ПРОИЗВОДНЫЕ СУЛЬФОНАМИДОВ И ФАРМАЦЕВТИЧЕСКАЯ КОМПОЗИЦИЯ НА ИХ ОСНОВЕ

Изобретение относится к новым производным сульфонамидов формулы (I) или их фармацевтически приемлемым солям: , где R1 означает -ОН или -NHOH; R2 означает водород; R3 означает алкил, алкоксиалкил, арилалкил, пиридилалкил или морфолинилалкил; А означает пиперидил или тетрагидрофуранил; n равно 0; Е означает ковалентную связь; С1-С4-алкилен, -С(=O)-, -С(=O)O- или -SO2-; Х означает водород, алкил, арил, арилалкил, алкоксиалкил, морфолинил или тетрагидропиранил; каждый из G и G’ означает -C(R5)=C(R5), где R5 и R5 означают водород, М означает группу -CH-; z означает группу -(CR7R7’)a-L-R8, где а равно 0; каждый из R7 и R7означает водород; L означает ковалентную связь; и R8 означает галоген или алкокси. Соединения формулы (I) являются ингибиторами металлопротеаз и могут найти применение для лечения артрит, раковых опухолей и других заболеваний. 2 н. и 13 з.п. ф-лы, 7 табл.

АРОМАТИЧЕСКАЯ СУЛЬФОНГИДРОКСАМОВАЯ КИСЛОТА В КАЧЕСТВЕ ИНГИБИТОРА МЕТАЛЛОПРОТЕАЗ

Изобретение относится к области медицины и касается способа лечения заболеваний, связанных с патологической активностью матриксных металлопротеаз, с помощью соединений формулы I, соединений формулы I, а также способа получения указанных соединений. Изобретение повышает эффективность лечения. 25 с. и 111 з.п. ф-лы, 152 табл.

ЗАМЕЩЕННЫЕ ПРОИЗВОДНЫЕ 4-АМИНОЦИКЛОГЕКСАНА

Изобретение относится к новым соединениям общей формулы (1), которые обладают сродством к µ-опиоидному рецептору и ORL1-рецептору, к лекарственным средствам, содержащим эти соединения, и к применению этих соединений для получения лекарственных средств, пригодных для лечения боли, страха, стресса и других заболеваний или состояний. В общей формуле (1)Y, Y′, Y, Y′, Y, Y′, Yи Y′ означают -H; Rи Rнезависимо друг от друга означают -H или -CH; при условии что Rи Rоба одновременно не означают -H; Q означает: -C-арил, незамещенный или моно- или многократно замещенный -F, -Cl, -Br или -I; или-гетероарил; Rозначает: -C-алкил, незамещенный или моно- или многократно замещенный -OR, где Rозначает незамещенный -C-алкил; незамещенный -C-циклоалкил-C-алкил; незамещенный -C-алкил-C-циклоалкил; -C-арил, незамещенный или моно- или многократно замещенный -F, -Cl, -Br, -I, -CN, -Rили -OR, где Rозначает незамещенный -C-алкил; или -гетероарил; n означает 0; X означает -NR-; Rозначает -H или -R; где Rозначает ...

ЧЕТЫРЕХЗАМЕЩЕННЫЕ БЕНЗОЛЫ

Изобретение относится к новым соединениям Формулы III или к его фармацевтически приемлемым солям, в которой: Rи Rнезависимо выбраны из группы, состоящей из: (a) H, (b) (C-C)алкила, (c) C-Cалкила, прерванного одной или более групп -O-, (d) (C-C)алкил-(C-C)циклоалкила и (e) (CH)Q, где n=1-2 и где Q обозначает ароматическую кольцевую систему, имеющую от 5 до 6 кольцевых атомов C, и причем Q может быть независимо замещен группами числом до 3, выбранными из галогена, при условии, что Rи Rодновременно не обозначают H, причем каждый алкил Rи Rможет быть независимо замещен одной или более групп, выбранных из группы, состоящей из галогена, гидрокси, циано, CFили C-Cалкила, или Rи Rвместе с углеродом, к которому они присоединены, образуют 3-7-членное циклоалкильное или 6-членное гетероциклоалкильное кольцо, включающее один атом кислорода и которое в случае необходимости несет C-Cалкильный заместитель, или Rи Rвместе с углеродом, к которому они присоединены, образуют 3-7-членное циклоалкильное кольцо ...

ИНГИБИТОРЫ ПРОДУЦИРОВАНИЯ / СЕКРЕЦИИ β-АМИЛОИДНОГО БЕЛКА

Описывается соединение общей формулы (3): где R15 представляет гетероциклическую группу, выбранную из 3-7-членной насыщенной или 4-7-членной ненасыщенной моноциклической гетероциклической группы, имеющей 1-4 атома, выбранных из атома азота, атома кислорода и атома серы, или 7-14-членной полициклической гетероциклической группы, имеющей 1-4 атома, выбранных из атома азота, атома кислорода и атома серы, которая может иметь заместитель; R16представляет циклоалкильную группу, имеющую 3-7 атомов углерода, моноциклическую ароматическую углеводородную группу, имеющую 6-14 атомов углерода, или гетероциклическую группу, выбранную из 3-7-членной насыщенной или 4-7-членной ненасыщенной моноциклической гетероциклической группы, имеющей 1-4 атома, выбранных из атома азота, атома кислорода и атома серы, которая может иметь заместитель; R17представляет моноциклическую ароматическую углеводородную группу, имеющую 6-14 атомов углерода, или гетероциклическую группу, выбранную из 4-7-членной ненасыщенной ...

КРИСТАЛЛИЧЕСКИЕ ФОРМЫ КОМПЛЕКСОВ, ПОЛЕЗНЫЕ В КАЧЕСТВЕ ИНГИБИТОРОВ SGLT2, И СПОСОБЫ ИХ ПОЛУЧЕНИЯ

Изобретение относится к кристаллической форме комплекса (2S,3R,4R,5S,6R)-2-(4-хлор-3-(4-(2-иклопропоксиэтокси)бензил)фенил)-6-(гидроксиметил)тетрагидро-2Н-пиран-3,4,5-триол, бис(L-пролин), характеризующаяся паттерном дифракции рентгеновских лучей на порошке, включающим пики при 4,08, 17,19 и 21,12 градусов 2θ (±0.05 градусов 2θ), где указанный паттерн дифракции рентгеновских лучей на порошке получают с применением излучения CuK. Предоставленный комплекс обладает ингибиторным действием на зависимый от натрия транспортер SGLT. 4 н. и 3 з.п. ф-лы, 1 табл., 3 ил., 7 пр.

ПРОЛЕКАРСТВА КЕТАМИНА, ЕГО КОМПОЗИЦИИ И ПРИМЕНЕНИЯ

Изобретение относится к соединениям или к их фармацевтически приемлемым солям, являющимся пролекарствами кетамина, которые выбраны из следующих структур:Изобретение также относится к фармацевтической композиции, модулирующей противодействие рецептора NMDA, на основе указанных соединений. Технический результат – получены новые соединения и фармацевтическая композиция на их основе, которые могут найти применение в медицине для лечения заболеваний, связанных с рецептором NMDA, включая депрессию и боль. 8 н. и 7 з.п. ф-лы, 6 табл., 109 пр.

ОСНОВНЫЕ ЛИНЕЙНЫЕ СОЕДИНЕНИЯ NK-2 АНТАГОНИСТА И СОДЕРЖАЩИЕ ИХ ЛЕКАРСТВЕННЫЕ ВЕЩЕСТВА

... 1. Соединение общей формулы (I) где X1 представляет собой группу -NR6-CO-, -СО-, -NR6-CS-; R1 представляет собой арильную группу, выбранную из пиридина, тиофена, бензола, нафталина, дифенила, фенилтиофена, бензотиофена, бензофурана, N-индола, замещенного группой R7, где указанная арильная группа может быть также замещенной одной или несколькими независимыми группами, выбранными из группы, состоящей из галогена, С1-С6-алкила, необязательно замещенного не более, чем тремя атомами фтора (то есть, трифторметила), С1-С6-алкилоксила, необязательно замещенного не более, чем тремя атомами фтора (то есть трифторметилоксильной группы), -ОН, -NHR7, -N(R7)2, -SR7, -CONHR7, -COR7, -COOR7, -R8COOR7, -OR8COOR7, -R8COR7, -CONHR7, -R8CONHR7, -NHCOR7, -нитро, где R7 представляет собой водород или С1-С6-алкил с неразветвленной или разветвленной цепью, и R8 представляет собой С1-С6-алкиленовую группу с неразветвленной или разветвленной цепью; R6 выбран из группы, состоящей из водорода или С1-С6-алкила с неразветвленной ...

ПРИМЕНЕНИЕ АНТАГОНИСТОВ CXCR2 ДЛЯ ПРЕДОТВРАЩЕНИЯ И/ИЛИ ЛЕЧЕНИЯ ПЕРИФЕРИЧЕСКОЙ НЕВРОПАТИИ, ВЫЗВАННОЙ ХИМИОТЕРАПИЕЙ (CIPN)

СЕЛЕКТИВНЫЕ К BCL-2 АГЕНТЫ, ВЫЗЫВАЮЩИЕ АПОПТОЗ, ДЛЯ ЛЕЧЕНИЯ РАКА И ИММУННЫХ ЗАБОЛЕВАНИЙ

... 1. Соединение формулы Iили его терапевтически приемлемая соль, пролекарство или соль пролекарства,где Аявляется N или С(А);один, или два, или три, или каждый из А, В, Dи Eнезависимо выбраны из R, OR, SR, S(O)R, SOR, C(O)R, C(O)OR, OC(O)R, NHR, N(R), C(O)NHR, C(O)N(R), NHC(O)R, NHC(O)OR, NRC(O)NHR, NRC(O)N(R), SONHR, SON(R), NHSOR, NHSONHRили N(CH)SON(CH)R, а остальные независимо выбраны из H, F, Cl, Br, I, CN, CF, C(O)OH, C(O)NHили C(O)ORиYпредставляет собой H, CN, NO, C(O)OH, F, Cl, Br, I, CF, OCF, CFCF, OCFCF, R, OR, C(O)R, C(O)OR, SR, NH, NHR, N(R), NHC(O)R, C(O)NH, C(O)NHR, C(O)N(R), NHS(O)Rили NHSOR;или Ви Yвместе с атомами, с которыми они связаны, образуют имидазол или триазол иодин, или два, или каждый из А, Dи Eнезависимо выбраны из R, OR, SR, S(O)R, SOR, C(O)R, C(O)OR, OC(O)R, NHR, N(R), C(O)NHR, C(O)N(R), NHC(O)R, NHC(O)OR, NHC(O)NHR, N(CH)C(O)N(CH)R, SONHR, SON(R), NHSOR, NHSONHRили N(CH)SON(CH)R, а остальные независимо выбраны из H, F, Cl, Br,I, CF, C(O)OH, C(O)NHили C(O)OR; ...

Способ получения производного 2,3,4,5-тетрагидро-1,5-бензоксазепин-4-она

Изобретение касается гетероциклических соединений, в частности производного 2,3,4,5-тетрагидро-1,5- бензоксазепин-4-она - 3(S)-tl(S)- карбокси75-(4-пиперидил)-пентил -амино-4-оксо-2 ,3,4,5-тетрагидро-I,5- бензоксазепин-5-уксусной кислоты(ОА), которая обладает антигипертонической активностью и может найти применение в медицине. Для выявления новой активности у соединений указанного класса был разработан способ синтеза ОА. Получение ОА ведут из 3(S)(l- бензилоксикарбонил-4 пиперидил)-1 - алкоксикарбонилпентил -амино-2,3,4,5- тетрагидро-1,5(5Н)-бензоксазепин-4 она и низшего алкилгалогенацетата при комнатной температуре с последующей обработкой сначала кислотой, а затем основанием для удаления защитных бензилоксикарбонильной и низших алкильных групп. Испытания показьша- ют, что ОА в дозе 300 мкг/кг ингиби- рует гипертоническое действие ангио- тензина на 100% на всех промежутках времени - от 5 до 120 мин. В указанной дозе ОА не оказьшает токсического действия. СО со СА 00 IND tsD ...

SULFONAMIDDERIVATE ALS ASPARTYLPROTEASE-INHIBITOREN

New 2-alkoxy-4-halo-6-alkylphenyl-substituted (hetero)cyclic ketoenols, useful as total or selective herbicides and pesticides, e.g. insecticides, acaricides and nematocides for plant protection

... 2-Alkoxy-4-halo-6-alkylphenyl-substituted cyclic keto-enol compounds (I), derived from pyrrole, furan, thiophene, pyran, 1,3-thiazine, cyclopentane, cyclohexane or pyrazole, are new. Also new are 19 classes of intermediates, e.g. 2-alkoxy-4-halo-6-alkylphenylacetic acids (XXVII) and various ester or amide derivatives. Cyclic keto-enol derivatives of formula R-Ar (I) are new. Ar : 2-alkoxy-4-halo-6-alkylphenyl; R : cyclic keto-enol residue of formula (a) - (c); T 1N(D), O or S; T 2-C(A)=C(D)-O-, -C(A)(B)-C(Q 1>)(Q 2>)-, -C(A)(B)-C(Q 3>)(Q 4>)-C(Q 5>)(Q 6>)- or -N(A)-N(D)-; A : H; alkyl, alkenyl, alkoxyalkyl or alkylthioalkyl (all optionally substituted (os) by halo); os, optionally unsaturated cycloalkyl (optionally having at least one ring atom replaced by a heteroatom); or aryl, aralkyl or heteroaryl (all os by halo, alkyl, haloalkyl, alkoxy, haloalkoxy, CN or NO 2); B : H, alkyl or alkoxyalkyl; or C(A)(B) : os, (un)saturated ring (optionally containing heteroatom(s)); D : H; or alkyl, ...

Verfahren zur Herstellung von Oxaphenanthridinen

Novel compounds

Novel dihydroxytetrahydropyran compounds, their preparation and use

The invention comprises dihydroxytetrahydropyran compounds of the general formula wherein each R represents a hydrogen atom or a C1 to C3 alkyl group and X represents -CHO, -CH2OH, -CO2H or -CO2R1, wherein R1 is a C1 to C18 saturated or olefinically unsaturated aliphatic hydrocarbyl group. They are prepared by the hydroxylation, preferably with hydrogen peroxide in the presence of tungstic acid, of a 3, 4 dihydro-1, 2-pyran of the general formula or by the conversion of one X group into another. The compounds of the invention may be polymerized by heating to form polyhemiacetals, i.e. a polymer of formula when X is -CHO, of formula when X is -CO2H, of formula when X is -CO2R1 and of the Formula V wherein the CO2R1 group is replaced by CH2OH when X is -CH2OH; x being an integer greater than one. If desired the above polymers can be cross-linked with, for example, polycarboxylic acids or polyisocyanates ...

Chemical compounds

(4-Arylsulfonylamino)-tetrahydropyran-4-carboxylicacid hydroxamides.

(4-arylsulfonylamino)- etrah dropyran-4-carboxylic acid hydroxamides

S-nitrosothiols as agents for the treatment of circulatory dysfunctions.

Novel S-nitrosothiols derivatives of penicillamine or glutathione, which correspond to following general formula (I) in which: A and B are phenyl groups or together form the rest -CH2-Q-CH2- constituting a ring of six units in which Q represents an atom of oxygen, of sulfur, or a group N-R3, in which R3 is hydrogen or an alkyl group C1 -C4; R1 is an acyl rest, which may be an aliphatic acyl group C1-C5 or a rest of glutamic acid bound via its non amino acid carboxyl; R2 is a hydroxyl group or a glycine rest bound via a peptide bond; with the proviso that if R1 is an aliphatic acyl rest then R2 is a hydroxyl group, and if R1 is a rest of glutamic acid then R2 is a glycine rest. The novel compounds have vasodilating activity and inhibit the aggregation of the platelets, which make them useful for the treatment of dysfunctions of the circulatory system, specially at cardiovascular level.

(4-Arylsulfonylamino)-Tetrahydropyran-4-Carboxylic acid hydroxamides.

A compound of the formula or a pharmaceutical acceptable salt thereof. wherein Q is: (CrC6) alkyl, (C6-Ci0) aryl, (6-Ci0)aryloxy, (Cz'-Cg) heteroaryl or a combination of 2 or 3 of them together or with (C2-C9) heteroaryloxy..

3- or 4-monosubstituted phenol and thiophenol derivatives useful as H3 ligands.

Process for making 5-lipoxygenase inhibitors having varied heterocyclic ring systems.

A novel process intermediate, tetrahydro-4-[3-(4-flourophenyl)thio]phenyl-2h-pyran-4-carboxamide, of the formula: is described, as well as its use in a process of preparing 5-lipoxygenase inhibitors of the formula: which comprises establishing a reaction mixture consisting of: an electron deficient monocyclic or benzo-fused bicyclic n-heterocycle containing two nitrogen atoms of the formula: in an aprotic solvent; in the presence of a carbonate of the formula: (m2)-co3, where m is an alkali metal, group 1/1a element, selected from the group consisting of lithium, li; sodium,na; potassium, k; rubidium,rb; and cesium, cs; followed by heating of said reaction mixture under a nitrogen atmosphere; whereby there is produced the desired compound of the above-recited formula ...

S-nitrosothiols as agents for the treatment of circulatory dysfunctions

Sufamato hydroxamic acid metalloprotease inhibitor.

A sulfamato hydroxamic acid compound that inter alia inhibits matrix metalloprotease activity is disclosed as are a process for preparing the same, intermediate compounds useful in those sytheses, and a treatment process that comprises administering a contemplated sulfamato hydroxamic acid compound in a mmp enzyme-inhibiting effective amount to a host having a condition associated with pathological matrix metalloprotease activity.

(4-arylsulfonylamino)- etrah dropyran-4-carboxylic acid hydroxamides

Process for making5-lipoxygenase inhibitors having varied heterocyclic ring systems.

A process described for preparing a compound of formula (1.3.0): where - is - comprising: establishing a reaction mixture consisting of - and - in an aprotic solvent; in the presence of NaOH or KOH; optionally in the presence of a phase transfer catalyst, especially a quaternary ammonium salt or a phosphonium salt; followed by heating said reaction mixture under a nitrogen atmosphere; in a preferred embodiment the aprotic solvent is DMSO, the strong base in solid form is NaOH in powder or pellet form, and the phase transfer catalyst is tetra-n-butylammonium chloride (TBAC); wherein the starting material of formula (2.0.0) is prepared as follows: are reacted together in a solvent consisting of a straight or branched chain aliphatic alcohol; in the presence of a strong base consisting of NaOH or KOH; further in the presence of a transition metal catalyst comprising a palladium metal complex; and still further in the presence of an auxiliary ligand comprising a bidentate, chiral, axially dissymmetric ...

Aromatic sulfone hydroxamates and their use as protease inhibitors

This invention is directed to aromatic sulfone hydroxamates (also known as 'aromatic sulfone hydroxamic acids") and sahs thereof that, inter alia, inhibit matrix mctalloprotcinasc (also known as "matrix mctalloprolcasc' or "MMP") activity andfor aggrecanase activity. Thb invention also is directed to a prevention or treatment method that comprises administering such a com-pound or salt in an MMP-inhibtting and/or aggrecanase-inhibiting effective amount to an animal, particularly a mammal having (or disposed to having) a pathological condition associated with MMP and/or aggrecanase activity.

3-OR 4-Monosubstituted phenol and thiophenolderivatives useful as H3 ligands

Pyrazole analogs

COMPOUNDS AND USES THEREOF FOR THE MODULATION OF HEMOGLOBIN

Aromatic sulfone hydroxamates and their use as protease inhibitors.

Process for making 5-lipoxygenase inhibitors having varied heterocyclic ring systems.

Process for making 5-lipoxygenase inhibitors having varied heterocyclic ring systems.

S-nitrosothiols as agents for the treatment of circulatory dysfunctions.

Aromatic sulfone hydroxamates and their use as protease inhibitors.

3-OR 4-Monosubstituted phenol and thiophenolderivatives useful as H3 ligands

S-nitrosothiols as agents for the treatment of circulatory dysfunctions

Sulfamoto hydroxamic acid metalloprotease inhibitor

COMPOUNDS AND USES THEREOF FOR THE MODULATION OF HEMOGLOBIN

Pyrazole analogs

Process for making 5-lipoxygenase inhibitors having varied heterocyclic ring systems

Process for making 5-lipoxygenase inhibitors having varies heterocyclyc ring systems-reference to opening applications

Sulfamoto hydroxamic acid metalloprotease inhibitor

3-OR 4-Monosubstituted phenol and thiophenolderivatives useful as H3 ligands

S-nitrosothiols as agents for the treatment of circulatory dysfunctions

AS H3-LIGANDEN APTITUDE 3ODER 4MONOSUBSTITUIERTE PHENOLUND of THIOPHENOL DERIVATIVES

2, 4, 6-PHENYLSUBSTITUIERTE CYCLI KETOENOLE

MORE CYCLOHEXENONOXIMETHER, PROCEDURES AND INTERMEDIATE PRODUCTS FOR YOUR PRODUCTION AND YOUR USE THAN HERBICIDES

SULFONE AMIDE DERIVATIVES AS ASPARTYLPROTEASE INHIBITORS

Procedure for the production new secondary p-Aminophenylamidine as well as their acid addition salts

Procedure for the production new secondary p-Aminophenylamidine as well as their acid addition salts

Procedure for the production new secondary p-Aminophenylamidine as well as their acid addition salts

PROCEDURE FOR THE PRODUCTION OF NEW FLUORENONDERIVATE

(4-SULFONYLAMINO) - TETRAHYDROPYRAN-4-CARBONSÄURE HYDROXAMIDEN

S-NITROSOTHIOLE ONE AS AGENTIEN FOR THE TREATMENT OF MALFUNCTIONINGS OF THE CYCLE

Procedure for the production of new 2-Aryltetrahydropyran-3-amine and their salts

Compounds and pharmaceutical compositions as cathepsin s inhibitors

Inhibitors of diacylglycerol acyltransferase (DGAT)

Aryl alkyl acid derivatives for and use thereof

Biphenyl-substituted spirocyclic ketoenols

The invention relates to new compounds of the formula (I) in which W, X, Y, Z and CKE have the meanings given above, to a plurality of processes and intermediates for their preparation and to their use as pesticides and/or herbicides, and also to selective herbicidal compositions comprising, firstly, the compounds of the formula (I) and, secondly, at least one crop plant compatibility enhancer compound. The invention relates further to boosting the activity of crop protection compositions comprising compounds of the formula (I) by adding ammonium salts or phosphonium salts and, if appropriate, penetrants.

Acylamino-substituted cyclic carboxylic acid derivatives and their use as pharmaceuticals

The present invention relates to compounds of the formula (I) wherein A, Y, Z, R to R and R have the meanings indicated in the claims, which are valuable pharmaceutical active compounds. Specifically, they are inhibitors of the endothelial differentiation gene receptor 2 (Edg-2, EDG2), which is activated by lysophosphatidic acid (LPA) and is also termed as LPA receptor, and are useful for the treatment of diseases such as atherosclerosis, myocardial infarction and heart failure, for example. The invention furthermore relates to processes for the preparation of the compounds of the formula (I), their use and pharmaceutical compositions comprising them.

SPIROCYCLIC AMIDES AS CANNABINOID RECEPTOR MODULATORS

Aryl substituted heterocyclyl sulfones

The invention relates to aryl substituted heterocyclyl sulfones as voltage gated calcium channel blockers, to pharmaceutical compositions containing these compounds and also to these compounds for use in the treatment and/or prophylaxis of pain and further diseases and/or disorders.

Indane derivatives as mGluR7 modulators

The present invention provides compounds of formula (I) and pharmaceutically acceptable salts thereof, wherein R1, R2, R3, R4 ...

