting ...

CYCLOPENTYL ACIDS AS LPA ANTAGONISTS

The present invention provides compounds of Formula (I) or a stereoisomer, tautomer, or pharmaceutically acceptable salt or solvate thereof, wherein all the variables are as defined herein. These compounds are selective LPA receptor inhibitors. 4. The compound according to claim 3 , wherein L is a covalent bond or Calkylene.5. The compound according to claim 4 , wherein:{'sup': 3a', '3b, 'sub': '1-4', 'Rand Rare independently hydrogen or Calkyl;'}{'sup': 3a', '3b, 'sub': '3-4', 'or alternatively, Rand Rtogether, with the carbon atom they are attached to, form Ccycloalkyl.'}6. The compound according to claim 5 , wherein Ris COH.7. The compound according to claim 6 , wherein:{'sup': 1', '2', '3', '4', '6', '1', '2', '3', '6', '4', '2', '3', '6', '1', '4', '1', '2', '6', '3', '4', '6, 'sub': 1-6', '1-4', '1-4, 'X, X, X, and Xare independently CR; or X, Xand Xare CRand Xis N; or Xand Xare CRand Xand Xare N; or Xand Xare CRand Xand Xare N; and Ris independently hydrogen, halo, hydroxyl, Calkyl, Chaloalkyl, or Calkoxy.'}11. The compound according to claim 1 , which is selected from any one of Examples 1 to 89 claim 1 , or a stereoisomer claim 1 , a tautomer claim 1 , or a pharmaceutically acceptable salt or solvate thereof.12. A pharmaceutical composition comprising one or more compounds according to claim 1 , or a stereoisomer claim 1 , tautomer claim 1 , or pharmaceutically acceptable salt or solvate thereof; and a pharmaceutically acceptable carrier or diluent.13. (canceled)14. A method of treating a disease claim 1 , disorder claim 1 , or condition associated with dysregulation of lysophosphatidic acid receptor 1 (LPA) in a patient having the disease claim 1 , disorder claim 1 , or condition claim 1 , comprising administering a therapeutically effective amount Use of a compound or a stereoisomer claim 1 , tautomer claim 1 , or pharmaceutically acceptable salt or solvate thereof according to .15. The method according to claim 14 , wherein the disease claim 14 , ...

PSMA Imaging Agents

Compounds for targeting and agents for imaging, prostate-specific membrane antigen (PSMA) are disclosed. Methods of synthesizing compounds and imaging agents, as well as methods for imaging PSMA are also disclosed. The imaging agents disclosed are suitable for PET and SPECT imaging. 2. The compound of claim 1 , wherein in Formula VI claim 1 , Xis N.3. The compound of claim 1 , wherein in Formula VI claim 1 , Xis H and Xis (CH)—Rwherein at least one CHof (CH)is replaced by CONH.4. The compound of claim 1 , wherein in Formula VI claim 1 , Xis H and Xis (CH)—Rwherein at least one CHof (CH)is replaced by CONH.5. The compound of claim 1 , wherein in Formula VI claim 1 , at least one CHof (CH)—Rof either Xor Xis replaced by triazole.6. The compound of claim 1 , wherein in Formula VI claim 1 , Ris a radioisotope.8. The compound of claim 7 , wherein in Formula VIII claim 7 , Xis CH.9. The compound of claim 7 , wherein in Formula VIII claim 7 , Xis CH.10. The compound of claim 7 , wherein in Formula VIII claim 7 , at least one CHof (CH)is optionally replaced by O.11. The compound of claim 7 , wherein in Formula VIII claim 7 , Xis N.12. The compound of claim 7 , wherein in Formula VIII claim 7 , Xis CH.14. The method of claim 13 , wherein in Formula VI claim 13 , Xis N.15. The method of claim 13 , wherein in Formula VI claim 13 , Xis H and Xis (CH)—Rwherein at least one CHof (CH)is replaced by CONH.16. The method of claim 13 , wherein in Formula VI claim 13 , Xis H and Xis (CH)—Rwherein at least one CHof (CH)is replaced by CONH.17. The method of claim 13 , wherein in Formula VI claim 13 , at least one CHof (CH)—Rof either Xor Xis replaced by triazole.18. The method of claim 13 , wherein in Formula VI claim 13 , Ris a radioisotope.19. The method of claim 13 , wherein in Formula VIII claim 13 , Xis CH.20. The method of claim 13 , wherein in Formula VIII claim 13 , Xis CH.21. The method of claim 13 , wherein in Formula VIII claim 13 , at least one CHof (CH)is optionally replaced ...

INSECTICIDAL COMPOUNDS

The present invention relates to novel triazole derivatives of formula (I) having insecticidal activity, to processes and intermediates for preparing them, to insecticidal, acaricidal, nematicidal or molluscicidal compositions comprising them and to methods of using them to combat and control insect, acarine, nematode or mollusc pests 2. The method according to wherein A claim 1 , A claim 1 , Aand Aare C—X and each X is independently selected from hydrogen claim 1 , halogen claim 1 , cyano claim 1 , methyl claim 1 , trifluoromethyl and methoxy.3. The method according to wherein Ais CH claim 2 , C—CN or C—F; and A claim 2 , Aand Aare CH.4. The method according to wherein Ris hydrogen claim 1 , methyl or ethyl.5. The method according to wherein Ris hydrogen claim 1 , trifluoromethyl or halogen.6. The method according to wherein Gis oxygen.7. The method according to wherein Qis phenyl claim 1 , pyridyl claim 1 , furanyl claim 1 , thiophenyl claim 1 , pyrazolyl or 1 claim 1 ,2 claim 1 ,3-thiadiazolyl; each optionally substituted by one to four substituents independently selected from cyano claim 1 , nitro claim 1 , hydroxy claim 1 , bromo claim 1 , chloro claim 1 , fluoro claim 1 , methyl claim 1 , trifluoromethyl claim 1 , methoxy claim 1 , trifluoromethoxy claim 1 , methylthio claim 1 , methylsulfinyl claim 1 , methylsulfonyl and phenyl.8. The method according to wherein Qis phenyl or pyridyl; each optionally substituted by one claim 7 , two or three substituents independently selected from cyano claim 7 , nitro claim 7 , chloro claim 7 , fluoro claim 7 , methyl claim 7 , ethyl claim 7 , trifluoromethyl claim 7 , methoxy and trifluoromethoxy.9. The method according to wherein Qis a moiety of formula (A);{'sup': 1', '5, 'Yand Yare each independently selected from hydrogen, cyano, fluoro, chloro, bromo, methyl, ethyl, trifluoromethyl and methoxymethyl; and'}{'sup': 2', '4, 'Yand Yare each independently selected from hydrogen, fluoro, chloro and methyl.'}10. The method ...

COMPOUNDS AND METHODS FOR INDUCING CHONDROGENESIS

The present invention provides compounds and compositions for the amelioration of arthritis and joint injuries by inducing mesenchymal stem cells into chondrocytes. 2. The method of claim 1 , wherein{'sup': 1', '2', '2, '(a) Lis a bond, Lis —C(O)NH—, ring B is phenyl, Ris —CN or phenyl, and subscript m is 1, or'}{'sup': 1', '2', '1, 'sub': '2', '(b) Ris —C(O)OH, subscript n is 1, ring A is phenyl, Lis —C(O)NH—, and Lis a bond or —CH—, or'}{'sup': 1', '2', '2, 'sub': '2', '(c) each of ring A and ring B is phenyl, Ris —C(O)OH or combined with L, subscript n is 1, and at least one Ris selected from the group consisting of H, —CN and —COH.'}5. The method of claim 4 , wherein each Ris independently selected from the group consisting of —C(O)R claim 4 , —C(O)OR claim 4 , Calkyl-C(O)OR claim 4 , —NRC(O)OR claim 4 , —NRC(O)NRR claim 4 , —SOOR claim 4 , —SONRR claim 4 , —NRSOR claim 4 , and —CN.6. The method of claim 4 , wherein each Ris independently selected from the group consisting of —CH—C(O)OH claim 4 , —C(O)Me claim 4 , —NHC(O)NH claim 4 , —NHC(O)OMe claim 4 , —NHSOMe claim 4 , —SONH claim 4 , —SONHMe claim 4 , —SOH claim 4 , —C(O)OH claim 4 , and —CN.7. The method of claim 4 , whereinring A is phenyl; andsubscript n is 1.8. The method of claim 4 , whereinring A is selected from the group consisting of biphenyl and pyridyl, orsubscript n is 2.11. The method of claim 10 , wherein each Ris independently selected from the group consisting of H claim 10 , —CHNHCONH claim 10 , —CHNHCOOMe claim 10 , —CHNHMe claim 10 , —CHOPh claim 10 , 2-CN claim 10 , 4-CN claim 10 , —C(O)OH claim 10 , —CONHOH claim 10 , —OCF2H claim 10 , —POH claim 10 , —SOH claim 10 , phenyl claim 10 , pyridyl claim 10 , imidazole and tetrazole.13. The method of claim 12 , wherein{'sup': '2', 'sub': 2', '2', '2', '2', '2', '2', '2', '2, 'each Ris independently selected from the group consisting of H, Me, —Cl, —CHOH, —CHCHOH, —CHNH, —C(O)Me, —C(O)OH, —C(O)NH, —CN, morpoholine, 3,4-difluorophenyl and —SONH; ...

CYCLIC COMPOUNDS AND METHODS OF MAKING AND USING THE SAME

The present invention provides compounds, or pharmaceutically acceptable salts thereof, for inhibiting the growth of a microbe; treating a mammal having a microbial infection, mucositis, an ophthalmic infection, an otic infection, a cancer, or a infection; inhibiting the growth of a species; modulating an immune response in a mammal; or antagonizing unfractionated heparin, low molecular weight heparin, or a heparin/low molecular weight heparin derivative. 211-. (canceled)1388-. (canceled)89. A pharmaceutical composition comprising a compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , and a pharmaceutically acceptable carrier.90. The composition of further comprising an excipient chosen from purified water claim 89 , propylene glycol claim 89 , polyethyleneglycol (PEG) 400 claim 89 , glycerin claim 89 , DMA claim 89 , ethanol claim 89 , benzyl alcohol claim 89 , citric acid/sodium citrate (pH3) claim 89 , citric acid/sodium citrate (pH5) claim 89 , tris(hydroxymethyl)amino methane HCl (pH7.0) claim 89 , 0.9% saline claim 89 , and 1.2% saline claim 89 , or any combination thereof.91. The composition of further comprising an excipient chosen from propylene glycol claim 89 , purified water claim 89 , and glycerin.92. The composition of further comprising an excipient chosen from 20% w/v propylene glycol in saline claim 89 , 30% w/v propylene glycol in saline claim 89 , 40% w/v propylene glycol in saline claim 89 , 50% w/v propylene glycol in saline claim 89 , 15% w/v propylene glycol in purified water claim 89 , 30% w/v propylene glycol in purified water claim 89 , 50% w/v propylene glycol in purified water claim 89 , 30% w/v propylene glycol and 5 w/v ethanol in purified water claim 89 , 15% w/v glycerin in purified water claim 89 , 30% w/v glycerin in purified water claim 89 , 50% w/v glycerin in purified water claim 89 , 20% w/v Kleptose in purified water claim 89 , 40% w/v Kleptose in purified water claim 89 , and 25% w/v Captisol in ...

Arginine methyltransferase inhibitors and uses thereof

Described herein are compounds of Formula (I), pharmaceutically acceptable salts thereof, and pharmaceutical compositions thereof. Compounds of the present invention are useful for inhibiting arginine methyltransferase activity. Methods of using the compounds for treating arginine methyltransferase-mediated disorders are also described.

TRICYCLIC COMPOUNDS AND USES THEREOF IN MEDICINE

The present invention relates to novel tricyclic compounds which can bind to FXR and act as modulators of the FXR, or a stereoisomer, a geometric isomer, a tautomer, an N-oxide, a hydrate, a solvate, a metabolite, a pharmaceutically acceptable salt or a prodrug thereof, and the uses of the compounds for the treatment of diseases and/or conditions mediated by FXR. The invention further provides a pharmaceutical composition containing the compound disclosed herein and a method of treatment of diseases and/or conditions mediated by FXR comprising administering the compound or the pharmaceutical composition. 2. (canceled)3. The compound of claim 1 , wherein{'sup': '1', 'sub': 1-6', '1-6', '1-6', '3-6', '2-6', '2-6', '2-6', '1-6', '1-6', '6-10', '1-9, 'each Ris independently H, deuterium, F, Cl, Br, I, hydroxy, amino, nitro, cyano, Calkyl, Chaloalkyl, Chaloalkoxy, Ccycloalkyl, Cheterocyclyl, Calkenyl, Calkynyl, Calkylamino, Calkoxy, Caryl or Cheteroaryl;'}{'sup': '2', 'sub': 1-6', '1-6', '1-6', 'C1-6', '1-6', '3-6', '1-6', '2-6', '1-6', '1-6, 'Ris H, deuterium, F, Cl, Br, I, hydroxy, amino, nitro, cyano, Calkyl, Chaloalkyl, Chaloalkoxy, alkoxy—C-alkyl, Ccycloalkyl, Chydroxyalkyl, Cheterocyclyl, Calkylamino or Calkoxy; and'}{'sub': 1-6', '2-6', '2-6', '3-6', '1-6', '1-6', '1-6', '1-6', '1-6', '1-6', '1-6', '2-9', '6-10', '1-9, 'sup': I', '2', '9, 'Wherein each of said hydroxy, amino, Calkyl, Calkenyl, Calkynyl, Ccycloalkyl, Chaloalkyl, Calkylamino, Calkoxy, Chaloalkoxy, Chydroxyalkyl, Calkoxy—C-alkyl, Cheterocyclyl, Caryl and Cheteroaryl of Rand Ris independently and optionally substituted with one or more R; or'}{'sup': '1', 'sub': 1-3', '1-3', 'h3', 'C3-6', '2-9', '2-4', '2-4', '1-3', '1-3', '6-10', '1-9, 'wherein each Ris independently H, deuterium, F, Cl, Br, I, hydroxy, amino, nitro, cyano, Calkyl, Chaloalkyl, Chaloalkoxy, cycloalkyl, Cheterocyclyl, Calkenyl, Calkynyl, Calkylamino, Calkoxy, Caryl or Cheteroaryl;'}{'sup': '2', 'sub': 1-3', '1-3', '1-3', '1-3', '1-3', ...

PSMA Imaging Agents

Compounds for targeting and agents for imaging, prostate-specific membrane antigen (PSMA) are disclosed. Methods of synthesizing compounds and imaging agents, as well as methods for imaging PSMA are also disclosed. The imaging agents disclosed are suitable for PET and SPECT imaging. 2. The method of claim 1 , wherein in Formula IV claim 1 , Xis NH.4. The method of claim 1 , wherein in Formula IV claim 1 , Xis an aryl.6. The method of claim 1 , wherein in Formula IV claim 1 , Xis a single bond.7. The method of claim 1 , wherein in Formula IV claim 1 , Ris a radioisotope.8. The method of claim 1 , wherein in Formula IV claim 1 , Xis C(O) and Xis a sugar.9. The method of claim 1 , wherein in Formula V claim 1 , Xis CH.10. The method of claim 1 , wherein in Formula V claim 1 , Xis N.11. The method of claim 1 , wherein in Formula V claim 1 , Xis CH.12. The method of claim 1 , wherein in Formula V claim 1 , Xis N.13. The method of claim 1 , wherein in Formula V claim 1 , wherein one CHis replaced by an aryl.14. The method of claim 1 , wherein Ris O.15. The method of claim 1 , wherein Ris S.17. The compound of claim 16 , wherein in Formula IV claim 16 , Xis NH.19. The compound of claim 16 , wherein in Formula IV claim 16 , Xis an aryl.21. The compound of claim 16 , wherein in Formula IV claim 16 , Xis a single bond.22. The compound of claim 16 , wherein in Formula IV claim 16 , Ris a radioisotope.23. The compound of claim 16 , wherein in Formula IV claim 16 , Xis C(O) and Xis a sugar.26. The compound of claim 25 , wherein in Formula V claim 25 , Xis CH.27. The compound of claim 25 , wherein in Formula V claim 25 , Xis N.28. The compound of claim 25 , wherein in Formula V claim 25 , Xis CH.29. The compound of claim 25 , wherein in Formula V claim 25 , Xis N.30. The compound of claim 25 , wherein in Formula V claim 25 , wherein one CHis replaced by an aryl.31. The compound of claim 25 , wherein Ris O.32. The compound of claim 25 , wherein Ris S. This Continuation application ...

Benzamides and nicotinamides as syk modulators

The present invention is directed to compounds of formula I and pharmaceutically acceptable salts, esters, and prodrugs thereof which are inhibitors of Syk kinase. The present invention is also directed to intermediates used in making such compounds, the preparation of such a compound, pharmaceutical compositions containing such a compound, methods of inhibition Syk kinase activity, methods of inhibition the platelet aggregation, and methods to prevent or treat a number of conditions mediated at least in part by Syk kinase activity, such as Non Hodgkin's Lymphoma.

