СПОСОБЫ ПОЛУЧЕНИЯ ЗАМЕЩЕННЫХ АРИЛКОНДЕНСИРОВАННЫХАЗАПОЛИЦИКЛИЧЕСКИХ СОЕДИНЕНИЙ, ПРОМЕЖУТОЧНЫЕ ПРОДУКТЫ И СПОСОБЫ ИХ ПОЛУЧЕНИЯ

Изобретение относится к новому способу получения замещенных арилконденсированных азаполициклических соединений формул (II) и (VIII), новым промежуточным продуктам и способам их получения. Замещенные арилконденсированные азаполициклические соединения формулы (II) обладают свойствами связываться с нейроновыми никотиновыми ацетилхолиновыми специфическими рецепторными сайтами и могут быть использованы при модулировании холинергической функции для лечения различных заболеваний. Способ получения соединения формулы (II) где R6 представляет собой водород, R2 и R3 выбраны независимо из водорода, галогена, (С1-С6)алкила, необязательно замещенного от 1 до 3 атомами фтора и (С1-С6)алкокси, необязательно замещенного от 1 до 3 атомами фтора, включает гидрирование соединения формулы (1а)': полученного из соединения формулы (III), с получением промежуточно образующихся соединений формулы (IX) и (VII): Соединение (VII) при обработке основанием циклизуется, с получением соединения формулы (VIII), которое ...

Способ получения бициклических сложных эфиров или их фармацевтически приемлемых солей

Изобретение относится к гетероциклическим соединениям, в частности к получению бициклических сложных эфиров ф-лы I.: CO-Z-RI о,-Из &CHi Изобретение относится к способу получения новых соединений - бициклических сложных эфиров формулы I co-z-Ri ° №тсн где R,) - Н или галоген, или метил; m - целое число, равное 1 или 2; или NH-группа; R - хинуклидинил или радикал ф-лы: №) А. S-A, где RJ - С(-Сз алкил; р и q - целое число равно 0 или 1, или их фармацевтически приемлемых солей, которые обладают направленным против мигрени действием. Цель - разработка способа получения соединений, обладающих указанным действием. Получение ведут из соединения ф-лы I, где ГО имеет группу X, которая обозначает ОН, С1 или Вг, или С(-С4 ацилокси- группа, a R, Rj и m - указаны выше с соединением ф-лы H-Z-R, где Z и R - указаны выые. Целевой продукт выделяют в свободном виде или в виде фармацевтически приемлемой соли. где R - атом водорода или галогена, или метил, m - целое число, равное 1 или 2, Z.0 или NH-группа, ...

PSYCHOTROPIC POLYCYCLIC IMIDES

Aryl fused azaplycyclic compounds

COMPOUNDS THAT INHIBIT MCL-1 PROTEIN

Aryl fused azapolycyclic compounds.

Compounds of formula and their pharmaceutically acceptable salts, wherein r1, r2, r3 and n are defined as in the specification, intermediates in the synthesis of such compounds, pharmaceutical compositions containing such compounds and methods of using such compounds in the treatment of neurological and psychological disorders are claimed.

Aryl fused azapolycyclic compounds.

COMPOUNDS THAT INHIBIT MCL-1 PROTEIN

Aryl fused azapolycyclic compounds

Azabicycloalkanes as CCR5 modulators.

Aryl fused azaplycyclic compounds

Use of GABAA inverse agonists in combination with nicotine receptor partial agonists, estrogen, selective estrogen modulators, or Vitamin E for the treatment of cognitive disorders.

A pharmaceutical composition and method of treatment of diseases of cognitive dysfunction in a mammal comprising administration of a GABAA inverse agonist, or a pharmaceutically acceptable salt thefeof; and a nicotine receptor partial agonist, an estrogenic agent, selective estrogen receptor modulator or vitamin E or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier. The GABAA inverse agonist, and nicotine receptor partial agonist, estrogen, selective estrogen receptor modulator or vitamin E are present in amounts that render the composition effective enhancing cognition or in the treatment of diseases of cognitive dysfunction including but not limited to Alzheimer's Disease (AD), mild cognitive impairment, age-related cognitive decline, vascular dementia, Parkinson's disease, Huntington's disease, memory impairment associated with depression or anxiety, schizophrenia, Down's syndrome, stroke, traumatic brain injury (TBI), AIDS associated dementia and ...

8-Azabicyclo(3,2,1) octane-88-azabicycle(3,2,1) oct-6-ene-, 9- azabicycle(3,3,1) nonana-9-aza-3- oxabicylo(3,3,1) nonane-and 9-aza-3- thiabicyclo(3,3,1) nonane derivatives, their preparation and their use as insecticides.

A compound of formula (i)wherein a represents a bidentate group of the formula -ch2-x-ch2- (wherein x is methylene, sulfur or oxygen), x'c=cy or x'wc-cyz (wherein x, w, y and z are independently hydrogen, hydorxy, acyloxy, alkoxy, alkylsilyloxy, cyano or halogen, or x' and w or y and z together with the carbon to which they are attached form a carbonyl group), provided that a is not ch2-ch2; ar is an optionally substituted phenyl or 5- or 6-membered heterocyclic ring system containing from 1 to 3 heteroatoms individualy slected from nitrogen, oxygen and sulfur atoms, and at least one unsaturation (double bond)between adjacent atoms in the ring, said heterocyclic ring being optionally fused to a benzene ring, wherein the substituents, if present, are selected from halogen atoms, cyano, alkyl, alkenyl, alkynyl, alkoxy, haloalkenyl, alkylthio and alkyl amino groups, any of which groups contain up to six carbon atoms; r is hydrogen or cyano or a group selected from alkyl, aryl, heteroaryl, ...

Azabicycloalkanes as ccr5 modulators

Aryl fused azapolycyclic compounds.

Azabicycloalkanes as CCR5 modulators.

Use of GABA a inverse agonists in combination withnicotine receptor partial agonists, estrogen, sel ective estrogen modulators, or bitamin E for the treatment of cognitive disorders.

8-AzabicycloÄ3.2.1Üoctane-, 8-azabicycloÄ3.2.1Üoct-6-ene 9-azabicycloÄ3.3.1Ünonane- 9-aza-3-oxabicycloÄ3.3.1Ünonane-and 9-aza-3-thiabicycloÄ3.3.1Ünonane derivatives their preparation and their use as insecticides

Aryl fused azapolycyclic compounds.

COMPOUNDS THAT INHIBIT MCL-1 PROTEIN

Azabicycloalkanes as ccr5 modulators

Use of gaba inverse agonists in combination with nicotine receptor partial agonists estrogen selective estrgen modulators or vitamin e for the treatment of cognitive dosorders

Aryl fused azapolycyclic compounds

Use of gaba inverse agonists in combination with nicotine receptor partial agonists estrogen selective estrgen modulators or vitamin e for the treatment of cognitive dosorders

Aryl fused azapolycyclic compounds

Azabicycloalkanes as ccr5 modulators

BINARY NK1/NK3 ANTAGONIST FOR THE TREATMENT OF SCHIZOPHRENIA

ARYL-CONDENSED AZAPOLYCYCLI DERIVATIVES

MACRO-CYCLIC PYRIMIDINE, THEIR PRODUCTION AND USE AS DRUGS

PROCEDURE FOR the PRODUCTION of the NEW ONE 2.5 - - DIMETHYL THIENO (2,3-F) MORPHANS

AZABICYCLOALKANE AS CCR5-MODULATOREN

TRICYCLI PYRIDONDERIVATE.

5- OR 6-RING-ENTHALTENDE MAKROCYCLI POLYAZA CONNECTIONS, PROCEDURES FOR YOUR PRODUCTION AND THESE CONTAINING PHARMACEUTICAL MEANS.

Improved method for producing intermediates for the production of macrocycles that are inhibitors of the proteasomic degradation of p27, such as argyrin and derivatives thereof

The present invention relates to an improved method for the synthesis of particular macrocycles that are inhibitors of the proteasomic degradation of p27, in particular argyrin and derivatives thereof.

Macrocyclics pyrimidines as Aurora kinase inhibitors

Macrocyclic derivative compounds that inhibit protein kinase enzymes are disclosed along with pharmaceutical compositions comprising these compounds and methods for synthesizing the same. Such compounds have utility in the treatment of proliferative diseases resulting from unregulated and/or disturbed kinase activity such as cancers, psoriasis, viral and bacterial infections, inflammatory and autoimmune diseases.

Cathepsin cysteine protease inhibitors

This invention relates to a compounds of formula (I) which are cysteine protease inhibitors, including but not limited to, inhibitors of cathepsins K, L, S and B. These compounds are useful for treating diseases in which inhibition of bone resorption is indicated, such as osteoporosis.

Benzo-fused macrocycles promote release of growth hormone

9-AZA-3(OXA OR THIA)BICYCLO(3,3,1)NONANE DERIVATIVES

IMMUNOREGULATION

ABSTRACT Donor tissue is treated prior to implantation in a recipient with a compound from the class known as epipolythiodioxopiperazines in order to prevent graft rejection.

DUAL NK1/NK3 ANTAGONISTS FOR TREATING SCHIZOPHRENIA

The use of compounds of the general formula wherein the substituents are as described in claim 1 or pharmaceutically active acid-addition salts thereof for the preparation of medicaments for the treatment of schizophrenia.

PREPARATION OF ANTIMICROBIAL FORMULATIONS USING 7-OXA-2-THIA-1,5-DIAZABICYCLO[3.3.1]NONANE-2,2-DIONE

Use of 7-oxa-2-thia-1,5-diazabicyclo[3.3.1]nonane-2,2--dione ("cyclotaurolidin") for the preparation of antimicrobial formulations, in particular antimicrobial solutions for technical or medical purposes and of aqueous lock solutions for catheters and port systems for preventing infections and sepsis of patients.

CATHEPSIN CYSTEINE PROTEASE INHIBITORS

This invention relates to a compounds of formula (I) which are cysteine protease inhibitors, including but not limited to, inhibitors of cathepsins K, L, S and B. These compounds are useful for treating diseases in which inhibition of bone resorption is indicated, such as osteoporosis.

ANTITUMORAL AND ANTIVIRAL COMPOUND

The novel compound pateamine of formula has antitumour and antiviral activity. Immunosuppressive activity is also present.

AZABICYCLIC AMIDES OR ESTERS OF HALOGENATED BENZOIC ACIDS

... 2098729 9211259 PCTABS00014 Compounds of formula (I) wherein Z is a di-azacyclic or azabicyclic side chain having 5-HT3 receptor antagonist activity.

TREATMENT OF IMMUNOREGULATORY DISORDERS

A therapeutic method is provided to elevate a depressed mammalian autologous mixed lymphocyte response and to alleviate the diseases associated therewith by the administration of an effective amount of certain selective delta opioid receptor antagonists to a mammal such as a human patient in need of such treatment.

ISOQUINOLINE AMIDES AND ESTERS AS 5 HT3 RECEPTOR ANTAGONISTS

... 2081350 9117161 PCTABS00008 Isoquinoline derivatives (I) having 5-HT3 receptor antagonist activity, a process for their preparation and their use as pharmaceuticals. In formula (I) E is NH or O, R1 is hydrogen, halogen, alkyl, alkoxy, hydroxy or nitro; Z is an azacyclic or azabicyclic side chain, such as a group of formula (a), (b) or (c) wherein; p is 1 or 2; q is 1 to 3; r is 1 to 3; R3 or R4 is hydrogen or alkyl, and Y is a group -CH2-X-CH2- wherein X is -CH2-, oxygen, sulphur or X is a bond; and (I) when the group CO-E-Z is in the 1-position and either R2 is in the 3-position and is hydrogen, alkyl, or alkoxy, or R2 is in the 4-position and is hydrogen CF3, alkyl, acyl, acylamino (substituted) phenyl or (substituted) amino, (substituted) aminocarbonyl or (substituted) aminosulphonyl; (II) the group CO-E-Z- is in the 3-position and either R2 is in the 1-position and is hydrogen, alkyl or alkoxy or R2 is in the 4-position and is hydrogen or alkoxy.

Verfahren zur Schädlingsbekämpfung

Verfahren zur Herstellung von neuen sekundären bzw. tertiären cyclischen Aminen bzw. Phosphinen

VERFAHREN ZUR HERSTELLUNG VON TERTIAEREN CYCLISCHEN AMINEN UND/ODER PHOSPHINEN.

PROCEDURE FOR THE PRODUCTION OF N-CHLORCARBONYLLACTAMEN.

Арилконденсированные азаполициклические соединения

Использование: в медицине. Задача: получение арилконденсированных азаполициклических соединений, фармацевтических композиций на их основе; разработка способов их применения для лечения нервных и психических расстройств, химических зависимостей и пристрастий, заболеваний воспалительной природы. Сущность изобретения: синтезированы соединения формулы (I) где R1, R2, R3 такие, как определено в формуле изобретения; получены фармацевтические композиции, содержащие такие соединения; разработаны способы их применения. 5 н. п. ф-лы.