5-lipoxygenase inhibitors

Hydroxamic and carboxylic acid derivatives having MMP and TNF inhibitory activity

TETRAHYDRO PYRAN DERIVATIVES

AMINOPHENYLAMIDINES, THEIR PRODUCTION AND THEIR PHARMACEUTICAL USE

CYCLOHEXANE-1,3-DIONE DERIVATIVES AND THEIR USE FOR CONTROLLING UNDESIRABLE PLANT GROWTH

SULFAMATO HYDROXAMIC ACID METALLOPROTEASE INHIBITOR

A sulfamato hydroxamic acid compound that inter alia inhibits matrix metalloprotease activity is disclosed as are a process for preparing the same, intermediate compounds useful in those syntheses, and a treatment process that comprises administering a contemplated sulfamato hydroxamic acid compound in a MMP enzyme-inhibiting effective amount to a host having a condition associated with pathological matrix metalloprotease activity.

2,4,6-PHENYL SUBSTITUTED CYCLIC KETOENOLS

The present invention relates to novel 2,4,6-phenyl-substituted cyclic ketoenols of the formula (I) (see formula I) in which W, X, Y and CKE have the abovementioned meanings, to a plurality of processes for their preparation and to their use as pesticides and/or herbicides. Moreover, the invention relates to selectively herbicidal compositions containing firstly 2,4,6-phenyl-substituted cyclic ketoenols and secondly a compound which improves crop plant tolerance.

TETRASUBSTITUTED BENZENES

Tetrasubstituted benzenes that act as modulators of gamma secretase and their use in the treatment of one or more symptoms of treating neurodegenerative disorders, e.g., Alzheimer's disease, are described.

CALCIUM-SENSING RECEPTOR-ACTIVE COMPOUNDS

A compound of general formula I their use as calcium receptor-active compounds for the prophylaxis, treatment or amelioration of physiological disorders or diseases associated with disturbances of CaSR activity, such as hyperparathyroidism, pharmaceutical compositions comprising said compounds, methods of treating diseases with said compounds, and the use of said compounds in the manufacture of medicaments.

CYCLIC TRIAZO SODIUM CHANNEL BLOCKERS

The present invention relates to triazine compounds having sodium channel blocking properties, and to use of the compounds for preparation of medicaments for treatment of associated disorders. The compounds are of formula (I): in which z is a single bond or an optionally substituted linking group, R1 is a halo-alkyl group; and A is an optionally substituted aromatic heterocyclic or carbocyclic ring system; or a salt thereof.

NOVEL CEPHALOTAXANE DERIVATIVES AND PROCESS FOR THEIR PREPARATION

The present invention concerns a new general process for asymmetric hemisynthesis of harringtonines and their analogs, that are alcaloïds used in chimiotherapy. This process comprises direct esterification of a natural cephalotaxine with an acylating compound constituted of a side chain precursor which backbone and fonctionalization are entirely preformed.

CYCLOALKYL INHIBITORS OF POTASSIUM CHANNEL FUNCTION

Novel cycloalkyl compounds useful as inhibitors of potassium channel function (especially inhibitors of the Kv1subfamily of voltage gated K+ channels, especially inhibitors Kv1.5 which has been linked to the ultra-rapidly activating delayed rectifier K+ current IKur), methods of using such compounds in the prevention and treatment of arrhythmia and IKur-associated conditions, and pharmaceutical compositions containing such compounds.

S-NITROSOTHIOLS AS AGENTS FOR THE TREATMENT OF CIRCULATORY DYSFUNCTIONS

... ▓▓▓The invention relates to novel S-nitrosothiols derived from penicillamine or ▓glutathione of general formula (I), wherein A and B are phenyl groups or ▓together represent a -CH2-Q-CH2- radical forming a six-membered ring in which ▓Q represents an oxygen or sulfur atom or an N-R3 radical, wherein R3 is ▓hydrogen or an C1-C4 alkyl group; R1 is an acyl radical which may be a C1-C5 ▓aliphatic acyl radical or a glutamic acid radical bonded by its non-amino acid ▓carboxyl; R2 is a hydroxyl group or a glycine radical bonded by peptidic ▓linkage in such a way that R2 is an hydroxyl group when R1 is an aliphatic ▓acyl radical and R2 is a glycine radical when R1 is a glutamic acid radical. ▓Said novel compounds exhibit vasodilating and blood platelet aggregation ▓inhibiting activity and are useful in the treatment of circulatory system ▓dysfunctions, especially cardiovascular dysfunctions.▓ ...

HEPATITIS B ANTIVIRAL AGENTS

The present invention discloses compounds of Formula (I), or pharmaceutically acceptable salts, esters, or prodrugs thereof: which inhibit the protein(s) encoded by hepatitis B virus (HBV) or interfere with the function of the HBV life cycle of the hepatitis B virus and are also useful as antiviral agents. The present invention further relates to pharmaceutical compositions comprising the aforementioned compounds for administration to a subject suffering from HBV infection. The invention also relates to methods of treating an HBV infection in a subject by administering a pharmaceutical composition comprising the compounds of the present invention.

N-(3-(2-(4-CHLOROPHENOXY)ACETAMIDO)BICYCLO[1.1.1]PENTAN-1-YL)-2-CYCLOBUTANE-1-CARBOXAMIDE DERIVATIVES AND RELATED COMPOUNDS AS ATF4 INHIBITORS FOR TREATING CANCER AND OTHER DISEASES

The invention is directed to substituted bridged cycloalkane derivatives. Specifically, the invention is directed to compounds according to Formula (I) wherein X, a, b, C, D, L2, L3, Y1, Y2, R2, R4, R5, R6, z2, z4, z5, and z6 are as defined herein, and salts thereof. The invention is further directed to pharmaceutical compositions comprising a compound of the invention. The invention is still further directed to compounds for use in methods of inhibiting the ATF4 (activating transcription factor 4) pathway and treatment of disorders associated therewith, such as e.g. cancer, neurodegenerative diseases and many other diseases, using a compound of the invention or a pharmaceutical composition comprising a compound of the invention. Preferred compounds of the invention are N-(3-(2-(4-chlorophenoxy) acetamido)bicyclo[1.1.1]pentan-l-yl)-2-cyclobutane-l-carboxamide derivatives and related compounds.

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.

PROCESSES FOR THE PREPARATION OF SGLT2 INHIBITORS

CYCLYLAMINE DERIVATIVES AS CALCIUM CHANNEL BLOCKERS

Methods and compounds effective in ameliorating conditions characterized by unwanted calcium channel activity, particularly unwanted N-type and/or T-type calcium channel activity are disclosed. Specifically, a series of compounds of substituted or unsubstituted cyclylamine derivatives as shown in formulas (1).

GUANIDINE COMPOUND

... [Problem] To provide a compound which is useful as an active ingredient of a pharmaceutical composition, especially of a pharmaceutical composition for the prophylaxis and/or treatment of VAP-1 associated diseases. [Solution] As a result of intensive studies on a compound having VAP-1 inhibitory activity, the inventors have achieved the present invention by discovering that a compound of the present invention or a salt thereof has excellent VAP-1 inhibitory activity and is thus useful for the prophylaxis and/or treatment of VAP-1 associated diseases, especially for the prophylaxis and/or treatment of diabetic nephropathy or diabetic macular edema. The present invention also relates to a pharmaceutical composition, particularly a pharmaceutical composition for the prophylaxis and/or treatment of VAP-1 associated diseases, said pharmaceutical composition containing a compound of the present invention or a salt thereof and an excipient.

CARBOPEPTOIDS AND CARBONUCLEOTOIDS

Librairies are synthesized with oligomeric carbopeptoids and carbonucleotoids. Carbopeptoids are oligosaccharides having carbohydrate subunits linked to one another by amide bonds. Carbonucleotoids are oligosaccharides having carbohydrate subunits linked to one another by phosphodiester bonds. Carbopeptoid librairies may be fabricated using automated polypeptide synthesizers. Carbonucleotoid librairies may be fabricated using automated polynucleotide synthesizers.

Procédé de préparation d'esters organiques contenant du soufre

Procédé de préparation d'esters organiques du 2-(2-diéthylaminoéthoxy)-éthanol

Procédé de préparation de nouveaux esters d'aminoalcools secondaires

Verfahren zur Herstellung perfluorierter aliphatischer Carbonsäuren

Verfahren zur Herstellung neuer Indolverbindungen

Verfahren zur Herstellung von Oxaphenanthridinen

Verfahren zur Herstellung von Nitrilen substituierter cycloaliphatischer oder heterocyclischer Säuren

VERFAHREN ZUR HERSTELLUNG NEUER FLUORENONE.

Verfahren zur Herstellung heterocyclisch substituierter Derivate der Essigsäure

Verfahren zur Herstellung von in 2-Stellung durch einen Arylrest substituierten 3-Amino-tetrahydropyranen

Substituted 4-aminocyclohexane derivatives

The invention relates to compounds that have an affinity to the μ-opioid receptor and the ORL 1-receptor, methods for their production, medications containing these compounds and the use of these compounds for the treatment of pain and other conditions.

Guanidine compound

[Problem] The present invention provides a compound which is useful as an active ingredient of a pharmaceutical composition, in particular, a pharmaceutical composition for preventing and/or treating VAP-1-related diseases. [Means for Solution] The present inventors have conducted intensive studies on a compound having a VAP-1 inhibitory activity, and as a result, they have found that the compound or a salt thereof of the present invention exhibits an excellent VAP-1 inhibitory activity and is useful for preventing and/or treating VAP-1-related diseases, in particular, diabetic nephropathy or diabetic macular edema, thereby completing the present invention. In addition, the present invention relates to a pharmaceutical composition, in particular, a pharmaceutical composition for preventing and/or treating VAP-1-related diseases, which comprises the compound or a salt thereof of the present invention, and an excipient.

TETRASUBSTITUTED BENZENES

Tetrasubstituted benzenes that act as modulators of gamma secretase and their use in the treatment of one or more symptoms of treating neurodegenerative disorders, e.g., Alzheimer's disease, are described. 162.-. (canceled)64. The compound of claim 63 , wherein Rand Rare independently selected from the group consisting of (a) H claim 63 , (b) (C-C)alkyl and (c) (C-C)alkyl-(C-C)cycloalkyl provided that both Rand Rare not H claim 63 , wherein each alkyl or cycloalkyl of Rand Ris optionally independently substituted with one or more groups selected from the group consisting of halo claim 63 , hydroxy claim 63 , cyano claim 63 , CFand (C-C)alkyl claim 63 ,or{'sub': 1', '2', '1', '4', '3', '1', '4, 'Rand Rtaken together with the carbon to which they are attached form a 3-7 membered cycloalkyl or heterocycloalkyl ring which optionally bears a C-Calkyl substituent that can be optionally independently substituted with one or more groups selected from the group consisting of halo, hydroxy, oxo, cyano, CFand (C-C)alkyl,'}or{'sub': 1', '2', '20', '21', '20', '21', '3', '1', '4, 'Rand Rare taken together with the carbon to which they are attached form a 3-7 membered cycloalkyl ring substituted with Rand Rwherein Rand Rtaken together with the carbon or carbons to which they are attached form a 3-7 membered cycloalkyl ring wherein each cycloalkyl is optionally independently substituted with one or more groups selected from the group consisting of halo, hydroxy, cyano, CFand (C-C)alkyl;'}Y is —O—,{'sub': '4', 'claim-text': [{'sub': 0', '3', '3', '7, '(a) (C-C)alkyl(C-C)cycloalkyl,'}, '(b) trifluoroethyl and', '(c) trifluoropropyl;', {'sub': 6', '3', '2', '1', '4', '2', '2', '3', '6', '6', '2', '6, 'Z is a phenyl ring optionally bearing up to 3 substituents independently selected from the group consisting of halogen, R, CF, CN, NO, OH, (C-C)alkoxy, OCHCHOCH, SR, S(O)Rand S(O)R;'}], 'Ris selected from the group consisting of'}{'sub': 5', '3, 'claim-text': [{'sub': '6', 'Ris selected ...

BCL-2 SELECTIVE APOPTOSIS-INDUCING AGENTS FOR THE TREATMENT OF CANCER AND IMMUNE DISEASES

Disclosed are compounds which inhibit the activity of anti-apoptotic Bcl-2 or Bcl-xL proteins, compositions containing the compounds and methods of treating diseases during which are expressed anti-apoptotic Bcl-2 protein. 6. The method of claim 1 , wherein the compound is selected from the group consisting of:4-(4-((4′-chloro-1,1′-biphenyl-2-yl)methyl)piperazin-1-yl)-N-((3-nitro-4-((tetrahydro-2H-pyran-4-ylmethyl)amino)phenyl)sulfonyl)-2-phenoxybenzamide;4-(4-((4′-chloro-1,1′-biphenyl-2-yl)methyl)piperazin-1-yl)-2-phenoxy-N-((4-((tetrahydro-2H-pyran-4-ylmethyl)amino)phenyl)sulfonyl)benzamide;2-(benzyloxy)-4-(4-((4′-chloro-1,1′-biphenyl-2-yl)methyl)piperazin-1-yl)-N-((3-nitro-4-((tetrahydro-2H-pyran-4-ylmethyl)amino)phenyl)sulfonyl)benzamide;4-(4-((4′-chloro-1,1′-biphenyl-2-yl)methyl)piperazin-1-yl)-N-((3-nitro-4-((tetrahydro-2H-pyran-4-ylmethyl)amino)phenyl)sulfonyl)-2-(2-phenylethoxy)benzamide;4-(4-((4′-chloro-1,1′-biphenyl-2-yl)methyl)piperazin-1-yl)-N-((3-nitro-4-((tetrahydro-2H-pyran-4-ylmethyl)amino)phenyl)sulfonyl)-2-(phenylthio)benzamide;4-(4-((4′-chloro-1,1′-biphenyl-2-yl)methyl)piperazin-1-yl)-2-(phenylthio)-N-((4-((tetrahydro-2H-pyran-4-ylmethyl)amino)phenyl)sulfonyl)benzamide;4-(4-((4′-chloro-1,1′-biphenyl-2-yl)methyl)piperazin-1-yl)-N-((4-((3-morpholin-4-ylpropyl)amino)-3-nitrophenyl)sulfonyl)-2-(phenylthio)benzamide;4-(4-((4′-chloro-1,1′-biphenyl-2-yl)methyl)piperazin-1-yl)-N-((3-nitro-4-((tetrahydro-2H-pyran-4-ylmethyl)amino)phenyl)sulfonyl)-2-(phenylsulfonyl)benzamide;4-(4-((4′-chloro-1,1′-biphenyl-2-yl)methyl)piperazin-1-yl)-N-((3-nitro-4-((tetrahydro-2H-pyran-4-ylmethyl)amino)phenyl)sulfonyl)-2-(phenylsulfinyl)benzamide;2-benzyl-4-(4-((4′-chloro-1,1′-biphenyl-2-yl)methyl)piperazin-1-yl)-N-((3-nitro-4-((tetrahydro-2H-pyran-4-ylmethyl)amino)phenyl)sulfonyl)benzamide;2-benzyl-4-(4-((4′-chloro-1,1′-biphenyl-2-yl)methyl)piperazin-1-yl)-N-((4-((tetrahydro-2H-pyran-4-ylmethyl)amino)phenyl)sulfonyl)benzamide;2-benzyl-4-(4-((4′-chloro-1,1′-biphenyl-2-yl) ...

APOPTOSIS-INDUCING AGENTS FOR THE TREATMENT OF CANCER AND IMMUNE AND AUTOIMMUNE DISEASES

Disclosed are compounds which inhibit the activity of anti-apoptotic Bcl-2 proteins, compositions containing the compounds and methods of treating diseases during which is expressed anti-apoptotic Bcl-2 protein. 112-. (canceled)15. A compound or a therapeutically acceptable salt thereof , wherein the compound is selected from the group consisting of:4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-en-1-yl]methyl}piperazin-1-yl)-2-(2,3-difluorophenoxy)-N-({4-[(3-morpholin-4-ylpropyl)amino]-3-nitrophenyl}sulfonyl)benzamide;2-(4-amino-3-chlorophenoxy)-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-en-1-yl]methyl}piperazin-1-yl)-N-({4-[(3-morpholin-4-ylpropyl)amino]-3-nitrophenyl}sulfonyl)benzamide;4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-en-1-yl]methyl}piperazin-1-yl)-2-(2,5-dichlorophenoxy)-N-({4-[(3-morpholin-4-ylpropyl)amino]-3-nitrophenyl}sulfonyl)benzamide;N-(4-((4-aminotetrahydro-2H-pyran-4-yl)methylamino)-3-nitrophenylsulfonyl)-2-(3-chlorophenoxy)-4-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-enyl)methyl)piperazin-1-yl)benzamide;4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-en-1-yl]methyl}piperazin-1-yl)-2-(3-fluorophenoxy)-N-({4-[(3-morpholin-4-ylpropyl)amino]-3-nitrophenyl}sulfonyl)benzamide;2-(2-chlorophenoxy)-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-en-1-yl]methyl}piperazin-1-yl)-N-({4-[(3-morpholin-4-ylpropyl)amino]-3-nitrophenyl}sulfonyl)benzamide;2-(2-chloro-4-fluorophenoxy)-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-en-1-yl]methyl}piperazin-1-yl)-N-({4-[(3-morpholin-4-ylpropyl)amino]-3-nitrophenyl}sulfonyl)benzamide;4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-en-1-yl]methyl}piperazin-1-yl)-2-(2-fluorophenoxy)-N-({4-[(3-morpholin-4-ylpropyl)amino]-3-nitrophenyl}sulfonyl)benzamide;4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-en-1-yl]methyl}piperazin-1-yl)-2-(2-fluorophenoxy)-N-({4-[(2-morpholin-4-ylethyl)amino]-3-nitrophenyl}sulfonyl)benzamide;2-(3-chlorophenoxy)-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-en-1- ...

Guanidine compound

[Problem] The present invention provides a compound which is useful as an active ingredient of a pharmaceutical composition, in particular, a pharmaceutical composition for preventing and/or treating VAP-1-related diseases. [Means for Solution] The present inventors have conducted intensive studies on a compound having a VAP-1 inhibitory activity, and as a result, they have found that the compound or a salt thereof of the present invention exhibits an excellent VAP-1 inhibitory activity and is useful for preventing and/or treating VAP-1-related diseases, in particular, diabetic nephropathy or diabetic macular edema, thereby completing the present invention. In addition, the present invention relates to a pharmaceutical composition, in particular, a pharmaceutical composition for preventing and/or treating VAP-1-related diseases, which comprises the compound or a salt thereof of the present invention, and an excipient.

AMIDE DERIVATIVES, PROCESS FOR PREPARATION THEREOF AND USE THEREOF AS INSECTICIDE

An object of the present invention is to provide a compound represented by Formula (1): 114-. (canceled) The present invention relates to a compound represented by Formula (1):wherein A, A, Aand Aeach represent a carbon atom, a nitrogen atom or an oxidized nitrogen atom;Rand Reach represent a hydrogen atom, an optionally substituted alkyl group or an optionally substituted C1-C4 alkylcarbonyl group;Gand Geach represent an oxygen atom or a sulfur atom;X, which may be identical or different, represents a hydrogen atom, a halogen atom, a C1-C3 alkyl group or a trifluoromethyl group;n is an integer of 0 to 4; andQand Qeach represent an optionally substituted phenyl group, an optionally substituted naphthyl group or an optionally substituted heterocyclic group,an insecticide comprising the compound as the active ingredient, and a process for preparation thereof and use thereof.International Publication WO 2000/55120 and U.S. Pat. No. 6,548,514 describe a compound similar to the compound of the present invention for the use as medicament, but they do not describe on the insecticidal activity of the compound. The compound clearly does not fall within the scope of claims of the present invention.International Publication WO 2000/7980 describes a compound similar to the compound of the present invention for the use as medicament, but it does not describe on the insecticidal activity of the compound. The compound clearly does not fall within the scope of claims of the present invention.US Patent Laid-Open No. 2002-032238 describes a compound similar to the compound of the present invention for the use as medicament, but it does not describe on the insecticidal activity of the compound. The compound clearly does not fall within the scope of claims of the present invention.The object of the present invention is to provide a pesticide having a high insecticidal efficacy. Another object of the present invention is to provide a compound represented by Formula (1), a process for ...

Compounds and uses thereof for the modulation of hemoblogin

Provide herein are compounds and pharmaceutical compositions suitable as modulators of hemoglobin, methods and intermediates for their preparation, and methods for their use in treating disorders mediated by hemoglobin and disorders that would benefit from tissue and/or cellular oxygenation.

Novel Compounds

The invention relates to 1-(3-sulfonylphenyl)-3-(cyclopent-2-en-1-yl)urea derivatives, and their use in treating or preventing diseases and conditions mediated by the CXCR2 receptor. In addition, the invention relates to compositions containing the derivatives and processes for their preparation.

INHIBITORS OF HISTONE DEACETYLASE

The present invention relates to compounds of formula (I): 5. The compound of or a pharmaceutically acceptable salt claim 4 , hydrate claim 4 , solvate claim 4 , or prodrug thereof claim 4 , wherein Ris selected from phenyl claim 4 , 2-pyridinyl claim 4 , 3-pyridinyl claim 4 , 4-pyridinyl claim 4 , 2-pyrimidinyl claim 4 , 4-pyrimidinyl claim 4 , 5-pyrimidinyl claim 4 , 2-pyrazinyl claim 4 , oxazolyl claim 4 , thiazolyl claim 4 , and isoxazolyl.12. A pharmaceutical composition comprising an effective amount of a compound of or a pharmaceutically acceptable salt claim 1 , hydrate claim 1 , solvate claim 1 , or prodrug thereof and a pharmaceutical carrier claim 1 , diluent claim 1 , or excipient.13. A method of treating claim 1 , alleviating claim 1 , and/or preventing a condition wherein said condition is associated with histone deacetylase activity in a subject comprising administering to the subject in need thereof an effective amount of a compound of or a pharmaceutically acceptable salt claim 1 , hydrate claim 1 , solvate or prodrug thereof.14. The method of claim 13 , wherein the condition is selected from a neurological disorder claim 13 , memory loss or impairment claim 13 , cognitive function disorder or impairment claim 13 , extinction learning disorder claim 13 , fungal disease or infection claim 13 , inflammatory disease claim 13 , hematological disease claim 13 , and neoplastic disease.15. The method of claim 14 , wherein the condition is selected from:a cognitive function disorder or impairment associated with Alzheimer's disease, Huntington's disease, seizure induced memory loss, schizophrenia, Rubinstein Taybi syndrome, Rett Syndrome, Fragile X, Lewy body dementia, vascular dementia, ADHD, dyslexia, bipolar disorder and social, cognitive and learning disorders associated with autism, traumatic head injury, or attention deficit disorder, anxiety disorder, conditioned fear response, panic disorder, obsessive compulsive disorder, posttraumatic stress ...

Substituted Aromatic Sulfur Compounds and Methods of Their Use

Compounds of formula II are described: 2. The compound of claim 1 , wherein A is at the 4-position of the phenyl ring.4. The compound of claim 1 , wherein Rand Rare each —CH.5. The compound of claim 3 , wherein Ris —OH.6. The compound of claim 3 , wherein Ris substituted or unsubstituted heterocycloalkyl.7. The compound of claim 3 , wherein Ris —NRR.8. The compound of claim 7 , wherein Ris H.9. The compound of claim 8 , wherein Ris substituted or unsubstituted alkyl.10. The compound of claim 8 , wherein Ris substituted or unsubstituted aryl.11. The compound of claim 8 , wherein Ris substituted or unsubstituted aralkyl.12. The compound of claim 8 , wherein Ris substituted or unsubstituted heteroaryl.13. The compound of claim 8 , wherein Ris substituted or unsubstituted heteroaralkyl.14. The compound of claim 8 , wherein Ris substituted or unsubstituted cycloalkyl.15. The compound of claim 8 , wherein Ris substituted or unsubstituted heterocycloalkyl.16. The compound of claim 8 , wherein Ris substituted or unsubstituted alkyene oxide.17. The compound of claim 8 , wherein Ris —NHCOcycloalkyl.18. The compound of claim 8 , wherein Rand R claim 8 , together with the atoms through which they are attached claim 8 , form a substituted or unsubstituted heterocycloalkyl ring.19. The compound of claim 3 , wherein Ris —CH.20. The compound of claim 19 , wherein Ris substituted or unsubstituted alkyl.21. The compound of claim 19 , wherein Ris substituted or unsubstituted aryl.22. The compound of claim 19 , wherein Ris substituted or unsubstituted aralkyl.23. The compound of claim 19 , wherein Ris substituted or unsubstituted heteroaryl.24. The compound of claim 19 , wherein Ris substituted or unsubstituted heteroaralkyl.25. The compound of claim 19 , wherein Ris substituted or unsubstituted cycloalkyl.26. The compound of claim 19 , wherein Ris substituted or unsubstituted heterocycloalkyl.27. The compound of claim 19 , wherein Ris substituted or unsubstituted alkyene oxide.28. The ...