HOMOPIPERAZINE-BASED CATALYSTS FOR NEUTRALIZATION OF ORGANOPHOSPHORUS-BASED COMPOUNDS

Novel compositions of matter based on homopiperazine precursor materials and forming a homopiperazine-based ligand are disclosed, along with suitable techniques and materials for the synthesis and utilization thereof. In particular various synthetic schemes and techniques for applying the disclosed compositions of matter as a decontaminating agent. The decontaminating agents include homopiperazine-based ligand-metal complexes that are particularly effective at neutralizing toxicity of nerve agents, pesticides, and other toxic organophosphorus-based compounds. In preferred approaches, the homopiperazine-based ligand-metal complexes act as catalysts to facilitate substitution of a leaving group of the organophosphorus-based compound with a functional group that does not permit the organophosphorus-based compound to inactivate acetylcholinesterase upon introduction of the organophosphorus-based compound to a living organism such as insects and mammals. Advantageously, the catalytic homopiperazine-based ligand-metal complexes are formed using inexpensive, readily-available precursor materials, and may be utilized to neutralize toxins without relying on damaging caustic reactants or environmentally unfriendly organic solvents. 1. A method , comprising: neutralizing toxicity of one or more organophosphorus-based compounds by reacting the organophosphorus-based compound(s) with a homopiperazine-based ligand-metal complex.2. The method as recited in claim 1 , the reacting comprising substituting a leaving group of the organophosphorus-based compound with a hydroxyl moiety conjugated to the homopiperazine-based ligand-metal complex.3. The method as recited in claim 1 , wherein a metal cation of the homopiperazine-based ligand-metal complex is selected from a group consisting of: Cu claim 1 , Zn claim 1 , Co claim 1 , Fe claim 1 , and Ni.4. The method as recited in claim 1 , wherein the neutralizing does not use any environmentally unfriendly materials.5. The method as ...

HETEROCYCLIC P2Y14 RECEPTOR ANTAGONISTS

Disclosed are compounds of formulas (I)-(IX) for treating or preventing a disease or disorder responsive to antagonism of a P2YR receptor agonist in a mammal in need thereof, wherein R-R, X, Y, Z, X′, Y′, Z′, and A are as defined herein, that are useful in treating an inflammatory such as asthma, cystic fibrosis, and sterile inflammation of the kidney. 2. The compound or salt of claim 1 , wherein X claim 1 , Y claim 1 , and Z are all CH.3. (canceled)6. A pharmaceutical composition comprising a compound or salt of and a pharmaceutically acceptable carrier.7. A method for antagonizing a P2YR receptor in a mammal in need thereof claim 1 , comprising administering to the mammal an effective amount of a compound or salt of .8. A method for treating or preventing an inflammatory condition in a mammal in need thereof claim 1 , comprising administering to the mammal an effective amount of a compound or salt of .9. The of claim 8 , wherein the inflammatory condition is selected from the group consisting of asthma claim 8 , cystic fibrosis claim 8 , and sterile inflammation of the kidney.11. The compound or salt of claim 10 , wherein Ris COOH.1318.-. (canceled)21. (canceled)23. A pharmaceutical composition comprising a compound or salt of and a pharmaceutically acceptable carrier.24. A method for antagonizing a P2YR receptor in a mammal in need thereof claim 10 , comprising administering to the mammal an effective amount of a compound or salt of .25. A method for treating or preventing an inflammatory condition in a mammal in need thereof claim 10 , comprising administering to the mammal an effective amount of a compound or salt of .26. The method of claim 25 , wherein the inflammatory condition is selected from the group consisting of asthma claim 25 , cystic fibrosis claim 25 , and sterile inflammation of the kidney. This patent application claims the benefit of U.S. Provisional Patent Application No. 62/628,699 filed Feb. 9, 2018, the disclosure of which is incorporated ...

GPR40 AGONISTS FOR THE TREATMENT OF TYPE II DIABETES

Disclosed are compounds, compositions and methods for treating of disorders that are affected by the modulation of the GPR40 receptor. Such compounds are represented by Formula (I), as follows: 2. The compound of wherein X is S.3. The compound of wherein X is O and Y is N.4. The compound of wherein L is —CHO— claim 1 , —CH═CH— claim 1 , or —(CH)—.5. The compound of wherein L is —CHO—.6. The compound of wherein Ris selected from the group consisting of phenyl claim 1 , pyridin-4-yl claim 1 , thienyl claim 1 , benzothiophenyl claim 1 , benzofuranyl claim 1 , and indolyl; wherein said benzothiophenyl claim 1 , benzofuranyl claim 1 , and indolyl are attached to the core (X)-(Y) containing ring via its benzo ring; and wherein Ris optionally independently substituted with one or two substituents selected from methyl claim 1 , methoxy claim 1 , or fluoro.7. The compound of wherein Ris selected from the group consisting of phenyl claim 6 , pyridin-4-yl claim 6 , and thienyl; wherein Ris optionally independently substituted with one or two substituents selected from methyl claim 6 , methoxy claim 6 , or fluoro.8. The compound of wherein Ris selected from the group consisting of 2-fluoro-5-methoxy-phenyl claim 1 , 5-fluoro-2-methoxy-pyrid-4-yl claim 1 , 6-methoxybenzothiophen-4-yl claim 1 , thien-3-yl claim 1 , 3-(dimethylamino)phenyl claim 1 , 2-fluoro-4-methoxy-phenyl claim 1 , phenyl claim 1 , 2-fluorophenyl claim 1 , 2-methoxyphenyl claim 1 , 3 claim 1 ,5-dimethoxyphenyl claim 1 , 1H-indol-4-yl claim 1 , benzofuran-4-yl claim 1 , 3-methoxyphenyl claim 1 , 5-methoxypyrid-3-yl claim 1 , 2-methoxypyrid-4-yl claim 1 , and 5-cyano-2-fluoro-phenyl.9. The compound of wherein Ris Ccycloalkyl.10. The compound of wherein Ris cyclopropyl.23. A pharmaceutical composition comprising a compound of and at least one of a pharmaceutically acceptable carrier claim 1 , a pharmaceutically acceptable excipient claim 1 , and a pharmaceutically acceptable diluent.24. A pharmaceutical ...

GPR40 AGONISTS FOR THE TREATMENT OF TYPE II DIABETES

Disclosed are compounds, compositions and methods for treating of disorders that are affected by the modulation of the GPR40 receptor. Such compounds are represented by Formula (II) as follows: 2. The compound of wherein Xis S.3. The compound of wherein Xis O and Yis N.4. The compound of wherein Yis C(R) claim 1 , wherein Ris hydrogen claim 1 , methyl claim 1 , or t-butyl.5. The compound of wherein Lis —CHO— claim 1 , (Z)—CH═CH— claim 1 , (E) —CH═CH— claim 1 , or —(CH)—.6. The compound of wherein Ris selected from the group consisting of phenyl claim 1 , pyridin-4-yl claim 1 , thienyl claim 1 , benzothiophenyl claim 1 , benzofuranyl claim 1 , and indolyl; wherein said benzothiophenyl claim 1 , benzofuranyl claim 1 , and indolyl are attached to the core (X)—(Y) containing ring via its benzo ring; and wherein Ris optionally independently substituted with one or two substituents selected from methyl claim 1 , methoxy claim 1 , or fluoro.7. The compound of wherein Ris selected from the group consisting of phenyl claim 6 , pyridin-4-yl claim 6 , and thienyl; wherein Ris optionally independently substituted with one or two substituents selected from methyl claim 6 , methoxy claim 6 , or fluoro.8. The compound of wherein Ris Ccycloalkyl.9. The compound of wherein Ris cyclopropyl.21. A pharmaceutical composition comprising a compound of and at least one of a pharmaceutically acceptable carrier claim 1 , a pharmaceutically acceptable excipient claim 1 , and a pharmaceutically acceptable diluent.22. A pharmaceutical composition comprising a compound of and at least one of a pharmaceutically acceptable carrier claim 20 , a pharmaceutically acceptable excipient claim 20 , and a pharmaceutically acceptable diluent.23. The pharmaceutical composition of claim 21 , wherein the composition is a solid oral dosage form.24. The pharmaceutical composition of claim 22 , wherein the composition is a solid oral dosage form.25. The pharmaceutical composition of claim 21 , wherein the ...

GPR40 AGONISTS FOR THE TREATMENT OF TYPE II DIABETES

Disclosed are compounds, compositions and methods for treating of disorders that are affected by the modulation of the GPR40 receptor. Such compounds are represented by Formula (III) as follows: 2. The compound of wherein Yis N.3. The compound of wherein Lis —CHO— claim 1 , (E)-CH═CH— claim 1 , or —(CH)—.4. The compound of wherein Lis —CHO—.5. The compound of wherein Ris selected from the group consisting of phenyl claim 1 , pyridin-4-yl claim 1 , and thienyl; wherein Ris optionally independently substituted with one or two substituents selected from Calkyl claim 1 , methoxy claim 1 , or fluoro.6. The compound of wherein Ris selected from the group consisting of phenyl and pyridin-4-yl; wherein Ris optionally independently substituted with one or two substituents selected from methoxy or fluoro.7. The compound of wherein Ris 2-fluoro-5-methoxyphenyl or 5-fluoro-2-methoxy-pyridin-4-yl.8. The compound of wherein Ris Ccycloalkyl.9. The compound of wherein Ris cyclopropyl.10. The compound of wherein Ris hydrogen.22. A pharmaceutical composition comprising a compound of and at least one of a pharmaceutically acceptable carrier claim 1 , a pharmaceutically acceptable excipient claim 1 , and a pharmaceutically acceptable diluent.23. A pharmaceutical composition comprising a compound of and at least one of a pharmaceutically acceptable carrier claim 22 , a pharmaceutically acceptable excipient claim 22 , and a pharmaceutically acceptable diluent.24. The pharmaceutical composition of claim 22 , wherein the composition is a solid oral dosage form.25. The pharmaceutical composition of claim 23 , wherein the composition is a solid oral dosage form.26. The pharmaceutical composition of claim 22 , wherein the composition is a syrup claim 22 , an elixir or a suspension.27. The pharmaceutical composition of claim 23 , wherein the composition is a syrup claim 23 , an elixir or a suspension.28. A method of treating a disorder modulated by the GPR40 receptor claim 1 , comprising ...

SULFONYLUREAS AND RELATED COMPOUNDS AND USE OF SAME

The present invention provides for certain sulfonyl ureas and related compounds which have advantageous properties and show useful activity in the inhibition of activation of the NLRP3 inflammasome. Such compounds are useful in the treatment of a wide range of disorders in which the inflammation process, or more specifically the NLRP3 inflammasome, have been implicated as being a key factor. 2. The compound of wherein Ris selected from the group consisting of Cor Ccycloalkyl claim 1 , 5-membered or 6-membered heteroaryl claim 1 , bicyclic heteroaryl wherein at least one ring is heteroaryl claim 1 , phenyl claim 1 , biphenyl claim 1 , phenylheterocyclyl claim 1 , 5-membered or 6-membered heterocyclyl claim 1 , and heterocyclylcycloalkyl claim 1 , all of which may be optionally substituted.3. The compound of or wherein Ris selected from the group consisting of pyrazole claim 1 , furan claim 1 , tetrahydrofuran claim 1 , tetrahydropyran claim 1 , pyran claim 1 , pyrrolidine claim 1 , pyrrole claim 1 , triazole claim 1 , tetrazole claim 1 , imidazole claim 1 , pyridine claim 1 , morpholine claim 1 , piperazine claim 1 , piperidine claim 1 , substituted phenyl claim 1 , phenylheteroaryl claim 1 , phenylheterocyclyl claim 1 , biphenyl claim 1 , quinoline claim 1 , isoquinoline claim 1 , naphthyl claim 1 , pyrazine and pyrimidine claim 1 , all of which may be optionally substituted as appropriate.4. The compound of any one of the preceding claims wherein Ris 5-membered heterocyclyl or heteroaryl claim 1 , each of which may be optionally substituted claim 1 , comprising at least one ring heteroatom selected from N claim 1 , O and S.5. The compound of wherein Ris 5-membered nitrogen heterocyclyl or 5-membered nitrogen heteroaryl claim 4 , each of which may be optionally substituted.6. The compound of or wherein Ris 5-membered heterocyclyl or 5-membered heteroaryl claim 4 , each of which may be optionally substituted claim 4 , comprising at least two ring nitrogen atoms.7. ...

COMPOUNDS FOR SUPPRESSING A PERIPHERAL NERVE DISORDER INDUCED BY AN ANTI-CANCER AGENT

The present invention provides a medicament that suppresses (or mitigates) various neurological symptoms caused by a peripheral nerve disorder induced by an anti-cancer agent. 1. A method for suppressing a peripheral nerve disorder induced by an anti-cancer agent, which comprises administering a compound represented by the formula (II):wherein{'sup': '1′', 'R is'}(1) an aliphatic hydrocarbon group optionally having substituent(s),(2) an aromatic hydrocarbon group optionally having substituent(s),(3) a heterocyclic group optionally having substituent(s),{'sup': 1a′', '1a′, '(4) a group represented by the formula: —OR wherein R is a hydrogen atom or an aliphatic hydrocarbon group optionally having substituent(s), or'}(5) a group represented by the formula:{'sup': 1b′', '1c′, 'wherein R and R are the same or different and each is a hydrogen atom or an aliphatic hydrocarbon group optionally having substituent(s),'}X is methylene, NH, a sulfur atom or an oxygen atom,Y is methylene optionally having substituent(s) or NH optionally having substituent(s),ring A′ is a 5- to 8-membered ring optionally having 1 to 4 substituents selected from the group consisting of(i) an aliphatic hydrocarbon group optionally having substituent(s),(ii) an aromatic hydrocarbon group optionally having substituent(s),{'sup': 2′', '2′, '(iii) a group represented by the formula: —OR wherein R is a hydrogen atom or an aliphatic hydrocarbon group optionally having substituent(s), and'}(iv) a halogen atom,Ar′ is an aromatic hydrocarbon group optionally having substituent(s),a group represented by the formula:is a group represented by the formula:s is an integer of 0 to 2,t is an integer of 1 to 3, andthe total of s and t is 4 or less;provided that when X is methylene, then Y should be methyleneoptionally having substituent(s),or a salt thereof or a prodrug thereof. This application is a Continuation of U.S. application Ser. No. 13/971,159, filed Aug. 20, 2013, which is a Continuation of U.S. ...

HETEROCYCLIC COMPOUNDS AS PESTICIDES

The present application relates to the use of heterocyclic compounds for controlling animal pests including arthropods, insects and nematodes, to novel heterocyclic compounds, to processes for their preparation and to intermediates for preparing the heterocyclic compounds. 118-. (canceled)24. A composition comprising at least one compound of formula (I) according to .25. A method for controlling pests claim 19 , comprising allowing the compound of formula (I) according to to act on the pests and/or their habitat claim 19 , provided that treatments of humans are excluded.26. The method according to claim 25 , wherein the pests are insects claim 25 , arachnids claim 25 , or nematodes.27. The method according to claim 25 , wherein the pests are nematodes.28. The compound according to claim 19 , wherein A is 3-fluoropyrazin-2-yl claim 19 , B is 2-(trifluoromethyl)phenyl claim 19 , R3 claim 19 , R4 claim 19 , R5 are H claim 19 , and Z is oxygen.29. The compound according to claim 19 , wherein A is 3-fluoropyrazin-2-yl claim 19 , B is 2-chlorophenyl claim 19 , R3 claim 19 , R4 claim 19 , R5 are H claim 19 , and Z is oxygen.30. The compound according to claim 19 , wherein A is 3-fluoropyrazin-2-yl claim 19 , B is 2-bromophenyl claim 19 , R3 claim 19 , R4 claim 19 , R5 are H claim 19 , and Z is oxygen.31. The compound according to claim 19 , wherein A is 3-fluoropyrazin-2-yl claim 19 , B is 2-iodophenyl claim 19 , R3 claim 19 , R4 claim 19 , R5 are H claim 19 , and Z is oxygen.32. The compound according to claim 19 , wherein A is 3-fluoropyrazin-2-yl claim 19 , B is 2 claim 19 ,6-difluorophenyl claim 19 , R3 claim 19 , R4 claim 19 , R5 are H claim 19 , and Z is oxygen.33. The compound according to claim 19 , wherein A is 3-fluoropyrazin-2-yl claim 19 , B is 3-(trifluoromethyl)pyridine-2-yl claim 19 , R3 claim 19 , R4 claim 19 , R5 are H claim 19 , and Z is oxygen.34. The compound according to claim 19 , wherein A is 2-chloropyrazin-5-yl claim 19 , B is 2-(trifluoromethyl) ...

PROCESS FOR THE PREPARATION OF TRIAZOLES

The present invention discloses the efficient preparation of 2-substituted-4-amido-1,2,3-triazoles. 2. A process according to wherein the conversion is effected thermally or in the presence of an activating agent.3. A process according to wherein the activating agent comprises one or more inorganic bases claim 2 , alkali metal salts of simple alcohols claim 2 , aliphatic or aromatic amines claim 2 , strong acids and/or copper salts. The present invention discloses the efficient preparation of 2-substituted-4-amido-1,2,3-triazoles.2-Substituted-4-amido-1,2,3-triazoles are class of heterocycles that have demonstrated important applications as, for example, pest control agents (e.g., structure 1a, WO 2014/053450 A1) or pharmaceuticals (e.g., structure 1b, WO 2014/051055 A1).Despite these useful properties, a simple and efficient procedure for the large scale preparation of these compounds has not yet been developed. While 4-amido-1,2,3-triazoles are readily prepared by standard acylation of 4-amino-1,2,3-triazoles, these amino-derivatives are themselves difficult to prepare. Several syntheses of 4-amino-1,2,3-triazoles have been reported based on the introduction of the 4-amino group to a pre-existing 1,2,3-triazole, such as via the Curtius rearrangement (WO 2014/053450 A1, WO 2014/051055 A1), or by addition of a nitrogen nucleophile to a suitably activated triazole according to the procedure of Begtrup and co-workers (1, 1981, 503-513). These syntheses tend to be long and involve energetic or exotic compounds that are not conveniently handled in technical scale reactions.Nikitin and co-workers have described a preparation of 2-phenyl-4-amino-1,2,3-triazole by the reduction of the corresponding 4-nitrotriazole (1992, 28, 2334-2343), which could then be acylated to the corresponding 4-amido-1,2,3-triazole by a variety of methods known to one skilled in the art. This intermediate amine can be prepared by reaction of an aryl diazonium salt with the extremely sensitive ...