DERIVATIVES OF MONO DISUBSTITUTED INDOLES AS INHIBITORS OF REPLICATION DENGUE VIRUSES

Азаполициклические соединения

Использование: фармацевтика, медицина. Задача: создание конденсированных с арилом азаполициклических соединений, применяющихся для лечения неврологических и психических расстройств. Сущность изобретения: заявляются соединения формулы (I) и их фармацевтически приемлемые соли, в которых R1, R2, R3 и n представляют собой указанные в описании, промежуточные соединения в синтезе таких соединений, фармацевтические композиции, содержащие такие соединения, и способы применения таких соединений для лечения неврологических и психологических расстройств. 2 н.п. ф-лы, 5 з.п. ф-лы, 49 прим.

ARILKONDENSIROVANNYEAZAPOLITsIKLIChESKIE COMPOUNDS

СОЕДИНЕНИЯ, КОТОРЫЕ ИНГИБИРУЮТ БЕЛОК MCL-1

The invention provides myeloid cell leukemia 1 protein (Mcl-1) inhibitors, methods of their preparation, related pharmaceutical compositions and methods of using the same. For example, provided herein are compounds of Formula Iand pharmaceutically acceptable salts thereof and pharmaceutical compositions containing said compounds. The compounds and compositions provided herein may be used, for example, in the treatment of diseases or conditions, such as cancer.

АЗАПОЛИЦИКЛИЧЕСКИЕ СОЕДИНЕНИЯ, КОНДЕНСИРОВАННЫЕ С АРИЛОМ

... (57) Заявляются соединения формулы (I) и их фармацевтически приемлемые соли, в которых R1, R2, R3 и n представляют собой указанные в описании, промежуточные соединения в синтезе таких соединений, фармацевтические композиции, содержащие такие соединения, и способы применения таких соединений для лечения неврологических и психологических расстройств. Международная заявка была опубликована вместе с отчетом о международном поиске.

МАКРОЦИКЛИЧЕСКИЕ ПИРИМИДИНЫ, ИХ ПОЛУЧЕНИЕ И ИХ ПРИМЕНЕНИЕ В КАЧЕСТВЕ ЛЕКАРСТВЕННЫХ СРЕДСТВ

В заявке описаны макроциклические пиримидиновые производные общей формулы (I) в которой R1-R5, X, Y, A, B, m и n имеют указанные в описании значения, в качестве ингибиторов циклинзависимых киназ, а также описаны способ получения этих соединений и их применение в качестве лекарственных средств для лечения различных заболеваний. Международная заявка была опубликована вместе с отчетом о международном поиске.

КОНДЕНСОВАНІ З АРИЛОМ АЗАПОЛІЦИКЛІЧНІ СПОЛУКИ

Винахід стосується сполук формули (I) та їх фармацевтично прийнятних солей, де R1, R2 та R3 є визначеними, інтермедіатів для синтезу цих сполук, фармацевтичних композицій, що містять такі сполуки, та способів використання цих сполук у лікуванні неврологічних та психологічних розладів (І).

АЗАПОЛІЦИКЛІЧНІ СПОЛУКИ, КОНДЕНСОВАНІ З АРИЛОМ

Заявляються сполуки формули (І) і їх фармацевтично прийнятні солі, в яких R1, R2, R3 і n являють собою зазначене в описі, проміжні сполуки в синтезі таких сполук, фармацевтичні композиції, що містять такі сполуки, і засоби застосування таких сполук для лікування неврологічних і психологічних розладів.

АЗАПОЛИЦИКЛИЧЕСКИЕ СОЕДИНЕНИЯ, КОНДЕНСИРОВАННЫЕ С АРИЛОМ

... 1. Соединение формулы где R1представляет собой водород, (C1-C6)алкил, неконъюгированный (C3-C6)алкенил, XC(=O)R13, бензил или -CH2CH2-O-(C1-C4) алкил; R2и R3независимо выбирают из водорода, (C2-C6)алкенила, (C2-C6 )алкинила, гидрокси, нитро, амино, гало, циано, -SOq(C1-C6)алкила, где q равно нулю, одному или двум, (C1-C6)алкиламино-, [(C1-C6)алкил]2амино-, -CO2 R4, CONR5R6, -SO2NR7R8, -C(=O)R13, -XC(=O)R13, арил-(C0-C3)алкила- или арил-(C0-C3 )алкил-O-, где указанный арил выбирают из фенила и нафтила, гетероарил-(С0-C3)алкила- или гетероарил-(C0-C3 )алкил-O-, где указанный гетероарил выбирают из 5-7-членных ароматических колец, содержащих от одного до четырех гетероатомов, выбранных из кислорода, азота и серы, X2(C0-C6)алкила- и X2(C1 -C6)алкокси-(C0-C6)алкила-, где X2отсутствует или X2представляет собой (C1-C6)алкиламино- или [(C1-C6)алкил]2амино-, и где (C0 -C6)алкильная или (C1-C6)алкокси-(C0-C6)алкильная части указанных X2(C0-C6)алкила- или X2(C1-C6)алкокси-(С0-C6)алкила- содержат, ...

AZAPOLYCYCLIC COMPOUNDS CONDENSATED WITH ARYL

AZAPOLYCYCLIC COMPOUNDS CONDENSED WITH ARYL

TETRAHYDRONAPHTHALENE DERIVATIVES THAT INHIBIT MCL-1 PROTEIN

Арил-сопряженные азаполициклические соединения, содержащащая их композиция и применение

... 1. Технический результат Усиление лечебных свойств без побочных явлений. 2. Суть Соединения, формулы I (значения R1, R2и R3даны в описании) их фармацевтически приемлемые соли, содержащая их фармацевтическая композиция и применение в медицине для модулирования холинергической функции. 3. Область применения Медицина. Пунк.: 8 незав. 24 зав.

Compounds, which inhibit activity of protein Mcl-and-1

Aryl Fused Azapolycyclic Compounds, Composition Containing the Same and Use Thereof

Piperazinedione derivs prepn

DUAL NK1/NK3 ANTAGONISTS FOR TREATING SCHIZOPHRENIA

8-AZABICYCLO/3.2.1/OCTANE-, 8-AZABICYCLO/3.2.1/OCT-6-ENE-, 9-AZABIBYCLO/3.3.1/NONANE-, 9-AZA-3-AZABICYCLO/3.3.1/NONANE- AND 9-AZA-3-THIABICYCLO/3.3.1/NONANE- DERIVATIVES, THEIR PREPARATION AND THEIR USE AS INSECTICIDES

A compound of formula (I) wherein A, R, R1 and Ar are disclosed in the first claim; an insecticidal, acaricidal or nematicidal composition comprising a compound of formula (I) and a suitable carrier or diluent therefor; a method of combating and controlling insect, acarine or nematode pests at a locus which comprises treating the pests or the locus of the pests with an effective amount of a compound of formula (I) or a composition as hereinbefore described.

DUAL NK1/NK3 ANTAGONISTS FOR TREATING SCHIZOPHRENIA

MCL-1 INHIBITORS

ARYL FUSED AZAPOLYCYCLIC COMPOUNDS

CATHEPSIN CYSTEINE PROTEASE INHIBITORS

This invention relates to a compounds of formula (I) which are cysteine protease inhibitors, including but not limited to, inhibitors of cathepsins K, L, S and B. These compounds are useful for treating diseases in which inhibition of bone resorption is indicated, such as osteoporosis.

MACROCYCLICS PYRIMIDINES AS AURORA KINASE INHIBITORS

Macrocyclic derivative compounds that inhibit protein kinase enzymes are disclosed along with pharmaceutical compositions comprising these compounds and methods for synthesizing the same. Such compounds have utility in the treatment of proliferative diseases resulting from unregulated and/or disturbed kinase activity such as cancers, psoriasis, viral and bacterial infections, inflammatory and autoimmune diseases.

3-AZA-6,8-DIOXABICYCLO[3.2.1]OCTANES AND ANALOGUES AND COMBINATORIAL LIBRARIES

The present invention relates to new highly functionalized heterobicycle derivatives of general formula (I), prepared by a process which involves only two steps by using, as starting products, commercially available, or easily prepared, α-amino ketones and α,β-dihydroxy acids or α-amino-β-hydroxy acids or α-hydroxy-β-amino acids or α,β-dithiol acids derivatives and to libraries containing compounds of formula (I) and to the generation of such combinatorial libraries composed of compounds of formula (I), in individual synthesis, mixture synthesis, split and recombine synthesis and parallel synthesis either in manual or automated fashion.

ANTIBIOTIC AND PHARMACEUTICAL PREPARATION

NEW MATERIAL:A compound shown by the formula I [R1 and R2 are H or organic residue bonded through C or SO2; X is group shown by the formula II W formula V (R4 is H, OH, halogen, etc.; R5 is bifunctional group bonded through two carbons; △- is bonded to para-position of R1O of benzene ring and "square"- is lined to meta-position); R8 is carboxy or group derived from it; Y is CO or group shown by the formula VI (R7 and -OR1 wherein R1 is organic residue bonded through carbon atom form 5-membered ring)] or its salt. EXAMPLE: 25-Demethylthio-25-methylsulfonyl-TAN-528A. USE: A remedy for microbism of mammals or an antibacterial agent. PREPARATION: For example, antibiotic TAN-528A shown by the formula VII obtained by cultivating a bacterium belonging to the genus Streptomyces is reacted with m-chloroperbenzoic acid, dichloromethane is distilled away, the residue is extracted with an ACOEt solution and the example compound is collected from the extracted solution. COPYRIGHT: (C)1986,JPO&Japio ...

アリール縮合アザ多環状化合物

... 【化1】 本発明は、式(I)の化合物及びその薬学的に許容可能な塩(式中、R1、R2及びR3は本明細書中に定義される)、前記化合物の合成のための中間体、前記化合物を含有する医薬組成物、並びに神経及び精神の障害の治療における前記化合物の使用方法に向けられている。 ...

BICYCLO COMPOUND

PURPOSE: To provide the new compound exhibiting a cymerine-like activity and useful as a therapeutic agent, etc., for immune deficient diseases, autoimmune diseases, etc. CONSTITUTION: A compound of formula I [R1, R2 are H, lower alkyl; R3, R4 are H, lower alkyl, carboxyl, lower alkoxycarbonyl; R5 is H, lower alkyl; X is O, NR6 (R6 is H, lower alkyl, alkoxy, etc.); A is alkyl; (n) is 0, 1]. For example, (6,6-dimethyl-9-oxo)-3,5-dithio-8-oxabicyclo[5,2,1]decane. The compound of formula I is obtained by subjecting a dithiol compound of formula II to an oxidative ring-closing reaction. COPYRIGHT: (C)1993,JPO&Japio ...

СПОСОБЫ ПОЛУЧЕНИЯ ЗАМЕЩЕННЫХ АРИЛКОНДЕНСИРОВАННЫХАЗАПОЛИЦИКЛИЧЕСКИХ СОЕДИНЕНИЙ, ПРОМЕЖУТОЧНЫЕ ПРОДУКТЫ И СПОСОБЫ ИХ ПОЛУЧЕНИЯ

Изобретение относится к новому способу получения замещенных арилконденсированных азаполициклических соединений формул (II) и (VIII), новым промежуточным продуктам и способам их получения. Замещенные арилконденсированные азаполициклические соединения формулы (II) обладают свойствами связываться с нейроновыми никотиновыми ацетилхолиновыми специфическими рецепторными сайтами и могут быть использованы при модулировании холинергической функции для лечения различных заболеваний. Способ получения соединения формулы (II) где R6 представляет собой водород, R2 и R3 выбраны независимо из водорода, галогена, (С1-С6)алкила, необязательно замещенного от 1 до 3 атомами фтора и (С1-С6)алкокси, необязательно замещенного от 1 до 3 атомами фтора, включает гидрирование соединения формулы (1а)': полученного из соединения формулы (III), с получением промежуточно образующихся соединений формулы (IX) и (VII): Соединение (VII) при обработке основанием циклизуется, с получением соединения формулы (VIII), которое ...

ИНГИБИТОРЫ ЦИСТЕИНПРОТЕАЗ КАТЕПСИНОВ

Изобретение относится к конкретным соединениям, приведенным в формуле изобретения. Соединения по изобретению предназначены для ингибирования активности катепсина K. Соединения предназначены для приготовления лекарственного средства, пригодного для лечения остеопороза, остеопороза, вызываемого глюкокортикоидами, болезни Педжета, аномально увеличенного метаболизма костной ткани, периодонтального заболевания, потери зубов, переломов костей, ревматоидного артрита, остеоартрита, перипротезного остеолиза, несовершенного остеогенеза, атеросклероза, тучности, глаукомы, хронического обструктивного легочного заболевания, метастатического костного заболевания, злокачественной гиперкальцемии или множественной миеломы. 4 н. и 2 з.п. ф-лы, 1 табл., 159 пр.