Ketamine derivatives and compositions thereof

Ketamine derivatives and pharmaceutical compositions thereof are disclosed. When administered orally the ketamine derivatives provide increased bioavailability of ketamine in the systemic circulation. The ketamine derivatives can be used to treat neurological diseases, psychological diseases and pain.

Inhibitor of indoleamine-2,3-dioxygenase (ido)

The present disclosure provides compounds of Formula (I). The compounds described herein may be useful in treating a disease associated with IDO, for example, cancer or an infectious disease (e.g., viral or bacterial infectious diseases). Also, provided in the present disclosure are pharmaceutical compositions, kits, methods, and uses including or using a compound described herein.

TREPROSTINIL DERIVATIVES AND COMPOSITIONS AND USES THEREOF

The present disclosure provides treprostinil derivatives that can act as prodrugs of treprostinil. The treprostinil derivatives can be used to treat any conditions responsive to treatment with treprostinil, including pulmonary hypertension, such as pulmonary arterial hypertension. 124-. (canceled)26. A pharmaceutical composition comprising the compound of claim 25 , or a pharmaceutically acceptable salt claim 25 , solvate claim 25 , hydrate claim 25 , clathrate claim 25 , polymorph or stereoisomer thereof claim 25 , and one or more pharmaceutically acceptable excipients or carriers.27. The pharmaceutical composition of claim 26 , which is formulated for oral administration of the compound.28. The pharmaceutical composition of claim 26 , which is formulated for parenteral administration of the compound.29. The pharmaceutical composition of claim 28 , which is formulated for intravenous or subcutaneous administration of the compound.30. The pharmaceutical composition of claim 26 , which is formulated for topical administration of the compound.31. The pharmaceutical composition of claim 30 , which is formulated for transdermal administration or pulmonary administration by inhalation of the compound.32. A method of treating a medical condition responsive to treatment with treprostinil claim 25 , comprising administering to a subject in need of treatment a therapeutically effective amount of the compound of claim 25 , or a pharmaceutically acceptable salt claim 25 , solvate claim 25 , hydrate claim 25 , clathrate claim 25 , polymorph or stereoisomer thereof.33. The method of claim 32 , wherein the medical condition is selected from the group consisting of pulmonary hypertension claim 32 , pulmonary arterial hypertension claim 32 , portopulmonary hypertension claim 32 , pulmonary fibrosis claim 32 , interstitial lung disease claim 32 , asthma claim 32 , cardiovascular disease claim 32 , heart failure claim 32 , congestive heart failure claim 32 , conditions requiring ...

SULFINYLAMINOBENZAMIDE AND SULFONYLAMINOBENZAMIDE DERIVATIVES

Provided is a compound of Formula (I): 25-. (canceled)6. The method of claim 1 , wherein Ris selected from the group consisting of: Calkyl claim 1 , —NRR claim 1 , 6-10 membered aryl claim 1 , 5-10 membered heteroaryl claim 1 , Ccycloalkyl claim 1 , and 4-12 membered heterocyclyl claim 1 , wherein each Calkyl claim 1 , 6-10 membered aryl claim 1 , 5-10 membered heteroaryl claim 1 , Ccycloalkyl claim 1 , and 4-12 membered heterocyclyl is further substituted with one or more Rgroups.7. The method of claim 1 , wherein Ris selected from the group consisting of: —H claim 1 , —CN claim 1 , —F claim 1 , methyl claim 1 , methoxy and Chaloalkoxy.8. The method of claim 7 , wherein Ris selected from the group consisting of: —H and —F.9. The method of claim 1 , wherein Ris selected from the group consisting of: —H claim 1 , halo claim 1 , —OH claim 1 , —CN claim 1 , Calkyl claim 1 , Calkoxy claim 1 , Chydroxyalkyl claim 1 , Cheteroalkyl claim 1 , —SF claim 1 , —S(O)R claim 1 , —S(O)(NH)R claim 1 , —S(O)(NR)R claim 1 , —S(O)(NH)NRR claim 1 , —S(O)(NR)NRR claim 1 , —NRSOR claim 1 , —NRS(O)NRR claim 1 , —NRC(O)NRR claim 1 , —NRC(O)OR claim 1 , —C(O)R claim 1 , —C(O)OR claim 1 , —C(O)NRR claim 1 , and —NO claim 1 , wherein each of the Calkyl claim 1 , Calkoxy claim 1 , Chydroxyalkyl claim 1 , and Cheteroalkyl claim 1 , is further substituted with one or more Rgroups.10. The method of claim 9 , wherein Ris selected from the group consisting of: —H claim 9 , —F claim 9 , —Cl claim 9 , —OH claim 9 , —CN claim 9 , —S(O)R claim 9 , —C(O)R claim 9 , —SF claim 9 , —NO claim 9 , Calkyl claim 9 , and Calkoxy claim 9 , and wherein said Calkyl or Calkoxy is optionally substituted with one or more —F claim 9 , and Ris selected from the group consisting of Calkyl claim 9 , Ccycloalkyl claim 9 , Chydroxyalkyl claim 9 , Cheteroalkyl claim 9 , wherein the Calkyl claim 9 , Ccycloalkyl claim 9 , Chydroxyalkyl claim 9 , and Cheteroalkyl claim 9 , are optionally substituted with one or more Rgroups ...

SULFONIUM COMPOUNDS, THEIR PREPARATION AND USE

Compounds of the formula (I), (Ia) or (Ib) wherein A, and A is for example (II) is 1 or 2; X is C-Calkylene or CO; Y is for example O, O(CO), O(CO)O, Ris for example hydrogen, d-dsalkyl, C-Ccycloalkyl, phenyl, naphthyl, anthracyl, phenanthryl, biphenylyl, fluorenyl or C-Cheteroaryl, all of which optionally are substituted; Rand Rfor example are C-Chaloalkylene which is optionally substituted, or Rand Rare phenylene, which optionally is substituted; Ris a group (A) or a group (B); Rand Rfor example are C-Calkyl; or Rand Ror Rand Rtogether form a straight-chain C-Calkylene, Rand Rtogether form a straight-chain C-Calkylene; R, R, Rand Rifor example are C-Calkyl; M for example is C-Calkylene, C-Calkenylene, C-Calkynylene; Rand Rare for example hydrogen, C-Calkyl; R, R, R, Rand Rare for example hydrogen, C-Calkyl, C-Calkenyl, C-Ccycloalkyl, or two radicals Rand R, Rand R, Rand Rand/or Rand Rtogether form a straight-chain C-Calkylene, or Rand Rtogether form 1,2-phenylene, Rand Rfor example are hydrogen, C-Calkyl; R, Rand Rfor example are hydrogen, C-Calkyl; are suitable as thermo-acid generators. 3: A heat-curable composition comprising(a) at least one compound which is capable of undergoing cationic polymerization; and{'claim-ref': {'@idref': 'CLM-00001', 'claim 1'}, '(b) at least one compound of formula I, Ia or Ib according to .'}4: The heat-curable composition according to claim 3 , wherein the compound which is capable of undergoing cationic polymerization has at least one group selected from the group consisting of an epoxy group claim 3 , oxetane group and vinyl ether group.5: The heat-curable composition according to claim 3 , where the compound which is capable of undergoing cationic polymerization is an epoxy resin.6: The heat-curable composition according to claim 3 , further comprising at least one component selected from the group consisting of solvent claim 3 , reactive diluents claim 3 , photoinitiators claim 3 , photoacid generators claim 3 , pigments ...

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. ...

INHIBITOR OF INDOLEAMINE-2,3-DIOXYGENASE (IDO)

The present disclosure provides compounds of Formula (I). The compounds described herein may be useful in treating a disease associated with IDO, for example, cancer or an infectious disease (e.g., viral or bacterial infectious diseases). Also, provided in the present disclosure are pharmaceutical compositions, kits, methods, and uses including or using a compound described herein. 36-. (canceled)8. (canceled)9. (canceled)10. The compound of claim 1 , wherein Rand Rare joined to form a substituted or unsubstituted 3- to 6-membered carbocyclic ring claim 1 , or substituted or unsubstituted 3- to 8-membered heterocyclic ring.11. The compound of claim 1 , wherein Rand Rare joined to form a substituted or unsubstituted cyclopropyl claim 1 , substituted or unsubstituted cyclobutyl claim 1 , substituted or unsubstituted cyclopentyl claim 1 , or substituted or unsubstituted cyclohexyl ring.12. (canceled)13. (canceled)14. The compound of claim 1 , wherein Rand Rare each independently substituted or unsubstituted C-Calkyl claim 1 , substituted or unsubstituted C-Ccycloalkyl claim 1 , or substituted or unsubstituted 3- to 12-membered heterocyclyl.1620-. (canceled)2325-. (canceled)2730-. (canceled)32. A pharmaceutical composition comprising a compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , and a pharmaceutically acceptable excipient.33. A method of treating a disease associated with IDO claim 1 , the method comprising administering to a subject in need thereof an effective amount of a compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , or a pharmaceutical composition comprising an effective amount of a compound of or a pharmaceutically acceptable salt thereof.34. The method of claim 33 , wherein the disease associated with IDO is cancer.35. The method of claim 33 , wherein the disease associated with IDO is cancer claim 33 , which is selected from the group consisting of lung cancer claim 33 , breast cancer claim 33 , ...

3-AMIDOBENZAMIDES AND USES THEREOF FOR INCREASING CELLULAR LEVELS OF A3G AND OTHER A3 FAMILY MEMBERS

Disclosed are novel benzamide compounds and the uses thereof for treating diseases and disorders in a patient in need thereof by increasing cellular levels of A3G and/or other members of the A3 family of proteins in the patient. The disclosed compounds include -benzamide compounds that may be administered to treat an HIV-1 infection or cancer in a patient. 2. The compound of claim 1 , wherein n is 0.3. The compound of claim 1 , wherein X is C.4. The compound of claim 1 , wherein Ris methoxy.6. The compound of claim 5 , wherein Ris C1-C6-alkoxy.7. The compound of claim 5 , wherein Ris H claim 5 , C1-C6-alkyl optionally substituted with C1-C6-alkoxy claim 5 , hydroxyl claim 5 , C1-C6-alkylamino claim 5 , C1-C6 dialkylamino claim 5 , phenyl claim 5 , benzyl claim 5 , benzo[1 claim 5 ,3]diox8yl claim 5 , pyridin-2-yl claim 5 , pyridin-3-yl claim 5 , pyridin-4-yl claim 5 , C3-C6-cycloalkyl optionally substituted with methyl claim 5 , C1-C6-alkoxy claim 5 , N-piperidinyl claim 5 , and tetrahydrofuran-2-yl.8. The compound of claim 5 , wherein R claim 5 , R claim 5 , R claim 5 , R claim 5 , and Rare independently selected from H claim 5 , C1-C6-alkoxy claim 5 , and halo.9. The compound of claim 5 , wherein one or more of R claim 5 , R claim 5 , are Rare methoxy.10. The compound of claim 9 , wherein one or more of Rand Rare chloro.12. A pharmaceutical composition comprising the compound of and a pharmaceutical carrier.13. The pharmaceutical composition of comprising an effective amount of the compound for increasing levels of A3G and/or other members of the A3 family of proteins after the composition is administereing to a patient in need thereof.14. A method for treating HIV-1 infection in a patient in need thereof claim 13 , the method comprising administering the pharmaceutical composition of to the patient.15. A method for treating cancer in a patient in need thereof claim 13 , the method comprising administering the pharmaceutical composition of to the patient. The ...

TREPROSTINIL DERIVATIVES AND COMPOSITIONS AND USES THEREOF

The present disclosure provides treprostinil derivatives that can act as prodrugs of treprostinil. The treprostinil derivatives can be used to treat any conditions responsive to treatment with treprostinil, including pulmonary hypertension, such as pulmonary arterial hypertension.

COMPOUNDS AND USES THEREOF FOR THE MODULATION OF HEMOGLOBIN

Provide herein are compounds and pharmaceutical compositions suitable as modulators of hemoglobin, methods and intermediates for their preparation, and methods for their use in treating disorders mediated by hemoglobin and disorders that would benefit from tissue and/or cellular oxygenation. 4. (canceled)7. The compound of claim 2 , wherein ring B is substituted with 1-3: halo claim 2 , C-Calkyl claim 2 , COR claim 2 , or COOR; and{'sup': '15', 'sub': 1', '6', '6', '10', '1', '6', '6', '10, 'Ris C-Calkyl, C-Caryl, 5-10 membered heteroaryl or a 4-10 membered heterocyclyl containing up to 5 ring heteroatoms, wherein the heteroatom is selected from the group consisting of O, N, S, and oxidized forms of N and S, wherein the C-Calkyl, C-Caryl, 5-10 membered heteroaryl or 4-10 membered heterocyclyl is optionally substituted.'}8. (canceled)10. A composition comprising a compound of and at least one pharmaceutically acceptable excipient.11. A method for increasing oxygen affinity of hemoglobin S in a subject claim 2 , the method comprising administering to a subject in need thereof a therapeutically effective amount of a compound of .12. A method for treating oxygen deficiency associated with sickle cell anemia or acute respiratory distress syndrome claim 2 , the method comprising administering to a subject in need thereof a therapeutically effective amount of a compound of .13. A composition comprising a compound of and at least one pharmaceutically acceptable excipient.14. A method for increasing oxygen affinity of hemoglobin S in a subject claim 9 , the method comprising administering to a subject in need thereof a therapeutically effective amount of a compound of .15. A method for treating oxygen deficiency associated with sickle cell anemia or acute respiratory distress syndrome claim 9 , the method comprising administering to a subject in need thereof a therapeutically effective amount of a compound of .16. A method for increasing oxygen affinity of hemoglobin S in a ...

Novel compounds for selective histone deacetylase inhibitors, and pharmaceutical composition comprising the same

The present invention relates to novel urea derivatives and, more particularly, to novel urea derivatives with histone deacetylase (HDAC) inhibitory activity, isomers thereof, pharmaceutically acceptable salts thereof, their use for the preparation of a medicaments comprising the same, a pharmaceutical composition comprising the same, a treatment method using the composition, and a method for preparing novel urea derivatives. The novel urea derivatives as selective histone deacetylase (HDAC) inhibitors are effective for the treatment of histone deacetylase-mediated diseases such as malignant tumors, inflammatory diseases, rheumatoid arthritis, neurodegeneration, etc.

COMPOUNDS AND USES THEREOF FOR THE MODULATION OF HEMOGLOBIN

Provide herein are compounds and pharmaceutical compositions suitable as modulators of hemoglobin, methods and intermediates for their preparation, and methods for their use in treating disorders mediated by hemoglobin and disorders that would benefit from tissue and/or cellular oxygenation. 2. (canceled)3. The compound of claim 1 ,{'sub': 2', '2', '2, 'wherein Y—Z is —CHO— or —CHCH—.'}4. The compound of claim 3 , wherein Ris C-Calkoxy.6. (canceled)7. The compound of claim 1 , wherein ring B is substituted with 1-3substituents selected from halo claim 1 , C-Calkyl claim 1 , COR claim 1 , and COOR; and{'sup': '15', 'sub': 1', '6', '6', '10, 'Ris C-Calkyl, C-Caryl, 5-10 membered heteroaryl or a 4-10 membered heterocyclyl containing up to 5 ring heteroatoms, wherein the heteroatom is selected from the group consisting of O, N, S, and oxidized forms of N and S, wherein the alkyl, aryl, heteroaryl or heterocyclyl is optionally substituted.'}8. (canceled)9. (canceled)10. A composition comprising a compound of claim 1 , and at least one pharmaceutically acceptable excipient.11. A method for increasing oxygen affinity of hemoglobin S in a subject claim 1 , the method comprising administering to a subject in need thereof a therapeutically effective amount of a compound of .12. A method for treating sickle cell disease claim 2 , the method comprising administering to a subject in need thereof a therapeutically effective amount of a compound of . This application is a continuation of U.S. application Ser. No. 15/688,185, filed Aug. 28, 2017, which is a continuation of U.S. application Ser. No. 14/836,869, filed Aug. 26, 2015, now U.S. Pat. No. 9,776,960, which is a continuation of U.S. application Ser. No. 14/599,341, filed Jan. 16, 2015, which is a continuation of U.S. application Ser. No. 13/815,735, filed Mar. 15, 2013, now U.S. Pat. No. 8,952,171, which are incorporated herein by reference in their entirety.This invention provides compounds and pharmaceutical compositions ...

HEPATITIS B ANTIVIRAL AGENTS

The present invention discloses compounds of Formula (I), or pharmaceutically acceptable salts, esters, or prodrugs thereof: 11. A pharmaceutical composition claim 1 , comprising a compound or a combination of compounds according to claim 1 , in combination with a pharmaceutically acceptable carrier or excipient.12. A method of treating or preventing an HBV infection in a subject in need thereof claim 1 , comprising administering to the subject a therapeutically effective amount of a compound or a combination of compounds according to .13. The method of claim 12 , further comprising administering to the subject at least one additional therapeutic agent selected from the group consisting of HBV polymerase inhibitors claim 12 , interferon claim 12 , viral entry inhibitors claim 12 , viral maturation inhibitors claim 12 , capsid assembly or core protein inhibitors or modulators claim 12 , reverse transcriptase inhibitors claim 12 , TLR-agonists claim 12 , inducers of cellular viral RNA sensor claim 12 , therapeutic vaccines claim 12 , RNA interence (RNAi) or small interfering RNA (siRNA) and combinations thereof.14. The method of claim 13 , wherein the compound and the at least one additional therapeutic agent are co-formulated.15. The method of claim 13 , wherein the at least one additional therapeutic agent is administered at a lower dose and/or frequency than that which is therapeutically effective when said agent is administered alone. This application is a divisional of U.S. application Ser. No. 15/450,125, filed on Mar. 6, 2017, which claims the benefit of U.S. Provisional Application No. 62/304,671, filed on Mar. 7, 2016, and 62/337,675, filed on May 17, 2016. The entire teachings of the above applications are incorporated herein by reference.The present invention relates generally to novel antiviral agents. Specifically, the present invention relates to compounds which can inhibit the protein(s) encoded by hepatitis B virus (HBV) or interfere with the function ...

ANTIBACTERIAL AGENTS

Antibacterial compounds of formula (I) are provided: 2. A compound of wherein G is selected from the group consisting of:(1) —C≡C—,(2) —C≡C—C≡C—,{'sup': 3G', '3G, '(3) —CR═CR—C≡C—, and'}{'sup': 3G', '3G, '(4) —C≡C—CR═CR—.'}3. A compound of wherein G is selected from the group consisting of:(1) —C≡C—,(2) —C≡C—C≡C—,(3) —CH═CH—C≡C—, and(4) —C≡C—CH═CH—.4. A compound of wherein G is —C≡C—.5. A compound of wherein G is —C≡C—C≡C—.6. A compound of wherein G is —CH═CH—C≡C—.8. A compound of wherein G is —C≡C—CH═CH—.10. A compound of any one of - wherein X is —(C═O)NR—.11. A compound of wherein X is —(C═O)NH—.12. A compound of any one of - wherein Q is —(C═O)N(R claim 10 ,R).13. A compound of wherein Q is —(C═O)NHOH.14. A compound of any one of - wherein n is 0.15. A compound of any one of - wherein Ris H.16. A compound of any one of - wherein Y is substituted or unsubstituted aryl.17. A compound of wherein Y is substituted or unsubstituted phenyl.18. A compound of wherein Y is unsubstituted phenyl.19. A compound of any one of - wherein A is selected from the group consisting of:{'sub': 2', '0-4', '2', '0-4, 'sup': 1a', '2a', '3a, '(1) —(CH)C(R,R)(CH)OR,'}{'sub': 2', '0-4, 'sup': 1a', '2a', '4a', '5a, '(2) —(CH)C(R,R)N(R,R), and'}{'sup': 1a', '2a, '(3) —CH(R,R).'}20. A compound of wherein A is selected from the group consisting of —CH(CH) claim 19 , —CHOH claim 19 , —CHNH claim 19 , —CHCHOH claim 19 , —CHCHNHand —C(CH)OH.21. A compound of wherein A is —C(CH)NH.22. A compound of any one of - wherein A is selected from the group consisting of:{'sub': 3', '10, '(1) substituted or unsubstituted C-C-cycloalkyl,'}(2) substituted or unsubstituted aryl,(3) substituted or unsubstituted heterocyclyl, and(4) substituted or unsubstituted heteroaryl.26. A compound of any one of - wherein D is present.27. A compound of wherein D is substituted or unsubstituted heteroaryl.29. A compound of wherein D is substituted or unsubstituted aryl.30. A compound of wherein D is substituted or ...

INHIBITORS OF HISTONE DEACETYLASE

The present invention relates to compounds of formula (I): 10. A pharmaceutical composition comprising an effective amount of a compound of or a pharmaceutically acceptable salt claim 1 , hydrate claim 1 , solvate claim 1 , or prodrug thereof and a pharmaceutical carrier claim 1 , diluent claim 1 , or excipient.11. A method of treating claim 1 , alleviating claim 1 , and/or preventing a condition in a subject comprising administering to the subject in need thereof an effective amount of a compound of or a pharmaceutically acceptable salt claim 1 , hydrate claim 1 , solvate or prodrug thereof.12. The method of claim 11 , wherein the condition is selected from a neurological disorder claim 11 , memory loss or impairment claim 11 , cognitive function disorder or impairment claim 11 , extinction learning disorder claim 11 , fungal disease or infection claim 11 , inflammatory disease claim 11 , hematological disease claim 11 , and neoplastic disease.13. The method of claim 11 , wherein the condition is selected from:a cognitive function disorder or impairment associated with Alzheimer's disease, Huntington's disease, seizure induced memory loss, schizophrenia, Rubinstein Taybi syndrome, Rett Syndrome, Fragile X, Lewy body dementia, vascular dementia, ADHD, dyslexia, bipolar disorder and social, cognitive and learning disorders associated with autism, traumatic head injury, or attention deficit disorder, anxiety disorder, conditioned fear response, panic disorder, obsessive compulsive disorder, posttraumatic stress disorder, phobia, social anxiety disorder, substance dependence recovery or Age Associated Memory Impairment (AAMI), or Age Related Cognitive Decline (ARCD);a hematological disease selected from acute myeloid leukemia, acute promyelocytic leukemia, acute lymphoblastic leukemia, chronic myelogenous leukemia, myelodysplastic syndromes, and sickle cell anemia;a cancer; andan extinction learning disorder selected from a fear extinction deficit and post-traumatic ...

COMPOUNDS CONTAINING A SULFONIC GROUP AS KAT INHIBITORS

The present invention provides compounds, pharmaceutically acceptable compositions thereof, and methods of using the same. 2. The compound according to claim 1 , wherein L is a 3-atom linker.4. The compound according to claim 1 , wherein L is a 4-atom linker.6. (canceled)7. The compound according to claim 1 , wherein L is a 5-atom linker.9. The compound according to claim 1 , wherein Z is optionally substituted Caliphatic.10. (canceled)11. The compound according to claim 1 , wherein Z is —Cy.1214-. (canceled)15. The compound according to claim 1 , wherein Ring B is an optionally substituted 3-7 membered saturated or partially unsaturated heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen claim 1 , oxygen and sulfur.1622-. (canceled)23. The compound according to claim 1 , wherein Ring A is phenyl.24. The compound according to claim 1 , wherein Ring A is a 8-10 membered bicyclic heteroaryl ring having 1-3 heteroatoms independently selected from nitrogen oxygen and sulfur.25. The compound according to claim 1 , wherein Ring A is a 3-7 membered saturated or partially unsaturated heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen claim 1 , oxygen and sulfur.28. A pharmaceutical composition comprising a compound or pharmaceutically acceptable salt thereof according to claim 1 , and a pharmaceutically acceptable excipient.29. A method of treating a disease or disorder associated with KAT-5 in a subject in need thereof claim 1 , comprising administering to the subject an effective amount of a compound or pharmaceutically acceptable salt thereof according to .30. A method of modulating protein acetylation in a subject in need thereof claim 1 , comprising administering to the subject an effective amount of a compound or pharmaceutically acceptable salt thereof according to .31. A method of treating cancer in a subject claim 1 , comprising administering to the subject an effective amount of a compound or pharmaceutically ...