TRIAZOLE COMPOUNDS AND PREPARATION METHOD THEREFOR AND USE THEREOF

Certain triazole compounds have good LPAR1 antagonistic activity and selectivity, low toxicity, and good metabolic stability, and can be used for preventing or treating the LPAR1-related disease or disorder. The ICvalue of some triazole compounds can be below 300 nM, even 50 nM. The range of CCof the triazole compounds can be greater than 200 μM. They also show good metabolic stability in human, fancy rats, and house mice. 7. Compounds of formulas M-1 claim 5 , M-2 claim 5 , M-3 claim 5 , M-4 claim 5 , M-5 claim 5 , M-6 claim 5 , M-7 claim 5 , M-8 claim 5 , M-9 claim 5 , M-10 claim 5 , M-11 claim 5 , M-12 claim 5 , M-13 claim 5 , M-14 claim 5 , M-15 claim 5 , M-16 claim 5 , M-17 claim 5 , M-18 claim 5 , M-19 claim 5 , M-20 claim 5 , M-21 claim 5 , M-22 claim 5 , M-23 claim 5 , M-24 claim 5 , M-25 claim 5 , M-26 claim 5 , M-27 claim 5 , M-28 claim 5 , M-29 claim 5 , M-30 claim 5 , M-31 claim 5 , M-32 claim 5 , M-33 claim 5 , M-34 claim 5 , M-35 claim 5 , M-36 claim 5 , M-37 and M-38 claim 5 , wherein claim 5 , the compounds described above are defined as in .8. Compounds of formulas 1-3A claim 5 , 1-4A claim 5 , 1-6A claim 5 , 2-5A claim 5 , 2-6A claim 5 , 2-7A claim 5 , 2-9A claim 5 , 3-1A claim 5 , 4-1A claim 5 , 4-2A claim 5 , 4-3A claim 5 , 4-4A claim 5 , 4-5A claim 5 , 5-5A claim 5 , 5-6A claim 5 , 6-2 claim 5 , 6-3 claim 5 , 6-5A claim 5 , 6-6A claim 5 , 6-9A claim 5 , 7-2 claim 5 , 7-4 claim 5 , 7-5 claim 5 , 7-6 claim 5 , 7-7 claim 5 , 7-8A claim 5 , 9-1A claim 5 , 9-2A claim 5 , 9-3A claim 5 , 9-4A claim 5 , 10-2A claim 5 , 10-4A claim 5 , 10-6A claim 5 , 10-7A claim 5 , 10-8A claim 5 , 13-2 claim 5 , 13-3 claim 5 , 13-4 claim 5 , 13-5 claim 5 , 13-6A claim 5 , 13-7A claim 5 , 13-9A claim 5 , 14-2A claim 5 , 14-3A claim 5 , 14-4A claim 5 , 14-5A claim 5 , 15-2A claim 5 , 15-3A claim 5 , 15-4A claim 5 , 15-5A claim 5 , 15-7A claim 5 , 16-5A claim 5 , 16-6A claim 5 , 16-7B claim 5 , 16-8A claim 5 , 16-9A claim 5 , 16-10A claim 5 , 16-11A claim 5 , 16-12A claim ...

KDM1A INHIBITORS FOR THE TREATMENT OF DISEASE

Disclosed herein are new compounds and compositions and their application as pharmaceuticals for the treatment of diseases. Methods of inhibition of KDM1A, methods of increasing gamma globin gene expression, and methods to induce differentiation of cancer cells in a human or animal subject are also provided for the treatment of diseases such as acute myelogenous leukemia. 158.-. (canceled)60. The process of claim 59 , wherein the step of converting comprises reacting the compound of formula 3 with 1 claim 59 ,3-dimethyl-1 claim 59 ,3-diazinane-2 claim 59 ,4 claim 59 ,6-trione in the presence of Pd(PPh).61. The process of claim 60 , wherein an excess of 1 claim 60 ,3-dimethyl-1 claim 60 ,3-diazinane-2 claim 60 ,4 claim 60 ,6-trione is used.62. The process of claim 59 , further comprising the step of purifying the N-[(2S)-1-(4-(methyl)piperazin-1-yl)-5-[[(1R claim 59 ,2S)-2-(4-fluorophenyl)cyclopropyl]amino]-1-oxopentan-2-yl]-4-(1H-1 claim 59 ,2 claim 59 ,3-triazol-1-yl)benzamide.65. The process of claim 64 , wherein the step of reacting is conducted in the presence of sodium borohydride. This application is a continuation of U.S. application Ser. No. 16/672,083, filed Nov. 1, 2019, which is a continuation of U.S. application Ser. No. 15/952,073, filed Apr. 12, 2018, now Issued U.S. Pat. No. 10,519,118, which is a continuation of U.S. application Ser. No. 15/043,121, filed Feb. 12, 2016, now Issued U.S. Pat. No. 9,981,922, which claims the benefit of priority of U.S. Provisional Application No. 62/115,474, filed Feb. 12, 2015, the disclosures of which are hereby incorporated by reference as if written herein in their entireties.The present disclosure relates to new compounds and compositions and their application as pharmaceuticals for the treatment of diseases.Inhibiting the enzyme KDM1A (also known as lysine-specific demethylase 1, LSD1, Flavin-containing Amine Oxidase Domain-Containing Protein, AOF2, BRAF35-HDAC Complex Protein BHC110, FAD-Binding Protein BRAF35- ...

AFIBROTIC COMPOUNDS, DEVICES, AND USES THEREOF

Described herein are compounds of Formula (I), modified polymers and implantable elements comprising compounds of Formula (II), as well as compositions and methods of use thereof. In particular, the compounds, modified polymers, implantable elements and related compositions may be used in methods for the prevention and treatment of a disease, disorder or condition in a subject. 2. The polymer of claim 1 , wherein Ring Mis phenyl.3. The polymer of claim 1 , wherein each of R claim 1 , R claim 1 , R claim 1 , and Ris independently hydrogen or alkyl (C-Calkyl).45-. (canceled)6. The polymer of claim 1 , wherein one of Rand Ris hydrogen and the other of Rand Ris C-Calkyl (e.g. claim 1 , —CH) claim 1 , and each of Rand Ris independently hydrogen.7. The polymer of claim 1 , wherein each of m and n is independently 1 or 2.89-. (canceled)10. The polymer of claim 1 , wherein X is O or absent.11. (canceled)12. The polymer of claim 1 , wherein Ring Zis heterocyclyl.1314-. (canceled)1719-. (canceled)21. The polymer of claim 20 , wherein the compound is a compound shown in Table 2.22. The polymer of claim 20 , wherein the polymer is a hydrogel-forming polymer.2326-. (canceled)27. The polymer of claim 20 , wherein the polymer comprises an increase in % N (as compared with unmodified polymer) of 0.1 to 10% N by weight claim 20 , where % N is determined by elemental analysis and corresponds to the amount of compound of Formula (II) in the modified polymer.2829-. (canceled)31. The alginate of claim 30 , wherein Ring Mis phenyl.32. The alginate of claim 30 , wherein each of R claim 30 , R claim 30 , R claim 30 , and Ris independently hydrogen or alkyl (C-Calkyl).3335-. (canceled)36. The alginate of claim 30 , wherein each of m and n is independently 1 or 2.3738-. (canceled)39. The alginate of claim 30 , wherein X is O or absent.40. (canceled)41. The alginate of claim 30 , wherein Ring Zis heterocyclyl.4243-. (canceled)4648-. (canceled)50. The alginate of claim 30 , wherein the ...

ENHANCEMENT OF NUCLEIC ACID POLYMERIZATION BY AROMATIC COMPOUNDS

The invention relates to compounds, methods and compositions for improving on nucleic acid polymerization, including DNA replication by in vitro primer extension to generate, for example, polymers for nanopore-based single molecule sequencing of a DNA template. A nucleic acid polymerase reaction composition is provided with polymerization enhancement moieties, which allows enhanced DNA polymerase activity with nucleotide analogs, resulting in improved length of primer extension products for sequencing applications. 2. The method of claim 1 , wherein Ar1 is monocyclic carbocyclic aryl.3. The method of claim 1 , wherein Ar1 is monocyclic heterocyclic aryl.4. The method of claim 1 , wherein Ar1 is bicyclic aryl.5. The method of claim 1 , wherein Ar1 is tricyclic aryl.6. The method of claim 1 , wherein Ar1 is unsubstituted aryl.7. The method of claim 1 , wherein Ar1 is substituted aryl.8. The method of claim 1 , wherein Ar2 is a 5-membered monocyclic aromatic ring selected from the group consisting of thiophene claim 1 , 1 claim 1 ,2-thiazole claim 1 , 1 claim 1 ,3-thiazole claim 1 , furan claim 1 , 1 claim 1 ,2-oxazole claim 1 , 1 claim 1 ,3-oxazole claim 1 , 1H-pyrrole claim 1 , 1H-pyrazole claim 1 , oxadiazole claim 1 , thiadiazole claim 1 , 1 claim 1 ,2 claim 1 ,4-triazole claim 1 , 1 claim 1 ,2 claim 1 ,3-triazole and 1H-imidazole.9. The method of claim 1 , wherein Ar2 is a 6-membered monocyclic aromatic ring selected from the group consisting of benzene claim 1 , pyridine claim 1 , pyridazine claim 1 , pyrimidine and pyrazine.10. The method of claim 1 , wherein Ar2 is a 9-membered fused bicyclic aromatic ring system selected from the group consisting of benzofuran claim 1 , 1 claim 1 ,3-benzoxazole claim 1 , furo[3 claim 1 ,2-b]pyridine claim 1 , furo[3 claim 1 ,2-c]pyridine claim 1 , furo[2 claim 1 ,3-c]pyridine claim 1 , furo[2 claim 1 ,3-b]pyridine claim 1 , indole claim 1 , 1H-benzimidazole claim 1 , 1H-pyrrolo[3 claim 1 ,2-b]pyridine claim 1 , 1H-pyrrolo[3 ...

TRIAZOLE-SUBSTITUTED ARYLAMIDES AS P2X3 AND P2X2/3 MODULATORS

Compounds of the formula I: 161-. (canceled)63. The compound of claim 62 , wherein Ris phenyl substituted once or twice with halo or methyl.64. The compound of claim 62 , wherein claim 62 , Ris 4-methyl-phenyl claim 62 , 2-fluoro-4-methyl-phenyl claim 62 , 2-chloro-4-fluoro-phenyl claim 62 , 4-chloro-2-fluoro-phenyl claim 62 , 2 claim 62 ,4-dichloro-phenyl claim 62 , 2 claim 62 ,4-difluoro-phenyl claim 62 , or 2-chloro-4-methyl-phenyl.65. The compound of claim 62 , wherein claim 62 , Ris pyridin 2-yl substituted with methyl or halo at the 5-position.66. The compound of claim 62 , wherein claim 62 , Ris 5-methyl-pyridin-2-yl claim 62 , 5-chloro-pyridin-2-yl claim 62 , 5-fluoro-pyridin-2-yl claim 62 , 5-methyl-3-fluoro-pyridin-2-yl claim 62 , 5-methyl-3-chloro-pyridin-2-yl claim 62 , 3 claim 62 ,5-difluoro-pyridin-2-yl or 3 claim 62 ,5-dichloro-pyridin-2-yl.67. The compound of claim 62 , wherein Ris hydrogen.68. The compound of claim 67 , wherein Ris hydrogen.69. The compound of claim 68 , wherein Ris hydrogen or methyl.70. The compound of claim 67 , wherein Rand Rare hydrogen.71. The compound of claim 63 , wherein Ris triazolyl optionally substituted once or twice with any of Calkyl claim 63 , hetero-Calkyl claim 63 , Calkoxy claim 63 , phenyl claim 63 , heterocyclyl claim 63 , C-cycloalkyl claim 63 , Ccycloalkyl-Calkyl or cyano.72. The compound of claim 70 , wherein Ris triazolyl substituted with Calkyl or halo-Calkyl.73. The compound of claim 70 , wherein Ris triazolyl optionally substituted once with methyl claim 70 , ethyl claim 70 , n-propyl claim 70 , n-butyl claim 70 , isopropyl claim 70 , isobutyl claim 70 , tert-butyl claim 70 , cyclopropyl claim 70 , cyclobutyl claim 70 , cyclopropylmethyl claim 70 , phenyl claim 70 , trifluoromethyl claim 70 , difluoromethyl claim 70 , fluoromethyl claim 70 , pentafluoro-ethyl claim 70 , 1 claim 70 ,1-difluoro-ethyl claim 70 , 2 claim 70 ,2-difluoroethyl claim 70 , 1-methoxy-ethyl claim 70 , 1-ethoxy-ethyl claim 70 , 2- ...

ALPHA-TRUXILLIC ACID DERIVATIVES AND PHARMACEUTICAL COMPOSITIONS THEREOF

The present invention provides a compound, and method of inhibiting the activity of a Fatty Acid Binding Protein (FABP) comprising contacting the FABP with a compound, said compound having the structure: Formula (I) 3. The compound of claim 1 , wherein when one of Ror Ris —C(═O)OH and R claim 1 , R claim 1 , R claim 1 , R claim 1 , R claim 1 , R claim 1 , R claim 1 , R claim 1 , Rand Rare each H claim 1 , then the other of Ror Ris other than —C(═O)ORwhere Ris tolyl claim 1 , 1-naphthalene or 2-naphthalene claim 1 , or —C(═O)O-alkyl-Rwhere the alkyl is a branched Calkyl and the Ris phenyl.4. The compound of claim 1 , wherein when one of Ror Ris —C(═O)OH and the other of Ror Ris —C(═O)ORwhere Ris 1-naphthalene or 2-naphthalene claim 1 , then one of R claim 1 , R claim 1 , R claim 1 , R claim 1 , R claim 1 , R claim 1 , R claim 1 , R claim 1 , Rand Ris other than —H; or{'sub': 1', '2', '1', '2', '13', '13', '3', '4', '5', '6', '7', '8', '9', '10', '11', '12, 'wherein when one of Ror Ris —C(═O)OH and the other of Ror Ris —C(═O)ORwhere Ris 1-naphthalene or 2-naphthalene, then two of R, R, R, R, R, R, R, R, Rand Ris other than —H; or'}{'sub': 1', '2', '1', '2', '13', '13', '3', '4', '5', '6', '7', '8', '9', '10', '11', '12, 'herein when one of Ror Ris —C(═O)OH and the other of Ror Ris —C(═O)ORwhere Ris 1-naphthalene or 2-naphthalene, then four of R, R, R, R, R, R, R, R, Rand Ris other than —H.'}56.-. (canceled)7. The compound of claim 1 ,wherein{'sub': 1', '2', '13, 'claim-text': {'sub': '13', 'wherein Ris cycloalkyl, aryl or heteroaryl; and'}, 'one of Ror Ris —C(═O)OR,'}{'sub': 1', '2, 'the other of Ror Ris —C(═O)OH.'}8. The compound of claim 1 ,wherein{'sub': 1', '2', '14, 'claim-text': {'sub': 14', '3, 'wherein Ris CF, cycloalkyl, aryl or heteroaryl; and'}, 'one of Ror Ris —C(═O)O-alkyl-R,'}{'sub': 1', '2, 'the other of Ror Ris —C(═O)OH.'}910.-. (canceled)117. The compound of claim 1 , wherein the aryl or heteroaryl is a substituted aryl or heteroaryl claim 1 , wherein ...

Substituted Heterocycles as c-MYC Targeting Agents

Disclosed are substituted heterocycle compounds including substituted pyrazoles, substituted pyrimidines, and substitute triazoles. The substituted heterocycles disclosed herein are shown to be useful in inhibiting c-MYC and may be utilized as therapeutics for treating cancer and cell proliferative disorders. 2. The compound of claim 1 , wherein at least one of Rand Ris an aryl group claim 1 , a benzyl group claim 1 , a heteroaryl group claim 1 , a cycloalkyl group claim 1 , or a cycloheteroalkyl group claim 1 , and Rand Roptionally are substituted at one or more positions with one or more of alkyl claim 1 , alkoxy claim 1 , haloalkyl claim 1 , haloalkoxy claim 1 , hydroxyl claim 1 , halo claim 1 , cyano claim 1 , amido claim 1 , hydrazonyl claim 1 , carbonyl claim 1 , carboxyl claim 1 , and alkoxycarbonyl.3. The compound of claim 1 , wherein m is 0 and Ris hydrogen; or wherein Ris hydrogen.4. The compound of claim 1 , wherein Ris an aryl group claim 1 , a benzyl group claim 1 , a heteroaryl group claim 1 , a cycloalkyl group claim 1 , or a cycloheteroalkyl group claim 1 , and Roptionally is substituted at one or more positions with one or more of alkyl claim 1 , alkoxy claim 1 , haloalkyl claim 1 , haloalkoxy claim 1 , hydroxyl claim 1 , halo claim 1 , cyano claim 1 , amido claim 1 , hydrazonyl claim 1 , carbonyl claim 1 , carboxyl claim 1 , and alkoxycarbonyl; and wherein Ris hydrogen.5. The compound of claim 1 , wherein m is 0 and Ris hydrogen; and wherein Ris an aryl group claim 1 , a benzyl group claim 1 , a heteroaryl group claim 1 , a cycloalkyl group claim 1 , or a cycloheteroalkyl group claim 1 , and Roptionally is substituted at one or more positions with one or more of alkyl claim 1 , alkoxy claim 1 , haloalkyl claim 1 , haloalkoxy claim 1 , hydroxyl claim 1 , halo claim 1 , cyano claim 1 , amido claim 1 , hydrazonyl claim 1 , carbonyl claim 1 , carboxyl claim 1 , and alkoxycarbonyl.14. A pharmaceutical composition comprising a compound of and a suitable ...