СПОСОБ ПОЛУЧЕНИЯ S-(+)-КЛОПИДОГРЕЛЯ РАЗДЕЛЕНИЕМ ОПТИЧЕСКИХ ИЗОМЕРОВ

... 1. Способ получения S-(+)-клопидогреля, включающий ! ! (1) получение диастереомерной соли, представленной формулой 4, путем реакции рацемической карбоновой кислоты клопидогреля, представленной формулой 2а, с (+)-цинхонином, представленным следующей формулой 3; ! (2) получение карбоновой кислоты S-(+)-клопидогреля, представленной выше формулой 2b, путем обработки диастереомерной кислоты, представленной выше формулой 4, в кислых условиях; и ! (3) получение S-(+)-клопидогреля, представленного выше формулой 1, путем реакции карбоновой кислоты S-(+)-клопидогреля, представленной выше формулой 2а, с метанолом в кислых условиях. ! 2. Способ по п.1, где (+)-цинхонин, представленный выше формулой 3, используют в количестве в интервале от 0,5 до 1 эквивалента на 1 эквивалент рацемической карбоновой кислоты клопидогреля, представленной выше формулой 2а. ! 3. Способ по п.1, где карбоновую кислоту S-(+)-клопидогреля, представленную выше формулой 2а, оптические изомеры разделяют экстракцией с использованием ...

МАКРОЦИКЛИЧЕСКИЕ ЛАКТАМЫ И ИХ ФАРМАЦЕВТИЧЕСКИЕ ПРИМЕНЕНИЯ

Соединение формулы в которой R1 представляет собой CH(Re)C(=O)N(Ra)Rb или (CH2)kN(Rc)Rd, где k обозначает 0,1 или 2; Ra и Rb независимо представляют собой водород или необязательно замещенный (С1-8)алкил, (С3-7)циклоалкил, (С3-7)циклоалкил(С1-4)алкил, арил, арил(С1-4)алкил, гетероарил или гетероарил(С1-4)алкил, Rc и Rd независимо представляют собой водород или необязательно замещенный (C1-8)алкил, (С3-7)циклоалкил, (С3-7)циклоалкил(С1-4)алкил, арил, арил(С1-4)алкил, гетероарил, гетероарил(С1-4)алкил, хроман-4-ил, изохроман-4-ил, тиохроман-4-ил, изотиохроман-4-ил, 1,1-диоксо-1лямбда*6*-тиохроман-4-ил, 2, 2-диоксо-2лямбда*6*-изотиохроман-4-ил, 1,2,3,4-тетрагидрохинолин-4-ил, 1,2,3,4-тетрагидроизохинолин-4-ил, 1,2,3,4-тетрагидронафтален-1-ил, 1,1-диоксо-1,2,3,4-тетрагидро-1лямбда*6*-бензо[е][1, 2]тиазин-4-ил, 2,2-диоксо-1,2,3,4-тетрагидро-2лямбда*6*-бензо[с][1,2]тиазин-4-ил, 1,1-диоксо-3,4-дигидро-1Н-1лямбда*6*-бензо[с][1,2]оксатин-4-ил, 2,2-диоксо-3,4-дигидро-2Н-2лямбда*6*-бензо[е][1, 2]оксатин ...

Способ анализа индинилина, полученного из карбазола и n-нитрозофенола

ARYLKONDENSIERTE AZAPOLYCYCLISCHE DERIVATE

Organic compounds

Cyclic tertiary amine compound and organic electroluminescent device containing the compound

NOVEL ANTITUMORAL AND ANTIVIRAL COMPOUND

N-CHLOROCARBONYL LACTAMS

8-AZABICYCLO 3.2.1) OCTAN, 8-AZABICYCLO 3.2.1) OCT-6-EN, 9-AZABICYCLO 3.3.1) NONAN, 9-AZA-3 OXABICYCLO 3.3.1) NONAN AND 9-AZA-3-THIABICYCLO 3.3.1) NONAN DERIVATIVES, YOUR PRODUCTION AND YOUR USE AS INSECTICIDES

Procedure for the production of new Triazolobenzoxazol or - benzothiazolderivaten and their salts

PROCEDURE FOR the PRODUCTION of the NEW ONE 2.5 - - DIMETHYL THIENO (2,3-F) MORPHANS

DERIVATIVES OF DC 107

AZABICYCLO-BENZAMIDE AND BENZOATE DERIVATIVES

IMPROVED PROCESSES FOR THE PREPARATION OF BENZO (CHALCOGENO) (4,3,2-CD) INDAZOLES

IMMUNOREGULATION

Aryl fused azapolycyclic compounds

Macrocyclic lactams and pharmaceutical use thereof

MACROCYCLIC COMPOUNDS FOR TREATMENT OF MEDICAL DISORDERS

Macrocyclic Complement Factor D inhibitors, pharmaceutical compositions, and uses thereof, as well as processes for their manufacture are provided. The compounds provided include Formula I, Formula II, Formula III, Formula IV, Formula V, Formula VI, Formula VII, and Formula VIII or a pharmaceutically acceptable salt, prodrug, isotopic analog, N-oxide, or isolated isomer thereof, optionally in a pharmaceutically acceptable composition. The inhibitors described herein target Factor D and inhibit or regulate the complement cascade. 5. The compound of claim 1 , wherein B2 is a six membered heteroaryl substituted with 1 or 2 groups selected from R.6. A pharmaceutical composition comprising a compound of or a pharmaceutically acceptable salt thereof claim 1 , and a pharmaceutically acceptable carrier.11. The compound of claim 7 , wherein B1 is a six membered heteroaryl substituted with 1 claim 7 , 2 claim 7 , or 3 groups selected from R.12. A pharmaceutical composition comprising a compound of or a pharmaceutically acceptable salt thereof claim 7 , and a pharmaceutically acceptable carrier.18. The compound of claim 14 , wherein B2 is a six membered heteroaryl substituted with 1 or 2 groups selected from R.19. A pharmaceutical composition comprising a compound of or a pharmaceutically acceptable salt thereof claim 14 , and a pharmaceutically acceptable carrier.24. The compound of claim 20 , wherein B1 is a six membered heteroaryl substituted with 1 claim 20 , 2 claim 20 , or 3 groups selected from R.25. A pharmaceutical composition comprising a compound of or a pharmaceutically acceptable salt thereof claim 20 , and a pharmaceutically acceptable carrier. This application is a continuation of International Application No. PCT/US2018/020531, which claims the benefit of U.S. Application No. 62/465,600 filed Mar. 1, 2017; U.S. Application No. 62/466,252 filed Mar. 2, 2017; and U.S. Application No. 62/500,287 filed May 2, 2017. The entirety of these applications is hereby ...

COMPOUNDS THAT INHIBIT MCL-1 PROTEIN

Provided herein are compounds that are useful intermediates that may used to synthesize myeloid cell leukemia 1 protein (Mcl-1) inhibitors. Also provided are Mcl-1 inhibitors, methods of their preparation, related pharmaceutical compositions, and methods of using the same. For example, provided herein are compounds of Formula I, This application is a continuation of U.S. patent application Ser. No. 15/376,456, filed Dec. 12, 2016, which is a continuation of U.S. patent application Ser. No. 14/839,149, filed Aug. 28, 2015, now U.S. Pat. No. 9,562,061, which claims the benefit of U.S. Provisional Patent Application No. 62/043,929, filed Aug. 29, 2014, now expired, each of which is hereby incorporated by reference in its entirety and for all purposes as if fully set forth herein.The present invention relates to compounds that inhibit myeloid cell leukemia 1 protein (Mcl-1, also abbreviated as MCL-1 or MCL1); methods of treating diseases or conditions, such as cancer, using the compounds; and pharmaceutical compositions containing the compounds.One common characteristic of human cancer is overexpression of Mcl-1. Mcl-1 overexpression prevents cancer cells from undergoing programmed cell death (apoptosis), allowing the cells to survive despite widespread genetic damage.Mcl-1 is a member of the Bcl-2 family of proteins. The Bcl-2 family includes pro-apoptotic members (such as BAX and BAK) which, upon activation, form a homo-oligomer in the outer mitochondrial membrane that leads to pore formation and the escape of mitochondrial contents, a step in triggering apoptosis. Antiapoptotic members of the Bcl-2 family (such as Bcl-2, Bcl-XL, and Mcl-1) block the activity of BAX and BAK. Other proteins (such as BID, BIM, BIK, and BAD) exhibit additional regulatory functions.Research has shown that Mcl-1 inhibitors can be useful for the treatment of cancers. MCI-1 is overexpressed in numerous cancers. See Beroukhim et al. (2010) Nature 463, 899-905. Cancer cells containing ...

OPIOID AGONISTS AND USES THEREOF

Provided are compounds, including those of Formula I; and pharmaceutically acceptable salts and solvates thereof. The compounds described herein relate to and/or have application(s) in (among others) the fields of drug discovery, pharmacotherapy, physiology, organic chemistry and polymer chemistry. 2. The compound of claim 1 , wherein Ris hydrogen.3. The compound of any one of the preceding claims claim 1 , wherein Ris alkyl.4. The compound of any one of the preceding claims claim 1 , wherein Ris cyclopropylmethyl.5. The compound of any one of the preceding claims claim 1 , wherein G is O and represents a double bond.6. The compound of any one of the preceding claims claim 1 , wherein Ris hydrogen.7. The compound of any one of the preceding claims claim 1 , wherein Ris selected from optionally substituted alkyl claim 1 , optionally substituted amino claim 1 , and —X-POLY.8. The compound of any one of the preceding claims claim 1 , wherein Ris optionally substituted amino.9. The compound of any one of the preceding claims claim 1 , wherein Ris amino substituted with an optionally substituted aryl or optionally substituted alkyl.10. The compound of any one of the preceding claims claim 1 , wherein Ris amino substituted with an optionally substituted phenyl.12. The compound of claim 11 , wherein q is 1.13. The compound of any one or claim 11 , wherein X is —NH—.14. The compound of any one of or claim 11 , wherein X is —O—.15. The compound of any one of to claim 11 , wherein POLY is a poly(alkylene oxide) oligomer.16. The compound of any one of to claim 11 , wherein POLY is a poly(ethylene oxide) oligomer.17. The compound of any one of to claim 11 , wherein POLY is capped with an optionally substituted alkyl.18. The compound of any one of to claim 11 , wherein POLY is capped with a methyl claim 11 , trifluoromethyl claim 11 , or methyl substituted with a carboxy group.20. The compound of claim 19 , wherein X is —O—.21. The compound of claim 19 , wherein X is —NH—.22. ...

COMPOUNDS THAT INHIBIT MCL-1 PROTEIN

Provided herein are myeloid cell leukemia 1 protein (Mcl-1) inhibitors, methods of their preparation, related pharmaceutical compositions, and methods of using the same. For example, provided herein are compounds of Formula I, 2. The method of claim 1 , wherein the cancer is a hematological malignancy.3. The method of claim 1 , wherein the cancer is acute myelogenous leukemia.4. The method of claim 1 , wherein the cancer is multiple myeloma.5. The method of claim 1 , wherein the cancer is non-Hodgkin's lymphoma.6. The method of claim 1 , wherein the method further comprises administering to the patient a therapeutically effective amount of at least one additional pharmaceutically active compound.7. The method of claim 6 , wherein the at least one additional pharmaceutically active compound is carfilzomib.8. The method of claim 1 , wherein b is a double bond.9. The method of claim 1 , wherein R is Cl.10. The method of claim 1 , wherein Ris Calkyl.11. The method of claim 4 , wherein Ris CH.12. The method of claim 1 , wherein Ris H and Ris Calkyl.13. The method of claim 1 , wherein Ris H and Ris Calkyl.16. The method of claim 15 , wherein the cancer is a hematological malignancy.17. The method of claim 15 , wherein the cancer is acute myelogenous leukemia.18. The method of claim 15 , wherein the cancer is multiple myeloma.19. The method of claim 15 , wherein the cancer is non-Hodgkin's lymphoma.20. The method of claim 15 , wherein the method further comprises is administering to the patient a therapeutically effective amount of at least one additional pharmaceutically active compound.21. The method of claim 20 , wherein the at least one additional pharmaceutically active compound is carfilzomib.23. The method of claim 22 , wherein the cancer is a hematological malignancy.24. The method of claim 22 , wherein the cancer is acute myelogenous leukemia.25. The method of claim 22 , wherein the cancer is multiple myeloma.26. The method of claim 22 , wherein the cancer is non- ...