Compounds and uses thereof for the modulation of hemoglobin

Provide herein are compounds and pharmaceutical compositions suitable as modulators of hemoglobin, methods and intermediates for their preparation, and methods for their use in treating disorders mediated by hemoglobin and disorders that would benefit from tissue and/or cellular oxygenation.

AMIDE DERIVATIVES, PROCESS FOR PREPARATION THEREOF AND USE THEREOF AS INSECTICIDE

An object of the present invention is to provide a compound represented by Formula (1): 114-. (canceled) The present invention relates to a compound represented by Formula (1):wherein A, A, Aand Aeach represent a carbon atom, a nitrogen atom or an oxidized nitrogen atom;Rand Reach represent a hydrogen atom, an optionally substituted alkyl group or an optionally substituted C1-C4 alkylcarbonyl group;Gand Geach represent an oxygen atom or a sulfur atom;X, which may be identical or different, represents a hydrogen atom, a halogen atom, a C1-C3 alkyl group or a trifluoromethyl group;n is an integer of 0 to 4; andQand Qeach represent an optionally substituted phenyl group, an optionally substituted naphthyl group or an optionally substituted heterocyclic group,an insecticide comprising the compound as the active ingredient, and a process for preparation thereof and use thereof.International Publication WO 2000/55120 and U.S. Pat. No. 6,548,514 describe a compound similar to the compound of the present invention for the use as medicament, but they do not describe on the insecticidal activity of the compound. The compound clearly does not fall within the scope of claims of the present invention.International Publication WO 2000/7980 describes a compound similar to the compound of the present invention for the use as medicament, but it does not describe on the insecticidal activity of the compound. The compound clearly does not fall within the scope of claims of the present invention.US Patent Laid-Open No. 2002-032238 describes a compound similar to the compound of the present invention for the use as medicament, but it does not describe on the insecticidal activity of the compound. The compound clearly does not fall within the scope of claims of the present invention.The object of the present invention is to provide a pesticide having a high insecticidal efficacy. Another object of the present invention is to provide a compound represented by Formula (1), a process for ...

USP30 INHIBITORS

The application relates to phenyl- or naphthylsulfonamide derivatives of the structural formula (I). The compounds are described as inhibitors of USP30 (ubiquitin specific peptidase 30) useful for the treatment of conditions involving mitochondrial defects including neurodegenerative diseases such as Alzheimer's and Parkinson's or a neoplastic disease such as leukemia. 5. The compound of claim 2 , or a pharmaceutically acceptable salt thereof claim 2 , wherein Ris 3-7 membered cycloalkyl optionally substituted with one or more substituents selected from the group consisting of (C-C)alkyl claim 2 , (C-C)alkoxy claim 2 , (C-C)alkylthio claim 2 , hydroxyl claim 2 , halogen claim 2 , and halo(C-C)alkyl; phenyl optionally substituted with one or more substituents selected from the group consisting of halogen claim 2 , CN claim 2 , —COH claim 2 , —COMe claim 2 , (C-C)alkyl claim 2 , halo(C-C)alkyl claim 2 , (C-C)alkoxy claim 2 , and hydroxyl; 5-6 membered heterocyclyl optionally substituted with one or more substituents selected from the group consisting of (C-C)alkyl claim 2 , halo(C-C)alkyl claim 2 , and (C-C)alkoxy;{'sub': 1', '4', '1', '4', '1', '4, '5-6 membered heteroaryl optionally substituted with one or more substituents selected from the group consisting of halogen, (C-C)alkyl, halo(C-C)alkyl, and (C-C)alkoxy; or adamantyl.'}6. The compound of claim 5 , or a pharmaceutically acceptable salt thereof claim 5 , wherein Ris (C-C)alkyl optionally substituted with one or more substituents selected from the group consisting of halogen claim 5 , —CN claim 5 , hydroxyl claim 5 , (C-C)alkyl claim 5 , halo(C-C)alkyl claim 5 , (C-C)alkoxy claim 5 , halo(C-C)alkoxy claim 5 , and (C-C)alkylthio; 3-7 membered cycloalkyl optionally substituted with one or more substituents selected from the group consisting of halogen claim 5 , CN claim 5 , hydroxyl claim 5 , (C-C)alkyl claim 5 , halo(C-C)alkyl claim 5 , (C-C)alkoxy claim 5 , halo(C-C)alkoxy claim 5 , and (C-C)alkylthio; 5-6 ...

SULFIDE ALKYL COMPOUNDS FOR HBV TREATMENT

The present invention includes a method of inhibiting, suppressing or preventing HBV infection in an individual in need thereof, comprising administering to the individual a therapeutically effective amount of at least one compound of the invention. 2. The compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein Ris morpholinyl.4. A composition comprising a compound according to claim 1 , or a salt claim 1 , solvate claim 1 , or N-oxide thereof claim 1 , further comprising at least one pharmaceutically acceptable carrier.5. A method of treating an HBV infection in an individual in need thereof claim 1 , comprising administering to the individual a therapeutically effective amount of a compound according to .6. The method of claim 5 , further comprising administering to the individual at least one additional therapeutic agent selected from the group consisting of an HBV vaccine claim 5 , HBV polymerase inhibitor claim 5 , interferon claim 5 , pegylated interferon claim 5 , viral entry inhibitor claim 5 , viral maturation inhibitor claim 5 , BAY 41-4109 claim 5 , reverse transcriptase inhibitor claim 5 , a TLR-agonist claim 5 , AT-61 ((E)-N-(1-chloro-3-oxo-1-phenyl-3-(piperidin-1-yl)prop-1-en-2-yl)benzamide) claim 5 , and AT-130 ((E)-N-(1-bromo-1-(2-methoxyphenyl)-3-oxo-3-(piperidin-1-yl)prop-1-en-2-yl)-4-nitrobenzamide) claim 5 , and a combination thereof.7. The method of claim 6 , wherein the pegylated interferon is pegylated interferon alpha (IFN-α) claim 6 , pegylated interferon lambda (IFN-λ) claim 6 , or pegylated interferon gamma (IFN-γ).8. The method of claim 6 , wherein the reverse transcriptase inhibitor is at least one of Zidovudine claim 6 , Didanosine claim 6 , Zalcitabine claim 6 , ddA claim 6 , Stavudine claim 6 , Lamivudine claim 6 , Abacavir claim 6 , Emtricitabine claim 6 , Entecavir claim 6 , Apricitabine claim 6 , Atevirapine claim 6 , ribavirin claim 6 , acyclovir claim 6 , famciclovir claim 6 , valacyclovir claim 6 , ...

Neprilysin inhibitors

In one aspect, the invention relates to compounds having the formula: where R 1 -R 5 and X are as defined in the specification, or a pharmaceutically acceptable salt thereof. These compounds have neprilysin inhibition activity. In another aspect, the invention relates to pharmaceutical compositions comprising such compounds; methods of using such compounds; and processes and intermediates for preparing such compounds.

Treprostinil derivatives and compositions and uses thereof

The present disclosure provides treprostinil derivatives that can act as prodrugs of treprostinil. The treprostinil derivatives can be used to treat any conditions responsive to treatment with treprostinil, including pulmonary hypertension, such as pulmonary arterial hypertension.

POLYMERIZABLE COMPOSITION COMPRISING AN OXIME SULFONATE AS THERMAL CURING AGENT

The present invention relates to a polymerizable composition comprising at least one ethylenically unsaturated, polymerizable compound and at least one oxime sulfonate compound of the formula I 144-. (canceled)47: The compound of formula I according to claim 45 , where{'sup': '14', 'X is S or NRand'}{'sup': 14', '6', '14a', '8', '9', '10', '11', '4', '5', '6', '7', '8', '9', '10', '11, 'sub': 1', '12', '3', '8', '1', '8', '1', '4', '2, 'Ris C-C-alkyl, which may be interrupted by one or more O, S, NRor CO and/or may be substituted by one or more identical or different radicals Rselected from CN, COR, COOR, CONRR, phenyl and C-C-cycloalkyl which may interrupted by one or two CO groups and where the two last-mentioned radicals may be substituted by one or more identical or different radicals selected from C-C-alkyl, C-C-haloalkyl, F, Cl, Br, I, CN, NO, SR, OR, NRR, COR, COORand CONRR;'}{'sub': 2', '12', '3', '8', '1', '8', '1', '4', '2, 'sup': 6', '14a', '8', '9', '10', '11', '4', '5', '6', '7', '8', '9', '10', '11, 'C-C-alkenyl, which may be interrupted by one or more O, S, NRor CO and/or may be substituted by one or more identical or different radicals Rselected from CN, COR, COOR, CONRR, phenyl and C-C-cycloalkyl which may interrupted by one or two CO groups and where the two last-mentioned radicals may be substituted by one or more identical or different radicals selected from C-C-alkyl, C-C-haloalkyl, F, Cl, Br, I, CN, NO, SR, OR, NRR, COR, COORand CONRR;'}{'sub': 3', '12', '1', '8, 'sup': 14b', '8', '9', '10', '11, 'C-C-cycloalkyl, which may be interrupted by one or more CO and/or may be substituted by one or more identical or different radicals Rselected from C-C-alkyl, CN, COR, COOR, CONRR;'}{'sup': 14c', '4', '5', '6', '7', '8', '9', '10', '11, 'sub': 1', '8', '1', '4', '2, 'phenyl, which may be substituted by one or more identical or different radicals Rselected from C-C-alkyl, C-C-haloalkyl, F, Cl, Br, I, CN, NO, SR, OR, NRR, COR, COOR, CONRRand phenyl,'}or ...

Compounds and uses thereof for the modulation of hemoglobin

Provide herein are compounds and pharmaceutical compositions suitable as modulators of hemoglobin, methods and intermediates for their preparation, and methods for their use in treating disorders mediated by hemoglobin and disorders that would benefit from tissue and/or cellular oxygenation.

BENZENESULFONAMIDO AND RELATED COMPOUNDS FOR USE AS AGONISTS OF RORy AND THE TREATMENT OF DISEASE

The invention provides benzenesulfonamido and related compounds, pharmaceutical compositions, methods of promoting RORγ activity, increasing the amount of IL-17 in a subject, and treating cancer using such benzenesulfonamido and related compounds. 2. The compound of claim 1 , wherein A is phenylene or 5-6 membered heteroarylene.3. The compound of or claim 1 , wherein Rrepresents independently for each occurrence halogen or Calkyl.5. The compound of any one of - claim 1 , wherein A is phenylene.6. The compound of any one of - claim 1 , wherein A is a 5-6 membered heteroarylene.7. The compound of any one of - claim 1 , wherein n is 1.8. The compound of any one of - claim 1 , wherein n is 1 or 2.9. The compound of any one of - claim 1 , wherein Ris Chaloalkyl.10. The compound of any one of - claim 1 , wherein Ris trifluoromethyl.12. The compound of any one of - claim 1 , wherein Ris Calkyl optionally substituted with 1 claim 1 , 2 claim 1 , or 3 substituents independently selected from the group consisting of —COR claim 1 , halogen claim 1 , hydroxyl claim 1 , and Calkoxy.13. The compound of any one of - claim 1 , wherein Ris Calkyl substituted with —COR.14. The compound of any one of - claim 1 , wherein Ris ethyl or propyl.15. The compound of any one of - claim 1 , wherein X is —O-aralkyl claim 1 , —O-heteroaralkyl claim 1 , —O-phenyl claim 1 , —O-heteroaryl claim 1 , —O-(partially unsaturated bicyclic carbocyclyl) claim 1 , —O—(Calkylene)-(Ccycloalkyl) claim 1 , —N(R)-aralkyl claim 1 , —N(R)-phenyl claim 1 , —N(R)-(partially unsaturated bicyclic carbocyclyl) claim 1 , or —N(R)—(Calkylene)-(Ccycloalkyl) claim 1 , each of which is optionally substituted with 1 claim 1 , 2 claim 1 , or 3 substituents independently selected from the group consisting of halogen claim 1 , Chaloalkyl claim 1 , Calkyl claim 1 , Ccycloalkyl claim 1 , Calkoxy claim 1 , and Chaloalkoxy.16. The compound of any one of - claim 1 , wherein X is —O-aralkyl claim 1 , —O-(partially unsaturated ...

NEPRILYSIN INHIBITORS

In one aspect, the invention relates to compounds having the formula: 131- (canceled)33. (2S ,4R)-5-(3′-chlorobiphenyl-4-yl)-4-formylamino-2-hydroxymethyl-2-methyl-pentanoic acid or a pharmaceutically-acceptable salt thereof.34. A pharmaceutical composition comprising the compound of or and a pharmaceutically acceptable carrier.35. The pharmaceutical composition of claim 34 , further comprising an ATreceptor antagonist.36. A method for treating hypertension claim 34 , heart failure claim 34 , or renal disease claim 34 , comprising administering to a patient a therapeutically effective amount of the compound of or . This application claims the benefit of U.S. Provisional Application No. 61/772,721, filed on Mar. 5, 2013; the entire disclosure of which is incorporated herein by reference.The present invention relates to novel compounds having neprilysin-inhibition activity. The invention also relates to pharmaceutical compositions comprising such compounds, processes and intermediates for preparing such compounds and methods of using such compounds to treat diseases such as hypertension, heart failure, pulmonary hypertension, and renal disease.Neprilysin (neutral endopeptidase, EC 3.4.24.11) (NEP), is an endothelial membrane bound Zn metallopeptidase found in many organs and tissues, including the brain, kidneys, lungs, gastrointestinal tract, heart, and the peripheral vasculature. NEP degrades and inactivates a number of endogenous peptides, such as enkephalins, circulating bradykinin, angiotensin peptides, and natriuretic peptides, the latter of which have several effects including, for example, vasodilation and natriuresis/diuresis, as well as inhibition of cardiac hypertrophy and ventricular fibrosis. Thus, NEP plays an important role in blood pressure homeostasis and cardiovascular health.NEP inhibitors, such as thiorphan, candoxatril, and candoxatrilat, have been studied as potential therapeutics. Compounds that inhibit both NEP and angiotensin-I converting ...

AMIDE DERIVATIVES, PROCESS FOR PREPARATION THEREOF AND USE THEREOF AS INSECTICIDE

A compound represented by Formula (1): 114-. (canceled) The present invention relates to a compound represented by Formula (1):wherein A, A, Aand Aeach represent a carbon atom, a nitrogen atom or an oxidized nitrogen atom;Rand Reach represent a hydrogen atom, an optionally substituted alkyl group or an optionally substituted C1-C4 alkylcarbonyl group;Gand Geach represent an oxygen atom or a sulfur atom;X, which may be identical or different, represents a hydrogen atom, a halogen atom, a C1-C3 alkyl group or a trifluoromethyl group;n is an integer of 0 to 4; andQand Qeach represent an optionally substituted phenyl group, an optionally substituted naphthyl group or an optionally substituted heterocyclic group,an insecticide comprising the compound as the active ingredient, and a process for preparation thereof and use thereof.International Publication WO 2000/55120 and U.S. Pat. No. 6,548,514 describe a compound similar to the compound of the present invention for the use as medicament, but they do not describe on the insecticidal activity of the compound. The compound clearly does not fall within the scope of claims of the present invention.International Publication WO 2000/7980 describes a compound similar to the compound of the present invention for the use as medicament, but it does not describe on the insecticidal activity of the compound. The compound clearly does not fall within the scope of claims of the present invention.US Patent Laid-Open No. 2002-032238 describes a compound similar to the compound of the present invention for the use as medicament, but it does not describe on the insecticidal activity of the compound. The compound clearly does not fall within the scope of claims of the present invention.The object of the present invention is to provide a pesticide having a high insecticidal efficacy. Another object of the present invention is to provide a compound represented by Formula (1), a process for preparation of the compound, an insecticide ...

HEPATITIS B ANTIVIRAL AGENTS

The present invention discloses compounds of Formula (I), or pharmaceutically acceptable salts, esters, or prodrugs thereof: 210-. (canceled)11. A pharmaceutical composition comprising a compound according to and a pharmaceutically acceptable carrier or excipient.12. A method of treating or preventing an HBV infection in a subject in need thereof claim 1 , comprising administering to the subject a therapeutically effective amount of a compound or a combination of compounds according to .13. The method of claim 12 , further comprising administering to the subject at least one additional therapeutic agent selected from the group consisting of HBV polymerase inhibitors claim 12 , interferon claim 12 , viral entry inhibitors claim 12 , viral maturation inhibitors claim 12 , capsid assembly or core protein inhibitors or modulators claim 12 , reverse transcriptase inhibitors claim 12 , TLR-agonists claim 12 , inducers of cellular viral RNA sensor claim 12 , therapeutic vaccines claim 12 , RNA interference (RNAi) or small interfering RNA (siRNA) and combinations thereof.14. The method of claim 13 , wherein the compound and the at least one additional therapeutic agent are co-formulated.15. The method of claim 13 , wherein the at least one additional therapeutic agent is administered at a lower dose and/or frequency than that which is therapeutically effective when said agent is administered alone. This application is a continuation of U.S. application Ser. No. 16/715,602, filed on Dec. 16, 2019, which is a continuation application of U.S. application Ser. No. 16/194,608, filed on Nov. 19, 2018, now U.S. Pat. No. 10,538,532, issued on Jan. 21, 2020, which is a divisional of U.S. application Ser. No. 15/450,125, filed on Mar. 6, 2017, now U.S. Pat. No. 10,179,792, issued on Jan. 15, 2019, which claims the benefit of U.S. Provisional Application No. 62/304,671, filed on Mar. 7, 2016, and 62/337,675, filed on May 17, 2016. The entire teachings of the above applications are ...

COMPOUNDS AND USES THEREOF FOR THE MODULATION OF HEMOGLOBIN

Provide herein are compounds and pharmaceutical compositions suitable as modulators of hemoglobin, methods and intermediates for their preparation, and methods for their use in treating disorders mediated by hemoglobin and disorders that would benefit from tissue and/or cellular oxygenation. 19.-. (canceled) This application is a continuation application and claims the benefit under 35 U.S.C. § 120 to U.S. Utility application Ser. No. 14/836,869, filed Aug. 26, 2015; which is a continuation application and claims the benefit under 35 U.S.C. § 120 to U.S. Utility application Ser. No. 14/599,341 filed Jan. 16, 2015; which is a continuation application and claims the benefit under 35 U.S.C. § 120 to U.S. Utility application Ser. No. 13/815,735 filed Mar. 15, 2013, now U.S. Pat. No. 8,952,171, issued on Feb. 10, 2015; each are incorporated herein by reference in their entirety.This invention provides compounds and pharmaceutical compositions suitable as allosteric modulators of hemoglobin, methods and intermediates for their preparation, and methods for their use in treating disorders mediated by hemoglobin and disorders that would benefit from tissue and/or cellular oxygenation.Sickle cell disease is a disorder of the red blood cells, found particularly among those of African and Mediterranean descent. The basis for sickle cell disease is found in sickle hemoglobin (HbS), which contains a point mutation relative to the prevalent peptide sequence of hemoglobin (Hb).Hemoglobin (Hb) transports oxygen molecules from the lungs to various tissues and organs throughout the body. Hemoglobin binds and releases oxygen through conformational changes. Sickle hemoglobin (HbS) contains a point mutation where glutamic acid is replaced with valine, allowing HbS to become susceptible to polymerization to give the HbS containing red blood cells their characteristic sickle shape. The sickled cells are also more rigid than normal red blood cells, and their lack of flexibility can lead to ...

HEPATITIS B ANTIVIRAL AGENTS

The present invention discloses compounds of Formula (I), or pharmaceutically acceptable salts, esters, or prodrugs thereof: 110-. (canceled)11. A pharmaceutical composition claim 16 , comprising a compound according to and a pharmaceutically acceptable carrier or excipient.12. A method of treating or preventing an HBV infection in a subject in need thereof claim 16 , comprising administering to the subject a therapeutically effective amount of a compound according to .13. The method of claim 12 , further comprising administering to the subject at least one additional therapeutic agent selected from the group consisting of HBV polymerase inhibitors claim 12 , interferon claim 12 , viral entry inhibitors claim 12 , viral maturation inhibitors claim 12 , capsid assembly or core protein inhibitors or modulators claim 12 , reverse transcriptase inhibitors claim 12 , TLR-agonists claim 12 , inducers of cellular viral RNA sensor claim 12 , therapeutic vaccines claim 12 , RNA interference (RNAi) or small interfering RNA (siRNA) and combinations thereof.14. The method of claim 13 , wherein the compound and the at least one additional therapeutic agent are co-formulated.15. (canceled)17. The compound of claim 16 , wherein:n at each occurrence is independently 0, 1, or 2;{'sub': '21', 'Rat each occurrence is independently halogen, CN, methyl, methoxy, or cyclopropyl;'}{'sub': '22', 'Ris halogen, CN, methyl, or methoxy;'}{'sub': '23', 'Ris hydrogen or halogen;'}{'sub': 10', '1', '3, 'Each Ris independently hydrogen, halogen, hydroxyl, or optionally substituted C-Calkyl; and'}{'sub': '30', 'Ris hydrogen or an acyl group derived from an amino acid.'}18. The compound of claim 16 , wherein:{'sub': '21', 'Each Ris fluorine;'}{'sub': '22', 'Ris chlorine;'}{'sub': '23', 'Ris hydrogen or fluorine; and'}{'sub': '10', 'Each Ris independently hydrogen, halogen, hydroxyl, hydroxymethyl, fluoromethyl, trifluoromethyl, or methoxymethyl.'}19. The compound of claim 16 , wherein Ris an acyl ...

SULFIDE ALKYL COMPOUNDS FOR HBV TREATMENT

The present invention includes a method of inhibiting, suppressing or preventing HBV infection in an individual in need thereof, comprising administering to the individual a therapeutically effective amount of at least one compound of the invention. 2. (canceled)3. (canceled)4. A composition comprising a compound according to claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , further comprising at least one pharmaceutically acceptable carrier.5. A method of treating an HBV infection in an individual in need thereof claim 1 , comprising administering to the individual a therapeutically effective amount of a compound according to .6. The method of claim 5 , further comprising administering to the individual at least one additional therapeutic agent selected from the group consisting of an HBV vaccine claim 5 , HBV polymerase inhibitor claim 5 , interferon claim 5 , pegylated interferon claim 5 , viral entry inhibitor claim 5 , viral maturation inhibitor claim 5 , BAY 41-4109 claim 5 , reverse transcriptase inhibitor claim 5 , a TLR-agonist claim 5 , AT-61 ((E)-N-(1-chloro-3-oxo-1-phenyl-3-(piperidin-1-yl)prop-1-en-2-yl)benzamide) claim 5 , and AT-130 ((E)-N-(1-bromo-1-(2-methoxyphenyl)-3-oxo-3-(piperidin-1-yl)prop-1-en-2-yl)-4-nitrobenzamide) claim 5 , and a combination thereof.7. The method of claim 6 , wherein the pegylated interferon is pegylated interferon alpha (IFN-α) claim 6 , pegylated interferon lambda (IFN-λ) claim 6 , or pegylated interferon gamma (IFN-γ).8. The method of claim 6 , wherein the reverse transcriptase inhibitor is at least one of Zidovudine claim 6 , Didanosine claim 6 , Zalcitabine claim 6 , ddA claim 6 , Stavudine claim 6 , Lamivudine claim 6 , Abacavir claim 6 , Emtricitabine claim 6 , Entecavir claim 6 , Apricitabine claim 6 , Atevirapine claim 6 , ribavirin claim 6 , acyclovir claim 6 , famciclovir claim 6 , valacyclovir claim 6 , ganciclovir claim 6 , valganciclovir claim 6 , Tenofovir claim 6 , Adefovir claim 6 , ...