VDR-SILENT VITAMIN D DERIVATIVE AS INHIBITORS OF SREBP AND PHARMACEUTICAL USE THEREOF

Provided are vitamin Dderivatives of formula (I), pharmaceutical compositions thereof, and pharmaceutical or medical uses thereof for treating metabolic disease, a liver disease, obesity, diabetes, cardiovascular disease, or cancer in a patient in need thereof. 2. (canceled)4. (canceled)5. The Compound of claim 1 , wherein one Ris hydrogen and the other Rare independently hydrogen claim 1 , alkyl claim 1 , haloalkyl claim 1 , or halo; or a stereoisomer claim 1 , mixture of stereoisomers claim 1 , and/or a pharmaceutically acceptable salt thereof.6. The Compound of claim 1 , wherein two Rare each hydrogen and the third Ris alkyl claim 1 , haloalkyl claim 1 , or halo; or a stereoisomer claim 1 , mixture of stereoisomers claim 1 , and/or a pharmaceutically acceptable salt thereof.7. (canceled)8. The Compound of claim 1 , wherein two Rare each hydrogen and the third Ris halo; or a stereoisomer claim 1 , mixture of stereoisomers claim 1 , and/or a pharmaceutically acceptable salt thereof.9. The Compound of claim 1 , wherein one Ris hydrogen and the other two Rare independently halo; or a stereoisomer claim 1 , mixture of stereoisomers claim 1 , and/or a pharmaceutically acceptable salt thereof.12. The Compound of claim 11 , wherein one of X and Y is CRand the other is CH; or a stereoisomer claim 11 , mixture of stereoisomers claim 11 , and/or a pharmaceutically acceptable salt thereof.13. (canceled)14. The Compound of claim 11 , wherein one of X and Y is CRand the other is N; or a stereoisomer claim 11 , mixture of stereoisomers claim 11 , and/or a pharmaceutically acceptable salt thereof.1518-. (canceled)19. The Compound of claim 11 , wherein Ris phenyl optionally substituted with 1 claim 11 , 2 claim 11 , or 3 Rgroups; or a stereoisomer claim 11 , mixture of stereoisomers claim 11 , and/or a pharmaceutically acceptable salt thereof.20. The Compound of claim 11 , wherein Ris 5-membered heteroaryl optionally substituted with 1 claim 11 , 2 claim 11 , or 3 Rgroups; or a ...

SELECTIVE ANDROGEN RECEPTOR DEGRADER (SARD) LIGANDS AND METHODS OF USE THEREOF

This invention is directed to pyrrole, pyrazole, imidazole, triazole, and morpholine based selective androgen receptor degrader (SARD) compounds including cyclic and heterocyclic anilide rings and their synthetic precursors, and mono-, di-, or multi-substituted N-heterocyclic rings, R-isomers, non-hydroxylated and/or non-chiral propanamides in treating androgen receptor dependent diseases and conditions such as hyperproliferations of the prostate including pre-malignancies and benign prostatic hyperplasia, prostate cancer, advanced prostate cancer, castration resistant prostate cancer, triple negative breast cancer, other cancers expressing the androgen receptor, androgenic alopecia or other hyperandrogenic dermal diseases, Kennedy's disease, amyotrophic lateral sclerosis (ALS), abdominal aortic aneurysm (AAA), and uterine fibroids, and to methods for reducing the levels of androgen receptor-full length (AR-FL) including pathogenic or resistance mutations, AR-splice variants (AR-SV), and pathogenic polyglutamine (polyQ) polymorphisms of AR in a subject. 10. The method of claim 1 , wherein Q claim 1 , Q claim 1 , Qand Qis hydrogen. CN claim 1 , NO claim 1 , CF claim 1 , F claim 1 , Cl claim 1 , Br claim 1 , I claim 1 , NHCOOR claim 1 , N(R) claim 1 , NHCOR claim 1 , COR claim 1 , alkyl claim 1 , alkoxy claim 1 , or substituted or unsubstituted phenyl.12. The method of claim 1 , wherein said androgen receptor dependent disease or condition in said subject responds to at least one of AR-splice variant (AR-SV) degradation activity claim 1 , full length (AR-FL) degradation activity claim 1 , AR-SV inhibitory claim 1 , or AR-FL inhibitory activity claim 1 , comprising administering to the subject a therapeutically effective amount of a compound according to or .13. The method of claim 1 , wherein said androgen receptor dependent disease or condition is breast cancer in said subject.14. The method of claim 13 , wherein said subject has AR expressing breast cancer claim 13 ...

IRE-1alpha INHIBITORS

The invention provides compounds which directly inhibit IRE-1α activity in vitro, prodrugs, and pharmaceutically acceptable salts thereof. Such compounds and prodrugs are useful for treating diseases associated with the unfolded protein response and can be used as single agents or in combination therapies. 19-. (canceled)11. The compound of claim 10 , wherein Het is thienyl optionally substituted with alkyl.12. A pharmaceutical composition claim 10 , comprising the compound of claim 10 , and a pharmaceutically acceptable vehicle.13. A method of treating a disease associated with the unfolded protein response claim 10 , comprising administering to a patient in need thereof an effective amount of the compound of .15. A pharmaceutical composition claim 14 , comprising the compound of claim 14 , and a pharmaceutically acceptable vehicle.16. A method of treating a disease associated with the unfolded protein response claim 15 , comprising administering to a patient in need thereof an effective amount of the compound of . This application claims the benefit of and incorporates by reference Ser. No. 61/257,696 filed Nov. 3, 2009.The invention relates to IRE-1α inhibitors and their therapeutic uses.Protein folding stress in the endoplasmic reticulum of a cell initiates a signal transduction cascade termed the unfolded protein response or UPR. A key enzyme, inositol requiring enzyme 1 (IRE-1α), relieves protein folding stress by enhancing molecular chaperone activity and therefore protects cells from stress induced apoptosis. Inhibitors of IRE-1 α are useful for treating at least B cell autoimmune diseases, certain cancers, and some viral infections.The invention provides IRE-1α inhibitor compounds and prodrugs and pharmaceutically acceptable salts thereof. The invention also provides pharmaceutical compositions and methods of using the IRE-1α inhibitor compounds, prodrugs, and pharmaceutically acceptable salts thereof therapeutically to treat disorders associated with the ...

WNT Signaling Pathway Inhibitors for Treatments of Disease

Compounds and compositions are provided as inhibitors of the Wnt/β-catenin pathway for the treatment of diseases that implicate the same.

Surfactant-Enabled Transition Metal-Catalyzed Chemistry

In one embodiment, the present application discloses mixtures comprising (a) water in an amount of at least 1% wt/wt of the mixture; (b) a transition metal catalyst; and (c) one or more solubilizing agents; and methods for using such mixtures for performing transition metal mediated bond formation reactions. 114.-. (canceled)16. The method of claim 15 , wherein the transition metal mediated bond formation is performed in an aqueous solvent.17. The method of claim 15 , wherein the transition metal catalyst is selected from an organo-palladium or -nickel reagent claim 15 , organo-copper or -gold reagent claim 15 , organo-rhodium or -iridium complex claim 15 , or an organo-ruthenium claim 15 , -iron claim 15 , or -osmium reagent claim 15 , wherein the catalyst is capable of promoting cross-coupling reactions claim 15 , or other reactions characteristic of catalysis by these metals claim 15 , that form a carbon-carbon claim 15 , carbon-heteroatom or carbon-hydrogen bond.18. The method of claim 15 , wherein Yis methyl.19. The method of claim 15 , wherein the solubilizing agent is selected from the group consisting of Poloxamer 188 claim 15 , Polysorbate 80 claim 15 , Polysorbate 20 claim 15 , Vit E-TPGS claim 15 , Solutol HS 15 claim 15 , PEG-40 Hydrogenated castor oil (Cremophor RH40) claim 15 , PEG-35 Castor oil (Cremophor EL) claim 15 , PEG-8-glyceryl capylate/caprate (Labrasol) claim 15 , PEG-32-glyceryl laurate (Gelucire 44/14) claim 15 , PEG-32-glyceryl palmitostearate (Gelucire 50/13); Polysorbate 85 claim 15 , polyglyceryl-6-dioleate (Caprol MPGO) claim 15 , mixtures of high and low HLB emulsifiers; sorbitan monooleate (Span 80) claim 15 , Capmul MCM claim 15 , Maisine 35-1 claim 15 , glyceryl monooleate claim 15 , glyceryl monolinoleate claim 15 , PEG-6-glyceryl oleate (Labrafil M 1944 CS) claim 15 , PEG-6-glyceryl linoleate (Labrafil M 2125 CS) claim 15 , oleic acid claim 15 , linoleic acid claim 15 , propylene glycol monocaprylate (e.g. Capmul PG-8 or Capryol ...

1,4,5-SUBSTITUTED 1,2,3-TRIAZOLE ANALOGUES AS ANTAGONISTS OF THE PREGNANE X RECEPTOR

In an aspect, the invention relates to 1,4,5-substituted 1,2,3-triazole and 1,2,4,5-substituted imidazoles, which are modulators the pregnane X receptor (“PXR”); synthesis methods for making the compounds; pharmaceutical compositions comprising the compounds; and methods of modulating an adverse drug reaction in a mammal using the compounds and pharmaceutical compositions; methods of treatment of a disorder of uncontrolled cellular proliferation, such as a cancer, using the compounds and pharmaceutical compositions; methods of modulating pregnane X receptor activity in a mammal using the compounds and pharmaceutical compositions. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present invention. 2. The compound of claim 1 , wherein Ris alkoxy and Ris alkoxy.3. The compound of claim 1 , wherein Ris methoxy.4. The compound of claim 1 , wherein Ris methyl.5. The compound of claim 1 , wherein Ris tert-butyl.6. The compound of claim 1 , wherein Ris hydroxy claim 1 , halogen claim 1 , methyl claim 1 , ethyl claim 1 , methoxy claim 1 , or ethoxy; wherein Ris fluoro or methyl; wherein Ris hydroxy claim 1 , halogen claim 1 , methyl claim 1 , ethyl claim 1 , methoxy claim 1 , or ethoxy; wherein Ris fluoro claim 1 , chloro claim 1 , bromo claim 1 , cyano claim 1 , methyl claim 1 , ethyl claim 1 , propyl claim 1 , isopropyl claim 1 , —CHF claim 1 , —CHCl claim 1 , —(C═O)CH claim 1 , or —CH(C═O)OCH claim 1 , wherein Ris hydrogen claim 1 , hydroxy claim 1 , or methyl; wherein Ris hydrogen claim 1 , hydroxy claim 1 , or methyl; and wherein Ris propyl claim 1 , isopropyl claim 1 , n-butyl claim 1 , tert-butyl claim 1 , or sec-butyl.12. A pharmaceutical composition comprising a therapeutically effective amount of the compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , and a pharmaceutically acceptable carrier.18. The method of claim 15 , wherein the mammal is a human.19. ...

CHEMICAL MOLECULES THAT INHIBIT THE SLICING MECHANISM FOR TREATING DISEASES RESULTING FROM SPLICING ANOMALIES

The present invention relates to a compound of one of the formulas I to XXI; a pharmaceutical composition comprising at least one such compound; and the use of at least one such compound in preparing a drug to treat, in a subject, a genetic disease resulting from at least one splicing anomaly. 2. A compound selected from the group consisting of:N-(3-Dimethylamino-propyl)-3-(4-trifluoromethoxy-phenylamino)-benzamide;4-(4-Methoxy-phenylamino)-3-methyl-N-(3-methyl-butyl)-benzamide;3-Methyl-N-(3-methyl-butyl)-4-(4-trifluoromethoxy-phenylamino)-benzamide;N-(2-Dimethylamino-ethyl)-2-(4-trifluoromethoxy-phenylamino)-benzamide;N-(2-Diethylamino-ethyl)-2-(4-trifluoromethoxyphenylamino)-benzamide;N-(2-Diethylamino-propyl)-2-(4-trifluoromethoxy-phenylamino)-benzamide;(N-Diethylamino)-{1-[4-(4-Methoxy-phenylamino)-phenyl]-1H-1,2,3-triazol-4-yl}-methylamine;(N-Diethylamino)-{1-[4-(4-trifluoromethoxyphenylamino)-phenyl]-1H-1,2,3-triazol-4-yl}-methylamine;(N-Diethylamino)-{1-[4-(4-N-dimethylamino-phenylamino)-phenyl]-1H-1,2,3-triazol-4-yl}-methylamine;N-(3-Imidazol-1-yl-propyl)-2-(4-methoxy-phenylamino)-benzamide;N-(3-Imidazol-1-yl-propyl)-2-(4-trifluoromethoxy-phenylamino)-benzamide;2-(4-Dimethylamino-phenylamino)-N-(3-imidazol-1-yl-propyl)-benzamide;N-(4-Diethylamino-1-methyl-butyl)-2-(4-dimethylaminophenylamino)-benzamide;N-(2-Dimethylamino-ethyl)-4-(4-trifluoromethoxy-phenylamino)-benzamide;N-(2-Dimethylamino-ethyl)-4-(4-dimethylamino-phenylamino)-benzamide;N-(2-Dimethylamino-ethyl)-4-(4-methoxy-phenylamino)-3-methyl-benzamide;N-(3-Diethylamino-propyl)-4-(4-methoxy-phenylamino)-benzamide;N-(3-Diethylamino-propyl)-4-(4-methoxy-phenylamino)-3-methyl-benzamide;N-(3-Diethylamino-propyl)-3-methyl-4-(4-trifluoromethoxy-phenylamino)-benzamide;N-(3-Diethylamino-propyl)-4-(4-dimethylamino-phenylamino)-3-methyl-benzamide;N-(2-Dimethylamino-ethyl)-3-methyl-4-(4-trifluoromethoxy-phenylamino)-benzamide;3-{1-[4-(4-Methoxy-phenylamino)-phenyl]-1H-1,2,3-triazol-4-yl}-propan-1-ol;(N- ...

1,4,5-SUBSTITUTED 1,2,3-TRIAZOLE ANALOGUES AS ANTAGONISTS OF THE PREGNANE X RECEPTOR

In an aspect, the invention relates to 1,4,5-substituted 1,2,3-triazole and 1,2,4,5-substituted imidazoles, which are modulators the pregnane X receptor (“PXR”); synthesis methods for making the compounds; pharmaceutical compositions comprising the compounds; and methods of modulating an adverse drug reaction in a mammal using the compounds and pharmaceutical compositions; methods of treatment of a disorder of uncontrolled cellular proliferation, such as a cancer, using the compounds and pharmaceutical compositions; methods of modulating pregnane X receptor activity in a mammal using the compounds and pharmaceutical compositions. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present invention. 2. The compound of claim 1 , wherein Ris alkoxy and Ris alkoxy.3. The compound of claim 1 , wherein Ris methoxy.4. The compound of claim 1 , wherein Ris methyl.5. The compound of claim 1 , wherein Ris tert-butyl.6. The compound of claim 1 , wherein Ris hydroxy claim 1 , halogen claim 1 , methyl claim 1 , ethyl claim 1 , methoxy claim 1 , or ethoxy; wherein Ris fluoro or methyl; wherein Ris hydroxy claim 1 , halogen claim 1 , methyl claim 1 , ethyl claim 1 , methoxy claim 1 , or ethoxy; wherein Ris fluoro claim 1 , chloro claim 1 , bromo claim 1 , cyano claim 1 , methyl claim 1 , ethyl claim 1 , propyl claim 1 , isopropyl claim 1 , —CHF claim 1 , —CHCl claim 1 , —(C═O)CH claim 1 , or —CH(C═O)OCH claim 1 , wherein Ris hydrogen claim 1 , hydroxy claim 1 , or methyl; wherein Ris hydrogen claim 1 , hydroxy claim 1 , or methyl; and wherein Ris propyl claim 1 , isopropyl claim 1 , n-butyl claim 1 , tert-butyl claim 1 , or sec-butyl.12. A pharmaceutical composition comprising a therapeutically effective amount of the compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , and a pharmaceutically acceptable carrier.18. The method of claim 15 , wherein the mammal is a human.19. ...

Compounds which have a protective activity with respect to the action of toxins and of viruses with an intracellular mode of action

The subject matter of the present invention is novel families of compounds which are aromatic amine, imine, aminoadamantane and benzodiazepine derivatives, medicaments comprising same and the use thereof as inhibitors of the toxic effects of toxins with intracellular activity, such as, for example, ricin, and of viruses that use the internalization pathway for infecting cells.

PROPELLANE DERIVATES AND SYNTHESIS

Disclosed herein are compounds of the general Formula (I), and methods of synthesizing substituted bicyclo[1.1.1 jpentanes. The synthetic methods described herein use a [1.1.1]propellane, a Group VIII transition metal compound, a hydride source and a reagent that can contribute a substituent to form a substituted bicyclo[1.1.1]pentane, such as a compound of the general Formula (I). 1. A method for preparing a substituted bicyclo[1.1.1]pentane compound comprising:combining [1.1.1]propellane;a Group VIII transition metal compound;a hydride source; anda reagent capable of contributing all or a part of a substituent group such that bicyclo[1.1.1]pentane is substituted with the substituent group.3. The method of claim 2 , wherein Ris —N claim 2 , halogen claim 2 , —CN claim 2 , —OH claim 2 , —SCN claim 2 , —NCO claim 2 , —NO claim 2 , —C(═NOR)(CN) claim 2 , —CH(═NOR) or —COH.4. The method of claim 2 , wherein Ris an optionally substituted Calkyl claim 2 , an optionally substituted Calkenyl claim 2 , an optionally substituted Calkynyl claim 2 , an optionally substituted cycloalkyl claim 2 , an optionally substituted cycloalkenyl claim 2 , an optionally substituted cycloalkynyl claim 2 , an optionally substituted aryl claim 2 , an optionally substituted heteroaryl claim 2 , an optionally substituted heterocyclyl claim 2 , an optionally substituted aryl(Calkyl) claim 2 , an optionally substituted heteroaryl(Calkyl) claim 2 , an optionally substituted heterocyclyl(Calkyl) claim 2 , an optionally substituted alkoxy claim 2 , an optionally substituted acyl claim 2 , an optionally substituted amino claim 2 , an optionally substituted alkoxyalkyl claim 2 , an optionally substituted acylalkyl claim 2 , an optionally substituted aminoalkyl claim 2 , an optionally substituted hydroxyalkyl claim 2 , an optionally substituted haloalkyl claim 2 , an optionally substituted haloalkoxy claim 2 , an optionally substituted arylthio claim 2 , or an optionally substituted alkylthio.5. The ...