HETEROCYCLIC COMPOUND AND USE THEREOF

Provided is a compound having an AMPA receptor function enhancing action, and useful as a prophylactic or therapeutic drug for depression, schizophrenia, Alzheimer's disease, attention deficit hyperactivity disorder (ADHD) and the like. The compound represented by formula (I): 3. The compound according to claim 1 , wherein ring D is a benzene ring claim 1 , or a salt thereof.4. The compound according to claim 1 , wherein Lis a bond claim 1 , —O— or —CH—O— claim 1 , or a salt thereof.5. The compound according to claim 1 , wherein Ris{'sub': 1-6', '1-6, '(1) Calkyl optionally substituted by 1 to 3 substituents selected from a halogen atom and Calkoxy;'}{'sub': '3-7', '(2) Ccycloalkyl;'}{'sub': 1-6', '1-6, '(3) phenyl optionally substituted by 1 to 3 substituents selected from a halogen atom, cyano, Calkyl optionally substituted by 1 to 3 halogen atoms and Calkoxy;'}(4) dihydrobenzofuranyl;(5) benzodioxolyl substituted by 1 to 3 halogen atoms;{'sub': '1-6', '(6) pyridyl optionally substituted by 1 to 3 substituents selected from a halogen atom and Calkyl optionally substituted by 1 to 3 halogen atoms;'}(7) pyrimidinyl;{'sub': '1-6', '(8) isoxazolyl substituted by 1 to 3 Calkyls;'}(9) tetrahydrofuranyl; or(10) pyrazolyl, or a salt thereof.8. 9-(4-(4-Chlorophenoxyl)phenyl)-3 claim 1 ,4 claim 1 ,6 claim 1 ,7 claim 1 ,8 claim 1 ,9-hexahydro-6 claim 1 ,9-ethanopyrido[2 claim 1 ,1-c][1 claim 1 ,2 claim 1 ,4]thiadiazine 2 claim 1 ,2-dioxide or a salt thereof.9. 9-(4-(4-Chlorophenoxyl)phenyl)-3 claim 1 ,4 claim 1 ,6 claim 1 ,7 claim 1 ,8 claim 1 ,9-hexahydropyrimido[2 claim 1 ,1-c][1 claim 1 ,2 claim 1 ,4]thiadiazine 2 claim 1 ,2-dioxide or a salt thereof.10. 9-(4-((6-(Trifluoromethyl)pyridin-2-yl)oxy)phenyl)-3 claim 1 ,4 claim 1 ,6 claim 1 ,7 claim 1 ,8 claim 1 ,9-hexahydro-6 claim 1 ,9-ethanopyrido[2 claim 1 ,1-c][1 claim 1 ,2 claim 1 ,4]thiadiazine 2 claim 1 ,2-dioxide or a salt thereof.11. A medicament comprising the compound according to or a salt thereof.12. The ...

CYSTEINE DERIVATIVE

Cysteine compounds represented by the following formula 111-. (canceled)13. A cysteine compound or salt thereof according to claim 12 , which is in the trans form.15. A cysteine compound or salt thereof according to claim 14 , which is in the trans form.1619-. (canceled)2224-. (canceled) This application is a divisional of U.S. patent application Ser. No. 13/686,384, filed on Nov. 27, 2012, which is a continuation of International Patent Application No. PCT/JP2011/062293, filed on May 27, 2011, and claims priority to Japanese Patent Application No. 2010-123169, filed on May 28, 2010, each of which are incorporated herein by reference in their entireties.1. Field of the InventionThe present invention relates to particular cysteine derivatives. Furthermore, the present invention relates to methods for producing particular cysteine derivatives, cosmetic agents which contain particular cysteine derivatives, and the like.2. Discussion of the BackgroundIn human pigment cells (melanocytes) in the skin, melanin is produced utilizing L-cysteine and L-tyrosine. When a greater amount of L-tyrosine, which is a starting material for eumelanin, is utilized for the synthesis of melanin, production of eumelanin is promoted and the skin becomes dark. On the other hand, when a greater amount of L-cysteine is utilized for the synthesis of melanin, production of eumelanin is suppressed, and the skin becomes closer to yellow. Therefore, it is considered that production of eumelanin is suppressed by supplying L-cysteine during melanin synthesis.Heretofore, many attempts have been made to utilize L-cysteine as cosmetics such as whitening agents utilizing L-cysteine and the like. However, L-cysteine is easily oxidized, and has problems such as poor stability and bad odor for formulating as a cosmetic agent or skin external preparation.To solve such problem, the development of a cysteine derivative with improved stability has been considered. JP-B-48-15938 discloses that L-2- ...

PIPERAZINE DERIVATIVES AS HIV PROTEASE INHIBITORS

The present invention is directed to compounds of Formula I pharmaceutical compositions comprising the same, and their use in the inhibition of HIV protease, the inhibition of HIV replication, the prophylaxis of infection by HIV, the treatment of infection by HIV, and the prophylaxis, treatment, and delay in the onset or progression of AIDS. 4. The compound of or a pharmaceutically acceptable salt thereof wherein Zis —NHR.11. The compound of claim 10 , or a pharmaceutically acceptable salt thereof wherein Ris —H claim 10 , —Calkyl or —OCalkyl wherein each of —Calkyl or —OCalkyl is unsubstituted or substituted with 1 to 3 substituents independently selected from halo claim 10 , —OH claim 10 , or —OCalkyl.12. The compound of claim 2 , or a pharmaceutically acceptable salt thereof wherein Rand Rare joined together with the carbon to which they are both attached to form (a) cyclohexyl claim 2 , (b) piperidinyl claim 2 , or (c) tetrahydro-(2H)-furan; wherein each group is unsubstituted or substituted with one or two substituents independently selected at each occurrence from halo; —OH; —Calkyl unsubstituted or substituted with 1-3 of —F; —OCalkyl unsubstituted or substituted with 1-3 of —F; or —C(O)OCalkyl unsubstituted or substituted with 1-3 of —F.13. The compound of claim 2 , or a pharmaceutically acceptable salt thereof wherein Ris independently selected at each occurrence from halo.14. The compound of claim 1 , or a pharmaceutically acceptable salt thereof wherein p is 1 or 2.15. The compound of claim 4 , or a pharmaceutically acceptable salt thereof wherein Ris —H or —C(O)OCalkyl.18. A pharmaceutical composition comprising an effective amount of a compound according to claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , and a pharmaceutically acceptable carrier.19. A method for the treatment or prophylaxis of infection by HIV or for the treatment claim 1 , prophylaxis claim 1 , or delay in the onset of AIDS in a subject in need thereof claim 1 , which ...

ALPHA-AMINO PATEAMINE A DERIVATIVES AND METHODS FOR TREATING CHRONIC LYMPHOCYTIC LEUKEMIA

Pateamine A derivatives and pharmaceutical compositions that include the derivatives. The pateamine A derivatives are α-amino pateamine A derivatives that lack the C5-methyl group of pateamine A. 5. The compound of or , wherein A is selected from the group consisting of chloride , bromide , iodide , sulfate , phosphate , formate , acetate , trifluoroacetate , maleate , fumarate , succinate , tartrate , oxalate , citrate , malate , benzoate , toluenesulfonate , methanesulfonate , and benzenesulfonate.6. The compound of any one of - , wherein X is O and Y is R.7. The compound of claim 7 , wherein R is methyl claim 7 , trifluoromethyl claim 7 , or t-butyl.8. The compound of any one of - claim 7 , wherein X is O and Y is OR.9. The compound of claim 8 , wherein Ris methyl or t-butyl.10. The compound of any one of - claim 8 , wherein X is O and Y is N(R)R.11. The compound of claim 10 , wherein Ris hydrogen and Ris hydrogen claim 10 , or Ris hydrogen and Ris methyl.12. The compound of any one of - claim 10 , wherein X is O and Y is SR.13. The compound of claim 12 , wherein Ris methyl or t-butyl.14. The compound of any one of - claim 12 , wherein X is S and Y is R.15. The compound of claim 14 , wherein R is methyl.16. The compound of any one of - claim 14 , wherein X is S and Y is OR.17. The compound of claim 16 , wherein Ris methyl or t-butyl.18. The compound of any one of - claim 16 , wherein X is S and Y is N(R)R.19. The compound of claim 18 , wherein Ris hydrogen and Ris hydrogen claim 18 , or Ris hydrogen and Ris methyl.20. The compound of any one of - claim 18 , wherein X is S and Y is SR.21. The compound of claim 20 , wherein Ris methyl or t-butyl.22. The compound of any one of - claim 20 , wherein X is NH and Y is R.23. The compound of claim 22 , wherein R is methyl claim 22 , trifluoromethyl claim 22 , or t-butyl.24. The compound of any one of - claim 22 , wherein X is NH and Y is OR.25. The compound of claim 24 , wherein Ris methyl or t-butyl.26. The compound of ...

MCL1 INHIBITORS

The present disclosure generally relates to compounds of Formula (I) and pharmaceutical compositions that may be used in methods of treating cancer. 9. The compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein Ris selected from hydrogen claim 1 , hydroxyl claim 1 , and —OCH.12. The compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , selected from examples 1-211.14. A pharmaceutical composition comprising the compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , and a pharmaceutically acceptable excipient.15. A method of inhibiting MCL1 in a patient comprising administering the compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , to the patient.16. A method of treating cancer in a patient claim 1 , comprising administering the compound of claim 1 , or pharmaceutically acceptable salt thereof claim 1 , to the patient.17. The method of claim 16 , wherein the cancer is selected from breast cancer claim 16 , colorectal cancer claim 16 , skin cancer claim 16 , melanoma claim 16 , ovarian cancer claim 16 , kidney cancer claim 16 , small cell lung cancer claim 16 , non-small cell lung cancer claim 16 , lymphoma claim 16 , and leukemia.18. The method of claim 16 , further comprising administration of an additional therapeutic compound; wherein the additional therapeutic compound is an immune checkpoint inhibitor.19. The method of claim 18 , wherein the immune checkpoint inhibitor is selected from anti-PD-1 antibody claim 18 , anti-PD-L1 antibody claim 18 , and anti PD-1/PD-L1 interaction inhibitor.20. (canceled) This application claims the benefit of U.S. provisional application Ser. No. 62/934,400 filed on Nov. 12, 2019. The entire contents of the application are incorporated herein by reference in its entirety.This application generally relates to certain compounds that inhibit MCL1, pharmaceutical compositions comprising the compounds, use of the compounds to treat ...

BETA-AMINO PATEAMINE A DERIVATIVES AND METHODS FOR TREATING CHRONIC LYMPHOCYTIC LEUKEMIA

Pateamine A derivatives, pharmaceutical compositions that include the derivatives, and methods for treating chronic lymphocytic leukemia using the derivatives. 5. The compound of claim 3 , wherein A is selected from the group consisting of chloride claim 3 , bromide claim 3 , iodide claim 3 , sulfate claim 3 , phosphate claim 3 , formate claim 3 , acetate claim 3 , trifluoroacetate claim 3 , maleate claim 3 , fumarate claim 3 , succinate claim 3 , tartrate claim 3 , oxalate claim 3 , citrate claim 3 , malate claim 3 , benzoate claim 3 , toluenesulfonate claim 3 , methanesulfonate claim 3 , and benzenesulfonate.6. The compound of claim 1 , wherein X is O and Y is R.7. (canceled)8. The compound of claim 1 , wherein X is O and Y is OR.9. (canceled)10. The compound of claim 1 , wherein X is O and Y is N(R)R.11. (canceled)12. The compound of claim 1 , wherein X is O and Y is SR.13. (canceled)14. The compound of claim 1 , wherein X is S and Y is R.15. (canceled)16. The compound of claim 1 , wherein X is S and Y is OR.17. (canceled)18. The compound of claim 1 , wherein X is S and Y is N(R)R.19. (canceled)20. The compound of claim 1 , wherein X is S and Y is SR.21. (canceled)22. The compound of claim 1 , wherein X is NH and Y is R.23. (canceled)24. The compound of claim 1 , wherein X is NH and Y is OR.25. (canceled)26. The compound of claim 1 , wherein X is NH and Y is N(R)R.27. (canceled)28. The compound of claim 1 , wherein X is NH and Y is SR.29. (canceled)30. The compound of claim 1 , wherein the C3-C12 alkyl group in which one or more carbons are replaced with O is selected from —CH—O—CH claim 1 , —CHCH—O—CH claim 1 , and —CHCH—O—CHCH—O—CH.31. The compound of claim 1 , wherein the C3-C12 alkyl group in which one or more carbons are replaced with N is selected from —CH—NH—CH claim 1 , —CH—N(CH) claim 1 , —CHCH—NH—CH claim 1 , and —CHCH—N(CH).3645-. (canceled)50. A pharmaceutical composition claim 1 , comprising a compound of and a pharmaceutically acceptable carrier.51. ...

AROMATIC HETEROCYCLYLAMINE DERIVATIVE HAVING TRPV4-INHIBITING ACTIVITY

The present invention is related to a compound represented by formula (I) 6. A pharmaceutical composition containing the compound according to claim 1 , or a pharmaceutically acceptable salt thereof.7. A pharmaceutical composition containing the compound according to claim 2 , or a pharmaceutically acceptable salt thereof.8. A pharmaceutical composition containing the compound according to claim 3 , or a pharmaceutically acceptable salt thereof.9. A pharmaceutical composition containing the compound according to claim 4 , or a pharmaceutically acceptable salt thereof.10. A pharmaceutical composition containing the compound according to claim 5 , or a pharmaceutically acceptable salt thereof. The present invention relates to a compound that has a TRPV4 inhibitory activity and is useful for the treatment and/or prevention of a TRPV4 receptor-mediated disorder, or a pharmaceutically acceptable salt thereof, and a pharmaceutical composition containing thereof.TRPV4 is one of a cation channel of the TRP (Transient Receptor Potential) superfamily. It was discovered as an osmotic-sensitivity receptor activated by hypotonic stimulus. Then, it was shown that TRPV4 had a temperature-sensitive property, that is, TRPV4 was activated at the body temperature rage, and TRPV4 is activated by heat and low pH. It is reported that the gene and protein of TRPV4 is expressed in brain, spinal code, peripheral nerve fiber, skin, kidney, trachea, cochlea and bone, etc. Moreover, it is also reported that TRPV4 is activated by the compounds, such as arachidonic acid, arachidonate metabolite, endocannabinoids, and phorbol ester. The increase of activation of the C-fiber by hypotonic stimulation under the inflammatory environment induced by inflammatory mediators is known, and it is also reported that TRPV4 relates to this activation. Furthermore, it is also reported that TRPV4 is activated by fluid pressure and mechanical stimuli, and TRPV4 relates to hyperalgesia caused by mechanical stimuli ...