COMPOUNDS AND USES THEREOF FOR THE MODULATION OF HEMOGLOBIN

Provide herein are compounds and pharmaceutical compositions suitable as modulators of hemoglobin, methods and intermediates for their preparation, and methods for their use in treating disorders mediated by hemoglobin and disorders that would benefit from tissue and/or cellular oxygenation. 119.-. (canceled)21. The compound of claim 20 , wherein ring B is optionally substituted 5-10 membered heteroaryl.22. The compound of claim 20 , wherein ring B is optionally substituted 4-10 membered heterocycle.23. The compound of claim 20 , wherein Ris OH.24. The compound of claim 20 , wherein Rand Rtogether with the nitrogen atom they are attached to form an optionally substituted 4-7 membered heterocycle.25. A pharmaceutical composition comprising a compound of and a pharmaceutically acceptable excipient.26. A method for treating sickle cell disease comprising administering to a subject in need thereof a compound of .27. A method for treating sickle cell disease comprising administering to a subject in need thereof a pharmaceutical composition of . This invention provides compounds and pharmaceutical compositions suitable as allosteric modulators of hemoglobin, methods and intermediates for their preparation, and methods for their use in treating disorders mediated by hemoglobin and disorders that would benefit from tissue and/or cellular oxygenation.Sickle cell disease is a disorder of the red blood cells, found particularly among those of African and Mediterranean descent. The basis for sickle cell disease is found in sickle hemoglobin (HbS), which contains a point mutation relative to the prevalent peptide sequence of hemoglobin (Hb).Hemoglobin (Hb) transports oxygen molecules from the lungs to various tissues and organs throughout the body. Hemoglobin binds and releases oxygen through conformational changes. Sickle hemoglobin (HbS) contains a point mutation where glutamic acid is replaced with valine, allowing HbS to become susceptible to polymerization to give the HbS ...

NOVEL MODULATORS OF THE 5-HYDROXYTRYPTAMINE RECEPTOR 7 AND THEIR METHOD OF USE

Pharmaceutical compositions of the invention comprise functionalized lactone derivatives having a disease-modifying action in the treatment of diseases associated with dysregulation of 5-hydroxytryptamine receptor 7 activity. 126.-. (canceled)29. The compound of claim 27 , wherein Ris Clinear alkyl.31. The compound of claim 27 , wherein Ris selected from the group consisting of phenyl claim 27 , 4-Me-phenyl claim 27 , 2-morpholino-phenyl claim 27 , 4-Cl-phenyl claim 27 , 4-cyano-2-morpholino-phenyl claim 27 , 4-methyl-2-morpholino-phenyl claim 27 , 4-hydroxy-2-morpholino-phenyl claim 27 , 4-OH-phenyl claim 27 , and 2-methyl-1H-benzo[d]imidazol-4-yl.33. A composition comprising an effective amount of at least one compound according to claim 27 , or a pharmaceutically acceptable salt thereof.34. The composition according to claim 33 , further comprising at least one excipient.35. A method of treating a disease associated with dysregulation of 5-hydroxytryptamine receptor 7 activity claim 27 , said method comprising administering to a subject an effective amount of at least one compound according to the to treat the disease.36. The method of claim 35 , wherein the at least one compound is administered in a composition further comprising at least one excipient.37. The method of claim 35 , wherein the disease associated with dysregulation of 5-hydroxytryptamine receptor 7 activity comprises: inflammatory bowel disease claim 35 , circadian rhythm disorder claim 35 , depression claim 35 , schizophrenia claim 35 , neurogenic inflammation claim 35 , hypertension claim 35 , peripheral claim 35 , vascular diseases claim 35 , migraine claim 35 , neuropathic pain claim 35 , peripheral pain claim 35 , allodynia claim 35 , thermoregulation disorder claim 35 , learning disorder claim 35 , memory disorder claim 35 , hippocampal signaling disorder claim 35 , sleep disorder claim 35 , attention deficit/hyperactivity disorder claim 35 , anxiety claim 35 , avoidant personality disorder ...

Ingenol-3-acylates iii and ingenol-3-carbamates

The invention relates to compounds of general formula I wherein R is heteroaryl optionally substituted by R7; or R is heterocycloalkyl or heterocycloalkenyl, optionally substituted by R8; or R is X wherein X is —NR11R12; and pharmaceutically acceptable salts, hydrates, or solvates thereof, for use—alone or in combination with one or more other pharmaceutically active compounds—in therapy, for preventing, treating or ameliorating diseases or conditions responsive to stimulation of neutrophil oxidative burst, responsive to stimulation of keratinocyte IL-8 release or responsive to induction of necrosis.

ANTI-FUNGALS COMPOUNDS TARGETING THE SYNTHESIS OF FUNGAL SPHINGOLIPIDS

The present invention provides a compound having the structure: 2. The compound of claim 1 ,{'sub': 3', '5', '4', '6, 'wherein when Rand Rare each —H and Rand Rare each —Br, then A is other than para-bromophenyl, meta-bromophenyl, ortho-tolyl or 3-quinolinyl; and'}{'sub': 3', '5', '6', '4, 'when R, Rand Rare each —H and Ris —Br, then A is other than 3,5-dibromo-ortho-hydroxyphenyl, para-bromophenyl, meta-bromophenyl or ortho-tolyl.'}3. The compound of or claim 1 , wherein the aryl or heteroaryl is substituted with halogen claim 1 , C-Calkyl claim 1 , —OH claim 1 , —O—(C-Calkyl) claim 1 , —CHF claim 1 , —CF claim 1 , —OCHFor —OCF.4. The compound of or claim 1 , wherein the fused aryl or fused heteroaryl is substituted with halogen claim 1 , C-Calkyl claim 1 , —OH claim 1 , —O—(C-Calkyl) claim 1 , —CHF claim 1 , —CF claim 1 , —OCHFor —OCF.5. The compound of or claim 1 , wherein one of R-Ris other than —H.6. The compound of or claim 1 , wherein two of R-Ris other than —H.7. The compound of any one of - claim 1 , wherein A is monosubstituted.8. The compound of any one of - claim 1 , wherein A is disubstituted.9. The compound of any one of - claim 1 , wherein A is trisubstituted.10. The compound of or claim 1 , wherein R claim 1 , R claim 1 , R claim 1 , and Rare each independently —H claim 1 , halogen claim 1 , C-Calkyl claim 1 , —OH claim 1 , —O—(C-Calkyl) claim 1 , —CHF claim 1 , —CF claim 1 , —OCHFor —OCF.11. The compound of claim 10 , wherein R claim 10 , R claim 10 , R claim 10 , and Rare each independently halogen claim 10 , —O—(C-Calkyl) claim 10 , —OCFor —CF.12. The compound of claim 11 , wherein R claim 11 , R claim 11 , R claim 11 , and Rare each independently halogen or —O—(C-Calkyl).13. The compound of claim 11 , wherein R claim 11 , R claim 11 , R claim 11 , and Rare each independently —Cl claim 11 , —Br claim 11 , —F claim 11 , —O—(C-Calkyl) claim 11 , —OCFor —CF.14. The compound of claim 12 , wherein R claim 12 , R claim 12 , R claim 12 , and Rare each ...

Liquid crystal compound having fluorine-containing alkenyl terminal group, liquid crystal composition and liquid crystal display device

To provide a liquid crystal compound satisfying at least one of high stability to heat, light and so forth, a high clearing point, a low minimum temperature of a liquid crystal phase, small viscosity, suitable optical anisotropy, large dielectric anisotropy, a suitable elastic constant and excellent compatibility with other liquid crystal compounds, a liquid crystal composition containing the compound, and a liquid crystal display device including the composition. 6. Use of at least one compound according to any one of to as a component of a liquid crystal composition.7. A liquid crystal composition , containing at least one compound according to any one of to .12. The liquid crystal composition according to , further containing at least one compound selected from the group of compounds represented by formulas (13) , (14) and (15) according to .13. The liquid crystal composition according to claim 7 , further containing at least one optically active compound and/or at least one polymerizable compound.14. The liquid crystal composition according to claim 7 , further containing at least one antioxidant and/or at least one ultraviolet light absorber.15. A liquid crystal display device claim 7 , including the liquid crystal composition according to . The invention relates to a liquid crystal compound, a liquid crystal composition and a liquid crystal display device. More specifically, the invention relates to a compound that has a fluorine-containing alkenyl terminal group and 2,3-difluoro-1,4-phenylene, and has a negative dielectric anisotropy, a liquid crystal composition containing the compound, and a liquid crystal display device including the composition.A liquid crystal display device is widely utilized for a display of a personal computer, a television and so forth. The device utilizes optical anisotropy, dielectric anisotropy or the like of a liquid crystal compound. As an operating mode of the liquid crystal display device, various modes are known, such as a ...

Benzo Annulenes as Antiviral Agents

The present disclosure is concerned with benzo annulene compounds that are capable of inhibiting a viral infection and methods of treating viral infections such as, for example, chikungunya, Venezuelan equine encephalitis, dengue, influenza, and zika, using these compounds. 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 Z is CH.3. The compound of claim 1 , wherein each of Rand Ris hydrogen.4. The compound of claim 1 , wherein Ris —OR.5. The compound of claim 1 , wherein Cyis selected from C5-C6 aryl and C4-C5 heteroaryl and substituted with 0 claim 1 , 1 claim 1 , or 2 groups independently selected from halogen claim 1 , —COH claim 1 , —CN claim 1 , —OH claim 1 , —NH claim 1 , C1-C8 alkyl claim 1 , C1-C8 haloalkyl claim 1 , C1-C8 alkylnitrile claim 1 , C1-C8 hydroxyalkyl claim 1 , C1-C8 alkoxy claim 1 , C1-C8 halohydroxyalkyl claim 1 , C1-C8 aminoalkyl claim 1 , C1-C8 alkylamino claim 1 , (C1-C8)(C1-C8) dialkylamino claim 1 , and Cy.6. The compound of claim 1 , wherein Cyis phenyl substituted with 0 claim 1 , 1 claim 1 , or 2 groups independently selected from halogen claim 1 , —COH claim 1 , —CN claim 1 , —OH claim 1 , —NH claim 1 , C1-C8 alkyl claim 1 , C1-C8 haloalkyl claim 1 , C1-C8 alkylnitrile claim 1 , C1-C8 hydroxyalkyl claim 1 , C1-C8 alkoxy claim 1 , C1-C8 halohydroxyalkyl claim 1 , C1-C8 aminoalkyl claim 1 , C1-C8 alkylamino claim 1 , (C1-C8)(C1-C8) dialkylamino and Cy.7. The compound of claim 1 , wherein Cyis phenyl substituted with a tert-butyl group.8. The compound of claim 1 , wherein Cyis C4-C5 heteroaryl substituted with 0 claim 1 , 1 claim 1 , or 2 groups independently selected from halogen claim 1 , —COH claim 1 , —CN claim 1 , —OH claim 1 , —NH claim 1 , C1-C8 alkyl claim 1 , C1-C8 haloalkyl claim 1 , C1-C8 alkylnitrile claim 1 , C1-C8 hydroxyalkyl claim 1 , C1-C8 alkoxy claim 1 , C1-C8 halohydroxyalkyl ...

CATALYSTS, METHODS OF MAKING, AND METHODS OF HYDROFLUORINATION

Some embodiments of the invention include inventive catalysts (e.g., catalysts of Formula (I)). Other embodiments include compositions comprising the inventive catalysts. Some embodiments include methods of using the inventive catalysts (e.g., in hydrofluorination of an organic compound). Further embodiments include methods for making the inventive catalysts. Additional embodiments of the invention are also discussed herein. 1. A catalyst selected from Formula (I){'br': None, 'i': 'x', 'resin-anion-HF\u2003\u2003(I)'} resin is an anion exchange resin,', {'sub': 4', '2', '4', '4', '4', '3', '3', '4', '3', '3', '4', '3', '2', '3', '3, 'sup': −', '−', '−', '−', '2−', '3−', '−', '−', '−', '−', '−', '−, 'anion is HSO, BzO, AcO, HPO, HPO, PO, MeSO, NO, ReO, CFSO, ClO, or CF(CF)SO, and'}, 'x is 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, or 25., 'wherein'}2. The catalyst of claim 1 , wherein the resin comprises a secondary ammonium group claim 1 , a tertiary ammonium group claim 1 , or a quaternary ammonium group.3. The catalyst of or claim 1 , wherein x is 5 claim 1 , 6 claim 1 , 7 claim 1 , 8 claim 1 , 9 claim 1 , 10 claim 1 , 11 claim 1 , 12 claim 1 , 13 claim 1 , 14 claim 1 , 15 claim 1 , 16 claim 1 , 17 claim 1 , 18 claim 1 , 19 claim 1 , or 20.4. The catalyst of any of - claim 1 , wherein x is 5 claim 1 , 10 claim 1 , or 15.5. The catalyst of any of - claim 1 , wherein the anion is HSO claim 1 , BzO claim 1 , AcO claim 1 , HPO claim 1 , HPO claim 1 , or PO.6. The catalyst of any of - claim 1 , wherein the anion is HSO.7. The catalyst of any of - claim 1 , wherein (1) the catalyst is resin-HSO-5HF claim 1 , resin-HSO-10HF claim 1 , or resin-HSO-15HF claim 1 , (2) the resin comprises a quaternary ammonium group or trimethylammonium claim 1 , or (3) both.8. A composition comprising the catalyst of any of - claim 1 , and a solvent.9. The composition of claim 8 , wherein the solvent is DCM (dichloromethane) claim 8 , DCE (1 claim ...

KETAMINE DERIVATIVES AND COMPOSITIONS THEREOF

Ketamine derivatives and pharmaceutical compositions thereof are disclosed. When administered orally the ketamine derivatives provide increased bioavailability of ketamine in the systemic circulation. The ketamine derivatives can be used to treat neurological diseases, psychological diseases and pain. 2. The method of claim 1 , wherein administering comprises orally administering.3. The method of claim 1 , wherein the pain is selected from back pain claim 1 , cancer pain claim 1 , carpal tunnel syndrome pain claim 1 , chronic pain claim 1 , diabetic peripheral neuropathy claim 1 , fibromyalgia claim 1 , migraine claim 1 , myofascial pain claim 1 , neuropathic pain claim 1 , neuralgia claim 1 , osteoarthritis claim 1 , peripheral neuropathy claim 1 , postoperative pain claim 1 , regional pain syndrome claim 1 , rheumatoid arthritis pain claim 1 , sciatica claim 1 , scoliosis pain claim 1 , spinal cord injury pain claim 1 , spinal stenosis claim 1 , trigeminal neuralgia claim 1 , and traumatic pain.7. The method of claim 1 , wherein the compound is selected from:1-((((S)-1-(2-chlorophenyl)-2-oxocyclohexyl)(methyl)carbamoyl)oxy)ethyl acetylglycinate (3);1-((((S)-1-(2-chlorophenyl)-2-oxocyclohexyl)(methyl)carbamoyl)oxy)ethyl (tert-butoxycarbonyl)glycinate (4);1-((((S)-1-(2-chlorophenyl)-2-oxocyclohexyl)(methyl)carbamoyl)oxy)ethyl (tert-butoxycarbonyl)-L-valinate (5);1-((((S)-1-(2-chlorophenyl)-2-oxocyclohexyl)(methyl)carbamoyl)oxy)ethyl 2-(3-methyloxetan-3-yl)acetate (6);1-((((S)-1-(2-chlorophenyl)-2-oxocyclohexyl)(methyl)carbamoyl)oxy)ethyl acetyl-L-alaninate (7);1-((((S)-1-(2-chlorophenyl)-2-oxocyclohexyl)(methyl)carbamoyl)oxy)ethyl acetyl-L-valinate (8);1-((((S)-1-(2-chlorophenyl)-2-oxocyclohexyl)(methyl)carbamoyl)oxy)ethyl 1-methylpiperidine-4-carboxylate (17);1-((((S)-1-(2-chlorophenyl)-2-oxocyclohexyl)(methyl)carbamoyl)oxy)ethyl isobutyrylglycinate (19);(S)-(((1-(2-chlorophenyl)-2-oxocyclohexyl)(methyl)carbamoyl)oxy)methyl 2-(3-methyloxetan-3-yl)acetate (22);1 ...

AMIDE COMPOUND

The present invention relates to compound (I) or a salt thereof which has a RORγt inhibitory action. In the formula (I), each symbol is as defined in the specification. 116.-. (canceled)18. The method of claim 17 , wherein the substituent that Ring A optionally further has is a fluorine atom or a chlorine atom.19. The method of claim 17 , wherein Ris a tert-butyl group claim 17 , a neopentyl group or a trimethylsilyl group.21. The method of claim 17 , wherein Ris a hydrogen atom or a methyl group.22. The method of claim 17 , wherein the compound is (3S)—N-((1R)-2-((4-tert-Butyl-3-fluorophenyl)amino)-1-(4 claim 17 ,4-difluorocyclohexyl)-2-oxoethyl)-5-oxopyrrolidine-3-carboxamide or a salt thereof.23. The method of claim 17 , wherein the compound is N-((1R)-2-((3 claim 17 ,5-Difluoro-4-(trimethylsilyl)phenyl)amino)-1-(4-methoxyphenyl)-2-oxoethyl)-3-hydroxy-N-methyl-1 claim 17 ,2-oxazole-5-carboxamide or a salt thereof.24. The method of claim 17 , wherein the compound is (2R)—N-(4-tert-Butyl-3 claim 17 ,5-difluorophenyl)-2-(((3-hydroxy-1 claim 17 ,2-oxazol-5-yl)acetyl)amino)-2-(1-methyl-1H-indazol-5-yl)acetamide or a salt thereof.25. The method of claim 17 , wherein the compound is (3R)—N-((1R)-2-((3-fluoro-4-(trimethylsilyl)phenyl)amino)-1-(4-(methoxymethyl)phenyl)-2-oxoethyl)-5-oxopyrrolidine-3-carboxamide or a salt thereof.26. The method of claim 17 , wherein the compound is selected from the group consisting of(3S)—N-((1R)-2-((3-fluoro-4-(trimethylsilyl)phenyl)amino)-1-(4-(methoxymethyl)phenyl)-2-oxoethyl)-5-oxopyrrolidine-3-carboxamide,N-((1R)-2-((3-fluoro-4-(trimethylsilyl)phenyl)amino)-1-(4-methoxyphenyl)-2-oxoethyl)-3-hydroxy-N-methyl-1,2-oxazole-5-carboxamide,N-(2-((3-fluoro-4-(trimethylsilyl)phenyl)amino)-1-(4-(methoxymethyl)phenyl)-2-oxoethyl)-5-oxopyrrolidine-3-carboxamide,(2R)-2-(((2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)acetyl)amino)-N-(3-fluoro-4-(trimethylsilyl)phenyl)-2-(4-(methoxymethyl)phenyl)acetamide,(2R)—N-(3-fluoro-4-(trimethylsilyl)phenyl)-2-(4 ...

FARNESOID X RECEPTOR AGONISTS AND USES THEREOF

Described herein are compounds that are farnesoid X receptor agonists, methods of making such compounds, pharmaceutical compositions and medicaments comprising such compounds, and methods of using such compounds in the treatment of conditions, diseases, or disorders associated with farnesoid X receptor activity. 2. The compound of claim 1 , or a pharmaceutically acceptable salt or solvate thereof claim 1 , wherein:{'sup': 3', '3', '3', '12, 'sub': 4', '10', '3', '10, 'Ris selected from substituted or unsubstituted C-Calkyl, substituted or unsubstituted C-Ccycloalkyl, or substituted or unsubstituted aryl, wherein if Ris substituted then Ris substituted with one or more Rgroups.'}3. The compound of or claim 1 , or a pharmaceutically acceptable salt or solvate thereof claim 1 , wherein:{'sup': '3', 'Ris selected from n-butyl, iso-butyl, tert-butyl, n-pentyl, tert-pentyl, neopentyl, isopentyl, sec-pentyl, 3-pentyl, n-hexyl, isohexyl, 3-methylpentyl, 2,3-dimethylbutyl, neohexyl, substituted or unsubstituted cyclopropyl, substituted or unsubstituted cyclobutyl, substituted or unsubstituted cyclopentyl, substituted cyclohexyl, and substituted phenyl.'}4. The compound of any one of - claim 1 , or a pharmaceutically acceptable salt or solvate thereof claim 1 , wherein:{'sup': '3', 'Ris selected from substituted cyclohexyl and substituted phenyl.'}6. The compound of claim 5 , or a pharmaceutically acceptable salt or solvate thereof claim 5 , wherein:{'sup': 'A', 'A is CR.'}7. The compound of claim 5 , or a pharmaceutically acceptable salt or solvate thereof claim 5 , wherein:A is N.8. The compound of any one of - claim 5 , or a pharmaceutically acceptable salt or solvate thereof claim 5 , wherein:{'sup': 1', '1', '2', '2', '1, 'Lis —X-L-, -L-X—;'}{'sup': 1', '10', '10', '10', '10', '10, 'sub': 2', '2', '2', '2, 'Xis —O—, —S—, —S(═O)—, —S(═O)—, —S(═O)NR—, —CH—, —C≡C—, —C(═O)—, —C(═O)O—, —OC(═O)—, —C(═O)NR—, —NRC(═O)—, —NRS(═O)—, or —NR—;'}{'sup': '2', 'sub': '2', 'Lis absent ...

Treprostinil derivatives and compositions and uses thereof

The present disclosure provides treprostinil derivatives that can act as prodrugs of treprostinil. The treprostinil derivatives can be used to treat any conditions responsive to treatment with treprostinil, including pulmonary hypertension, such as pulmonary arterial hypertension.

HEPATITIS B ANTIVIRAL AGENTS

The present invention discloses compounds of Formula (I), or pharmaceutically acceptable salts, esters, or prodrugs thereof: 11. A pharmaceutical composition claim 1 , comprising a compound or a combination of compounds according to claim 1 , in combination with a pharmaceutically acceptable carrier or excipient.12. A method of treating or preventing an HBV infection in a subject in need thereof claim 1 , comprising administering to the subject a therapeutically effective amount of a compound or a combination of compounds according to .13. The method of claim 12 , further comprising administering to the subject at least one additional therapeutic agent selected from the group consisting of HBV polymerase inhibitors claim 12 , interferon claim 12 , viral entry inhibitors claim 12 , viral maturation inhibitors claim 12 , capsid assembly or core protein inhibitors or modulators claim 12 , reverse transcriptase inhibitors claim 12 , TLR-agonists claim 12 , inducers of cellular viral RNA sensor claim 12 , therapeutic vaccines claim 12 , RNA interence (RNAi) or small interfering RNA (siRNA) and combinations thereof.14. The method of claim 13 , wherein the compound and the at least one additional therapeutic agent are co-formulated.15. The method of claim 13 , wherein the at least one additional therapeutic agent is administered at a lower dose and/or frequency than that which is therapeutically effective when said agent is administered alone. This application claims the benefit of U.S. Provisional Application No. 62/304,671, filed on Mar. 7, 2016, and 62/337,675, filed on May 17, 2016. The entire teachings of the above applications are incorporated herein by reference.The present invention relates generally to novel antiviral agents. Specifically, the present invention relates to compounds which can inhibit the protein(s) encoded by hepatitis B virus (HBV) or interfere with the function of the HBV life cycle, compositions comprising such compounds, methods for inhibiting ...