Oxexin 1 receptor antagonists

The disclosures herein relate to novel compounds of formula (1) and salts thereof, wherein V; W; X; Y; Z; R 1 ; R 2 ; R 3 ; R 4 and R 5 are defined herein, and their use in treating, preventing, ameliorating, controlling or reducing the risk of neurological or psychiatric disorders associated with orexin receptors.

EBNA1 INHIBITORS AND THEIR METHOD OF USE

Pharmaceutical compositions of the invention comprise EBNA1 inhibitors useful for the treatment of diseases caused by EBNA1 activity such as cancer, infectious mononucleosis, chronic fatigue syndrome, multiple sclerosis, systemic lupus erythematosus and rheumatoid arthritis. Pharmaceutical compositions of the invention also comprise EBNA1 inhibitors useful for the treatment of diseases caused by latent Epstein-Barr Virus (EBV) infection. Pharmaceutical compositions of the invention also comprise EBNA1 inhibitors useful for the treatment of diseases caused by lytic Epstein-Barr Virus (EBV) infection. 4. The method of claim 1 , wherein the compound is at least one selected from the group consisting of:3-{2-[3-(methylsulfamoyl)phenyl]ethynyl}-2-(1H-pyrrol-1-yl)benzoic acid;3-[2-(1H-indol-3-yl)ethynyl]-2-(1H-pyrrol-1-yl)benzoic acid;3-[2-(3-methanesulfonamidophenyl)ethynyl]-2-(1H-pyrrol-1-yl)benzoic acid;2-(1H-pyrrol-1-yl)-3-[2-(3-sulfamoylphenyl)ethynyl]benzoic acid;3-[2-(3-carbamoylphenyl)ethynyl]-2-(1H-pyrrol-1-yl)benzoic acid;3-(2-{imidazo[1,2-a]pyridin-6-yl}ethynyl)-2-(1H-pyrrol-1-yl)benzoic acid;3-[2-(2-hydroxypyridin-4-yl)ethynyl]-2-(1H-pyrrol-1-yl)benzoic acid;3-[2-(1H-indazol-6-yl)ethynyl]-2-(1H-pyrrol-1-yl)benzoic acid;3-{2-[3-(3,3-dimethyl-2-oxoazetidin-1-yl)phenyl]ethynyl}-2-(1H-pyrrol-1-yl)benzoic acid;3-(2-{3-[(2-carboxy-2,2-dimethylethyl)amino]phenyl}ethynyl)-2-(1H-pyrrol-1-yl)benzoic acid;3-(2-{imidazo[1,2-a]pyrazin-3-yl}ethynyl)-2-(1H-pyrrol-1-yl)benzoic acid;3-(2-{imidazo[1,2-a]pyridin-3-yl}ethynyl)-2-(1H-pyrrol-1-yl)benzoic acid;3-(2-{imidazo[1,2-a]pyridin-5-yl}ethynyl)-2-(1H-pyrrol-1-yl)benzoic acid;2-(1H-pyrrol-1-yl)-3-(2-{1H-pyrrolo[2,3-b]pyridin-5-yl}ethynyl)benzoic acid;3-[2-(1-methyl-1H-indol-4-yl)ethynyl]-2-(1H-pyrrol-1-yl)benzoic acid;3-[2-(1-methyl-1H-indol-5-yl)ethynyl]-2-(1H-pyrrol-1-yl)benzoic acid;3-[2-(1-benzothiophen-6-yl)ethynyl]-2-(1H-pyrrol-1-yl)benzoic acid;3-[2-(1H-indol-7-yl)ethynyl]-2-(1H-pyrrol-1-yl)benzoic acid;3-{2-[2-( ...

SUBSTITUTED PHENYLAZOLE DERIVATIVE

Compounds are provided having an excellent hypoglycemic effect and β cell- or pancreas-protecting effects, or pharmaceutically acceptable salts thereof, and a pharmaceutical composition having an excellent therapeutic effect and/or prophylactic effect on type 1 diabetes, type 2 diabetes, and the like, which cause hyperglycemia due to abnormal glucose metabolism. A compound represented by general formula (I), or a pharmaceutically acceptable salt thereof, is disclosed. 2. The compound of selected from the group consisting of:4-{4-[(1R)-1-{[6-(Cyclopropylcarbonyl)pyridin-3-yl]oxy}ethyl]-2H-1,2,3-triazol-2-yl}-N-[(1R,2R)-2,3-dihydroxy-1-methylpropyl)-2-fluorobenzamide;1-[4-(4-{1-[4-(Cyclopropylcarbonyl)phenoxy]propyl}-2H-1,2,3-triazol-2-yl)-2-fluorophenyl]-3-(2-hydroxyethyl)urea;1-(4-{4-[(1R)-1-{[6-(Cyclopropylcarbonyl)pyridin-3-yl]oxy}ethyl]-2H-1,2,3-triazol-2-yl}-2-fluorophenyl)-3-(2-hydroxyethyl)urea;4-(4-{1-[4-(Cyclopropylcarbonyl)phenoxy]propyl}-2H-1,2,3-triazol-2-yl)-2-fluoro-N-[(1R)-2-hydroxy-1-methylethyl]benzamide;4-(4-{1-[4-(Cyclopropylcarbonyl)phenoxy]propyl}-2H-1,2,3-triazol-2-yl)-2-fluoro-N-[(3S)-2-oxopyrrolidin-3-yl]benzamide;4-(4-{1-[4-(Cyclopropylcarbonyl)phenoxy]ethyl}-2H-1,2,3-triazol-2-yl)-2-fluoro-N-[(1R)-2-hydroxy-1-methylethyl]benzamide;4-(4-{(1R)-1-[4-(Cyclopropylcarbonyl)phenoxy]propyl}-2H-1,2,3-triazol-2-yl)-2-fluoro-N-[(1R)-2-hydroxy-1-methylethyl]benzamide;4-{4-[(1R)-1-{[6-(Cyclopropylcarbonyl)pyridin-3-yl]oxy}ethyl]-2H-1,2,3-triazol-2-yl}-2-fluoro-N-[(1R)-2-hydroxy-1-methylethyl]benzamide;4-{4-[(1R)-1-{[6-(Cyclopropylcarbonyl)pyridin-3-yl]oxy}ethyl]-2H-1,2,3-triazol-2-yl}-N-[(2S)-2,3-dihydroxypropyl]-2-fluorobenzamide;4-{4-[(1R)-1-{[6-(Cyclopropylcarbonyl)pyridin-3-yl]oxy}ethyl]-2H-1,2,3-triazol-2-yl}-2-fluoro-N-[(3S)-2-oxopyrrolidin-3-yl]benzamide; and1-[4-(4-{l-[4-(Cyclopropylcarbonyl)phenoxy]propyl}-2H-1,2,3-triazol-2-yl)-2-fluorophenyl]urea;or a pharmaceutically acceptable salt thereof.3. A pharmaceutical composition comprising the ...

Arginine methyltransferase inhibitors and uses thereof

Described herein are compounds of Formula (I), pharmaceutically acceptable salts thereof, and pharmaceutical compositions thereof. Compounds of the present invention are useful for inhibiting arginine methyltransferase activity. Methods of using the compounds for treating arginine methyltransferase-mediated disorders are also described.

COMPOUNDS AND METHODS FOR TREATING MALARIA

The present disclosure provides compounds, specifically pyrimidin-4,6-dicarboxylic acid amide derivatives, or pharmaceutically acceptable salts thereof and pharmaceutical compositions containing said compounds. Also provided are methods for treating a mammal having malaria, or killing or inhibiting the growth of a species, comprising administering to said mammal or contacting said species with, an effective amount of a pyrimidin--dicarboxylic acid amide derivative. 1144-. (canceled)146. A pharmaceutical composition comprising a compound of claim 145 , or a pharmaceutically acceptable salt thereof claim 145 , and a pharmaceutically acceptable carrier.148. The method of wherein the malaria is chloroquine-sensitive or chloroquine-resistant. The present disclosure was supported by funds from the U.S. Government (NIH/NIAID Grant No. 1R44AI090762-01) and the U.S. Government may therefore have certain rights in the disclosure.The present disclosure is directed, in part, to compounds, and pharmaceutically acceptable salts thereof, and compositions thereof for treating a mammal having malaria, or killing or inhibiting the growth of a species.World-wide, 41% of the population live in areas where malaria is transmitted, such as parts of Africa, Asia, Middle East, Central and South America, Hispaniola, and Oceania. Each year between 350 and 500 million cases of malaria occur worldwide, and over one million people die, most of them young children in sub-Saharan Africa. In areas of Africa with high malaria transmission, an estimated 990,000 people died of malaria in 1995. In 2002, malaria was the fourth cause of death in children in developing countries. In addition, malaria caused 10.7% of all children's deaths in developing countries.Antimicrobial peptides (AMPs) represent a component of the innate immune system that provides resistance to a variety of pathogenic bacteria. AMPs have provided new leads for developing antibiotics, because they play a central role in the innate ...

HETEROCYCLIC GROUP CONTAINED AMINO-METHANOL DERIVATIVE, AND SALT, SYNTHETIC METHOD AND USE THEREOF

The present invention provides a heterocyclic group contained amino-methanol derivative, and salt, a preparation method and use thereof, and belongs to the medical field. The heterocyclic group contained amino-methanol derivative and the salt thereof of the present invention are used for preparing medicines for immune suppression and for the treatment of organ transplant rejection, or medicines for treating immune mediated inflammatory diseases, such as multiple sclerosis, systemic lupus erythematosus and rheumatoid arthritis. 2. A salt of the compound according to .4. The compound according to claim 1 , wherein in Formula (I) claim 1 , R4=H claim 1 , alkyl claim 1 , aryl methyl claim 1 , carbonyl claim 1 , alkyl sulfonyl; ora physiologically salt thereof.9. (canceled)10. (canceled)11. The compound according to claim 1 , which is selected from the group consisting of:6-[5-(4-methoxyphenyl)-2-[1,3,4]oxdiazolyl]-2-amino-1,2,3,4-tetrahydro-naphthalen-2-yl-methanol6-[5-(4-ethoxyphenyl)-2-[1,3,4]oxdiazolyl]-2-amino-1,2,3,4-tetrahydro-naphthalen-2-yl-methanol,6-[5-(4-fluorophenyl)-2-[1,3,4]oxdiazolyl]-2-amino-1,2,3,4-tetrahydro-naphthalen-2-yl-methanol,6-[5-(3-fluorophenyl)-2-[1,3,4]oxdiazolyl]-2-amino-1,2,3,4-tetrahydro-naphthalen-2-yl-methanol,6-[5-(2-fluorophenyl)-2-[1,3,4]oxdiazolyl]-2-amino-1,2,3,4-tetrahydro-naphthalen-2-yl-methanol,6-[5-(4-pyridyl)-2-[1,3,4]oxdiazolyl]-2-amino-1,2,3,4-tetrahydro-naphthalen-2-yl-methanol,6-[5-(4-piperidyl)-2-[1,3,4]oxdiazolyl]-2-amino-1,2,3,4-tetrahydro-naphthalen-2-yl-methanol,1-{4-[5-(6-hydroxymethyl-6-amino-5,6,7,8-tetrahydro-naphthalen-2-yl)-2-[1,3,4]oxdiazolyl]-1-piperidyl}ethanone,6-[5-(3-methyl-4-methoxy phenyl)-2-[1,3,4]oxdiazolyl]-2-amino-1,2,3,4-tetrahydro-naphthalen-2-yl-methanol,7-{5-[4-(2-methoxyethoxy)phenyl]-2-[1,3,4]oxdiazolyl]-2-amino-1,2,3,4-tetrahydro-naphthalen-2-yl-methanol,7-[5-(3-trifluoromethyl-4-isopropoxyphenyl)-2-[1,3,4]oxdiazolyl]-2-amino-1,2,3,4-tetrahydro-naphthalen-2-yl-methanol,6-[5-(3-nitro-4-pyridyl ...

Synthesis of 4-(pentafluorosulfanyl)benzenediazonium tetrafluoroborate and Analogs

4-(pentafluorosulfanyl)benzenediazonium tetrafluoroborate salt was synthesized and isolated. The pentafluorosulfanyl salt was examined in a wide assortment of reactions to form novel SF 5 -bearing alkenes, alkynes, and biaryl derivatives using Heck-Matsuda, Sonogashira, and Suzuki coupling protocols. Dediazoniation of the salt furnished the corresponding p-SF 5 —C 6 H 4 X,C 6 H 4 OS(O)(CF 3 )═NSO 2 CF 3 , and p-SF 5 —C 6 H 4 —NTf 2 derivatives. The azide derivative p-SF 5 —C 6 H 4 N 3 entered into click chemistry with phenylacetylenes to furnish the corresponding triazoles. Various SF 5 -bearing alkenes were synthesized by coupling reactions using a metal catalyst. Fluorodediazoniation selectively furnished the fluoro derivative p-SF 5 —C 6 H 4 F. Homolytic dediazoniation gave the unsymmetrical biaryls, thus demonstrating the broad utility of pentafluorosulfanyl diazonium salts as building blocks of SF5-aromatics that are in high demand in many branches of chemistry including biomedicine and materials chemistry.

Compounds and Methods for Treating Mammalian Gastrointestinal Microbial Infections

Described herein are compounds, and pharmaceutically acceptable salts and prodrugs thereof, which are useful as inhibitors of IMPDH. In certain embodiments, a compound of the invention selectively inhibits a parasitic IMPDH versus a host IMPDH. Further, the invention provides pharmaceutical compositions comprising one or more compounds of the invention. The invention also relates to methods of treating various parasitic and bacterial infections in mammals. Moreover, the compounds may be used alone or in combination with other therapeutic or prophylactic agents, such as anti-virals, anti-inflammatory agents, antimicrobials and immunosuppressants. 8. A method of killing or inhibiting the growth of a microbe , comprising the step of contacting said microbe with an effective amount of a compound represented by any one of Formula I , Formula VI , Formula IX , Formula X , Formula XI , Formula XII , or Formula XIII.9. The method of claim 8 , wherein said microbe is a protozoon claim 8 , a bacterium claim 8 , or a fungus.10Toxoplasma, Eimeria, Cryptosporidium, Plasmodium, Babesia, Theileria, Neospora, Sarcocystis, Giardia, Entamoeba, Trichomonas, Tritrichomonas, Leishmania, Trypanosoma, Helicobacter, Borrelia, Salmonella, Shigella, Yersinia, Streptococcus, Campylobacter, Arcobacter, Bacteroides, Fusobacterium, Burkholderia, Clostridia, Neisseria, MycobacteriumAcinetobacter.. The method of claim 8 , wherein said microbe is a protozoon or a bacterium selected from the group consisting of the genera claim 8 , and11Toxoplasma, Eimeria, Cryptosporidium, Plasmodium, Babesia, Theileria, Neospora, Sarcocystis, Giardia, Entamoeba, Trichomonas, Tritrichomonas, LeishmaniaTrypanosoma.. The method of claim 9 , wherein said microbe is a protozoon; and said protozoon is selected from the group consisting of the genera and12Helicobacter, Borrelia, Salmonella, Shigella, Yersinia, Streptococcus, Campylobacter, Arcobacter, Bacteroides, Fusobacterium, Burkholderia, Clostridia, Neisseria, ...

HEXASUBSTITUTED BENZENES, SURFACES MODIFIED THEREWITH, AND ASSOCIATED METHODS

Phenyl rings provide a robust scaffold for molecular design, given the limited number of ring carbon atoms and the fixed geometry in between. However, it can be difficult to form highly substituted phenyl rings suitable for covalent attachment of multiple moieties thereto. Moreover, binding phenyl rings to a surface in a fixed geometry may be difficult. Hexasubstituted benzenes having certain structural features may alleviate the foregoing difficulties by providing versatile groups for further functionalization and surface attachment. Such hexasubstituted benzenes may have a structure of 2. The hexasubstituted benzene of claim 1 , wherein Nu claim 1 , Nu claim 1 , and Nuare each different.3. The hexasubstituted benzene of claim 2 , wherein the amines are orthogonally protected.4. The hexasubstituted benzene of claim 1 , wherein the reaction product of Nis NHor a surface-bound form thereof.5. The hexasubstituted benzene of claim 1 , wherein the reaction product of Nis a 1 claim 1 ,2 claim 1 ,3-triazole or a surface-bound form thereof.6. The hexasubstituted benzene of claim 1 , wherein at least one of Nu claim 1 , Nu claim 1 , and Nubears a binding functionality that undergoes molecular association with an analyte of interest.7. The hexasubstituted benzene of claim 6 , wherein the binding functionality is selected from the group consisting of a chelating ligand claim 6 , a crown ether claim 6 , a cryptand claim 6 , a porphyrin claim 6 , a calixarene claim 6 , an analyte-sensitive dye claim 6 , a pH-sensitive compound claim 6 , an antibody claim 6 , an enzyme claim 6 , a protein claim 6 , and a biological receptor.8. The hexasubstituted benzene of claim 6 , wherein at least one of Nu claim 6 , Nu claim 6 , and Nubears a detection functionality claim 6 , wherein the detection functionality allows the molecular association of the analyte with the binding functionality to be detected spectroscopically or electrochemically.9. The hexasubstituted benzene of claim 6 , ...