Epidithiodioxopiperazine compound or its derivatives, and the use thereof

The present invention relates to an epidithiodioxopiperazine derivative represented by the following Chemical Formula 1 or its reduced derivative; a method for preparing a compound represented by Chemical Formula 1 having improved intracellular permeability and mimicking the activity of 2-Cys-Prx in its reduced form in the cells; a pharmaceutical composition for preventing or treating vascular diseases comprising an epidithiodioxopiperazine compound or its derivatives or pharmaceutically acceptable salts thereof as an active ingredient; a drug delivery device for local administration including the pharmaceutical composition; and a pharmaceutical composition for inhibiting melanoma metastasis comprising the epidithiodioxopiperazine compound or its derivatives or pharmaceutically acceptable salts thereof as an active ingredient.

Compositions and Methods for Inhibiting Activity of Hypoxia-Inducible Transcription Factor Complex and Its Use for Treatment of Tumors

Disclosed are epidithiodiketopiperazine compounds, pharmaceutical compositions based thereon and methods of treating, reducing or inhibiting transcription and translation of hypoxia-inducible genes.

OPIOID AGONISTS AND USES THEREOF

Provided are compounds, including those of Formula I; and pharmaceutically acceptable salts and solvates thereof. The compounds described herein relate to and/or have application(s) in (among others) the fields of drug discovery, pharmacotherapy, physiology, organic chemistry and polymer chemistry. 2. The compound of claim 1 , wherein Ris hydrogen.3. The compound of any one of the preceding claims claim 1 , wherein Ris alkyl.4. The compound of any one of the preceding claims claim 1 , wherein Ris cyclopropylmethyl.5. The compound of any one of the preceding claims claim 1 , wherein G is O and represents a double bond.6. The compound of any one of the preceding claims claim 1 , wherein Ris hydrogen.7. The compound of any one of the preceding claims claim 1 , wherein Ris selected from optionally substituted alkyl claim 1 , optionally substituted amino claim 1 , and -X-POLY.8. The compound of any one of the preceding claims claim 1 , wherein Ris optionally substituted amino.9. The compound of any one of the preceding claims claim 1 , wherein Ris amino substituted with an optionally substituted aryl or optionally substituted alkyl.10. The compound of any one of the preceding claims claim 1 , wherein Ris amino substituted with an optionally substituted phenyl.12. The compound of claim 11 , wherein q is 1.13. The compound of any one or claim 11 , wherein X is —NH—.14. The compound of any one of or claim 11 , wherein X is —O—.15. The compound of any one of to claim 11 , wherein POLY is a poly(alkylene oxide) oligomer.16. The compound of any one of to claim 11 , wherein POLY is a poly(ethylene oxide) oligomer.17. The compound of any one of to claim 11 , wherein POLY is capped with an optionally substituted alkyl.18. The compound of any one of to claim 11 , wherein POLY is capped with a methyl claim 11 , trifluoromethyl claim 11 , or methyl substituted with a carboxy group.20. The compound of claim 19 , wherein X is —O—.21. The compound of claim 19 , wherein X is —NH—.22. ...

EPIDITHIODIOXOPIPERAZINE COMPOUND OR ITS DERIVATIVES, AND THE USE THEREOF

The present invention relates to an epidithiodioxopiperazine derivative represented by the following Chemical Formula 1 or its reduced derivative; a method for preparing a compound represented by Chemical Formula 1 having improved intracellular permeability and mimicking the activity of 2-Cys-Prx in its reduced form in the cells; a pharmaceutical composition for preventing or treating vascular diseases comprising an epidithiodioxopiperazine compound or its derivatives or pharmaceutically acceptable salts thereof as an active ingredient; a drug delivery device for local administration including the pharmaceutical composition; and a pharmaceutical composition for inhibiting melanoma metastasis comprising the epidithiodioxopiperazine compound or its derivatives or pharmaceutically acceptable salts thereof as an active ingredient. 2. The method of claim 1 , wherein Rto Rare each independently hydrogen claim 1 , linear or branched C1 to C6 alkyl or alkenyl claim 1 , alkoxybenzyl claim 1 , alkoxyalkyl or benzhydryl.3. The method of claim 1 , wherein Rto Rare each independently hydrogen claim 1 , methyl claim 1 , n-butyl claim 1 , allyl claim 1 , 4-methoxybenzyl claim 1 , 3-methoxypropyl or benzhydryl. This application is a continuation application of U.S. patent application Ser. No. 15/440,655, filed Feb. 23, 2017, which is a divisional application of U.S. patent application Ser. No. 14/286,929, filed May 23, 2014, which is a continuation-in-part of International Application No. PCT/KR2012/010073, filed Nov. 26, 2012, which application claims priority to Korean Patent Application No. 10-2013-0059351, filed May 24, 2013 and Korean Patent Application No. 10-2011-0124603, filed Nov. 25, 2011. These applications are incorporated herein by reference in their entireties.The Sequence Listing associated with this application is provided in text format in lieu of a paper copy, and is hereby incorporated by reference into the specification. The name of the text file containing the ...

THIOESTER PRODRUGS OF MACROCYCLES AS INHIBITORS OF HISTONE DEACETYLASES

The present invention provides a novel macrocyclic prodrug compound of general Formula (I), a pharmaceutical composition comprising a compound of Formula (I), and a method for treating diseases mediated by HDAC enzymes by administering a compound of Formula (I), wherein R, R, R, R, R, R, R, R, R, R, R, A and Z are defined herein. 117.-. (canceled)21. The method according to claim 18 , wherein the thiol compound 6 is coupled to a compound of formula 7 by treatment with HATU.22. The method according to claim 18 , wherein the compound of formula 9 is deprotected to the compound of formula 10 by treatment with trifluoroacetic acid.23. The method according to claim 19 , wherein the acid HX is selected from the group consisting of hydrochloric acid claim 19 , hydrobromic acid claim 19 , sulfuric acid claim 19 , phosphoric acid claim 19 , nitric acid claim 19 , acetic acid claim 19 , oxalic acid claim 19 , tartaric acid claim 19 , succinic acid claim 19 , malic acid claim 19 , fumaric acid claim 19 , maleic acid claim 19 , ascorbic acid claim 19 , benzoic acid claim 19 , tannic acid claim 19 , pamoic acid claim 19 , alginic acid claim 19 , polyglutamic acid claim 19 , methanesulfonic acid claim 19 , benzenesulfonic acid claim 19 , 4-nitrobenzene sulfonic acid claim 19 , 4-bromobenzene sulfonic acid claim 19 , toluensulfonic acid claim 19 , naphthalene sulfonic acid claim 19 , naphthalene disulfonic acid claim 19 , and polygalacturonic acid.24. The method according to claim 18 , wherein the compound of formula 9 is selected from the group consisting of:(R)—S-((E)-4-((7S,10S)-7-isopropyl-4,4-dimethyl-2,5,8,12-tetraoxo-9-oxa-16-thia-3,6,13,18-tetraazabicyclo[13.2.1]octadeca-1(17),15(18)-dien-10-yl)but-3-en-1-yl)-2-((tert-butoxycarbonyl)amino)-3-methylbutanethioate;(S)—S-((E)-4-((7S,10S)-7-isopropyl-4,4-dimethyl-2,5,8,12-tetraoxo-9-oxa-16-thia-3,6,13,18-tetraazabicyclo[13.2.1]octadeca-1(17),15(18)-dien-10-yl)but-3-en-1-yl)-2-((tert-butoxycarbonyl)amino)-3-methylbutanethioate;( ...

OPIOID AGONISTS AND USES THEREOF

Provided are compounds, including those of Formula I; and pharmaceutically acceptable salts and solvates thereof. The compounds described herein relate to and/or have application(s) in (among others) the fields of drug discovery, pharmacotherapy, physiology, organic chemistry and polymer chemistry. 2. The compound of claim 1 , wherein Ris hydrogen.3. The compound of any one of the preceding claims claim 1 , wherein Ris alkyl.4. The compound of any one of the preceding claims claim 1 , wherein Ris cyclopropylmethyl.5. The compound of any one of the preceding claims claim 1 , wherein G is O and represents a double bond.6. The compound of any one of the preceding claims claim 1 , wherein Ris hydrogen.7. The compound of any one of the preceding claims claim 1 , wherein Ris selected from optionally substituted alkyl claim 1 , optionally substituted amino claim 1 , and —X-POLY.8. The compound of any one of the preceding claims claim 1 , wherein Ris optionally substituted amino.9. The compound of any one of the preceding claims claim 1 , wherein Ris amino substituted with an optionally substituted aryl or optionally substituted alkyl.10. The compound of any one of the preceding claims claim 1 , wherein Ris amino substituted with an optionally substituted phenyl.12. The compound of claim 11 , wherein q is 1.13. The compound of any one or claim 11 , wherein X is —NH—.14. The compound of any one of or claim 11 , wherein X is —O—.15. The compound of any one of to claim 11 , wherein POLY is a poly(alkylene oxide) oligomer.16. The compound of any one of to claim 11 , wherein POLY is a poly(ethylene oxide) oligomer.17. The compound of any one of to claim 11 , wherein POLY is capped with an optionally substituted alkyl.18. The compound of any one of to claim 11 , wherein POLY is capped with a methyl claim 11 , trifluoromethyl claim 11 , or methyl substituted with a carboxy group.20. The compound of claim 19 , wherein X is —O—.21. The compound of claim 19 , wherein X is —NH—.22. ...

ALPHA-AMINO PATEAMINE A DERIVATIVES AND METHODS FOR TREATING CHRONIC LYMPHOCYTIC LEUKEMIA

Pateamine A derivatives and pharmaceutical compositions that include the derivatives. The pateamine A derivatives are α-amino pateamine A derivatives that lack the C5-methyl group of pateamine A. 5. The compound of claim 3 , wherein Ais selected from the group consisting of chloride claim 3 , bromide claim 3 , iodide claim 3 , sulfate claim 3 , phosphate claim 3 , formate claim 3 , acetate claim 3 , trifluoroacetate claim 3 , maleate claim 3 , fumarate claim 3 , succinate claim 3 , tartrate claim 3 , oxalate claim 3 , citrate claim 3 , malate claim 3 , benzoate claim 3 , toluenesulfonate claim 3 , methanesulfonate claim 3 , and benzenesulfonate.6. The compound of claim 1 , wherein Z is C1-C6 alkyl.7. The compound of claim 1 , wherein Z is methyl.8. The compound of claim 1 , wherein Z is C1-C6 haloalkyl.9. The compound of claim 1 , wherein Z is trifluoromethyl.10. The compound of claim 1 , wherein Z is C6-C10 aryl.11. The compound of claim 1 , wherein Z is phenyl.12. The compound of claim 1 , wherein Z is C3-C12 alkyl in which one or more carbons are replaced with O claim 1 , NH claim 1 , or N(CH).13. The compound of claim 1 , wherein Z is selected from —CH—O—CH claim 1 , —CHCH—O—CH claim 1 , and —CHCH—O—CHCH—O—CH.14. The compound of claim 1 , wherein Z is selected from —CH—NH—CH claim 1 , —CH—N(CH) claim 1 , —CHCH—NH—CH claim 1 , and —CHCH—N(CH).15. A pharmaceutical composition claim 1 , comprising a compound of and a pharmaceutically acceptable carrier.16. An antibody conjugate for the delivery of an α-amino pateamine derivative claim 1 , comprising a compound of covalently coupled directly or through a linker unit to an antibody or functional fragment thereof claim 1 , wherein the functional fragment is selected from the group consisting of Fab claim 1 , Fab′ claim 1 , F(ab′) claim 1 , and Fv fragments; linear antibodies; single-chain antibody molecules; an scFv; an IgG ΔCH2 claim 1 , a minibody claim 1 , a diabody claim 1 , a triabody claim 1 , a tetrabody claim ...