APOPTOSIS-INDUCING AGENTS FOR THE TREATMENT OF CANCER AND IMMUNE AND AUTOIMMUNE DISEASES

Disclosed are compounds which inhibit the activity of anti-apoptotic Bcl-2 proteins, compositions containing the compounds and methods of treating diseases during which is expressed anti-apoptotic Bcl-2 protein. 212-. (canceled) This application claims priority to U.S. Provisional Application Ser. No. 61/119,844 filed Dec. 4, 2008, which is incorporated by reference in its entirety.This invention pertains to compounds which inhibit the activity of Bcl-2 anti-apoptotic proteins, compositions containing the compounds, and methods of treating diseases during which anti-apoptotic Bcl-2 proteins are expressed.Anti-apoptotic Bcl-2 proteins are associated with a number of diseases. There is therefore an existing need in the therapeutic arts for compounds which inhibit the activity of anti-apoptotic Bcl-2 proteins.Overexpression of Bcl-2 proteins correlates with resistance to chemotherapy, clinical outcome, disease progression, overall prognosis or a combination thereof in various cancers and disorders of the immune system.Involvement of Bcl-2 proteins in bladder cancer, brain cancer, breast cancer, bone marrow cancer, cervical cancer, chronic lymphocytic leukemia, colorectal cancer, esophageal cancer, hepatocellular cancer, lymphoblastic leukemia, follicular lymphoma, lymphoid malignancies of T-cell or D-cell origin, melanoma, myelogenous leukemia, myeloma, oral cancer, ovarian cancer, non-small cell lung cancer, prostate cancer, small cell lung cancer, spleen cancer, and the like is described in commonly-owned PCT US 2004/36770, published as WO 2005/049593, and PCT US 2004/37911, published as WO 2005/024636.Involvement of Bcl-2 proteins in immune and autoimmune diseases is described in 2003, 3, 378-384; 2000, 110 (3), 584-90; 2000, 95 (4), 1283-92; and 2004, 351 (14), 1409-1419. Involvement of Bcl-2 proteins in arthritis is disclosed in commonly-owned U.S. Provisional Patent Application Ser. No. 60/988,479. Involvement of Bcl-2 proteins in bone marrow transplant rejection ...

COMPOSITIONS AND METHODS OF MAKING EXPANDED HEMATOPOIETIC STEM CELLS USING DERIVATIVES OF FLUORENE

This invention is directed to, inter alia, compounds, methods, systems, and compositions for the maintenance, enhancement, and expansion of hematopoietic stem cells derived from one or more sources of CD34+ cells. Sources of CD34+ cells include bone marrow, cord blood, mobilized peripheral blood, and non-mobilized peripheral blood. Also provided herein are compounds of Formula I 3. The compound of or , wherein{'sub': '3-6', 'A is a fused cyclic moiety selected from the group consisting of a Ccycloalkyl, heterocycloalkyl, and phenyl,'}wherein each heterocycloalkyl comprises from 3 to 6 ring members having 1 to 3 nitrogen atom ring members.4. The compound of or , wherein{'sub': '3-6', 'A is a fused cyclic moiety selected from the group consisting of a Ccycloalkyl and phenyl.'}5. The compound of or , wherein{'sub': '3-6', 'A is a fused Ccycloalkyl.'}6. The compound of any one of to , wherein{'sup': 4a', 'a', '4b', '4a', '4b, 'Ris —OR; Ris H; or Rand Rare combined to form an oxo moiety'}7. The compound of any one of to , wherein{'sup': 4a', 'a', '4b, 'Ris —OR; and Ris H.'}8. The compound of any one of to , wherein{'sup': 4a', 'a', 'b', '4b, 'Ris —NRR; and Ris H.'}9. The compound of any one of to , wherein{'sup': 1', 'b', '1a', 'b', '1a', 'b', '1', 'a', '1', 'b', 'a', '1', 'b', 'a', '1', 'b', '1a', 'b', '1', '1b', 'b', '1', '1b', 'b', '1a', 'b', '1a', 'b', '1a', '1a, 'Ris selected from the group consisting of —C(O)—NR—R, —NR—C(O)—R, —NR—X—C(O)—R, —C(O)—X—NR—R, —X—C(O)—NR—R, —X—NR—C(O)—R, —NR—C(O)—X—C(O)—R, —C(O)—NR—X—C(O)—R, —NR—C(O)—O—R, —O—C(O)—NR—R, —NR—R, and —C(O)—R.'}10. The compound any one of to , wherein{'sup': 1', '1a', '1a', 'a', 'a', 'a', '1a, 'Ris selected from the group consisting of —C(O)—NH—R, —NH—C(O)—R, —NH—C(O)—O—R, —O—C(O)—NH—R, —NH—R, and —C(O)—R.'}11. The compound any one of to , wherein{'sup': 1', '1a', '1b', '1a', 'b', '1a, 'Ris selected from the group consisting of —NH—C(O)—R, —NH—C(O)—R, —NH—C(O)—O—R, and —NR—R.'}12. The compound any one of to , ...

HETEROARYL SUBSTITUTED HETEROCYCLYL SULFONES

The invention relates to aryl substituted heterocyclyl sulfones as voltage gated calcium channel blockers, to pharmaceutical compositions containing these compounds and also to these compounds for use in the treatment and/or prophylaxis of pain and further diseases and/or disorders. 3. A compound according to claim 1 , wherein the compound of formula (I) is one diastereomer.4. A compound according to claim 3 , wherein the compound of formula (I) is one enantiomer.5. A compound according to claim 1 , wherein{'sup': '2', 'sub': 3', '2', '5', '2', '2', '3', '3', '2', '2', '2', '3', '2', '2', '2', '3', '2', '3', '2, 'Rrepresents H, CH, CH, CHCHCH, CH(CH), CHOH, CHOCH, CHNH, CHN(H)CHor CHN(CH).'}6. A compound according to claim 1 , wherein{'sup': '1', 'sub': 3', '2', '5', '2', '2', '3', '3', '2', '2', '2', '3', '2', '2', '2', '3', '2', '3', '2, 'Rrepresents H, CH, CH, CHCHCH, CH(CH), CHOH, CHOCH, CHNH, CHN(H)CHor CHN(CH).'}7. A compound according to claim 1 , wherein Arrepresents phenyl or pyridinyl claim 1 , substituted by zero or one or two or three substituents R claim 1 ,{'sup': '7', 'sub': 1-6', '3', '2', '2', '1-6', '1-6', '2', '1-6', '1-6', '2', '3', '2', '2', '2', '2', '1-6', '2', '1-6', '1-6', '2', '1-6', '1-6', '1-6', '2', '1-6', '3', '1-6', '1-6', '2', '1-6', '2', '2', '2', '1-6', '2', '1-6', '2', '3-10', '3-10, 'wherein each Ris independently selected from the group consisting of F; Cl; CN; C-alkyl; CF; CFH; CFH; C(═O)—C-alkyl; C(═O)-0H; C(═O)—O—C-alkyl; C(═O)—N(H)(OH); C(═O)—NH; C(═O)—N(H)(C-alkyl); C(═O)—N(C-alkyl); OH; OCF; OCFH; OCFH; OCFCl; OCFCl; O—C-alkyl; NH; N(H)(C-alkyl); N(C-alkyl); N(H)—C(═O)—C-alkyl; N(C-alkyl)-C(═O)—C-alkyl; N(H)—S(═O)—C-alkyl; SCF; S—C-alkyl; S(═O)—C-alkyl; S(═O)—C-alkyl; S(═O)—NH; S(═O)—N(H)(C-alkyl); S(═O)—N(C-alkyl); C-cycloalkyl; 3 to 7 membered heterocyclyl; O—C-cycloalkyl and O-(3 to 7 membered heterocyclyl).'}10. A compound according to claim 1 , wherein Arrepresents pyridinyl claim 1 , pyrazinyl claim 1 , pyridazinyl ...

ARYL SUBSTITUTED HETEROCYCLYL SULFONES

The invention relates to aryl substituted heterocyclyl sulfones as voltage gated calcium channel blockers, to pharmaceutical compositions containing these compounds and also to these compounds for use in the treatment and/or prophylaxis of pain and further diseases and/or disorders. 3. A compound according to claim 1 , wherein the compound of formula (I) is one diastereomer.4. A compound according to claim 3 , wherein the compound of formula (I) is one enantiomer.5. A compound according to claim 1 , wherein{'sup': '2', 'sub': 3', '2', '5', '2', '2', '3', '3', '2', '2', '2', '3', '2', '2', '2', '3', '2', '3', '2, 'Rrepresents H, CH, CH, CHCHCH, CH(CH), CHOH, CHOCH, CHNH, CHN(H)CHor CHN(CH).'}6. A compound according to claim 1 , wherein{'sup': '1', 'sub': 3', '2', '5', '2', '2', '3', '3', '2', '2', '2', '3', '2', '2', '2', '3', '2', '3', '2, 'Rrepresents H, CH, CH, CHCHCH, CH(CH), CHOH, CHOCH, CHNH, CHN(H)CHor CHN(CH).'}7. A compound according to claim 1 , wherein Ar represents phenyl or pyridinyl claim 1 , substituted by zero or one or two or three substituents R claim 1 ,{'sup': '7', 'sub': 1-6', '3', '2', '2', '1-6', '1-6', '2', '1-6', '1-6', '2', '3', '2', '2', '2', '2', '1-6', '2', '1-6', '1-6', '2', '1-6', '1-6', '1-6', '2', '1-6', '3', '1-6', '1-6', '2', '1-6', '2', '2', '2', '1-6', '2', '1-6', '2', '3-10', '3-10, 'wherein each Ris independently selected from the group consisting of F; Cl; CN; C-alkyl; CF; CFH; CFH; C(═O)—C-alkyl; C(═O)—OH; C(═O)—O—C-alkyl; C(═O)—N(H)(OH); C(═O)—NH; C(═O)—N(H)(C-alkyl); C(═O)—N(C-alkyl); OH; OCF; OCFH; OCFH; OCFCl; OCFCl; O—C-alkyl; NH; N(H)(C-alkyl); N(C-alkyl); N(H)—C(═O)—C-alkyl; N(C-alkyl)-C(═O)—C-alkyl; N(H)—S(═O)—C-alkyl; SCF; S—C-alkyl; S(═O)—C-alkyl; S(═O)—C-alkyl; S(═O)—NH; S(═O)—N(H)(C-alkyl); S(═O)—N(C-alkyl); C-cycloalkyl; 3 to 7 membered heterocyclyl; O—C-cycloalkyl and O-(3 to 7 membered heterocyclyl).'}10. A compound according to claim 1 , wherein Arrepresents phenyl claim 1 , substituted by one or two ...

DIPEPTIDYL KETOAMIDE COMPOUNDS AND THEIR USE FOR THE TREATMENT AND/OR PREVENTION OF FAT ACCUMULATION

The present invention relates to the use of dipeptidyl ketoamide compounds for preventing accumulation of triglycerides in adipose tissue or for reducing the amount of triglycerides in adipose tissue in a subject in need thereof and to novel dipeptidyl ketoamide compounds. 2. The method of claim 1 , wherein:X is selected from the group consisting of a single bond, an oxygen atom and a —NH— group,{'sub': 1', '1-8', '6-10', '1-4', '5-10', '1-4', '5-10, 'when X is O, Ris selected from the group consisting of a) C-alkyl, b) Caryl-Calkyl and c) Cheteroaryl-Calkyl wherein the Cheteroaryl ring system comprises 1 to 3 heteroatoms selected from the group consisting of nitrogen, oxygen and sulphur,'}{'sub': 1', '5', '6', '3', '1-6', '1-6', '5', '6', '3', '1-6', '1-6', '5-10', '0-2', '5', '6', '3', '1-6', '1-6', '3-6', '0-2', '5', '6', '3', '1-6, 'when X is an single bond or a —NH— group, Ris selected from the group consisting of d) phenyl optionally substituted by 1 to 3 substituents selected from the group consisting of OH, NRR, CN, CF, Clinear or branched alkyl; Clinear or branched alkoxy and halogen atoms; e) naphthyl optionally substituted by 1 to 3 substituents selected from the group consisting of OH, NRR, CN, CF, Clinear or branched alkyl, Clinear or branched alkoxy and halogen atoms; f) Cheterocyclyl-Calkyl wherein the heterocyclyl ring system is saturated or unsaturated and comprises 1 to 3 heteroatoms selected from the group consisting of nitrogen, oxygen and sulphur and is optionally substituted by 1 to 3 substituents selected from the group consisting of OH, NRR, CN, CF, Clinear or branched alkyl and halogen atoms; g) Clinear or branched alkyl and h) Ccycloalkyl-Calkyl optionally substituted by 1 to 3 substituents selected from the group consisting of OH, NRR, CN, CF, Clinear or branched alkyl and halogen atoms;'}{'sub': 2', '1-8', '1-8', '1-8', '3-6', '0-2, 'Ris selected from the group consisting of i) C-alkyl, j) C-alkoxy-O—C-alkyl and k) Ccycloalkyl-Calkyl;'}{' ...

TREPROSTINIL DERIVATIVES AND COMPOSITIONS AND USES THEREOF

The present disclosure provides treprostinil derivatives that can act as prodrugs of treprostinil. The treprostinil derivatives can be used to treat any conditions responsive to treatment with treprostinil, including pulmonary hypertension, such as pulmonary arterial hypertension. 128-. (canceled)31. The compound of claim 29 , wherein Ris hydrogen and —ORis derivatized.32. The compound of claim 29 , wherein Ris hydrogen and —ORis derivatized.33. The compound of claim 29 , wherein both —ORand —ORare derivatized claim 29 , optionally with the same moiety.34. The compound of claim 33 , wherein both —ORand —ORare derivatized with the same moiety.36. The pharmaceutical composition of claim 35 , wherein Ris hydrogen and —ORis derivatized.37. The pharmaceutical composition of claim 35 , wherein Ris hydrogen and —ORis derivatized.38. The pharmaceutical composition of claim 35 , wherein both —ORand —ORare derivatized claim 35 , optionally with the same moiety.39. The pharmaceutical composition of claim 38 , wherein both —ORand —ORare derivatized with the same moiety.40. The pharmaceutical composition of claim 35 , which is formulated for transdermal delivery of the compound.41. The pharmaceutical composition of claim 40 , which is configured as a transdermal patch.43. The method of claim 42 , wherein Ris hydrogen and —ORis derivatized.44. The method of claim 42 , wherein Ris hydrogen and —ORis derivatized.45. The method of claim 42 , wherein both —ORand —ORare derivatized claim 42 , optionally with the same moiety.46. The method of claim 45 , wherein both —ORand —ORare derivatized with the same moiety.47. The method of claim 42 , wherein the medical condition is selected from the group consisting of pulmonary hypertension claim 42 , pulmonary fibrosis claim 42 , ischemic diseases claim 42 , peripheral vascular disease claim 42 , peripheral ischemic lesions on the skin claim 42 , critical limb ischemia claim 42 , heart failure claim 42 , atherogenesis claim 42 , inflammatory ...

SULFIDE ALKYL COMPOUNDS FOR HBV TREATMENT

The present invention includes a method of inhibiting, suppressing or preventing HBV infection in an individual in need thereof, comprising administering to the individual a therapeutically effective amount of at least one compound of the invention. 19-. (canceled)11. The compound of claim 10 , or a pharmaceutically acceptable salt thereof claim 10 , wherein Ris selected from —H claim 10 , halo claim 10 , —OH claim 10 , —CN claim 10 , —C-alkyl claim 10 , —C-alkoxy claim 10 , and —CF.12. The compound of claim 10 , or a pharmaceutically acceptable salt thereof claim 10 , wherein Ris selected from —C-alkyl claim 10 , —C-heteroalkyl claim 10 , —C-cycloalkyl claim 10 , —C-heterocycloalkyl claim 10 , —(C-alkyl)-(C-cycloalkyl) claim 10 , and —(C-alkyl)-(C-heterocycloalkyl) claim 10 , wherein Rmay be optionally substituted with one or two groups independently selected from (═O) claim 10 , —OH claim 10 , —C-alkyl claim 10 , —C(O)OH claim 10 , and halo.13. The compound of claim 10 , or a pharmaceutically acceptable salt thereof claim 10 , wherein each Ris independently selected from halo and —C-alkyl.14. The compound of claim 10 , or a pharmaceutically acceptable salt thereof claim 10 , wherein Ris independently selected from H and halo.15. The compound of claim 10 , or a pharmaceutically acceptable salt thereof claim 10 , wherein each Ris halo.16. The compound of claim 10 , or a pharmaceutically acceptable salt thereof claim 10 , wherein Ris selected from —H claim 10 , halo claim 10 , —CN claim 10 , —C-alkyl claim 10 , —C-alkoxy claim 10 , and tri-halo-(C-alkyl).17. The compound of claim 10 , or a pharmaceutically acceptable salt thereof claim 10 , wherein Ris selected from —H claim 10 , halo claim 10 , —CN claim 10 , —CH claim 10 , —OCH claim 10 , and —CF.18. The compound of claim 10 , or a pharmaceutically acceptable salt thereof claim 10 , wherein Ris halo.19. The compound of claim 10 , or a pharmaceutically acceptable salt thereof claim 10 , wherein Ris selected from —C- ...

Novel glp-1 receptor stabilizers and modulators

Compounds that bind the glucagon-like peptide 1 (GLP-1) receptor, methods of their synthesis, methods of their therapeutic and/or prophylactic use, and methods of their use in stabilizing GLP-1 receptor in vitro for crystallization of the GLP-1 receptor are provided. Certain compounds may have activity as modulators or potentiators with respect to glucagon receptor, GIP receptor, GLP-1 and GLP-2 receptors, and PTH receptor on their own or in the presence of receptor ligands such as GIP(1-42), PTH(1-34), Glucagon(1-29), GLP-2(1-33), GLP-1(7-36), GLP-1(9-36), oxyntomodulin and exendin variants.

TREPROSTINIL DERIVATIVES AND COMPOSITIONS AND USES THEREOF

The present disclosure provides treprostinil derivatives that can act as prodrugs of treprostinil. The treprostinil derivatives can be used to treat any conditions responsive to treatment with treprostinil, including pulmonary hypertension, such as pulmonary arterial hypertension. 128-. (canceled)31. The method of claim 29 , wherein:{'sup': '3', 'sub': 1', '6, 'Rin each occurrence independently is C-Calkyl;'}{'sup': 4', '5', '4', '5, 'sub': 1', '3, 'Rand Rin each occurrence independently are hydrogen or C-Calkyl, or Rand Rand the carbon atom to which they are connected form a cyclopropyl ring;'}{'sup': 6', '3, 'Rin each occurrence independently is hydrogen or R;'}j in each occurrence independently is 0 or 1; andm in each occurrence independently is 1 or 2.32. The method of claim 31 , wherein:{'sup': '3', 'Rin each occurrence independently is methyl, ethyl, propyl, isopropyl, butyl, iso-butyl, sec-butyl or tert-butyl;'}{'sup': 4', '5, 'Rand Rin each occurrence independently are hydrogen, methyl, ethyl, propyl or isopropyl;'}{'sup': 6', '3, 'Rin each occurrence independently is hydrogen or R;'}j is 0; andm is 1.33. The method of claim 29 , wherein Ris hydrogen and —ORis derivatized.34. The method of claim 29 , wherein Ris hydrogen and —ORis derivatized.35. The method of claim 29 , wherein both —ORand —ORare derivatized.36. The method of claim 35 , wherein both —ORand —ORare derivatized with the same moiety.37. The method of claim 29 , wherein the medical condition is selected from the group consisting of pulmonary hypertension claim 29 , pulmonary fibrosis claim 29 , ischemic diseases claim 29 , peripheral vascular disease claim 29 , peripheral ischemic lesions on the skin claim 29 , critical limb ischemia claim 29 , heart failure claim 29 , atherogenesis claim 29 , inflammatory diseases claim 29 , diabetic neuropathic foot ulcer claim 29 , kidney malfunction and failure claim 29 , tumors claim 29 , cancers claim 29 , and pain associated with each of the preceding ...

COMPOUNDS AND USES THEREOF FOR THE MODULATION OF HEMOGLOBIN

Provided herein are compounds and pharmaceutical compositions suitable as modulators of hemoglobin, methods and intermediates for their preparation, and methods for their use in treating disorders mediated by hemoglobin and disorders that would benefit from tissue and/or cellular oxygenation. This application is a continuation of U.S. application Ser. No. 16/186,275, filed Nov. 9, 2018, which is a continuation of U.S. application Ser. No. 14/776,726, filed Sep. 14, 2015, now abandoned, which is the U.S. national stage application of International Patent Application No. PCT/US2014/022769, filed Mar. 10, 2014, which claims priority to U.S. application Ser. No. 61/905,803, filed Nov. 18, 2013.This invention provides compounds and pharmaceutical compositions suitable as allosteric modulators of hemoglobin, methods and intermediates for their preparation, and methods for their use in treating disorders mediated by hemoglobin and disorders that would benefit from tissue and/or cellular oxygenation.Sickle cell disease is a disorder of the red blood cells, found particularly among those of African and Mediterranean descent. The basis for sickle cell disease is found in sickle hemoglobin (HbS), which contains a point mutation relative to the prevalent peptide sequence of hemoglobin (Hb).Hemoglobin (Hb) transports oxygen molecules from the lungs to various tissues and organs throughout the body. Hemoglobin binds and releases oxygen through conformational changes. Sickle hemoglobin (HbS) contains a point mutation where glutamic acid is replaced with valine, allowing HbS to become susceptible to polymerization to give the HbS containing red blood cells their characteristic sickle shape. The sickled cells are also more rigid than normal red blood cells, and their lack of flexibility can lead to blockage of blood vessels. U.S. Pat. No. 7,160,910 discloses compounds that are allosteric modulators of hemoglobin. However, a need exists for additional therapeutics that can treat ...

CYCLOHEXYL SULFONE ROR GAMMA MODULATORS

Described are RORγ modulators of the formula (I), or stereoisomers, tautomers, pharmaceutically acceptable salts, solvates, or prodrugs thereof, wherein all substituents are defined herein. Also provided are pharmaceutical compositions comprising the same. Such compounds and compositions are useful in methods for modulating RORγ activity in a cell and methods for treating a subject suffering from a disease or disorder in which the subject would therapeutically benefit from modulation of RORγ activity, for example, autoimmune and/or inflammatory disorders. 2. A compound according to claim 1 , or a stereoisomer or pharmaceutically-acceptable salt thereof claim 1 , wherein Ris CF.3. A compound according to claim 1 , or a stereoisomer or pharmaceutically-acceptable salt thereof claim 1 , wherein{'sup': 1', '1a', '1a, 'sub': '1-6', 'Ris halo, phenyl substituted with 0-3 R, or Calkyl substituted with 0-3 R; and'}{'sup': 1a', 'a', 'b', 'f, 'sub': 3', '1-6', '2', 'r', '2', 'r, 'Ris, independently at each occurrence, hydrogen, CF, halo, Calkyl substituted with 0-3 R, —(CH)OR, and —(CH)-phenyl substituted with 0-3 R.'}4. A compound according to claim 1 , or a stereoisomer or pharmaceutically-acceptable salt thereof claim 1 , wherein:{'sup': 2', '2b', '2b', '2b', '11', '11', '2b', '2c', '2b', '2c', '11', '11', '2b', '11', '11', '2b', 'c', '2a', '2', '2', '2a', '2a, 'sub': 2', 'r', '2', 'r', '2', 'r', '2', 'r', '2', 'r', '2', 'r', '2', 'r', '2', 'r', 'p', '1-6', '2', 'r', 'p', 'p, 'Ris, independently at each occurrence, selected from hydrogen, ═O, —(CH)OR, —(CH)C(O)R, —(CH)OC(O)OR, —(CH)OC(O)NRR, —(CH)NRC(O)R, —(CH)NRC(O)OR, —(CH)NRR, —(CH)NRC(O)NRR, —NRS(O)R, Calkyl, —(CH)-4-10 membered heterocycle comprising carbon atoms, and 1-4 heteroatoms selected from N, O, and S(O)substituted with 0-3 R; or one Rtogether with an Ron an adjacent carbon combine to form a fused ring substituted with 0-3 R, wherein the fused ring is selected from a 4-7 membered heterocycle comprising carbon ...