Acadesine derivatives, products and compositions including same, therapuetic uses thereof, and methods for synthesizing same

Acadesine derivatives as a drug, as well as the derivatives for the treatment of cancer and in particular for the treatment of chronic myeloid leukemia are described. Also, product containing the derivatives and at least one second active ingredient as a combination product for simultaneous, separate or sequential administration, in the treatment of cancer, as well as a pharmaceutical composition containing the derivatives and a pharmaceutically acceptable carrier are described. Finally, a method for inhibiting the in vitro cell proliferation including the placement of an in vitro cell in contact with the derivatives and methods for synthesis of said derivatives and methods for synthesis of the derivatives are described.

POLYMORPHIC FORMS OF 2-(5-BROMO-4-(4-CYCLOPROPYLNAPHTHALEN-1-YL)-4H-1,2,4-TRIAZOL-3-YLTHIO)ACETIC ACID AND USES THEREOF

Crystalline polymorph forms of 2-(5-bromo-4-(4-cyclopropyl naphthalen-1-yl)-4H-1,2,4-triazol-3-ylthio)acetic acid are described. Pharmaceutical compositions and the uses of such compounds, compound forms, and compositions for the treatment of a variety of diseases and conditions are also presented. 2. The method of claim 1 , wherein the crystalline polymorph is further characterized by at least one further peak at 18.21 or 23.08° 20±0.1° 20.3. The method of claim 1 , wherein the crystalline polymorph exhibits an x-ray powder diffraction pattern substantially the same as the x-ray powder diffraction pattern shown in .4. The method of claim 1 , wherein the crystalline polymorph is prepared by a method comprising the step of crystallizing 2-(5-bromo-4-(4-cyclopropylnaphthalen-1-yl)-4H-1 claim 1 ,2 claim 1 ,4-triazol-3-ylthio)acetic acid from a mixture of water and ethyl acetate.5. The method of claim 1 , further comprising administering allopurinol.6. The method of claim 1 , further comprising administering febuxostat.8. The method of claim 7 , wherein the crystalline polymorph is further characterized by at least one further peak at 18.21 or 23.08° 20±0.1° 20.9. The method of claim 7 , wherein the crystalline polymorph exhibits an x-ray powder diffraction pattern substantially the same as the x-ray powder diffraction pattern shown in .10. The method of claim 7 , wherein the crystalline polymorph is prepared by a method comprising the step of crystallizing 2-(5-bromo-4-(4-cyclopropylnaphthalen-1-yl)-4H-1 claim 7 ,2 claim 7 ,4-triazol-3-ylthio)acetic acid from a mixture of water and ethyl acetate.11. The method of claim 7 , further comprising administering allopurinol.12. The method of claim 7 , further comprising administering febuxostat.14. The method of claim 13 , wherein the crystalline polymorph is further characterized by at least one further peak at 18.21 or 23.08 °2θ±0.1°2θ.15. The method of claim 13 , wherein the crystalline polymorph exhibits an x-ray powder ...

CYCLIC VINYLOGOUS AMIDES AS BROMODOMAIN INHIBITORS

Cyclic vinylogous amides of Formula I are disclosed 137-. (canceled)39. The method of claim 38 , wherein the disease or disorder is chronic inflammation.40. The method of wherein the disease or disorder is inflammatory colitis.41. The method of claim 38 , wherein the treatment of a disease or a disorder further comprises administering an additional therapeutic agent.43. The method of claim 38 , wherein the disease or disorder is autoimmune disease.44. The method of claim 38 , wherein the disease or disorder is cancer.45. The method of claim 44 , wherein the cancer is selected from breast cancer claim 44 , triple negative breast cancer claim 44 , prostate cancer claim 44 , acute leukemia claim 44 , chronic leukemia claim 44 , chronic lymphocytic leukemia claim 44 , colon cancer claim 44 , colorectal cancer claim 44 , multiple myeloma claim 44 , glioblastoma claim 44 , lung cancer claim 44 , and liver cancer.46. The method of claim 39 , wherein the disease or disorder is selected from multiple sclerosis claim 39 , inflammatory bowel disease claim 39 , Crohn's disease claim 39 , ulcerative colitis claim 39 , type I diabetes claim 39 , rheumatoid arthritis claim 39 , AIDS claim 39 , and asthma. This application claims priority from U.S. provisional application 61/872,303, filed Aug. 30, 2013, the entire disclosure of which is incorporated herein by reference.This invention was made with U.S. Government support under R01HG004508, R01CA87658 and R33DA029963 awarded by National Institutes of Health. The U.S. Government has certain rights in the invention.The present application relates generally to compositions for treating diseases that arise from inappropriate activity of proteins containing an acetyl-lysine. The compositions comprise a genus of cyclic vinylogous amides that are inhibitors of bromodomain.BRD4 is a member of the bromodomains and extra terminal domain (BET) family of proteins that recognize acetylated chromatin structures through their bromodomains and act ...

AMINO-SUBSTITUTED HETEROCYCLIC DERIVATIVES AS SODIUM CHANNEL INHIBITORS

The present invention relates to novel aminoindazolyl derivative compounds of Formula (I), the use of said compounds in treating diseases mediated by modulation of voltage-gated sodium channels in particular Nav1.7 AND to compositions containing said derivatives. 2. The compound according to claim 1 , wherein Ris chosen from a halogen atom claim 1 , a cyano group claim 1 , a linear or branched Calkyl group claim 1 , a linear or branched Chaloalkyl group claim 1 , a linear or branched Chaloalkoxy group claim 1 , —SO—CFgroup claim 1 , a benzyl group and —O-benzyl group; and{'sup': 'f', 'sub': '1-4', 'Ris a linear or branched Calkyl group.'}3. The compound according to claim 1 , wherein claim 1 , in Formula (ii) claim 1 , Gis a —CR— claim 1 , wherein Ris chosen from a hydrogen atom and a halogen atom.4. The compound according to claim 1 , wherein Ris a hydrogen atom and Ris a group of Formula (i) claim 1 , wherein each Gis independently —N— or —CR claim 1 , wherein Ris chosen from a hydrogen atom claim 1 , a cyano group claim 1 , a linear or branched Calkyl group claim 1 , a (Calkoxy)-(Calkyl) group claim 1 , and —OR claim 1 , wherein Ris chosen from a Calkyl group and a Chaloalkyl group.5. The compound according to claim 4 , wherein Ris a hydrogen atom and Ris a group of Formula (i) claim 4 , wherein Gis a —N— group.6. The compound according to claim 4 , wherein Ris a hydrogen atom and Ris a group of Formula (i) claim 4 , wherein one Gis a —N— group and the other Gis a —CRgroup.7. The compound according to claim 1 , wherein Ris chosen from a halogen atom claim 1 , a cyano group claim 1 , a linear or branched Calkyl group claim 1 , a linear or branched Chaloalkyl group and a linear or branched Chaloalkoxy group.8. The compound according to claim 7 , wherein Ris chosen from a chlorine claim 7 , a bromine atom claim 7 , a methyl group claim 7 , an ethyl group and a —CFgroup.9. The compound according to claim 1 , wherein both Gand Gare —N— group.10. The compound according ...

18F-LABELED PRECURSOR OF PET RADIOACTIVE MEDICAL SUPPLIES, AND PREPARATION METHOD THEREOF

The present invention relates to a precursor of positron emission tomography (PET) radioactive medical supplies, a preparation method thereof, and an application thereof, and more specifically, to a precursor having a tetravalent organic salt leaving group, a preparation method, and a method for preparing desired PET radioactive medical supplies in a high radiochemical yield within a short preparation time by introducing F using the same through a single step. The precursor having a tetravalent organic salt leaving group of the present invention can simplify the known complex multistep preparation of radioactive medical supplies into a single step, can save production costs because an excessive amount of a phase transfer catalyst is not required, facilitates separation of a compound after reaction, and enables rapid reaction velocity. The features are appropriate for the mass production of PET radioactive medical supplies by an automated synthesis system. 5. The precursor including a leaving group of a tetravalent organic salt of claim 1 ,wherein the precursor represented by Chemical Formula 1 is selected from the group consisting of 4-tert-butyl-3-methyl-1-[(2-naphthoxy)methyl]-1,2,3-triazolium trifluoromethanesulfonate;4-methoxycarbonyl-3-methyl-1-[(2-naphthoxy)methyl]-1,2,3-triazolium trifluoromethanesulfonate;4-[3,5-di(trifluoromethyl)phenyl]-3-methyl-1-[(2-naphthoxy)methyl]-1,2,3-triazolium trifluoromethanesulfonate;4-(4-methoxyphenyl)-3-methyl-1-[(2-naphthoxy)methyl]-1,2,3-triazolium trifluoromethanesulfonate;3-methyl-4-phenyl-1-(2-phenylethan-2-on-1-yl)-1,2,3-triazolium trifluoromethanesulfonate;4-tert-butyl-3-methyl-1-[(phenylthio)methyl]-1,2,3-triazolium trifluoromethanesulfonate;3-methyl-1-[(2-naphthoxy)methyl]-4-phenyl-1,2,3-triazolium trifluoromethanesulfonate;3-methyl-1-[3-(2-naphthoxy)-n-propyl]oxymethyl-4-phenyl-1,2,3-trizaolium trifluoromethanesulfonate;1-[1-methylsulfonyloxy-3-(2-naphthyl)-2-oxypropyl]oxymethyl-3-methyl-4-phenyl-1,2,3-triazolium ...

Polymorphic Forms of 2-(5-Bromo-4-(4-Cyclopropylnaphthalen-1-yl)-4H-1,2,4-Triazol-3-ylthio)Acetic Acid and Uses Thereof

Crystalline polymorph forms of 2-(5-bromo-4-(4-cyclopropyl naphthalen-1-yl)-4H-1,2,4-triazol-3-ylthio)acetic acid are described. Pharmaceutical compositions and the uses of such compounds, compound forms, and compositions for the treatment of a variety of diseases and conditions are also presented. 2. The method of claim 1 , wherein the crystalline polymorph is further characterized by at least one further peak at 18.21 or 23.08 °2θ±0.1 °2θ.3. The method of claim 1 , wherein the crystalline polymorph exhibits an x-ray powder diffraction pattern substantially the same as the x-ray powder diffraction pattern shown in .4. The method of claim 1 , wherein the crystalline polymorph is prepared by a method comprising the step of crystallizing 2-(5-bromo-4-(4-cyclopropylnaphthalen-1-yl)-4H-1 claim 1 ,2 claim 1 ,4-triazol-3-ylthio)acetic acid from a mixture of water and ethyl acetate.5. The method of claim 1 , further comprising administering allopurinol.6. The method of claim 1 , further comprising administering febuxostat.8. The method of claim 7 , wherein the crystalline polymorph is further characterized by at least one further peak at 18.21 or 23.08 °2θ±0.1 °2θ.9. The method of claim 7 , wherein the crystalline polymorph exhibits an x-ray powder diffraction pattern substantially the same as the x-ray powder diffraction pattern shown in .10. The method of claim 7 , wherein the crystalline polymorph is prepared by a method comprising the step of crystallizing 2-(5-bromo-4-(4-cyclopropylnaphthalen-1-yl)-4H-1 claim 7 ,2 claim 7 ,4-triazol-3-ylthio)acetic acid from a mixture of water and ethyl acetate.11. The method of claim 7 , further comprising administering allopurinol.12. The method of claim 7 , further comprising administering febuxostat.14. The method of claim 13 , wherein the crystalline polymorph is further characterized by at least one further peak at 18.21 or 23.08 °2θ±0.1 °2θ.15. The method of claim 13 , wherein the crystalline polymorph exhibits an x-ray powder ...

METHODS AND PROCESSES FOR THE PREPARATION OF KDM1A INHIBITORS

Provided in this disclosure are methods for the synthesis of substituted 2-arylcyclopropylamines and 2-heteroarylcyclopropylamines and related compounds. Also provided are methods for reduction of thioesters to aldehydes, and methods for reductive animation of cyclopropylamines. 2. The process of claim 1 , wherein said reductive amination conditions comprise reacting Compound 9 with Compound 6 in the presence of a borohydride reducing agent.3. The process of claim 2 , wherein the borohydride reducing agent is NaBH.4. The process of claim 3 , wherein the reaction is performed in a solvent comprising a lower carbinol.5. The process of claim 4 , wherein the lower carbinol is methanol.6. The process of claim 4 , wherein the lower carbinol is part of a co-solvent mixture.7. The process of claim 6 , wherein the co-solvent mixture comprises methanol and tetrahydrofuran.8. The process of claim 7 , wherein NaBHis added to a mixture of Compound 6 and Compound 9 in a mixture of methanol and tetrahydrofuran which has been cooled to −5° C.9. The process of claim 8 , wherein the NaBHis added in portions while maintaining the reaction mixture temperature at less than 22° C.10. The process of claim 9 , wherein the NaBHis added in at least 5 portions spaced at least 15 minutes apart.11. The process of claim 9 , further comprising stirring the reaction mixture at 20±5° C. following completion of the addition of NaBHin portions.12. The process of claim 11 , wherein the reaction mixture is stirred at 20±5° C. for at least 1 hour.13. The process of claim 12 , wherein the reaction mixture is stirred at 20±5° C. for at least 3 hours.14. The process of claim 13 , further comprising the steps of:a) stirring the reaction mixture until Compound 7 is present at least 75 area % by HPLC analysis;b) quenching the reaction mixture by the addition of saturated ammonium chloride; andc) filtering and concentrating the resulting mixture.15. The process of claim 7 , wherein NaBHis added to a mixture of ...

COMPOSITIONS AND METHODS FOR INHIBITING PHENYL TRIAZOLE MLL1-WDR5 PROTEIN-PROTEIN INTERACTION

The present disclosure relates to the field of medicinal chemistry, in particular to a phenyl triazole MLL1-WDR5 protein-protein interaction inhibitor (I) and a preparation method thereof, and pharmacodynamics experiments prove that the compound of the present disclosure has relatively strong MLL1-WDR5 protein-protein interaction inhibition activity. 2. The compound according to claim 1 , wherein X is hydrogen claim 1 , fluorine claim 1 , chlorine or methyl.3. The compound of claim 1 , wherein Y is —NR— claim 1 , —CONR— or —NRCO—; R claim 1 , Ror Reach independently is hydrogen claim 1 , methyl claim 1 , ethyl claim 1 , propyl claim 1 , cyclopropyl or isopropyl.4. The compound of claim 1 , wherein Y is —NR— claim 1 , —CONR— or —NRCO—; R claim 1 , Ror Reach independently is substituted phenyl claim 1 , and the substituent is methyl claim 1 , ethyl claim 1 , isopropyl claim 1 , t-butyl claim 1 , cyclopropyl claim 1 , methoxy claim 1 , cyano claim 1 , halogen claim 1 , trifluoromethyl or imidazolyl.5. The compound of claim 1 , wherein said substituted or unsubstituted nitrogen- or oxygen-containing 3 to 7 membered heterocyclic ring is aziridine claim 1 , azetidine claim 1 , tetrahydrogen pyrrole claim 1 , piperidine claim 1 , cycloheximide claim 1 , lactam claim 1 , tetrahydrofuran claim 1 , tetrahydropyran claim 1 , morpholine claim 1 , 1 claim 1 ,4-oxazaxane claim 1 , hexahydropyridazine claim 1 , imidazoline claim 1 , pyrazolidine claim 1 , piperazine claim 1 , the substituent is methyl claim 1 , ethyl claim 1 , phenyl claim 1 , hydroxyl claim 1 , amino claim 1 , hydroxymethyl claim 1 , or aminomethyl claim 1 , the substituent is halogen claim 1 , C-Calkyl claim 1 , C-Calkoxy claim 1 , amino claim 1 , hydroxyl claim 1 , thiol claim 1 , carboxyl claim 1 , cyano claim 1 , or trifluoromethyl.6. The compound of claim 1 , wherein Ris —NRCOR claim 1 , —CONRRor —NRR claim 1 , wherein R claim 1 , R claim 1 , Ror Ris C-Calkyl.7. The compound of claim 1 , wherein Ris ...

Novel compositions and processes for preparing 5-amino or substituted amino 1,2,3-triazoles and triazoles orotate formulations

New polymorphs of 5-amino or substituted amino 1,2,3-triazole and substituted derivatives thereof, of orotates of the carboxyamidotriazoles, of formulations of the triazoles and orotic acid in the ratio of 1:1 to 1:4 (base:acid) and of safer processes of the preparation of the same are disclosed. The compounds are useful in the control and treatment of diseases including, but not limited to solid cancers, macular degeneration, retinopathy, chronic myeloid leukemia, AIDS and diseases which rely on aberrant signal transduction. The improved processes to prepare the orotate formulations use stable, efficient and safer starting azide intermediate materials in the synthesis of new polymorphs of carboxyamidotriazole. 1. (canceled)2. (canceled)3. (canceled)4. (canceled)5. (canceled)6. (canceled)7. (canceled)8. (canceled)9. (canceled)10. (canceled)11. (canceled)12. (canceled)13. (canceled)14. (canceled)15. (canceled)16. (canceled)17. (canceled)18. (canceled)19. A polymorph form 1 of 5-amino-1-(4-(4-chlorobenzoyl)-3 ,5-dichlorobenzyl)-1 ,2 ,3-triazole-4-carboxamide obtainable by a process comprising:reacting diphenylphosphoryl azide with 3,5-dichloro-4-(4′-chlorobenzoyl)benzyl alcohol to obtain 3,5-dichloro-4-(4-chlorobenzoyl)benzylazide; andreacting 2-cyanoacetamide with 3,5-dichloro-4-(4-chlorobenzoyl)benzylazide to obtain 5-amino-1-(4-(4-chlorobenzoyl)-3,5-dichlorobenzyl)-1,2,3-triazole-4-carboxamide.20. A polymorph form 2 of 5-amino-1-(4-(4-chlorobenzoyl)-3 ,5-dichlorobenzyl)-1 ,2 ,3-triazole-4-carboxamide obtainable by a process comprising:reacting diphenylphosphoryl azide with 3,5-dichloro-4-(4′-chlorobenzoyl)benzyl alcohol to obtain 3,5-dichloro-4-(4-chlorobenzoyl)benzylazide; andreacting 2-cyanoacetamide with 3,5-dichloro-4-(4-chlorobenzoyl)benzylazide to obtain 5-amino-1-(4-(4-chlorobenzoyl)-3,5-dichlorobenzyl)-1,2,3-triazole-4-carboxamide.21. A polymorph form 1 of 5-amino-1-(4-(4-chlorobenzoyl)-3 ,5-dichlorobenzyl)-1 ,2 ,3-triazole-4-carboxamide obtainable by a ...