Benzoxazine-oxazolidinone compound displaced by a nitrogen-containing heterocycle, method of synthesis and application thereof

FIELD: organic chemistry. SUBSTANCE: invention relates to organic chemistry, namely to a compound of formula (I) or to isomers thereof, where X 1 and X 2 each constitute ; R 1 constitutes -NHR 3 , -NHCOR 3 , -NHSO 2 R 3 , -NHCOOR 3 , non-substituted 5-membered heteroaryl, wherein the non-substituted 5-membered heteroaryl in R 1 contains three N atoms; R 3 is independently selected from an atom of hydrogen, substituted or non-substituted C 1 -C 4 alkyl, non-substituted 3-6-membered cycloalkyl, non-substituted 4-membered heterocyclyc group, non-substituted 5-6-membered heteroaryl; wherein said non-substituted 4-membered heterocyclyc group and said non-substituted 5-6-membered heteroaryl in R 3 contain between one and three heteroatoms selected from N or O; the substituents in R 3 are each independently selected from F, C 1 -C 3 alkyle; R 2 constitutes a non-substituted , non-substituted , non-substituted ; Y 1 constitutes -S-, -S(=O)-, -S(O 2 )-, -C(F 2 )-; Y 2 constitutes -O-; a, b, c, d, e and f each equals 1. The invention also relates to a method of synthesis of a compound of the formula (I), a pharmaceutical composition based on the compound of the formula (I) and application thereof. EFFECT: technical result: new heterocyclic compounds are synthesized, said compounds useful in treatment and/or prevention of the microbial infection induced by Mycobacterium tuberculosis. 13 cl, 4 tbl, 39 ex РОССИЙСКАЯ ФЕДЕРАЦИЯ ФЕДЕРАЛЬНАЯ СЛУЖБА ПО ИНТЕЛЛЕКТУАЛЬНОЙ СОБСТВЕННОСТИ (12) (19) RU (11) (13) 2 744 784 C1 (51) МПК C07D 498/04 (2006.01) C07D 498/06 (2006.01) C07D 513/08 (2006.01) C07D 519/00 (2006.01) A61K 31/5383 (2006.01) A61K 31/541 (2006.01) A61P 31/06 (2006.01) ОПИСАНИЕ ИЗОБРЕТЕНИЯ К ПАТЕНТУ (52) СПК C07D 498/04 (2021.01); C07D 498/06 (2021.01); C07D 513/08 (2021.01); C07D 519/00 (2021.01); A61K 31/5383 (2021.01); A61K 31/541 (2021.01); A61P 31/06 (2021.01) (21)(22) Заявка: 2019134197, 28.03.2018 28.03.2018 Дата регистрации: Приоритет(ы): (30) Конвенционный приоритет ...

Recombinant methods and materials for producing epothilone and epothilone derivatives

에포틸론 폴리케티드 신타아제 (PKS)의 전부 또는 일부위를 암호화하는 재조합 핵산을, 암의 화학적 치료제, 항진균제, 그리고 면역 억제제로서 유용한 에포틸론, 에포틸론 유도체, 및 폴리케티드 생산을 위해서, 재조합 PKS 유전자의 발현에 이용한다. 에포틸론 폴리케티드 신타아제, 재조합 PKS Recombinant nucleic acid encoding all or part of the epothilone polyketide synthase (PKS) is recombinant for epothilones, epothilone derivatives, and polyketide production, useful as chemotherapy, antifungal, and immunosuppressive agents in cancer. It is used for expression of the PKS gene. Epothilone Polyketide Synthase, Recombinant PKS

Herbicidal 9-(5-isoxazolinemethoxyphenyl)imino-8-thia-1,6-diazabicyclo[4.3.0]nonan-7-one derivatines

본 발명은 다음 화학식 1로 표시되는 신규의 9-(5-이속사졸린메톡시페닐)이미노-8-치아-1,6-디아자비시클로[4.3.0]노난-7-온 유도체 및 이들을 유효성분으로 포함하는 제초제에 관한 것이다. The present invention provides a novel 9- (5-isoxazolinemethoxyphenyl) imino-8-thia-1,6-diazabicyclo [4.3.0] nonan-7-one derivative represented by the following formula (1) and these It relates to a herbicide containing as an active ingredient. 상기 화학식 1에서, R은 C 1 ∼C 5 의 알킬기, 페닐기 또는 치환된 페닐기이며, 이때 치환된 페닐기는 할로겐 원자, C 1 ∼C 3 의 알킬기, C 1 ∼C 3 의 알콕시기, C 1 ∼C 3 의 할로알킬기, 시아노기, 니트로기, 카르복실기 및 카르복실산 에스테르기 중에서 선택된 1 내지 3개의 치환기로 치환된 페닐기를 나타낸다. In Formula 1, R is C 1 ~C 5 alkyl group, a phenyl group or substituted phenyl group, substituted phenyl group wherein the alkoxy group of the alkyl group of a halogen atom, C 1 ~C 3, C 1 ~C 3, C 1 ~ C 3 represents a phenyl group substituted with 1 to 3 substituents selected from a haloalkyl group, cyano group, nitro group, carboxyl group and carboxylic acid ester group.

A sulphamoyl-benzothiadiazine derivative and preparation thereof

The invention comprises 6-chloro-7-sulphamoyl-2, 4-iminodimethylene-benzo-dihydro-1,2, 4-thiadiazine-1, 1-dioxide of the formula: <FORM:0955522/C2/1> and its preparation by treating 6-chloro-7-sulphamoyl - 2, 4 - methylenediiminodimethylene - benzo-dihydro-1, 2, 4-thiadiazine-1, 1-dioxide (obtainable by reaction of 5-chloro-2, 4-disulphamoyl-aniline with hexamethylene tetramine) with water under neutral or alkaline conditions at 0-110 DEG C. Specification 888,647 is referred to.ALSO:Pharmaceutical preparations having diuretic and saliuretic activity comprise 6-chloro-7-sulphamoyl - 2,4 - iminodimethylene - benzodihydro - 1,2,4 - thiadiazone - 1,1-dioxide and a carrier or excipient. The preparations suitably take the form of tablets, dragees, capsules, solutions suspensions or suppositories and may contain additional active compounds such as hypotensive agents. Specification 888,647 is referred to.

NEW 3,6-EPITHIA, EPIDITHIA OR EPITETRATHIAPIPERAZINE-2,5-DIONES, USEFUL IN PARTICULAR AS ANTIFUNGAL AND PROCESS FOR PREPARATION

Piperazinedione derivs prepn

Piperazinedione derivs. prepn. New cpds. of formula:- (where R is H, lower alkyl or lower alkoxy and n is 2 or 4) are prepared by reacting the corresp. diphenyl-piperazinedione with (a) the appropriate disodium sulphide to give the corresp. dithia or tetrathia deriv. or (b) thiolacetic acid to give the corresp. 3,6-dithioacetate which is then reacted with (1) hydroxylaminine to give the 3,6-epidithia deriv. (2) hydrazine hydrate to give the corresp. epitetrathia deriv. Compds. are used in antifungal medicaments.

Recombinant methods and materials for producing epothilone and epothilone derivatives

에포틸론 폴리케티드 신타아제 (PKS)의 전부 또는 일부위를 암호화하는 재조합 핵산을, 암의 화학적 치료제, 항진균제, 그리고 면역 억제제로서 유용한 에포틸론, 에포틸론 유도체, 및 폴리케티드 생산을 위해서, 재조합 PKS 유전자의 발현에 이용한다. 에포틸론 폴리케티드 신타아제, 재조합 PKS

DIBENZ (B, E) AZEPINE DERIVATIVES AND MEDICAMENTS CONTAINING THEREOF

The invention relates to dibenz[b,e]azepine derivatives of formula (I), in which A is a methylene, carbonyl, thiocarbonyl, carbimino, N-hydroxycarbimino or sulphonyl group; X is a valency bond or an oxygen or sulphur atom, a sulphinyl or sulphonyl group, a CH2S group or an NH group; n is a whole number from 1 to 3; and R<1> to R<4>, which can be the same or different, are, independently of each other, a hydrogen atom or an aliphatic group with 1-6 C-atoms, as well as their tautomers, enantiomers, diastereomers and their physiologically tolerated salts. In addition, the invention concerns drugs containing compounds of formula (I), in particular drugs for use in treating viral infections.

Psychotropic bicyclic imides

Substituted imides of the following formula are antipsychotic, anxiolytic agents with very little extrapyramidal side effects:

Mcl1 inhibitors

The present disclosure generally relates to compounds of Formula (I) and pharmaceutical compositions that may be used in methods of treating cancer.

Compounds of 1,5-disubstituted-3,7 diaza bicyclo 3.3.0! octanes and products containing the same

Overall, the invention provides the chemistry for the compounds and for the processes to prepare compounds derived from 1,5-diazacyclooctanes. This makes available high density, high melting point, thermally stable small and medium ring nitrogen heterocycles that may also contain N-nitro, C-nitro or other functional groups. The compounds include cyclooctanes, bicyclo octanes, propellanes and functionalized derivatives of the above compounds. The preparations can include transannular cyclizations. The materials have several applications; e.g., the polynitro compounds are energetic materials.

Recombinant methods and materials for producing epothilone and epothilone derivatives

Recombinant nucleic acids that encode all or a portion of the epothilone polyketide synthase (PKS) of sorangium cellulosum are used to express recombinant PKS genes in host cells for the production of epithilones, epothilone derivatives, and polyketides that are useful as cancer chemotherapeutics, fungicides, and immunosuppressants.

Patent FR2052963B1

Cysteine derivative

Cysteine compounds represented by the following formula wherein each symbol is as defined in the specification, and salts thereof, are superior in stability, have less odor, exhibit an eumelanin production suppressive effect, and are useful as cosmetic agents.

1,4 dialkyl 3,6 diphenylepi (thia, dithia or -tetrathia) 2,5 piperazinedione

Recombinant methods and materials for producing epothilone and eopthilone derivatives

编码环氧噻酮聚酮化合物合成酶(PKS)的全部或者部分的重组核酸被用于在宿主细胞中表达重组PKS基因，以生产用作肿瘤化学治疗剂，杀真菌剂，和免疫抑制剂的环氧噻酮，环氧噻酮衍生物和聚酮化合物。

1,1-dioxo-1,2,4-thiadiazolines - inters for general chemicals drugs,plant protection agents

Compounds that inhibit Mcl-1 protein

Provided herein are myeloid cell leukemia 1 protein (Mcl-1) inhibitors, methods of their preparation, related pharmaceutical compositions, and methods of using the same. For example, provided herein are compounds of Formula I, (I) and pharmaceutically acceptable salts thereof and pharmaceutical compositions containing the compounds. The compounds and compositions provided herein may be used, for example, in the treatment of diseases or conditions, such as cancer.

Method of sensitizing photographic emulsions and related sensitized emulsion

Compounds

- 1 - 2649/Abs Abstract Compounds of formula (I) and pharmaceutically acceptable salts thereof: (I) wherein X is a phenyl group or a monocyclic 5 or 6 membered heteroaryl group, either of which group is optionally fused to a saturated or unsaturated 5-7 membered carbocyclic or heterocyclic ring; A is a linking moiety; Z is oxygen or sulphur; and R is methyl or ethyl; having 5-HT3 receptor antagonist activity.

Vital body treatment, treating compound and manufacture

(57)【要約】本公報は電子出願前の出願データであるた め要約のデータは記録されません。

Substituted sulfonamido-macrocycles as tie2 inhibitors and salts thereof, pharmaceutical compositions comprising same, methods of preparing same and uses of same

The invention relates to substituted sulfonamido-macrocycles according to the general formula (I): in which R 1 , R 2 , R 4 , R 5 , A, B, C, L, X, Y, Z, n, and m are as defined in the claims, and salts, N-oxides, or solvates thereof, to pharmaceutical compositions comprising said substituted sulfonamido-macrocycles, to methods of preparing said substituted sulfonamido-macrocycles as well as the use thereof for manufacturing a pharmaceutical composition for the treatment of diseases of dysregulated vascular growth or of diseases which are accompanied with dysregulated vascular growth, wherein the compounds effectively interfere with Tie2 signalling.

Methods and Compositions for Treating Cancer

Compositions and methods for treating cancer, including hematologic cancers such as multiple myeloma, are disclosed. In some embodiments, chaetocin, chaetomin, or gliotoxin can be used to treat or ameliorate one or more symptoms or disorders associated with multiple myeloma.

Biological substance treatment method, treatment compound

Donor tissue is treated prior to implantation in a recipient with a compound from the class known as epipolythiodioxopiperazines in order to prevent graft rejection.

PROCESS FOR THE PREPARATION OF AZABICYLIC COMPOUNDS

Epidithiodioxopiperazine compound or its derivatives, and the use thereof

본 발명은 하기 화학식 1로 표시되는 에피디티오디옥소피페라진 유도체 또는 이의 환원형 유도체; 세포 내 침투성이 향상되고 세포 내에서 환원되어 2-Cys-Prx 활성을 모방하는 화학식 1로 표시되는 화합물의 제조방법; 상기 에피디티오디옥소피페라진 유도체 또는 이의 약학적으로 허용가능한 염을 유효성분으로 포함하는 혈관질환 예방 또는 치료용 약학적 조성물; 상기 약학적 조성물을 포함하는 국소투여용 약물전달 장치; 및 상기 에피티디오디옥소피페라진 유도체 또는 이의 약학적으로 허용가능한 염을 유효성분으로 포함하는 흑색종 전이 억제용 약학적 조성물에 관한 것이다. [화학식 1] The present invention relates to an epididioiodopyropazine derivative represented by the following formula (1) or a reduced derivative thereof; A process for producing a compound represented by the formula (1) wherein intracellular permeability is improved and reduced in a cell to mimic 2-Cys-Prx activity; A pharmaceutical composition for preventing or treating vascular diseases comprising the epididioidoxapiperazine derivative or a pharmaceutically acceptable salt thereof as an active ingredient; A drug delivery device for topical administration comprising the pharmaceutical composition; And a pharmaceutical composition for inhibiting melanoma metastasis comprising the epithioiodioxapiperazine derivative or a pharmaceutically acceptable salt thereof as an active ingredient. [Chemical Formula 1]

Psychotropic bicyclic imides.