HETEROCYCLIC SULFONE ROR GAMMA MODULATORS

Described are RORγ modulators of the formula (I), [INSERT CHEMICAL STRUCTURE HERE] or stereoisomers, tautomers, pharmaceutically acceptable salts, solvates, or prodrugs thereof, wherein all substituents are defined herein. Also provided are pharmaceutical compositions comprising the same. Such compounds and compositions are useful in methods for modulating RORγ activity in a cell and methods for treating a subject suffering from a disease or disorder in which the subject would therapeutically benefit from modulation of RORγ activity, for example, autoimmune and/or inflammatory disorders. 2. A compound of claim 1 , or a stereoisomer or pharmaceutically-acceptable salt thereof claim 1 , wherein{'sup': 1', '1a', '1a, 'sub': '1-6', 'Ris halo, phenyl substituted with 0-3 R, or Calkyl substituted with 0-3 R; and'}{'sup': 1a', 'a', 'b', 'f, 'sub': 3', '1-6', '2', 'r', '2', 'r, 'Ris, independently at each occurrence, hydrogen, CF, halo, Calkyl substituted with 0-3 R, —(CH)OR, and —(CH)-phenyl substituted with 0-3 R.'}3. A compound of claim 1 , or a stereoisomer or pharmaceutically-acceptable salt thereof claim 1 , wherein:{'sup': 2', '2c', '2a', '2b', '2d', '11', '11, 'sub': 2', '1-6', '2, 'Ris selected from hydrogen, SOR, Calkyl substituted with 0-3 R, pyrimidinyl, COR, —C(O)R, and —C(O)NRR;'}{'sup': 2a', 'a, 'sub': '1-6', 'Ris hydrogen or Calkyl substituted with 0-3 R;'}{'sup': 2b', 'a', 'a', 'a', 'a, 'sub': 1-6', '3-6', '2', 'r', 'p', '2', 'r, 'Ris hydrogen, Calkyl substituted with 0-3 R(Me, Et, tBu), Ccycloalkyl 5 substituted with 0-3 R, —(CH)-5-7 membered heterocycle comprising carbon atoms and 1-4 heteroatoms selected from N, O, and S(O)substituted with 0-3 R, or —(CH)-phenyl substituted with 0-3 R;'}{'sup': 2c', 'a', 'a', 'a', 'a', 'a, 'sub': 1-6', '2-6', '3-10', '6-10', '2', 'r', 'p, 'Ris, independently at each occurrence, hydrogen, Calkyl substituted with 0-3 R, Calkenyl substituted with 0-3 R, Ccycloalkyl substituted with 0-3 R, Caryl substituted with 0-3 R, or a ...

NEPRILYSIN INHIBITORS

In one aspect, the invention relates to compounds having the formula: 131-. (canceled)33: A compound selected from:(a) (2R,4R)-5-(3′-chlorobiphenyl-4-yl)-4-{[N′-(2,4-dinitrophenyl)-hydrazinooxalyl]-amino}-2-hydroxypentanoic acid;(b) (2R,4R)-5-(3′-chlorobiphenyl-4-yl)-2-hydroxy-4-[(N′-methylhydrazinooxalyl)-amino]pentanoic acid;(c) (2R,4R)-5-(3′-chlorobiphenyl-4-yl)-2-hydroxy-4-[(N′-isobutylhydrazinooxalyl)-amino]pentanoic acid;(d) (2R,4R)-5-(3′-chlorobiphenyl-4-yl)-2-hydroxy-4-[(N′-pyridin-4-yl-hydrazino-oxalyl)-amino]pentanoic acid;(e) (2R,4R)-5-(3′-chlorobiphenyl-4-yl)-2-hydroxy-4-[(N′-pyridin-3-yl-hydrazino-oxalyl)-amino]pentanoic acid;(f) (2R,4R)-5-(3′-chlorobiphenyl-4-yl)-2-hydroxy-4-{[N′-(6-hydroxy-pyrimidin-4-yl)-hydrazinooxalyl]amino}-pentanoic acid;(g) (2R,4R)-5-(3′-chlorobiphenyl-4-yl)-4-{[N′-(4,5-dihydro-1H-imidazol-2-yl)-hydrazinooxalyl]-amino}-2-hydroxypentanoic acid;(h) (2R,4R)-5-(3′-chlorobiphenyl-4-yl)-4-{[N′-(2-chloro-phenyl)-hydrazinooxalyl]-amino}-2-hydroxypentanoic acid;(i) (2R,4R)-5-(3′-chlorobiphenyl-4-yl)-4-{[N′-(2-fluoro-phenyl)-hydrazinooxalyl]-amino}-2-hydroxypentanoic acid;(j) (2R,4R)-5-(3′-chlorobiphenyl-4-yl)-4-{[N′-(3-chloro-phenyl)-hydrazinooxalyl]-amino}-2-hydroxypentanoic acid;(j) (2R,4R)-5-(3′-chlorobiphenyl-4-yl)-2-hydroxy-4-[(N′-o-tolyl-hydrazinooxalyl)-amino]-pentanoic acid;(k) (2R,4R)-5-(3′-chlorobiphenyl-4-yl)-2-hydroxy-4-[(N′-p-tolyl-hydrazinooxalyl)-amino]-pentanoic acid;(l) (2R,4R)-5-(3′-chlorobiphenyl-4-yl)-4-{[N′-(4-fluoro-phenyl)-hydrazinooxalyl]-amino}-2-hydroxypentanoic acid;(m) (2R,4R)-5-(3′-chlorobiphenyl-4-yl)-4-{[N′-(4-chloro-phenyl)-hydrazinooxalyl]-amino}-2-hydroxypentanoic acid;(n) (2R,4R)-4-{[N′-(4-bromophenyl)-hydrazinooxalyl]-amino}-5-(3′-chlorobiphenyl-4-yl)-2-hydroxypentanoic acid;(o) (2R,4R)-5-(3′-chlorobiphenyl-4-yl)-2-hydroxy-4-{[N′-(4-methoxyphenyl)-hydrazinooxalyl]amino}pentanoic acid;(p) (2R,4R)-5-(3′-chlorobiphenyl-4-yl)-2-hydroxy-4-[(N′-m-tolylhydrazinooxalyl)-amino]pentanoic acid;(q) (2R,4R)-5-(3′- ...

KETAMINE DERIVATIVES AND COMPOSITIONS THEREOF

Ketamine derivatives and pharmaceutical compositions thereof are disclosed. When administered orally the ketamine derivatives provide increased bioavailability of ketamine in the systemic circulation. The ketamine derivatives can be used to treat neurological diseases, psychological diseases and pain. 7. The compound of claim 6 , wherein Ris selected from hydrogen and Calkyl.10. The compound of claim 1 , wherein the compound is selected from:1-((((S)-1-(2-chlorophenyl)-2-oxocyclohexyl)(methyl)carbamoyl)oxy)ethyl acetylglycinate (3);1-((((S)-1-(2-chlorophenyl)-2-oxocyclohexyl)(methyl)carbamoyl)oxy)ethyl (tert-butoxycarbonyl)glycinate (4);1-((((S)-1-(2-chlorophenyl)-2-oxocyclohexyl)(methyl)carbamoyl)oxy)ethyl (tert-butoxycarbonyl)-L-valinate (5);1-((((S)-1-(2-chlorophenyl)-2-oxocyclohexyl)(methyl)carbamoyl)oxy)ethyl 2-(3-methyloxetan-3-yl)acetate (6);1-((((S)-1-(2-chlorophenyl)-2-oxocyclohexyl)(methyl)carbamoyl)oxy)ethyl acetyl-L-alaninate (7);1-((((S)-1-(2-chlorophenyl)-2-oxocyclohexyl)(methyl)carbamoyl)oxy)ethyl acetyl-L-valinate (8);1-((((S)-1-(2-chlorophenyl)-2-oxocyclohexyl)(methyl)carbamoyl)oxy)ethyl 1-methylpiperidine-4-carboxylate (17);1-(2-(isobutyramido)acetoyloxy)ethyl (S)-1-(2-chlorophenyl)-2-oxocyclohexylmethylcarbamate (19);(2-(3-methyloxetan-3-yl)acetoyloxy)methyl (S)-1-(2-chlorophenyl)-2-oxocyclohexylmethylcarbamate (22);1-((((S)-1-(2-chlorophenyl)-2-oxocyclohexyl)(methyl)carbamoyl)oxy)propyl 2-(3-methyloxetan-3-yl)acetate (24);1-(2-(3-methyloxetan-3-yl)acetoyloxy)-2-methylpropyl (S)-1-(2-chlorophenyl)-2-oxocyclohexylmethylcarbamate (26);1-((((S)-1-(2-chlorophenyl)-2-oxocyclohexyl)(methyl)carbamoyl)oxy)propyl acetylglycinate (27);1-(2-acetamidoacetoyloxy)-2-methylpropyl (S)-1-(2-chlorophenyl)-2-oxocyclohexylmethylcarbamate (28);(2-acetamidoacetoyloxy)methyl (S)-1-(2-chlorophenyl)-2-oxocyclohexylmethylcarbamate (31);((S)-2-acetamido-3-methylbutanoyloxy)methyl (S)-1-(2-chlorophenyl)-2-oxocyclohexylmethylcarbamate (32);((S)-2-acetamidopropanoyloxy)methyl ...

INHIBITORS OF HISTONE DEACETYLASE

The present invention relates to compounds of formula (I): 5. The compound of or a pharmaceutically acceptable salt claim 4 , hydrate claim 4 , solvate claim 4 , or prodrug thereof claim 4 , wherein Ris selected from phenyl claim 4 , 2-pyridinyl claim 4 , 3-pyridinyl claim 4 , 4-pyridinyl claim 4 , 2-pyrimidinyl claim 4 , 4-pyrimidinyl claim 4 , 5-pyrimidinyl claim 4 , 2-pyrazinyl claim 4 , oxazolyl claim 4 , thiazolyl claim 4 , and isoxazolyl.12. A pharmaceutical composition comprising an effective amount of a compound of or a pharmaceutically acceptable salt claim 1 , hydrate claim 1 , solvate claim 1 , or prodrug thereof and a pharmaceutical carrier claim 1 , diluent claim 1 , or excipient.13. A method of treating claim 1 , alleviating claim 1 , and/or preventing a condition wherein said condition is associated with histone deacetylase activity in a subject comprising administering to the subject in need thereof an effective amount of a compound of or a pharmaceutically acceptable salt claim 1 , hydrate claim 1 , solvate or prodrug thereof.14. The method of claim 13 , wherein the condition is selected from a neurological disorder claim 13 , memory loss or impairment claim 13 , cognitive function disorder or impairment claim 13 , extinction learning disorder claim 13 , fungal disease or infection claim 13 , inflammatory disease claim 13 , hematological disease claim 13 , and neoplastic disease.15. The method of claim 14 , wherein the condition is selected from:a cognitive function disorder or impairment associated with Alzheimer's disease, Huntington's disease, seizure induced memory loss, schizophrenia, Rubinstein Taybi syndrome, Rett Syndrome, Fragile X, Lewy body dementia, vascular dementia, ADHD, dyslexia, bipolar disorder and social, cognitive and learning disorders associated with autism, traumatic head injury, or attention deficit disorder, anxiety disorder, conditioned fear response, panic disorder, obsessive compulsive disorder, posttraumatic stress ...

Treprostinil derivatives and compositions and uses thereof

The present disclosure provides treprostinil derivatives that can act as prodrugs of treprostinil. The treprostinil derivatives can be used to treat any conditions responsive to treatment with treprostinil, including pulmonary hypertension, such as pulmonary arterial hypertension.

AMIDE DERIVATIVE

The present invention provides a useful medicament for the treatment and/or prophylaxis of a disease associated with the enhancement of OPN production including cancer, which comprises a compound of formula: 3. The compound according to or a pharmaceutically acceptable salt thereof wherein Ris Ccycloalkyl claim 1 , Cheterocycloalkyl claim 1 , Caryl claim 1 , or 5- to 10-membered heteroaryl wherein the Ccycloalkyl claim 1 , Cheterocycloalkyl claim 1 , Caryl claim 1 , and 5- to 10-membered heteroaryl may be optionally substituted with one group or the same or different two or more groups selected independently from the group consisting of halogen claim 1 , hydroxy claim 1 , amino claim 1 , mono- or di-Calkylamino claim 1 , Cacyl claim 1 , Cacylamino claim 1 , Calkyl claim 1 , Chaloalkyl claim 1 , Calkoxy claim 1 , and Chaloalkoxy at any replaceable positions;{'sup': '2', 'Ris hydrogen atom, amino, or hydroxy which is linked at the 2-position of the benzene ring;'}{'sup': 3', '3, 'sub': 1-6', '1-6', '1-6', '1-6, 'ORis linked at the 3-position of the benzene ring, and Ris phenyl which may be optionally substituted with one group or the same or different two or more groups selected independently from the group consisting of halogen, hydroxy, Calkyl, Chaloalkyl, Calkoxy, and Chaloalkoxy at any replaceable positions; and'}{'sup': '4', 'Ris hydrogen atom, halogen, or amino.'}4. The compound according to or a pharmaceutically acceptable salt thereof wherein Ris Ccycloalkyl claim 1 , tetrahydropyranyl claim 1 , pyridyl claim 1 , thienyl claim 1 , or phenyl wherein the Ccycloalkyl claim 1 , tetrahydropyranyl claim 1 , pyridyl claim 1 , thienyl claim 1 , and phenyl may be optionally substituted with one group or the same or different two or more groups selected independently from the group consisting of halogen claim 1 , hydroxy claim 1 , amino claim 1 , Cacyl claim 1 , Cacylamino claim 1 , Calkyl claim 1 , Chaloalkyl claim 1 , Calkoxy claim 1 , and Chaloalkoxy at any ...

TREPROSTINIL DERIVATIVES AND COMPOSITIONS AND USES THEREOF

The present disclosure provides treprostinil derivatives that can act as prodrugs of treprostinil. The treprostinil derivatives can be used to treat any conditions responsive to treatment with treprostinil, including pulmonary hypertension, such as pulmonary arterial hypertension. 124-. (canceled)26. The compound of claim 25 , wherein:{'sup': 6', '3, 'Rin each occurrence independently is hydrogen or R;'}{'sup': '3', 'sub': 1', '6, 'Rin each occurrence independently is C-Calkyl;'}{'sup': 9', '10', '9', '10, 'sub': 1', '6, 'Rand Rin each occurrence independently are C-Calkyl, or Rand Rand the nitrogen atom to which they are connected form a 3- to 6-membered heterocyclic ring;'}j in each occurrence independently is 0 or 1; andt in each occurrence independently is 1 or 2.28. The compound of claim 25 , wherein Ris hydrogen and —ORis derivatized.29. The compound of claim 25 , wherein Ris hydrogen and —ORis derivatized.30. The compound of claim 25 , wherein both —ORand —ORare derivatized claim 25 , optionally with the same group.31. The method of claim 25 , wherein the compound is administered orally.32. The method of claim 25 , wherein the compound is administered parenterally.33. The method of claim 32 , wherein the compound is administered subcutaneously or intravenously.34. The method of claim 25 , wherein the compound is administered topically.35. The method of claim 34 , wherein the compound is administered transdermally or by oral inhalation.37. The method of claim 36 , wherein ring A is cyclopropyl and u is an integer from 0 to 9 or from 0 to 5.39. The method of claim 36 , wherein the compound is administered orally.40. The method of claim 36 , wherein the compound is administered parenterally.41. The method of claim 40 , wherein the compound is administered subcutaneously or intravenously.42. The method of claim 36 , wherein the compound is administered topically.43. The method of claim 42 , wherein the compound is administered transdermally or by oral inhalation. ...

Neprilysin inhibitors

In one aspect, the invention relates to compounds having the formula: where R 1 -R 5 and X are as defined in the specification, or a pharmaceutically acceptable salt thereof. These compounds have neprilysin inhibition activity. In another aspect, the invention relates to pharmaceutical compositions comprising such compounds; methods of using such compounds; and processes and intermediates for preparing such compounds.

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. 157-. (canceled)59. The compound of claim 58 , wherein Ris a 6-membered heterocyclyl claim 58 , which may be optionally substituted.60. The compound of claim 58 , wherein Ris a fully saturated heterocyclyl claim 58 , which may be optionally substituted.61. The compound of claim 58 , wherein Ris a nitrogen heterocyclyl claim 58 , which may be optionally substituted.62. The compound of claim 58 , wherein Ris selected from the group consisting of tetrahydrofuran claim 58 , tetrahydropyran claim 58 , pyran claim 58 , pyrrolidine claim 58 , morpholine claim 58 , piperazine and piperidine claim 58 , all of which may be optionally substituted as appropriate.63. The compound of claim 58 , wherein Ris selected from the group consisting of tetrahydrofuran claim 58 , tetrahydropyran claim 58 , pyrrolidine claim 58 , morpholine claim 58 , piperazine and piperidine claim 58 , all of which may be optionally substituted as appropriate.64. The compound of claim 58 , wherein Ris selected from the group consisting of pyrrolidine claim 58 , piperazine and piperidine claim 58 , all of which may be optionally substituted as appropriate.65. The compound of claim 58 , wherein Ris piperidine claim 58 , optionally substituted as appropriate.69. The compound of claim 58 , wherein Ris selected from a substituted or hydrogenated indacene claim 58 , a 2 claim 58 ,6-dialkylphenyl claim 58 , a 2 claim 58 ,6-dialkyl-4-halophenyl claim 58 , a 2 claim 58 ,6-dicycloalkylphenyl claim 58 , and a 2 claim 58 ,6-dicycloalkyl-4-halophenyl.70. The compound of claim 58 , wherein Ris selected from hexahydroindacene claim ...

SULFINYLAMINOBENZAMIDE AND SULFONYLAMINOBENZAMIDE DERIVATIVES

Provided is a compound of Formula (I): 2. The compound of claim 1 , wherein Ris selected from the group consisting of: 5-10 membered carbobicyclic ring claim 1 , 6-12 membered heterobicyclic ring claim 1 , and 8-10 membered tricyclic ring claim 1 , wherein the 5-10 membered carbobicyclic ring claim 1 , 8-10 membered tricyclic ring claim 1 , or the 6-12 membered heterobicyclic ring may be fused claim 1 , bridged or spiro claim 1 , and wherein the 5-10 membered carbobicyclic ring claim 1 , the 6-12 membered heterobicyclic ring and the 8-10 membered tricyclic ring are substituted with one or more R3. The compound of claim 2 , wherein Ris selected from the group consisting of: 5-10 membered carbobicyclic ring claim 2 , 8-10 membered tricyclic ring claim 2 , and 6-12 membered heterobicyclic ring claim 2 , wherein the 5-10 membered carbobicyclic ring claim 2 , the 8-10 membered tricyclic ring claim 2 , or the 6-12 membered heterobicyclic ring are bridged claim 2 , and wherein the 5-10 membered carbobicyclic ring claim 2 , the 8-10 membered tricyclic ring claim 2 , and the 6-12 membered heterobicyclic are substituted with one or more R.4. The compound of claim 3 , wherein Ris selected from the group consisting of: 5-10 membered carbobicyclic ring claim 3 , and 6-12 membered heterobicyclic ring claim 3 , wherein the 5-10 membered carbobicyclic ring claim 3 , or the 6-12 membered heterobicyclic ring are bridged claim 3 , and wherein the 5-10 membered carbobicyclic ring claim 3 , and the 6-12 membered heterobicyclic are substituted with one R.5. The compound of any of wherein Q is selected from the group consisting of —S(O)— claim 1 , —S(O)— claim 1 , and —S(O)(NR)—.6. The compound of claim 1 , wherein Ris selected from the group consisting of: Calkyl claim 1 , —NRR claim 1 , 6-10 membered aryl claim 1 , 5-10 membered heteroaryl claim 1 , Ccycloalkyl claim 1 , and 4-12 membered heterocyclyl claim 1 , wherein each Calkyl claim 1 , 6-10 membered aryl claim 1 , 5-10 membered ...

NOVEL MODULATORS OF THE 5-HYDROXYTRYPTAMINE RECEPTOR 7 AND THEIR METHOD OF USE

Pharmaceutical compositions of the invention comprise functionalized lactone derivatives having a disease-modifying action in the treatment of diseases associated with dysregulation of 5-hydroxytryptamine receptor 7 activity. 17. A compound of claim 1 , wherein the compound is selected from the group consisting of:18. (R)-3-(2-(4-phenylpiperazin-1-yl)ethyl)-2 claim 1 ,8-dioxaspiro[4.5]decan-1-one claim 1 ,(R)-3-(2-(4-(4-hydroxyphenyl)piperazin-1-yl)ethyl)-2,8-dioxaspiro[4.5]decan-1-one,(R)-8-benzyl-3-(2-(4-(p-tolyl)piperazin-1-yl)ethyl)-2-oxa-8-azaspiro[4.5]decan-1-one,(R)-3-(2-(4-(p-tolyl)piperazin-1-yl)ethyl)-2-oxa-8-azaspiro[4.5]decan-1-one,(R)-methyl 1-oxo-3-(2-(4-(p-tolyl)piperazin-1-yl)ethyl)-2-oxa-8-azaspiro[4.5]decane-8-carboxylate,(R)-1-oxo-3-(2-(4-(p-tolyl)piperazin-1-yl)ethyl)-2-oxa-8-azaspiro[4.5]decane-8-carboxylate,(R)-8-acetyl-3-(2-(4-(p-tolyl)piperazin-1-yl)ethyl)-2-oxa-8-azaspiro[4.5]decan-1-one,(R)—N-methyl-1-oxo-3-(2-(4-(p-tolyl)piperazin-1-yl)ethyl)-2-oxa-8-azaspiro[4.5]decane-8-carboxamide,(R)-tert-butyl 3-(2-(4-(2-isopropylphenyl)piperazin-1-yl)ethyl)-1-oxo-2-oxa-8-azaspiro[4.5]decane-8-carboxylate,(R)-tert-butyl 3-(2-(3,4-dihydroisoquinolin-2(1H)-yl)ethyl)-1-oxo-2-oxa-8-azaspiro[4.5]decane-8-carboxylate,(R)-tert-butyl 1-oxo-3-(2-(4-(p-tolyl)piperazin-1-yl)ethyl)-2-oxa-8-azaspiro[4.5]decane-8-carboxylate,(R)-tert-butyl 3-(2-(4-(2-methyl-1H-benzo[d]imidazol-7-yl)piperazin-1-yl)ethyl)-1-oxo-2-oxa-8-azaspiro[4.5]decane-8-carboxylate,(R)-tert-butyl 3-(2-(4-(2-morpholinophenyl)piperazin-1-yl)ethyl)-1-oxo-2-oxa-8-azaspiro[4.5]decane-8-carboxylate,(R)-3-(2-(4-(2-isopropylphenyl)piperazin-1-yl)ethyl)-2-oxa-8-azaspiro[4.5]decan-1-one,(R)-3-(2-(3,4-dihydroisoquinolin-2(1H)-yl)ethyl)-2-oxa-8-azaspiro[4.5]decan-1-one,(R)-8-(methylsulfonyl)-3-(2-(4-(p-tolyl)piperazin-1-yl)ethyl)-2-oxa-8-azaspiro[4.5]decan-1-one,(R)-3-(2-(4-(2-isopropylphenyl)piperazin-1-yl)ethyl)-8-(methylsulfonyl)-2-oxa-8-azaspiro[4.5]decan-1-one,(R)-8-(methylsulfonyl)-3-(2-(4-(2- ...

AMIDE DERIVATIVES, PROCESS FOR PREPARATION THEREOF AND USE THEREOF AS INSECTICIDE

A compound represented by Formula (1): 114-. (canceled) The present invention relates to a compound represented by Formula (1):wherein A, A, Aand Aeach represent a carbon atom, a nitrogen atom or an oxidized nitrogen atom;Rand Reach represent a hydrogen atom, an optionally substituted alkyl group or an optionally substituted C1-C4 alkylcarbonyl group;Gand Geach represent an oxygen atom or a sulfur atom;X, which may be identical or different, represents a hydrogen atom, a halogen atom, a C1-C3 alkyl group or a trifluoromethyl group;n is an integer of 0 to 4; andQand Qeach represent an optionally substituted phenyl group, an optionally substituted naphthyl group or an optionally substituted heterocyclic group,an insecticide comprising the compound as the active ingredient, and a process for preparation thereof and use thereof.International Publication WO 2000/55120 and U.S. Pat. No. 6,548,514 describe a compound similar to the compound of the present invention for the use as medicament, but they do not describe on the insecticidal activity of the compound. The compound clearly does not fall within the scope of claims of the present invention.International Publication WO 2000/7980 describes a compound similar to the compound of the present invention for the use as medicament, but it does not describe on the insecticidal activity of the compound. The compound clearly does not fall within the scope of claims of the present invention.US Patent Laid-Open No. 2002-032238 describes a compound similar to the compound of the present invention for the use as medicament, but it does not describe on the insecticidal activity of the compound. The compound clearly does not fall within the scope of claims of the present invention.The object of the present invention is to provide a pesticide having a high insecticidal efficacy. Another object of the present invention is to provide a compound represented by Formula (1), a process for preparation of the compound, an insectcide ...