AROMATIC SULFONAMIDE DERIVATIVES

Substituted aromatic sulfonamides of formula (I) pharmaceutical compositions and combinations comprising said compounds and the use of said compounds for manufacturing a pharmaceutical composition for the treatment or prophylaxis of a disease. 7: The compound according to claim 1 , wherein:{'sup': '2', 'Ris phenyl,'}{'sup': 11', '11a', '11', '11, 'wherein said phenyl group is optionally independently substituted one to three times with R, or independently substituted one time with Rand optionally one to two times with R, or substituted with two adjacent substituents Rwhich together represent a methylendioxy group to form a 5-membered ring.'}8: The compound according to claim 1 , wherein:{'sup': '2', 'Ris a 5-membered monocyclic heteroaryl,'}{'sup': '11', 'claim-text': {'sup': 11a', '11, 'independently substituted one time with Rand optionally one to two times with R.'}, 'wherein said heteroaryl is optionally independently substituted one to three times with R, or'}11: The compound according to claim 1 , wherein:{'sup': '2', 'Ris a 6-membered monocyclic heteroaryl,'}{'sup': '11', 'claim-text': {'sup': 11a', '11, 'independently substituted one time with Rand optionally one to two times with R.'}, 'wherein said heteroaryl group is optionally independently substituted one to three times with R, or'}12: The compound according to claim 1 , wherein:{'sup': '2', 'Ris a [5,6]-annellated bicyclic heteroaryl,'}{'sup': '11', 'claim-text': {'sup': 11a', '11, 'independently substituted one time with Rand optionally one to two times with R.'}, 'wherein said heteroaryl group is optionally independently substituted one to three times with R, or'}13: The compound according to claim 1 , wherein:{'sup': '3', 'Ris hydrogen; and'}{'sup': '4', 'Ris hydrogen, methyl, or OH.'}14: The compound according to claim 1 , wherein:{'sup': '8', 'sub': 1', '4', '3', '6', '1', '4, 'Ris C-C-alkyl, C-C-cycloalkyl, or C-C-haloalkyl.'}15: The compound according to claim 1 , wherein:{'sup': '9', 'sub': 1', ...

MODULATORS OF INDOLEAMINE 2,3-DIOXYGENASE

Provided are IDO inhibitor compounds of Formula I and pharmaceutically acceptable salts thereof, their pharmaceutical compositions, their methods of preparation, and methods for their use in the prevention and/or treatment of diseases. 2. A compound or salt according to wherein n is 0.3. A compound according to wherein when one X is N claim 1 , said N is positioned adjacent to the carbon atom to which the depicted S—Ris bonded.4. A compound or salt according to wherein Ris Calkyl.5. A compound or salt according to wherein Ris t-butyl.6. A compound or salt according to wherein A is a benzene or pyridine ring.7. A compound or salt according to wherein Ris ortho to the depicted X-containing ring in Formula I.8. A compound or salt according to wherein Ris a 5-membered heterocycle or heteroaryl containing 1 to 4 heteroatoms selected from N claim 1 , S claim 1 , and O claim 1 , wherein said heterocycle or heteroaryl may optionally be substituted by a substituent selected from the group consisting of halogen claim 1 , Ccycloalkyl claim 1 , CHOH claim 1 , CHOCalkyl claim 1 , CalkyleneOC(O)Calkyl claim 1 , Calkyl optionally substituted by 1-3 halogens claim 1 , and wherein said CHOH is optionally converted into a prodrug by converting the CHOH group to a CHOC(O)CH claim 1 , CHOC(O)C(Calkyl) claim 1 , or OP(O)(OH)group claim 1 , or OP(O)(OCalkyl)group.9. A compound or salt according to wherein Ris a tetrazole ring optionally substituted by CHOH and wherein said CHOH is optionally converted into a prodrug by converting the CHOH group to a CHOC(O)CH claim 8 , CHOC(O)C(Calkyl) claim 8 , or OP(O)(OH)group claim 8 , or OP(O)(OCalkyl)group.10. A compound or salt according to wherein L is NHC(O)Calkylene.11. A compound or salt according to wherein L is NHC(O)CH.12. A compound or salt according to wherein Ris phenyl claim 1 , or a 4 to 6-membered heterocycle or heteroaryl containing 1 to 4 heteroatoms selected from N claim 1 , S claim 1 , and O; and wherein said phenyl claim 1 , ...

COMPOUNDS AND METHODS OF TREATING RNA-MEDIATED DISEASES

The present invention provides compounds, compositions thereof, and methods of using the same. 4. The compound of claim 2 , wherein Ligand is selected from the group consisting of a macrolide claim 2 , an alkaloid claim 2 , an aminoglycoside claim 2 , a tetracycline claim 2 , a SMN2 ligand selected from those shown in claim 2 , a pleuromutilin claim 2 , theophylline or an analogue thereof claim 2 , ribocil or an analogue thereof claim 2 , a substituted anthracene claim 2 , a substituted triptycene claim 2 , an oxazolidinone claim 2 , and CPNQ or an analogue thereof; wherein Ligand may be optionally substituted with one or more substituents.5. The compound of claim 2 , wherein Ligand is selected from the group consisting of erythromycin claim 2 , azithromycin claim 2 , berberine claim 2 , palmatine claim 2 , a paromomycin claim 2 , a neomycin claim 2 , a kanamycin claim 2 , doxycycline claim 2 , oxytetracycline claim 2 , pleuromutilin claim 2 , theophylline or an analogue thereof claim 2 , ribocil or an analogue thereof claim 2 , NVS-SM1 claim 2 , a substituted anthracene claim 2 , a substituted triptycene claim 2 , linezolid claim 2 , tedizolid claim 2 , and CPNQ or an analogue thereof; wherein Ligand may be optionally substituted with 1 claim 2 , 2 claim 2 , 3 claim 2 , or 4 substituents.6. The compound of claim 4 , wherein Tis selected from those shown in .7. The compound of claim 4 , wherein Tis selected from a polyethylene glycol (PEG) group claim 4 , an optionally substituted Caliphatic group claim 4 , or a peptide comprising 1-8 amino acids.8. The compound of claim 3 , wherein Tis selected from those shown in .9. The compound of claim 2 , wherein Ris selected from sulfonyl halides claim 2 , arenecarbonyl imidazoles claim 2 , active esters claim 2 , epoxides claim 2 , oxiranes claim 2 , oxidizing agents claim 2 , aldehydes claim 2 , alkyl halides claim 2 , benzyl halides claim 2 , or isocyanates; wherein Rreacts with an unconstrained 2′-hydroxyl group of a ...

METHANETHIONE COMPOUNDS HAVING ANTIVIRAL ACTIVITY

A compound of formula (I) is useful as an antiviral agent, in particular for the treatment of influenza. A method for preparing the compound of formula (I) and a composition including the compound of formula (I) are described. 127-. (canceled)29. The compound according to claim 28 , wherein each Ris independently selected from C1-C6 alkyl; OH; halogen; and RRN;{'sup': '2', 'Ris selected from H and C1-C6 alkyl;'}{'sup': '3', 'each Ris independently selected from C1-C6 alkyl;'}{'sup': '4', 'sub': '2', 'each Ris independently selected from NO; halogen; and C1-C6 alkyl;'}{'sup': 5', '6, 'each Rand Ris independently selected from H and C1-C6 alkyl;'}wherein any alkyl is optionally substituted with one or several halogen atoms;or a pharmaceutically acceptable salt thereof.30. The compound according to claim 28 , wherein any C1-C6 alkyl moiety is selected from C1-C3 alkyl;or a pharmaceutically acceptable salt thereof.31. The compound according to claim 30 , wherein any C1-C6 alkyl moiety is methyl;or a pharmaceutically acceptable salt thereof.32. The compound according to claim 28 , wherein n is 0 claim 28 , or a pharmaceutically acceptable salt thereof.33. The compound according to claim 28 , wherein m is 0 claim 28 , or a pharmaceutically acceptable salt thereof.34. The compound according to claim 28 , wherein U is C claim 28 , or a pharmaceutically acceptable salt thereof.35. The compound according to claim 28 , wherein Y is N claim 28 , or a pharmaceutically acceptable salt thereof.36. The compound according to claim 28 , wherein Y is NH claim 28 , or a pharmaceutically acceptable salt thereof.37. The compound according to claim 28 , wherein Y is O claim 28 , or a pharmaceutically acceptable salt thereof.38. The compound according to claim 28 , wherein X is N claim 28 , or a pharmaceutically acceptable salt thereof.39. The compound according to claim 28 , wherein X is NH claim 28 , or a pharmaceutically acceptable salt thereof.40. The compound according to claim 28 , ...

N-aryltriazole compounds as lpar antagonists

Provided herein are compounds of the formula (I): as well as pharmaceutically acceptable salts thereof, wherein the substituents are as those disclosed in the specification. These compounds, and the pharmaceutical compositions containing them, are useful for the treatment of inflammatory diseases and disorders such as, for example, pulmonary fibrosis.

COMPOUNDS FOR USE AS THERAPEUTIC AGENTS AFFECTING P53 EXPRESSION AND/OR ACTIVITY

The present disclosure relates to compound (I) 2. The compound according to selected from the group consisting of the compounds (9) claim 1 , (16) claim 1 , (17) claim 1 , (18) claim 1 , (19) claim 1 , (21) claim 1 , (22) claim 1 , (24) claim 1 , (25) claim 1 , (49) claim 1 , (50) claim 1 , (129) claim 1 , and pharmaceutically acceptable salts thereof.3. The compound according to selected from the group consisting of the compounds (9) claim 1 , (16) claim 1 , (17) claim 1 , (18) claim 1 , (19) claim 1 , (21) claim 1 , (22) claim 1 , (24) claim 1 , (25) claim 1 , (129) claim 1 , and pharmaceutically acceptable salts thereof.4. The compound according to selected from the group consisting of the compounds (49) claim 1 , (50) claim 1 , and pharmaceutically acceptable salts thereof.5. The compound according to selected from the group consisting of the compounds (9) claim 1 , (16) claim 1 , (17) claim 1 , (18) claim 1 , (19) claim 1 , (20) claim 1 , (21) claim 1 , (22) claim 1 , (23) claim 1 , (24) claim 1 , (25) claim 1 , (127) claim 1 , (128) claim 1 , (129) claim 1 , and pharmaceutically acceptable salts thereof.6. The compound according to selected from the group consisting of the compounds (130) claim 1 , (131) claim 1 , (132) claim 1 , (133) claim 1 , (134) claim 1 , (135) claim 1 , and pharmaceutically acceptable salts thereof.7. The compound according to selected from the group consisting of the compounds (37) claim 1 , (38) claim 1 , (39) claim 1 , (136) claim 1 , and pharmaceutically acceptable salts thereof.8. The compound according to selected from the group consisting of the compounds (48) claim 1 , (49) claim 1 , (50) claim 1 , (52) claim 1 , and pharmaceutically acceptable salts thereof.9. The compound according to selected from the group consisting of the compounds (83) claim 1 , (84) claim 1 , (85) claim 1 , (86) claim 1 , (87) claim 1 , (88) claim 1 , (89) claim 1 , (90) claim 1 , (91) claim 1 , (92) claim 1 , and pharmaceutically acceptable salts ...

CALPAIN MODULATORS AND THERAPEUTIC USES THEREOF

Disclosed herein are small molecule calpain modulator compositions, pharmaceutical compositions, the use and preparation thereof. 3. The compound of or , wherein:{'sub': 1', '3-10, 'Ais selected from the group consisting of optionally substituted 6-10 membered heterocyclyl provided the 6-10-membered heterocyclyl is not substituted with oxo; optionally substituted 5-, 8-, or 9-membered heteroaryl; and optionally substituted Ccarbocyclyl;'}{'sub': 2', '6-10', '3-10', '2', '2, 'Ais selected from the group consisting of optionally substituted 3-10 membered heterocyclyl, optionally substituted Caryl, optionally substituted 5-10 membered heteroaryl, optionally substituted Ccarbocyclyl, —CR—, —S—, —S(═O)—, —SO—, —O—, —C(═S)—, —C(═O)—, —NR—, —CH═CH—, —OC(O)NH—, —NHC(O)NH—, —NHC(O)O—, —NHC(O)—, —NHC(S)NH—NHC(S)O—, —NHC(S)—, and single bond;'}{'sub': 4', '6-10', '3-10', '1-4', '2, 'Ais selected from the group consisting of optionally substituted Caryl, optionally substituted 5-10 membered heteroaryl, optionally substituted 3-10 membered heterocyclyl, optionally substituted Ccarbocyclyl, optionally substituted Calkyl, —S—, S(═O)—, —SO—, —O—, —C(═S)—, —C(═O)—, —NR—, —CH═CH—, —OC(O)NH—, —NHC(O)NH—, —NHC(O)O—, —NHC(O)—, —NHC(S)NH—, —NHC(S)O—, —NHC(S)—, and single bond;'}{'sub': 3', '6-10', '3-10, 'Ais selected from the group consisting of optionally substituted Caryl, optionally substituted 5-10 membered heteroaryl, optionally substituted 3-10 membered heterocyclyl, and optionally substituted Ccarbocyclyl;'}{'sub': 6', '6-10', '3-10', '1-8', '1-6', '2-6, 'Ais selected from the group consisting of optionally substituted Caryl, optionally substituted 5-10 membered heteroaryl, optionally substituted 3-10 membered heterocyclyl, optionally substituted Ccarbocyclyl, optionally substituted Calkyl, optionally substituted —O—Calkyl, optionally substituted —OCalkenyl, and any natural or non-natural amino acid side chain; and'}{'sup': 2', '3, 'sub': 1-4', '3-7', '6-10, 'each R, R, and Rare ...

TRIAZOLE DERIVATIVE AND USE THEREOF

The present invention relates to a novel triazole derivative or a salt thereof. The triazole derivative or the salt thereof according to the present invention induces or promotes browning of white adipocytes, and differentiates stem cells, embryonic cells, or preadipocytes to brown adipocytes or beige adipocytes. A composition comprising the triazole derivative or the salt thereof according to the present invention can treat, prevent or alleviate obesity, obesity complications, diabetes, dyslipidemia, fatty liver, hypertension, metabolic syndrome, and insulin resistance syndrome. 4. The compound or pharmaceutically or sitologically acceptable salt thereof according to claim 1 , wherein the compound is selected from the group consisting of:4-(1-(2,4-dimethoxyphenyl)-1H-1,2,3-triazole-4-yl)benzene-1,2-diol;4-(1-(4-chlorophenyl)-1H-1,2,3-triazole-4-yl)benzene-1,2-diol;4-(1-(4-fluorophenyl)-1H-1,2,3-triazole-4-yl)benzene-1,2-diol;4-(1-(4-hydroxyphenyl)-1H-1,2,3-triazole-4-yl)benzene-1,2-diol;4-(1-(4-hydroxy-3-methylphenyl)-1H-1,2,3-triazole-4-yl)benzene-1,2-diol;(E)-N-(4-chlorophenethyl)-3-(3,4-dihydroxyphenyl)acrylamide;4-(1-(3-fluoro-4-hydroxyphenyl)-1H-1,2,3-triazole-4-yl)benzene-1,2-diol;4-(1-(3,4-difluorophenyl)-1H-1,2,3-triazole-4-yl)benzene-1,2-diol;4-(1-(2-fluoro-4-hydroxyphenyl)-1H-1,2,3-triazole-4-yl)benzene-1,2-diol;4-(1-(4-fluoro-3-hydroxyphenyl)-1H-1,2,3-triazole-4-yl)benzene-1,2-diol;4-(1-(3-fluorophenyl)-1H-1,2,3-triazole-4-yl)benzene-1,2-diol;4-(1-(3-fluoro-4-methoxyphenyl)-1H-1,2,3-triazole-4-yl)benzene-1,2-diol;4-(1-(2-fluorophenyl)-1H-1,2,3-triazole-4-yl)benzene-1,2-diol;4-(1-(2,3-difluoro-4-hydroxyphenyl)-1H-1,2,3-triazole-4-yl)benzene-1,2-diol;4-(1-(4-(2-hydroxyethoxy)phenyl)-1H-1,2,3-triazole-4-yl)benzene-1,2-diol;4-(1-(4-(2-(dimethylamino)ethoxy)phenyl)-1H-1,2,3-triazole-4-yl)benzene-1,2-diol hydrochloride;4-(1-(4-(3-(dimethylamino)-2-hydroxypropoxy)phenyl)-1H-1,2,3-triazole-4-yl)benzene-1,2-diol hydrochloride;N-(2-(diethylamino)ethyl)-4-(4-(3,4- ...