Substituted imides of the following formula are antipsychotic, anxiolytic agents with very little extrapyramidal side effects: <IMAGE> in which X is -O-, -S-, -SO-, -SO2-, -CR3R4-where R3 and R4, independently, are hydrogen, alkyl of 1 to 4 carbon atoms or, taken together with the carbon atom to which they are attached, R3 and R4 form a cycloalkyl group of 3 to 5 carbon atoms; Y is alkylene of 1 to 3 carbon atoms or alkenylene of 2 to 3 carbon atoms; n is one of the integers 0 to 1; m is one of the integers 2, 3, 4 or 5; R is phenyl, halophenyl, trifluoromethylphenyl, alkoxyphenyl in which the alkoxy substituent contains 1 to 3 carbon atoms, 2-pyrimidinyl, halopyrimidin-2-yl, 2-pyrazinyl, halopyrazin-2-yl, 2-pyridinyl, cyanopyridin-2-yl, halopyridin-2-yl, quinolyl, or haloquinolyl; or a pharmaceutically acceptable salt thereof.

Pharmaceutical composition for preventing or treating pulmonary arterial hypertension comprising epidithiodioxopiperazine compound or its derivatives, or pharmaceutically acceptable salts thereof

본 발명은 에피디티오디옥소피페라진(epidithiodioxopiperazine; ETP) 화합물 또는 이의 유도체; 또는 이들의 약학적으로 허용가능한 염을 포함하는 폐동맥고혈압의 예방 또는 치료용 약학적 조성물에 관한 것이다. The present invention relates to epidithiodioxopiperazine (ETP) compounds or derivatives thereof; Or it relates to a pharmaceutical composition for the prevention or treatment of pulmonary arterial hypertension comprising a pharmaceutically acceptable salt thereof.

Derivatives of macrocyclic polyesters of N-aryl-2-amino-4-aryl-pyrimidine as FTL3 and jak inhibitors

Oxa-, thia- and diazabicycloalkane derivatives, process for their preparation and their use as pharmaceuticals.

Compounds of formula (I) or a pharmaceutically acceptable salt thereof: < IMAGE > (I) wherein: j is 0 or 1 q is 0, 1 or 2 p is 0 and r is 2 or 3, or p is 1 and r is 2 X is O, S, SO or NR where R is hydrogen, C1-6 alkyl or C1-10 carboxylic acyl Y is NH or O when R1 is hydrogen either R1 is C1-6 alkoxy and one of R2, R3 and R4 is hydrogen and the other two are selected from hydrogen, halogen, CF3, C1-6 alkylthio, C1-7 acyl, C1-10 carboxylic acylamino, C1-6 alkyl S(O) n wherein n is 0, 1 or 2, nitro or amino, aminocarbonyl or aminosulphonyl optionally substituted by one or two groups selected from C1-6 alkyl, C3-8 cycloalkyl, C3-8 cycloalkyl C1-4 alkyl or phenyl C1-4 alkyl groups any of which phenyl moieties may be substituted by one or two groups selected from halogen, CF3, C1-6 alkyl or C1-6 alkoxy or R1 is hydrogen and R2, R3 and R4 are independently selected from hydrogen, C1-6 alkyl, hydroxy, C1-6 alkoxy, C1-6 alkylthio or halo or any two on adjacent carbon atoms together are C1-2 alkylenedioxy and the third is hydrogen, C1-6 alkyl, C 1-6 alkoxy or halo one of R5 and R6 is hydrogen, C1-6 alkyl, phenyl or phenyl-C1-6 alkyl, which phenyl moieties may be substituted by C1-6 alkyl, C1-6 alkoxy or halogen and the other is hydrogen or C1-6 alkyl and R7 is hydrogen, C1-6 alkyl, phenyl or phenyl-C1-3 alkyl, which phenyl moieties may be substituted by C1-6 alkyl, C1-6 alkoxy, CF3 or halogen having gastric motility enhancing activity, anti-emetic activity and/or 5-HT receptor antagonist activity, a process and intermediates for their preparation and their use as pharmaceuticals.

Piperazine derivatives as hiv protease inhibitors

Provided are compounds of Formula (I), pharmaceutical compositions comprising the same, and their use in the inhibition of HIV protease, the inhibition of HIV replication, the prophylaxis of infection by HIV, the treatment of infection by HIV, and the prophylaxis, treatment, and delay in the onset or progression of AIDS.

PYRAZOLO[1,5-a]PYRIMIDINE COMPOUNDS AS mTOR INHIBITORS

Tetrahydronaphthalene derivatives that inhibit mcl-1 protein

Cysteine derivative

The present invention provides a cysteine derivative superior in stability, which has less odor and an eumelanin production suppressive effect, and a cosmetic agent containing a cysteine derivative. A cysteine derivative represented by the following formula wherein each symbol is as defined in the specification, or a salt thereof, and a cosmetic agent containing a cysteine derivative.

MACROCYCLIC POLYETHYL N-ARYL-2-AMINO-4-ARYL-PYRIMIDINE DERIVATIVES

Tetrahydronaphthalene derivatives that inhibit mcl-1 protein

Pest control method

Method for producing cyclic organic compound

3-aza-6,8-dioxabicyclo [3.2.1] octanes and analogues and combinatorial libraries

The present invention relates to new highly functionalized heterobicycle derivatives of general formula (I), prepared by a process which involves only two steps by using, as starting products, commercially available, or easily prepared, α-amino ketones and α,β-dihydroxy acids or α-amino-β-hydroxy acids or α-hydroxy-β-amino acids or α,β-dithiol acids derivatives and to libraries containing compounds of formula (I) and to the generation of such combinatorial libraries composed of compounds of formula (I), in individual synthesis, mixture synthesis, split and recombine synthesis and parallel synthesis either in manual or automated fashion.

Piperazine derivatives as hiv protease inhibitors

Derivatives of macrocyclic n-aryl-2-amino-4-aryl-pyrimidine polyethers as inhibitors of ftl3 and jak

The present invention relates to a compound with the following formula: formula (I) or a salt and/or a pharmaceutically acceptable solvate thereof, in particular for use as a drug, in particular in the treatment of cancer, as well as to the pharmaceutical compositions that contain same and to the methods for preparing same.

Macrocyclic compound for use as NMR X-ray or radiodiagnostic agent

Compounds

Recombinant methods and materials for producing epothilone and epothilone derivatives

에포틸론 폴리케티드 신타아제 (PKS)의 전부 또는 일부위를 암호화하는 재조합 핵산을, 암의 화학적 치료제, 항진균제, 그리고 면역 억제제로서 유용한 에포틸론, 에포틸론 유도체, 및 폴리케티드 생산을 위해서, 재조합 PKS 유전자의 발현에 이용한다. Recombinant nucleic acid encoding all or part of the epothilone polyketide synthase (PKS) is recombinant for the production of epothilones, epothilone derivatives, and polyketides useful as chemotherapy, antifungal, and immunosuppressive agents in cancer. It is used for expression of the PKS gene.

Macrocyclic polyaza compounds containing rings with 5 or 6 members, methods for their preparation and pharmaceutical compositions containing same

Macrocyclic compounds of the general formula I <IMAGE> in which @is a single or double bond, q is the numbers 0-5, A and B, which are identical or different, are each a straight-chain or branched alkylene group with 2 to 6 carbon atoms, D is a nitrogen, oxygen atom, the group =C=O, =NR<2> with R<2> being a hydrogen atom or a C1-C6-alkyl group, the group <IMAGE> with R<3> being a hydrogen or halogen atom, a phenyl, a C1-C6-alkyl group which is optionally substituted by one or more phenyl and/or hydroxyl group(s), being the radical OR<5> where R<5> is a C1-C6-alkyl radical which is optionally substituted by 1 to 3 hydroxyl groups, being the substituent <IMAGE> where l is the numbers 0 and 1 and R<6> and R<7> are, independently of one another, hydrogen atoms, the radical R<5>, phenyl or benzyl radicals which are optionally substituted by 1 to 3 hydroxyl groups, or R<6> and R<7> are, together with the nitrogen atom, a saturated or unsaturated, 5- or 6-membered ring which optionally contains another nitrogen, oxygen, sulphur atom or a carbonyl group and which is optionally substituted by 1 to 3 radicals R<5>, or one of the substituents R<6> or R<7> is the radical <IMAGE> or being the substituent G where G is a second macrocycle which is bonded via a direct bond, a bis(carbonylamino) group (-NH-CO-CO-NH-) or via a C1-C20-alkylene group which optionally carries at the ends carbonyl (> CO) or carbonylamino (-NH-CO-) groups or oxygen atoms and optionally contains one or more oxygen atom(s), Z-, acyl- or hydroxyacyl-substituted imino groups or one to two C-C double and/or C-C triple bonds, and has the general formula II <IMAGE> in which D<1> has the same meaning as D with the exception that D<1> does not contain the substituent G, or is the radical -CH-, =C- or -N- and F<1> has the same meaning as F with the exception that F<1> does not ...

Pyrazolo[1,5-a]pyrimidine compounds as mTOR inhibitors

The present invention provides Pyrazolopyrimidine Compounds of Formula (I): wherein L, T, Z, U, V, W, R 3 , R 6 , R 7 , R 8 , and m are as defined herein, and pharmaceutically acceptable salts of such Pyrazolopyrimidine Compounds. The Pyrazolopyrimidine Compounds are useful in the treatment of cancer and other diseases or disorders wherein mTOR is deregulated.

Patent RU2017108932A3

MACROCYCLIC POLYETHYL N-ARYL-2-AMINO-4-ARYL-PYRIMIDINE DERIVATIVES

La présente invention concerne un composé de formule (I) suivante : ou un sel et/ou un solvate pharmaceutiquement acceptable de celui-ci, notamment pour son utilisation comme médicament, notamment dans le traitement du cancer, ainsi que les compositions pharmaceutiques le contenant et ses procédés de préparation. The present invention relates to a compound of formula (I) below: or a pharmaceutically acceptable salt and / or solvate thereof, especially for its use as a medicament, especially in the treatment of cancer, as well as pharmaceutical compositions containing it and its preparation processes.

Recombinant methods and materials for producing epothilone and epothilone derivatives

Recombinant nucleic acids that encode all or a portion of the epothilone polyketide synthase (PKS) are used to express recombinant PKS genes in host cells for the production of epothilones, epothilone derivatives, and polyketides that are useful as cancer chemotherapeutics, fungicides, and immunosuppressants.

Tetrahydronaphthalene derivatives that inhibit mcl-1 protein

Macrocyclic compounds that inhibit mcl-1 protein

Provided herein are myeloid cell leukemia 1 protein (Mcl-1) inhibitors, methods of their preparation, related pharmaceutical compositions, and methods of using the same. For example, provided herein are compounds of Formula I, or a stereoisomer thereof; and pharmaceutically acceptable salts thereof and pharmaceutical compositions containing the compounds. The compounds and compositions provided herein may be used, for example, in the treatment of diseases or conditions, such as cancer.

Compounds that inhibit MCL-1 protein

Provided herein are compounds that are useful intermediates that may used to synthesize myeloid cell leukemia 1 protein (Mcl-1) inhibitors. Also provided are Mcl-1 inhibitors, methods of their preparation, related pharmaceutical compositions, and methods of using the same. For example, provided herein are compounds of Formula I,and pharmaceutically acceptable salts thereof and pharmaceutical compositions containing the compounds. The compounds and compositions provided herein may be used, for example, in the treatment of diseases or conditions, such as cancer.

PSYCHOTROPIC BIZYCLIC IMIDES.

Substituted imides of the following formula are antipsychotic, anxiolytic agents with very little extrapyramidal side effects: <IMAGE> in which X is -O-, -S-, -SO-, -SO2-, -CR3R4-where R3 and R4, independently, are hydrogen, alkyl of 1 to 4 carbon atoms or, taken together with the carbon atom to which they are attached, R3 and R4 form a cycloalkyl group of 3 to 5 carbon atoms; Y is alkylene of 1 to 3 carbon atoms or alkenylene of 2 to 3 carbon atoms; n is one of the integers 0 to 1; m is one of the integers 2, 3, 4 or 5; R is phenyl, halophenyl, trifluoromethylphenyl, alkoxyphenyl in which the alkoxy substituent contains 1 to 3 carbon atoms, 2-pyrimidinyl, halopyrimidin-2-yl, 2-pyrazinyl, halopyrazin-2-yl, 2-pyridinyl, cyanopyridin-2-yl, halopyridin-2-yl, quinolyl, or haloquinolyl; or a pharmaceutically acceptable salt thereof.

Tetrahydronaphthalene derivatives that inhibit mcl-1 protein

MACROCYCLIC POLYA COMPOUNDS CONTAINING RINGS OF 5 OR 6 LINKS, PROCEDURE FOR THEIR PREPARATION AND PHARMACEUTICAL AGENTS CONTAINING THEM.