Amide derivatives, process for preparation thereof and use thereof as insecticide

The invention aims at providing highly effective insecticides. Compounds represented by the general formula (1); insecticides containing the same as the active ingredient; and a process for the production thereof: (1) wherein A, A, A and Aare each carbon, nitrogen, or oxidized nitrogen; R and R are each hydrogen, optionally substituted alkyl, or the like; G and G are each oxygen or sulfur; X’s may be the same or different from each other and are each hydrogen, halogeno, C alkyl, or trifluoromethyl; n is an integer of 0 to 4; Q is optionally substituted phenyl, an optionally substituted heterocyclic group, or the like; and Q is a phenyl or heterocyclic group having one or more substituents, at least one of the substituents being C haloalkoxy or the like.

Amide derivatives, process for their preparation and process for their use as insecticide

Amide derivatives, process for production of the same, and method for application thereof as insecticide

An object of the present invention is to provide a compound represented by Formula (1): wherein A 1 , A 2 , A 3 and A 4 each represent a carbon atom, a nitrogen atom or an oxidized nitrogen atom; R 1 and R 2 each represent a hydrogen atom, an optionally substituted alkyl group or an optionally substituted C1-C4 alkylcarbonyl group; G 1 and G 2 each represent an oxygen atom or a sulfur atom; X, which may be identical or different each other, represents a hydrogen atom, a halogen atom, a C1-C3 alkyl group or a trifluoromethyl group; n is an integer of 0 to 4; and Q 1 represents an optionally substituted phenyl group, an optionally substituted naphthyl group or an optionally substituted heterocyclic group; Q 2 represents a phenyl group or heterocyclic group having one or more substituents, at least one of the substituent being any of a C1-C4 haloalkoxy group, a C2-C6 perfluoroalkyl group, a C1-C6 perfluoroalkylthio group, a C1-C6 perfluoroalkylsulfinyl group and a C1-C6 perfluoroalkylsulfonyl group, an insecticide comprising the compound as the active ingredient, and a process for preparation thereof.

Amide derivatives, process for preparation thereof and use thereof as insecticide

SMALL MOLECULES THAT SENSITIZE HIV-1 INFECTED CELLS TO ANTIBODY DEPENDENT CELLULAR CYTOTOXICITY

Compounds and methods of treating HIV-1 in a human infected with HIV-1 or preventing HIV-1 infection in a human susceptible to infection with HIV-1 are provided. The compounds are of formula (I), (II), and (IA), wherein R-R, X, X′, Y, Y′, Z, and n are defined herein, and the methods comprises administering therapeutically effective amounts of these compounds to the human.

KETAMINE DERIVATIVES AND COMPOSITIONS THEREOF

Ketamine derivatives and pharmaceutical compositions thereof are disclosed. When administered orally the ketamine derivatives provide increased bioavailability of ketamine in the systemic circulation. The ketamine derivatives can be used to treat neurological diseases, psychological diseases and pain. 2. The compound of claim 1 , wherein p is 1.3. The compound of claim 1 , wherein Ris hydrogen.4. The compound of claim 1 , wherein Ris Calkyl.5. The compound of claim 1 , wherein Ris methyl.6. The compound of claim 1 , wherein Ris —NH.7. The compound of claim 1 , wherein p is 1; and Ris hydrogen.8. The compound of claim 1 , wherein p is 1; and Ris Calkyl.9. The compound of claim 1 , wherein p is 1; and Ris methyl.10. The compound of claim 1 , wherein p is 1; and Ris —NH.13. The compound of claim 1 , wherein the compound is selected from:1-((((S)-1-(2-chlorophenyl)-2-oxocyclohexyl)(methyl)carbamoyl)oxy)ethyl nicotinate (14);1-(isonicotinoyloxy)ethyl (S)-1-(2-chlorophenyl)-2-oxocyclohexylmethylcarbamate (18);(nicotinoyloxy)methyl (S)-1-(2-chlorophenyl)-2-oxocyclohexylmethylcarbamate (29);(4-methylpyridine-3-carboxyloyloxy)methyl (S)-1-(2-chlorophenyl)-2-oxocyclohexylmethylcarbamate (54);(2-methylpyridine-3-carboxyloyloxy)methyl (S)-1-(2-chlorophenyl)-2-oxocyclohexylmethylcarbamate (55);(6-methylpyridine-3-carboxyloyloxy)methyl (S)-1-(2-chlorophenyl)-2-oxocyclohexylmethylcarbamate (56);(S)-(((1-(2-chlorophenyl)-2-oxocyclohexyl)(methyl)carbamoyl)oxy)methyl 2-aminonicotinate (61);(nicotinoyloxy)methyl (R)-1-(2-chlorophenyl)-2-oxocyclohexylmethylcarbamate (67);(R)-(((1-(2-chlorophenyl)-2-oxocyclohexyl)(methyl)carbamoyl)oxy)methyl 2-aminonicotinate (73); anda pharmaceutically acceptable salt of any of the foregoing.14. A pharmaceutical composition comprising the compound of or a pharmaceutically acceptable salt thereof.15. The pharmaceutical composition of claim 14 , wherein the pharmaceutical composition comprises an oral dosage form.16. A method of providing a ...

(4-Arylsulfonylamino) tetrahydropyran-4-carboxylsyrehydroxamider

间二取代苯酚化合物及其制备方法与抗结核菌应用

本发明提供了一类通式为(Ⅰ)的间二取代苯酚化合物、其制备方法与应用。所述的间二取代苯酚化合物具有新的抗结核菌药母核结构和优秀的抗结核菌活性，特别是对耐药的变异结核菌株也具有很强的抑制活性。本发明还提供了所述的间二取代苯酚化合物的制备方法，该制备方法的原料廉价易得，无需使用高毒性和高污染试剂，反应步骤简单，可实现工业化生产；具有良好的药用前景。

Diesters of 6-cyano-2,2-tetrahydropyrandicarboxylates

A compound of the formula ##STR1## wherein R' is lower alkyl, is useful as an intermediate in the preparation of a corresponding tricarboxylate, which is a useful detergent builder.

Blc-2 selective agents causing apoptosis for treating cancer and immune diseases

FIELD: medicine, pharmaceutics. SUBSTANCE: invention refers to compounds of formula I and formula IV wherein the radical values are such as specified in cl. 1 and 4 of the patent claim, as well as to their therapeutically acceptable salts. Besides, the invention refers to a composition for treating cancer on the basis of the compounds of formula I, to using the compounds of formula I for preparing the therapeutic agent for treating cancer, as well as to using it for treating cancer. EFFECT: there are prepared and described the new compounds which inhibit anti-apoptotic Bcl-2 and Bcl-x protein activity. 17 cl, 481 ex

Substituted derivatives of 4-aminocyclohexane

FIELD: chemistry. SUBSTANCE: invention relates to novel compounds of general formula (1), which possess an affinity to the µ-opiod receptor and the ORL1-receptor. The invention also relates to the application of the said compounds for obtaining medications, which can be used in treatment of fear, stress and associated with stress syndromes, depressions, epilepsy, Alzheimer's disease, senile dementia, general cognitive dysfunctions, learning and memory disorders (as nootropic), withdrawal syndromes, alcohol and/or drug abuse and/or abuse of medications and/or alcohol, narcotic and medication addiction, etc. In general formula (1) (1) Y 1 , Y 1   ' , Y 2 , Y 2   ' , Y 3 , Y 3   ' , Y 4 and Y 4   ' in each case stand for -H; Q stands for -R 0 , -C(=O)-R 0 , -C(=O)OR 0 , -C(=O)NHR 0 , -C(=O)N(R 0 ) 2 or-C(=NH)-R 0 ; R 0 in each case stands for -C 1-8 -aliphate, -C 3-12 -cycloaliphate, -aryl, -heteroaryl, -C 1-8 -aliphate-C 3-12 -cycloaliphate, -C 1-8 -aliphate-aryl, -C 1-8 -aliphate-heteroaryl, -C 3-8 -cycloaliphate-C 1-8 -aliphate, -C 3-8 -cycloaliphate-aryl or -C 3-8 -cycloaliphate-heteroaryl; R 1 and R 2 independently on each other stand for -C- 1-8 -aliphate; R 3 stands for -C 1-8 -aliphate, -aryl, -heteroaryl or -C 1-8 -aliphate-C 3-12 -cycloaliphate; n stands for 0; X stands for -NR A -;R A stands for -C 1-8 -aliphate; R B stands for -C 1-8 -aliphate; on condition that R 1 , R 2 , R A and R B simultaneously do not stand for the non-substituted-C 1-8 -aliphate. EFFECT: increased efficiency of the application of the compounds. 9 cl, 11 tbl, 164 ex РОССИЙСКАЯ ФЕДЕРАЦИЯ (19) RU (11) (51) МПК C07D 209/12 C07D 209/14 C07D 401/04 C07D 251/48 C07C 211/40 C07C 233/36 ФЕДЕРАЛЬНАЯ СЛУЖБА C07C 233/46 ПО ИНТЕЛЛЕКТУАЛЬНОЙ СОБСТВЕННОСТИ C07C 311/18 C07D 211/62 C07D 213/12 (12) ОПИСАНИЕ (21)(22) Заявка: (13) 2 532 545 (2006.01) (2006.01) (2006.01) (2006.01) (2006.01) (2006.01) (2006.01) (2006.01) (2006.01) (2006.01) C07D C07D C07D A61K A61K A61K A61P A61P 213/ ...

Замещенные производные 4-аминоциклогексана

Изобретение относится к новым производным 4-аминоциклогексана, которые обладают сродством к µ-опиоидному рецептору и ORL1-рецептору. В формуле (1) Y 1 , Y 1 ', Y 2 , Y 2 ', Y 3 , Y 3 ', Y 4 и Y 4 ' означают -Н; Q означает -R 0 , -C(=O)-R 0 или -C(=NH)-R 0 ; R 0 и R 3 в каждом случае независимо означает -C 1-8 -алифат, -арил, -гетероарил, -C 1-8 -алифат-С 5 -циклоалифат, -C 1-8 -алифат-арил; R 1 и R 2 , независимо означают незамещенный -C 1-8 -алифат; -C 1-8 -алифат-C 5 -циклоалифат, -C 1-8 -алифат-арил; n означает 0; Х означает -NR A -; R A означает незамещенный -C 1-8 -алифат; R B означает незамещенный -C 1-8 -алифат; «алифат» представляет собой неразветвленный, насыщенный, незамещенный или моно- или многократно замещенный атомами -F углеводородный остаток; «циклоалифат» представляет собой насыщенный, незамещенный моноциклический углеводородный остаток, с 5 атомами углерода в цикле; «арил» означает фенил, который может быть замещенным -F, -R 0 и -OR 0 ; «гетероарил» означает 5-членный циклический ароматический остаток, который содержит 1 гетероатом, причем гетероатом представляет собой N или S, и гетероцикл может быть замещенным -F, -R 0 и -OR 0 ; гетероцикл может быть частью бициклической системы, включающей фенил. Изобретение также относится к лекарственному средству, содержащему указанные соединения, и к применению соединений для получения лекарственного средства для лечения: боли, стресса, эпилепсии, нарушений обучения и памяти, медикаментозной зависимости, сердечно-сосудистых заболеваний, нарушений приема пищи, локомоторных расстройств. 4 н. и 5 з.п. ф-лы, 10 табл., 164 пр. РОССИЙСКАЯ ФЕДЕРАЦИЯ (19) RU (11) 2 503 660 (13) C2 (51) МПК C07D C07C C07D A61K A61K A61K ФЕДЕРАЛЬНАЯ СЛУЖБА A61K ПО ИНТЕЛЛЕКТУАЛЬНОЙ СОБСТВЕННОСТИ A61P A61P A61P (12) ОПИСАНИЕ 209/04 (2006.01) 211/40 (2006.01) 333/10 (2006.01) 31/135 (2006.01) 31/132 (2006.01) 31/381 (2006.01) 31/404 (2006.01) 25/00 (2006.01) 1/00 (2006.01) 9/00 (2006.01) ИЗОБРЕТЕНИЯ К ПАТЕНТУ (72) Автор(ы ...

APOPTOSIS INDUCING AGENTS SELECTIVE FOR Bcl-2 FOR CANCER AND IMMUNE DISEASES TREATMENT

FIELD: pharmacy. SUBSTANCE: invention relates to specific heterocyclic compounds containing the sulphonyl amino carbonyl group. The invention also relates to a pharmaceutical composition based on this compound. EFFECT: new heterocyclic compounds with inhibitory activity in terms of anti-apoptotic Bcl-2 proteins are obtained. 2 cl, 3 tbl, 481 ex РОССИЙСКАЯ ФЕДЕРАЦИЯ (19) RU (11) (13) 2 621 052 C2 (51) МПК C07D 295/14 (2006.01) C07D 405/12 (2006.01) C07D 405/14 (2006.01) A61K 31/453 (2006.01) A61K 31/46 (2006.01) A61K 31/496 (2006.01) ФЕДЕРАЛЬНАЯ СЛУЖБА A61K 31/5377 (2006.01) ПО ИНТЕЛЛЕКТУАЛЬНОЙ СОБСТВЕННОСТИ A61P 35/00 (2006.01) (12) ФОРМУЛА (21)(22) Заявка: ИЗОБРЕТЕНИЯ К ПАТЕНТУ РОССИЙСКОЙ ФЕДЕРАЦИИ 2013133800, 19.07.2013 (24) Дата начала отсчета срока действия патента: 04.12.2009 Дата регистрации: Приоритет(ы): (30) Конвенционный приоритет: (43) Дата публикации заявки: 27.01.2015 Бюл. № 3 2 6 2 1 0 5 2 R U Адрес для переписки: 129090, Москва, ул. Б. Спасская, 25, строение 3, ООО "Юридическая фирма Городисский и Партнеры" (73) Патентообладатель(и): ЭББВИ ИНК. (US) (56) Список документов, цитированных в отчете о поиске: US 2007/072860 A1, 29.03.2007. US 2005/159427 A1, 21.07.2005. EA 9201 B1, 28.12.2007. (54) СЕЛЕКТИВНЫЕ К BCL-2 АГЕНТЫ, ВЫЗЫВАЮЩИЕ АПОПТОЗ, ДЛЯ ЛЕЧЕНИЯ РАКА И ИММУННЫХ ЗАБОЛЕВАНИЙ (57) Формула изобретения 1. Соединение, выбранное из: 2-(бензилокси)-4-(4-((4'-хлор-1,1'-дифенил-2-ил)метил)пиперазин-1-ил)-N-((3-нитро4-((тетрагидро-2Н-пиран-4-илметил)амино)фенил)сульфонил)бензамида; 4-(4-((4'-хлор-1,1'-дифенил-2-ил)метил)пиперазин-1-ил)-N-((3-нитро-4-((тетрагидро2Н-пиран-4-илметил)амино)фенил)сульфонил)-2-(2-фенилэтокси)бензамида; 2-бензил-4-(4-((4'-хлор-1,1'-дифенил-2-ил)метил)пиперазин-1-ил)-N-((3-нитро-4-( (тетрагидро-2Н-пиран-4-илметил)амино)фенил)сульфонил)бензамида; 2-бензил-4-(4-((4'-хлор-1,1'-дифенил-2-ил)метил)пиперазин-1-ил)-N-((4-((тетрагидро2Н-пиран-4-илметил)амино)фенил)сульфонил)бензамида; Стр.: 1 C 2 C 2 (45) Опубликовано: 31.05.2017 Бюл. № ...

适用作h3配体的3－或4－单取代酚及苯硫酚衍生物

本发明涉及式(1)的3－或4－单取代酚及苯硫酚衍生物，并涉及制备该衍生物的方法、制备该衍生物中使用的中间体、含有该衍生物的组合物和该衍生物的用途。所述3－或4－单取代酚及苯硫酚衍生物为H 3 配体且适用于多种疾病、障碍及病况，尤其适用于炎性、过敏性及呼吸疾病、障碍及病况。

3- or 4-monosubstituted phenol and thiophenol derivatives useful as h3 ligands

본 발명은 화학식 1의 3- 또는 4-단일치환된 페놀 및 싸이오페놀 유도체 및 이러한 유도체의 제조 방법, 이러한 제조에 유용한 중간체, 이것을 함유한 조성물 및 이것의 용도에 관한 것이다. The present invention relates to 3- or 4-monosubstituted phenol and thiophenol derivatives of formula (1) and to methods of preparing such derivatives, intermediates useful for such preparations, compositions containing them and the use thereof. 화학식 1 Formula 1 3- 또는 4-단일치환된 페놀 및 싸이오페놀 유도체는 H 3 리간드이며, 많은 질병, 질환 및 증상, 특히 염증성, 알러지성 및 호흡기 질병, 질환 및 증상에 유용하다. 3- or 4-monosubstituted phenols and thiophenol derivatives are H 3 ligands and are useful for many diseases, conditions and symptoms, in particular inflammatory, allergic and respiratory diseases, diseases and conditions.

胍化合物

本发明提供作为药物组合物、特别是作为VAP-1相关疾病的预防和／或治疗用药物组合物的有效成分有用的化合物。本发明人对于具有VAP-1抑制活性的化合物进行了广泛深入的研究，结果发现，本发明化合物或其盐显示优异的VAP-1抑制活性，对于VAP-1相关疾病、特别是糖尿病性肾病或糖尿病性黄斑水肿的预防和／或治疗有用，并完成了本发明。另外，本发明涉及含有本发明化合物或其盐和赋形剂的药物组合物，特别是VAP-1相关疾病的预防和／或治疗用药物组合物。

基质金属蛋白酶抑制剂

下式化合物或其药用盐或酯具有很有用的药理学性能，具体说是用来作为基质金属蛋白酶抑制剂，尤其对于间质胶原酶的抑制。式中的R 1 、R 2 、R 3 、R 4 、R 5 、n和y如说明书中所述。

作为用于治疗癌症和免疫疾病的bcl-2-选择性诱发细胞凋亡药剂的磺酰胺衍生物

作为用于治疗癌症和免疫疾病的BCL‑2‑选择性诱发细胞凋亡药剂的磺酰胺衍生物。公开了抑制抗细胞凋亡Bcl‑2或Bcl‑xL蛋白活性的化合物，含该化合物的组合物和治疗在其期间表达抗细胞凋亡Bcl‑2蛋白的疾病的方法。

Amide derivatives, process for preparation thereof and use thereof as insecticide

본 발명의 목적은 높은 효과를 갖는 살충제를 제공하는 것에 있다. An object of the present invention is to provide a pesticide having a high effect. 일반식 (1) General formula (1) (식 중, A 1 , A 2 , A 3 , A 4 는 각각 탄소원자, 질소원자 또는 산화된 질소원자를 나타내며, R 1 , R 2 는 각각 수소원자, 치환되어 있어도 좋은 알킬기 등을 나타내고, G 1 , G 2 는 각각 산소원자 또는 유황원자를 나타내고, X는 동일하거나 달라도 좋고, 수소원자, 할로겐 원자, C1-C3 알킬기, 트리플루오로메틸기를 나타내고, n은 0~4의 정수를 나타내고, Q 1 은 치환되어 있어도 좋은 페닐기, 치환되어 있어도 좋은 복소환기 등을 나타내고, Q 2 는 1개 이상의 치환기를 갖는 페닐기 혹은 복소환기이고, 그 치환기의 적어도 1개는 C1-C4 할로알콕시기 등인 것을 나타낸다.) Wherein A 1 , A 2 , A 3 , and A 4 each represent a carbon atom, a nitrogen atom, or an oxidized nitrogen atom, and R 1 and R 2 each represent a hydrogen atom, an optionally substituted alkyl group, or the like. G 1 and G 2 each represent an oxygen atom or a sulfur atom, X may be the same or different, a hydrogen atom, a halogen atom, a C1-C3 alkyl group, a trifluoromethyl group, n represents an integer of 0 to 4, and Q 1 represents a phenyl group which may be substituted, a heterocyclic group which may be substituted, and the like, Q 2 is a phenyl group or heterocyclic group having one or more substituents, and at least one of the substituents represents a C1-C4 haloalkoxy group or the like. ) 로 표시되는 화합물 및 이것을 유효 성분으로 함유하는 살충제 및 그 제조 방법. The compound represented by this, Insecticide containing this as an active ingredient, and its manufacturing method. 아미드 유도체, 아미드 유도체의 제조 방법, 살충제로서의 사용 방법  Amide Derivatives, Methods of Making Amide Derivatives, Methods of Use as Insecticides

3- or 4-monosubstituted phenol and thiophenol derivatives useful as H3 ligands

制备烷基－二卤代苯基取代的酮烯醇的中间体

用于制备烷基-二卤代苯基取代的酮烯醇的中间体化合物：式(XXII)、(XXV)、(XXVI)、(XXXV)和(VI)化合物，其中各代号意义见说明书。

Derivatives of hydroxamic and carboxylic acid showing mmp-inhibiting activity and pharmaceutical composition based on thereof

FIELD: organic chemistry, biochemistry, pharmacy. SUBSTANCE: invention describes derivatives of hydroxamic and carboxylic acid with MMP-inhibiting activity represented by the formula (I) where m = 0-1; X means SO 2 ; Y means OH or NHOH; R 1 means optionally substituted C 1-6 -alkyl or piperidinyl; R 2 means hydrogen atom or C 1-6 -alkyl; or CR 1 R 2 means optionally substituted cycloalkyl, piperidinyl or tetrahydropyranyl; each B is similar or different and means hydrogen atom, C 1-6 -alkylnaphthyl, C 1-6 - alkylphenyl, C 1-6 -alkyl, cycloalkyl that is condensed optionally with benzene, C 1-6 -alkylcycloalkyl, phenyl, furanyl, thiophenyl, pyrrolyl that are optionally condensed with benzene, C 1-6 -alkylbenzofuranyl, C 1-6 - alkylbenzothiophenyl, C 1-6 -alkylindolyl where any of these groups is substituted optionally, or B-N-B is piperidinyl substituted with =NOR 4 ; or when neither R 1 nor R 2 is not hydrogen atom then B-N-B means piperazinyl, piperidinyl, pyrrolidinyl optionally condensed with benzene and optionally substituted; R 4 means hydrogen atom, C 1-6 -alkyl, phenyl, C 1-6 -alkylphenol, pyridyl, pyrazinyl optionally substituted, and its salts, solvates, hydrates, protected amino, carboxy or protected derivatives of hydroxamic acid and pharmaceutical composition eliciting MMP-inhibiting activity. Described compounds can be used for treatment of prevention of state associated with activity of matrix metalloproteinases. EFFECT: valuable medicinal and biochemical properties of compounds. 13 cl 1 9950г сс ПЧ сэ (19) 13) ВО ^”_2 210 567 ^^ С2 ОМК С 07С 314/04, С 070 211/96, 233/72, 309/08, 401/12, 405/12, А 61 К 31/4409, 31/4178, 31/351, А 61 Р 35/00, 9/10, 11/06 РОССИЙСКОЕ АГЕНТСТВО ПО ПАТЕНТАМ И ТОВАРНЫМ ЗНАКАМ 12) ОПИСАНИЕ ИЗОБРЕТЕНИЯ К ПАТЕНТУ РОССИЙСКОЙ ФЕДЕРАЦИИ (21), (22) Заявка: 2000114881/04, 12.11.1998 (71) Заявитель: ДАРВИН ДИСКАВЕРИ ЛИМИТЕД (СВ) (24) Дата начала действия патента: 12.11.1998 (72) Изобретатель: БАКСТЕР Эндрю Дуглас (СВ), (30) Приоритет: ...

Hydroxamic acid and carboxylic acid derivatives having MMP and inhibitory activity

(57)【要約】 ｍは０−２であり；ＸはＳ（Ｏ） 1-2 であり；ＹはＯＨまたはＮＨＯＨおよび他の変数である式（Ｉ） 【化１】