LINKER MOLECULE FOR MULTIPLEX RECOGNITION BY ATOMIC FORCE MICROSCOPY (AFM)

Some of the embodiments of the present disclosure relate to a compound of the formula, and methods of preparing and using same. 6. The compound of claim 5 , wherein each m is independently 6 claim 5 , 7 claim 5 , 8 claim 5 , 9 claim 5 , 10 claim 5 , 11 claim 5 , or 12.8. The compound of claim 7 , wherein each T is independently a reactive group selected from the group consisting of ONH claim 7 , SH claim 7 , NH claim 7 , alkyne claim 7 , alkene claim 7 , vinyl sulfone claim 7 , maleimide claim 7 , carboxylic acids claim 7 , aldehyde claim 7 , ketone claim 7 , N.9. The compound of claim 8 , wherein each T is N.11. The compound of claim 10 , wherein the carbocycle is a bridged carbocycle.14. The compound of claim 13 , wherein the heteroaryl is selected from the group consisting of pyrrole claim 13 , furan claim 13 , thiophene claim 13 , thiazole claim 13 , isothiazole claim 13 , imidazole claim 13 , triazole claim 13 , tetrazole claim 13 , pyrazole claim 13 , oxazole claim 13 , isoxazole claim 13 , pyridine claim 13 , pyrazine claim 13 , pyridazine claim 13 , and pyrimidine.17. The compound of claim 16 , wherein each m is independently 12 claim 16 , 13 claim 16 , 14 claim 16 , 15 claim 16 , 16 claim 16 , 17 claim 16 , or 18.20. A method of conjugating a compound of with a target compound selected from the group consisting a polypeptide claim 16 , a oligonucleotide claim 16 , an aptamer claim 16 , and an antibody claim 16 , comprising reacting the reactive group of the compound of with the target compound. This application claims priority to U.S. Provisional Application No. 61/989,874 titled “LINKER MOLECULE FOR MULTIPLEX RECOGNITION BY ATOMIC FORCE MICROCOSPY (AFM)”, filed May 7, 2014, the entire disclosure of which is incorporated herein by reference.Inventions disclosed herein were made with government support under U54 CA143862 awarded by the National Institutes of Health. The government has certain rights in the inventions.Embodiments of the present disclosure ...

COMPOUNDS AND METHODS OF TREATING RNA-MEDIATED DISEASES

The present invention provides compounds, compositions thereof, and methods of using the same. 117-. (canceled)19. The method of claim 18 , wherein the Ligand is a kanamycin claim 18 , a paromomycin claim 18 , or a neomycin claim 18 , or an analog thereof claim 18 , wherein the Ligand is optionally substituted with 1 claim 18 , 2 claim 18 , or 3 substituents.20. The method of claim 18 , wherein the Ligand is kanamycin A claim 18 , paromomycin claim 18 , or neomycin B claim 18 , or an analog thereof claim 18 , wherein the Ligand is optionally substituted with 1 claim 18 , 2 claim 18 , or 3 substituents.22. The method of claim 18 , wherein Tis selected from a polyethylene glycol (PEG) group claim 18 , an optionally substituted Caliphatic group claim 18 , or a peptide comprising 1-8 amino acids.23. The method of claim 18 , wherein Ris selected from sulfonyl halides claim 18 , acyl imidazoles claim 18 , aryl esters claim 18 , heteroaryl esters claim 18 , epoxides claim 18 , alkyl halides claim 18 , benzyl halides claim 18 , and isocyanates.24. The method of claim 18 , wherein Ris selected from 1-methyl-7-nitroisatoic anhydride (1M7) claim 18 , benzoyl cyanide (BzCN) claim 18 , 2-methylnicotinic acid imidazolide (NAI) claim 18 , and 2-methyl-3-furoic acid imidazolide (FAI).26. The method of claim 25 , wherein the target RNA is an mRNA claim 25 , and the method comprises modulating the downstream protein expression associated with the mRNA.27. The method of claim 26 , wherein the compound irreversibly inhibits the activity of the mRNA.28. The method of claim 26 , wherein the Ligand is a kanamycin claim 26 , a paromomycin claim 26 , or a neomycin claim 26 , or an analog thereof claim 26 , wherein the Ligand is optionally substituted with 1 claim 26 , 2 claim 26 , or 3 substituents.29. The method of claim 26 , wherein the Ligand is kanamycin A claim 26 , paromomycin claim 26 , or neomycin B claim 26 , or an analog thereof claim 26 , wherein the Ligand is optionally ...

3-ARYL PROPIOLONITRILE COMPOUNDS FOR THIOL LABELING

The present invention relates to a process for labeling compounds comprising thiol moieties with 3-arylpropiolonitrile compounds, to 3-arylpropiolonitrile compounds substituted with tag moieties and to specific 3-arylpropiolonitrile linkers. 7. Compound according to claim 6 , wherein the compound of interest is a biomolecule claim 6 , wherein the biomolecule is an antibody or a protein. The present invention relates to a process for labeling compounds comprising thiol moieties with 3-arylpropiolonitrile compounds, to 3-arylpropiolonitrile compounds substituted with tag moieties and to specific 3-arylpropiolonitrile linkers.Over 90% of the human proteins contain cysteines, while in silico digest of the human proteome revealed that only about 15% of all human tryptic peptides detectable by mass spectroscopy (MS) contain at least one cysteine in their sequence. This observation combined with the presence of a highly reactive thiol group on its side chain makes cysteine an attractive target for chemical labeling. Cysteine is the only coded amino acid that carries a nucleophilic sulfhydryl (or thiol) group (—SH), which largely exceeds the reactivity of any other nucleophilic function susceptible to be present in proteins. As a result, chemospecific cysteine derivatization is by far the most widely used method for chemical tagging of proteins. Among the vast number of chemical cysteine modification methods reported in literature so far, reagents such as N-substituted maleimides, 4-vinylpyridines and iodoacetamides are most commonly used. All of them possess drawbacks preventing them from being ideal methodology for cysteine labeling, though being suited for this task. These drawbacks are mainly presence of undesired side reactions, in particular for iodoacetamides and maleimides, and instability of addition product in biological environments due to reversible thiol exchange and other side reactions.The present invention relates to a process for labeling compounds ...

Glycolate oxidase inhibitors for the treatment of disease

Described herein are compounds, methods of making such compounds, pharmaceutical compositions and medicaments containing such compounds, and methods of using such compounds to treat or prevent diseases or disorders associated with the enzyme glycolate oxidase (GO). Such diseases or disorders include, for example, disorders of glyoxylate metabolism, including primary hyperoxaluria, that are associated with production of excessive amounts of oxalate.

COMPOUNDS

A compound for use in the treatment of a disease ameliorated by the inhibition of Notum of formula (I): (I) 2. A compound according to claim 1 , wherein Ar is Cheteroaryl claim 1 , with an optional substituent.5. A compound according to claim 2 , wherein there are three heteroatoms in the ring.6. A compound according to claim 1 , wherein the substituent is selected from OH claim 1 , OMe claim 1 , OEt and NHCN.7. A compound according to claim 6 , wherein the substituent is OH.8. A compound according to claim 1 , wherein the substituent is CHOH.9. A compound according to claim 1 , wherein there is no substituent on Ar.1020-. (canceled)21. A compound according to claim 1 , wherein Ris Cl claim 1 , Ris CFand Ris Cl.2224-. (canceled)25. A pharmaceutical composition comprising a compound of claim 1 , and a pharmaceutically acceptable excipient.26. (canceled)28. A compound according to claim 1 , wherein the compound is selected from:4-[2,4-dichloro-3-(trifluoromethyl)phenyl]-1H-triazole (306);2-(2,4-dichloro-3-(trifluoromethyl)phenyl)-5-(methoxy-d3)-1,3,4-oxadiazole (241);2-(2,4-dichloro-3-(trifluoromethyl)phenyl)-5-ethoxy-1,3,4-oxadiazole (242);4,5-dideuterio-1-[2,4-dichloro-3-(trifluoromethyl)phenyl]triazole (308);5-[2,4-dichloro-3-(trifluoromethyl)phenyl]-1,3,4-oxadiazol-2-ol (261);2-(2,4-dichloro-3-(trifluoromethyl)phenyl)-5-methoxy-1,3,4-oxadiazole (243);1-[2,4-dichloro-3-(trifluoromethyl)phenyl]triazole (295); andN-(5-(2,4-dichloro-3-(trifluoromethyl)phenyl)-1,3,4-oxadiazol-2-yl)cyanamide, ammonia salt (246).29. 1-[2 claim 1 ,4-dichloro-3-(trifluoromethyl)phenyl]triazole (295).30. A method of treatment of a disease or disorder ameliorated by the inhibition of Notum claim 1 , comprising administering to a patient in need of treatment claim 1 , a compound as defined in .31. A method according to claim 30 , wherein the disease or disorder is a neurodegenerative disorder or a central nervous system disorder.32. A method according to claim 30 , wherein the disease or ...

Cyclohexanone compounds and herbicides comprising the same

The present invention provides a compound having an excellent efficacy for controlling weeds. A cyclohexanone compound of the formula (I): wherein m is an integer of 1, 2 or 3; n is an integer of any one of 1 to 5; X represents CH 2 , O, S, S(O) or S(O) 2 ; R 1 represents a hydrogen atom or a methyl group; R 2 and R 3 represents a hydrogen atom, a C 1-6 alkyl group and the like; R 4 represents a C 6-10 aryl group or a five- to six-membered heteroaryl group; G represents a hydrogen atom and the like; Z represents a halogen atom, a cyano group, a nitro group, a phenyl group, a C 1-6 alkyl group and the like; is useful as an active ingredient for herbicides.

Aryl lactam kinase inhibitors

The present disclosure is generally directed to compounds which can inhibit AAK1 (adaptor associated kinase 1), compositions comprising such compounds, and methods for inhibiting AAK1.

CARBAMOYLOXYMETHYL TRIAZOLE CYCLOHEXYL ACIDS AS LPA ANTAGONISTS

The present invention provides compounds of Formula (I): This application is a divisional application of U.S. patent application Ser. No. 16/038,739, filed Jul. 18, 2018, now allowed, which is a divisional application of U.S. patent application Ser. No. 15/628,104, filed on Jun. 20, 2017, now U.S. Pat. No. 10,071,078, issued Sep. 11, 2018, which claims priority to U.S. Provisional Application Ser. No. 62/352,792, filed Jun. 21, 2016, the entire content of which is incorporated herein by reference.The present invention relates to novel substituted triazole compounds, compositions containing them, and methods of using them, for example, for the treatment or prophylaxis of disorders associated with one or more of the lysophosphatidic acid (LPA) receptors.Lysophospholipids are membrane-derived bioactive lipid mediators, of which one of the most medically important is lysophosphatidic acid (LPA). LPA is not a single molecular entity but a collection of endogenous structural variants with fatty acids of varied lengths and degrees of saturation (Fujiwara et al., 2005, 280, 35038-35050). The structural backbone of the LPAs is derived from glycerol-based phospholipids such as phosphatidylcholine (PC) or phosphatidic acid (PA).The LPAs are bioactive lipids (signaling lipids) that regulate various cellular signaling pathways by binding to the same class of 7-transmembrane domain G protein-coupled (GPCR) receptors (Chun, J., Hla, T., Spiegel, S., Moolenaar, W., Editors, 2013, Wiley; ISBN: 978-0-470-56905-4 & Zhao, Y. et al, ()-2013, 1831, 86-92). The currently known LPA receptors are designated as LPA1, LPA2, LPA3, LPA4, LPA5 and LPA6 (Choi, J. W., 2010, 50, 157-186).The LPAs have long been known as precursors of phospholipid biosynthesis in both eukaryotic and prokaryotic cells, but the LPAs have emerged only recently as signaling molecules that are rapidly produced and released by activated cells, notably platelets, to influence target cells by acting on specific cell-surface ...

SECOND GENERATION INHIBITORS OF MITOCHONDRIAL PERMEABILITY TRANSITION PORE WITH IMPROVED PLASMA STABILITY

The present invention provides compounds useful as mitochondrial permeability transition pore (mtPTP) inhibitors, the compounds being of Formula (I), or a pharmaceutically acceptable salt thereof wherein Ris selected from the group of H, halogen, and C-Calkyl; and Ris selected from the group of H, CF, and halogen; with the proviso that at least one of Rand Ris halogen or CF. 2. The compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein Ris selected from the group of H claim 1 , F claim 1 , Cl claim 1 , Br claim 1 , and C-Calkyl; and Ris selected from H claim 1 , F claim 1 , Cl claim 1 , and Br; with the proviso that at least one of Rand Ris selected from the group of CF claim 1 , F claim 1 , Cl claim 1 , and Br. This application is the U.S. National Phase of PCT/US2020/043609, filed Jul. 24, 2020; which claims priority to and the benefit of the earlier filing of U.S. Provisional Application No. 62/878,278, filed on Jul. 24, 2019, which is incorporated by reference herein in its entirety.The nucleic acid and/or amino acid sequences described herein are shown using standard letter abbreviations, as defined in 37 C.F.R. § 1.822. A computer readable text file, entitled “2N94453.txt (Sequence Listing.txt)” created on or about Feb. 16, 2022, with a file size of 4 KB, contains the sequence listing for this application and is hereby incorporated by reference in its entirety.The present invention concerns compounds useful as mitochondrial permeability transition pore (mtPTP) inhibitors, as well as pharmaceutical compositions comprising them. In some embodiments are provided treatments of diseases and/or conditions associated with mtPTP function, such as those for multiple sclerosis, amyotrophic lateral sclerosis, Alzheimer's disease, Huntington's disease, Parkinson's disease, insulin-induced hypoglycemia, cerebral ischemia, brain damage from epilepsy or experimental trauma, Bethlem myopathy, pancreatitis, hepatitis, diabetic retinopathy, ...

IMPROVED SYNTHETIC METHODS OF MAKING (2H-1, 2, 3-TRIAZOL-2-YL) PHENYL COMPOUNDS AS OREXIN RECEPTOR MODULATORS

Processes for preparing (((3aR,6aS)-5-(4,6-dimethylpyrimidin-2-yl)hexahydropyrrolo[3,4-c]pyrrol-2(1H)-yl)(2-fluoro-6-(2H-1,2,3-triazol-2-yl)phenyl)methanone 2. The process of claim 1 , wherein:{'sup': '1', 'sub': 2', '3, 'Ris —H, or —COCH;'}{'sub': (1-2)', '3', '3', '2', '3', '2', '3', '3, 'X is —OCalkyl, —OC(CH), —OCHPh, —N(CH), or —N(CH)I.'} This application claims the benefit of U.S. provisional patent application No. 62/883,857 filed Aug. 7, 2019 and U.S. provisional patent application No. 62/971,265, filed Feb. 7, 2020, all of which are incorporated by reference herein in their entireties.The present invention relates to the synthesis methods making (((3aR,6aS)-5-(4,6-dimethylpyrimidin-2-yl)hexahydropyrrolo[3,4-c]pyrrol-2(1H)-yl)(2-fluoro-6-(2H-1,2,3-triazol-2-yl)phenyl)methanone (Seltorexant), a compound useful for modulation of the orexin receptor and for the treatment of disease states, disorders, and conditions mediated by orexin receptor activity.Orexin (or hypocretin) signaling is mediated by two receptors and two peptide agonists. The two orexin peptides (orexin A and orexin B) herein after referred to as orexins, bind to two high affinity receptors, termed orexin-1 and orexin-2 receptors. The orexin-1 receptor is selective in favor of orexin A, while the orexin-2 receptor binds both orexins with similar affinities. The orexins, are cleavage products of the same gene, prepro orexin. In the central nervous system neurons expressing prepro-orexin, the precursor from which orexin is produced, are found in the perifornical nucleus, the dorsal hypothalamus and the lateral hypothalamus (C. Peyron et al., 1998, 18(23), 9996-10015). Orexinergic cells in these nuclei project to many areas of the brain, extending rostrally to the olfactory bulbs and caudally to the spinal cord (van den Pol, A. N. et al., 1999, 19(8), 3171-3182).Citation of a reference herein shall not be construed as an admission that such reference is prior art to the present invention. All ...

HUMAN HELICASE DDX3 INHIBITORS AS THERAPEUTIC AGENTS

The present invention refers to compounds endowed with RNA helicase DDX3 inhibitory activity of formula I and II and their therapeutic use, in particular for the treatment of viral diseases. 3. A method for treating a viral disease comprising administering to a patient a compound or pharmaceutical acceptable salt claim 1 , solvate claim 1 , or stereoisomer of to a patient in need thereof.4. The method according to wherein the viral disease is modulated by DDX3.5. The method according to wherein the viral disease is caused by a virus that is resistant to at least one compound selected from the group consisting of: protease inhibitor claim 3 , nucleoside reverse transcriptase inhibitor claim 3 , non-nucleoside reverse transcriptase inhibitor and integrase inhibitor.6. The method according to wherein the viral disease is caused by a virus selected from the group consisting of: Human Immunodeficiency Virus 1 (HIV-1) claim 3 , Hepatitis C Virus claim 3 , Hepatitis B Virus claim 3 , Eastern Equine Encephalitis Virus claim 3 , Western Equine Encephalitis Virus claim 3 , Venezuelan Equine Encephalitis Virus claim 3 , Japanese Encephalitis Virus claim 3 , Tick Borne Encephalitis Virus claim 3 , Yellow Fever Virus claim 3 , St. Louis Encephalitis Virus claim 3 , Murray Valley Encephalitis Virus claim 3 , Powassan Virus claim 3 , Dengue Virus claim 3 , Zika Virus claim 3 , West Nile Virus claim 3 , Rubella Virus claim 3 , Cytomegalovirus claim 3 , O'nyong'nyong Virus claim 3 , Mayaro Virus claim 3 , Ross River Virus claim 3 , Sindbis Virus claim 3 , Vaccinia Virus claim 3 , Influenza Virus claim 3 , Norovirus claim 3 , SARS Coronavirus claim 3 , Chikunguya Virus claim 3 , Lassa Virus claim 3 , Ebola Virus claim 3 , Lujo Virus claim 3 , Pneumovirus claim 3 , Severe Fever With Thrombocytopenia Syndrome Virus claim 3 , Porcine Reproductive And Respiratory Syndrome Virus claim 3 , Poxvirus claim 3 , Bovine Viral Diarrhea Virus (BVDV) claim 3 , Border Disease Virus (BDV) of sheep ...