CONEXIONES MACROCICLICAS SEGUN LA FORMULA GENERAL I DE LA QUE ... PARA UNA UNION SENCILLA O DOBLE; Q PARA LA CIFRA 0-5, A Y B QUE SON IGUALES O DIFERENTES, EN CADA CASO PARA UN GRUPO DE ALKILES DE CADENA RECTA O RAMIFICADA, CON 2 A 6 ATOMOS DE CARBONO; D PARA UN ATOMO DE NITROGENO OXIGENO, EL GRUPO = C = O = NR2 CON R2 EN EL SIGNIFICADO DE UN ATOMO DE HIDROGENO O ATOMO DE HALOGENO DE UN GRUPO DE FENIL DE UN C1-C6 DE ALKIL QUE EN CASO DADO PUEDE SER SUSTITUIDO POR UN GRUPO DE FENIL O HIDROXIDO, DEL RESTO OR5, PARA LO QUE R5 PUEDE SER SUSTITUIDO POR UN GRUPO DE 1 A 3 HIDROXIDOS C1-C6-RESTO DE ALKIL DEL SUSTITUIDO -(C) INR6R7, PARA LO QUE I PARA LA CIFRA 0 Y 1 Y RE Y R7 INDEPENDIENTES ENTRE SI PARA ATOMO DE HIDROGENO, PARA EL RESTO R5, PARA CASO DADO SER SUSTITUIDO POR 1 A 3 GRUPOS DE HIDROXIDO RESTOS DE FENIL O BENZIL O R6 Y R7 CONJUNTAMENTE CON EL ATOMO DE NITROGENO PARA UN ATOMO SATURADO O NO SATURADO CON Y EN CASO DADO OTRO ATOMO MAS DE NITROGENO, OXIGENO, SULFURO Y GRUPO CARBONIL CONTENIENDO 5 O 6 ANILLOS QUE EN CASO DADO PUEDE SER SUSTITUIDO POR 1 A 3 RESTOS R5 O UN SUSTITUIDO R6 O R7 PARA EL RESTO -C-R5 ESTAN O SISTITUYEN G PARA LO QUE G CONTIENE A TRAVES DE UNA UNION DIRECTA UN GRUPO BIS(CARBONILAMONIO) (NH-CO-CO-NH) O UN GRUPO SOBRE C1-C20-ALKILES QUE EN CASO DADO CONTIENEN EN LOS EXTREMOS CARBONIL -(>CO) O CARBONILAMINO (-NH-CO) GRUPOS O ATOMOS DE NITROGENO Y CASO DADO UNO A VARIOS ATOMOS DE NITROGENO Z-, ALCYL, O HIDROXIALCYL SUSTITUIDO INMUNOGRUPOS O UNO A DOS C-C-DOBLE- Y/O C-C-TRIUNIONES, UNIDAS EN UN SEGUNDO MACROCICLO DE LA FORMULA GENERAL (II) EN DONDE: D1 TIENE EL MISMO SIGNIFICADO QUE D CON LA EXCEPCION DE QUE D1 NO CONTIENE LA G SUSTITUIDA, O EL RESTO -CH-, =C- O -N- ESTAN Y F1 TIENE EL MISMO SIGNIFICADO QUE F CON LA EXCEPCION DE QUE F1 NO CONTIENE LA G SUSTITUIDO O PARA EL RESTO -CH- O =C- ESTA E PARA UN ATOMO DE NITROGENO-SULFURO-OXIGENO O NR4-GRUPO CON R4 ENEL SIGNIFICADO DE UN GRUPO HIDROXIDO, DE R2 O CADO DADO HIDROXILADO O CARBOSILADO GRUPO ...

Synthesis of vinylcyclobutyl intermediates

Ｍｃｌ－１阻害剤の調製に有用な中間体を合成するための方法が本明細書で提供される。特に、本明細書では、化合物Ｆ（式中、Ｒ１及びＯＰＧ２は、本明細書に記載されている）又はその塩を合成するための方法が提供される。化合物Ｆは、化合物Ａ１又はその塩若しくは溶媒和物及び化合物Ａ２又はその塩若しくは溶媒和物の合成に有用であり得る。TIFF2023524259000239.tif71170

Method for producing cyclic organic compound

【課題】優れた不純物の抑制効果（品質向上）、反応釜サイズの減少、連続生産等を達成することができる、CSTR（連続槽型反応器）を用いて環状有機化合物を製造する方法を提供する。【解決手段】環状有機化合物を製造する方法であって、環状有機化合物の環化前駆体を少なくとも１基の連続槽型反応器において環化する環化反応工程を含む、前記方法である。好ましくは、前記環状有機化合物が、天然アミノ酸及び／又はアミノ酸類縁体により構成される、環状部を有するペプチド化合物であり、前記環状部を有するペプチド化合物が、４～１４個の天然アミノ酸及び／又はアミノ酸類縁体残基からなる環状部を含み、かつ、天然アミノ酸及びアミノ酸類縁体残基の総数が７～２０である、環状有機化合物を製造する方法である。【選択図】図１

Synthesis of vinyl cyclobutyl intermediates

En la presente se proporcionan procesos para sintetizar intermedios útiles en la preparación de inhibidores de Mcl-1. En particular, en la presente se proporcionan procesos para sintetizar el compuesto F, o una sal del mismo, en donde R¹ y OGP² se describen en la presente. El compuesto F puede ser útil para sintetizar el compuesto A1, o una sal o solvato del mismo, y el compuesto A2, o una sal o solvato del mismo. (F),<br /> (A1) y (A2). <br />

Potent immunosuppressive agents derivatives and use

Provided herein include compositions, all related stereoisomers as well as pharmaceutically acceptable salts provided as simplified analogs of pateamine A, in which the analogs generally are devoid of the C3-amino and C5-methyl groups, also referred to as desmethyl, desamino-pateamine A. Suitable analogs provide anticancer and antiproliferative effects in vivo and in vitro by a novel drugs mechanism of action described herein for pateamine A, including inhibition of eIF4A-dependent translation initiation. As with pateamine A, as described herein, suitable analogs cause cell cycle arrest or induce apoptosis in transformed cells. However, toxicity of such compounds to slow growing normal cells is low. In addition, such analogs, like pateamine A, target translation initiation factors and are useful as anticancer and antiproliferative agents in subjects in need thereof. Moreover, the analogs, like pateamine A, are valuable molecular probes for evalutaion of eukaryotic translation initiation and as lead compounds for development of improved anticancer agents.

Azabicyclo derivatives and pharmaceutical composition thereof

본 발명은 5-HT 3 수용체 길항제 활성을 지닌 일반식(I)의 아자비사이클로 유도체 및 이의 약제학적으로 허용되는 염에 관한 것이다. The present invention relates to azabicyclo derivatives of general formula (I) having 5-HT 3 receptor antagonist activity and pharmaceutically acceptable salts thereof. 상기식에서, In the above formula, A는 일반식 A is a general formula 또는 or 의 그룹이고, R 1 은 수소, C 1 -C 10 알킬, 아르알킬 또는 디(C 1 -C 4 ) 알킬아미노 (C 1 -C 6 )알킬이며, R 2 , R 3 및 R 4 는 동일하거나 상이할 수 있고 각각 수소, 아미노, 할로겐, C 1 -C 4 알콕시 또는 프탈이미드이고, R 1 is hydrogen, C 1 -C 10 alkyl, aralkyl or di (C 1 -C 4 ) alkylamino (C 1 -C 6 ) alkyl, and R 2 , R 3 and R 4 are the same or May be different and each is hydrogen, amino, halogen, C 1 -C 4 alkoxy or phthalimide, X 는 O 또는 NH이며, X is O or NH, R 은 C 1 -C 4 알킬이며, R is C 1 -C 4 alkyl, Y 는 NR, O 또는 S 이다. Y is NR, O or S.

Dc 107 derivatives (2)

DC 107 derivatives represented by general formula (I) or pharmacologically acceptable salts thereof, each having antibacterial and antitumor activities, wherein R1 represents CO(CR4AR4B)n1¢O(CH2)p1!n2OR5, wherein n1 represents an integer of 1 or 2; R4A and R4B are the same or different and each represents hydrogen or lower alkyl; p1 and n2 are each an integer of 1 to 10; and R5 represents hydrogen, lower alkyl, etc.; or formula (II), (wherein A1, A2, A3 and A4 are the same or different and each represents hydrogen, hydroxy, etc.); R2 represents hydrogen or COR6 (wherein R6 represents lower alkyl, aralkyl, optionally substituted aryl, etc.); R3 represents lower alkyl, lower alkenyl, aralkyl having optionally substituted aryl, alicyclic alkanoyloxy-alkyl, CH2OCOR7, etc., or R3 may form a bond together with Y; Y forms a bond together with R3 or Z; Z represents hydrogen or may form a bond together with Y; and W represents oxygen or NR8.

3-aza-6,8-dioxabicyclo[3.2.1]octanes and analogues and combinatorial libraries

The present invention relates to new highly functionalized heterobicycle derivatives of general formula (I), prepared by a process which involves onl y two steps by using, as starting products, commercially available, or easily prepared, .alpha.-amino ketones and .alpha.,.beta.-dihydroxy acids or .alpha .- amino-.beta.-hydroxy acids or .alpha.-hydroxy-.beta.-amino acids or .alpha.,.beta.-dithiol acids derivatives and to libraries containing compoun ds of formula (I) and to the generation of such combinatorial libraries compose d of compounds of formula (I), in individual synthesis, mixture synthesis, spl it and recombine synthesis and parallel synthesis either in manual or automated fashion.

Salts and polymorphs of certain mcl-1 inhibitors

The present disclosure relates salts and the crystalline forms of certain 3′,4,4′,5-tetrahydro-2H,2′H-spiro[benzo[b][1,4]oxazepine-3,1′-naphthalene] derivatives as well as pharmaceutical formulations and therapeutic uses thereof. The present disclosure also relates to preparing such salts, crystalline forms and pharmaceutical formulations.

大環Mcl-1抑制劑中間體的閉環合成

本文提供了用於合成以下之方法：Mcl-1抑制劑以及可用於製備Mcl-1抑制劑的中間體，例如化合物F，其中變量PG如本文所定義。具體地，本文提供了合成化合物A1及其鹽或溶劑化物和化合物A2及其鹽和溶劑化物之方法。 ，

用于制备环状有机化合物的方法

本发明的目的在于提供使用连续搅拌釜式反应器(CSTR)制备环状有机化合物的方法，所述方法能够实现优异的杂质抑制效果(质量改善)、反应釜尺寸的减小、连续生产等。为了解决上述问题，本发明人对使用CSTR的环化反应进行了研究，该反应器并未常规地用于环状化合物的环化反应。因此，本发明人已经发现与常规环化方法相比，本发明可以实现优异的杂质抑制效果(质量改善)、反应釜尺寸的减小、连续生产等。此外，本发明人已经发现，通过将常规上主要以精细化学品工厂水平使用的模拟方法应用于本发明的环化反应，由此实验性地预测环化反应的反应速率，并且在使用CSTR的环化反应中设定影响这些条件的流量(停留时间)、前体和环状有机化合物的浓度以及用于环化反应的温度等，甚至在环肽和杂环化合物的制备中可以有效地实现上述改善效果。

Derivate von dc 107

Mixed kappa/mu opioids and uses thereof

Síntesis de intermedios para inhibidores de mcl-1 macrocíclicos mediante un cierre de anillo

En la presente se proporcionan procesos para sintetizar inhibidores de Mcl-1 e intermedios tales como el compuesto F que se pueden utilizar para prepararlos donde el PG variable es como se define en la presente. En particular, en la presente se proporcionan procesos para sintetizar el compuesto A1, y sus sales o solvatos, y el compuesto A2, y sus sales y solvatos.

Salts and polymorphs of certain mcl-1 inhibitors

The present disclosure relates salts and the crystalline forms of certain 3',4,4',5-tetrahydro-2H,2'H-spiro[benzo[b][1,4]oxazepine-3,1'-naphthalene] derivatives as well as pharmaceutical formulations and therapeutic uses thereof. The present disclosure also relates to preparing such salts, crystalline forms and pharmaceutical formulations.

某些ｍｃｌ－１抑制劑之鹽及同質多形體

本揭露關於某些3',4,4',5-四氫-2H,2'H-螺[苯并[b][1,4]氧氮呯-3,1'-萘] (3',4,4',5-tetrahydro-2H,2'H-spiro[benzo[b][1,4]oxazepine-3,1'-naphthalene])衍生物之鹽及晶形，以及其醫藥配方與治療用途。本揭露亦關於製備此類鹽、晶形、及醫藥配方。

Mci-1拮抗劑之鹽形式及溶劑化物

本文揭露了以下物質的鹽和溶劑化物形式：(1S,3′R,6′R,7′S,8′E,11′S,12′R)-6-氯-7′-甲氧基-11′,12′-二甲基-3,4-二氫-2H,15′H-螺[萘-1,22′-[20]氧雜[13]硫雜[1,14]二氮雜四環[14.7.2.0 3,6 .0 19,24 ]二十五碳[8,16,18,24]四烯]-15′-酮13′,13′-二氧化物（AMG 176）：

Mci-1拮抗劑之無定形及結晶形式

本文揭露了(1S,3′R,6′R,7′S,8′E,11′S,12′R)-6-氯-7′-甲氧基-11′,12′-二甲基-3,4-二氫-2H,15′H-螺[萘-1,22′-[20]氧雜[13]硫雜[1,14]二氮雜四環[14.7.2.0 3,6 .0 19,24 ]二十五碳[8,16,18,24]四烯]-15′-酮13′,13′-二氧化物（AMG 176）的結晶和無定形形式：

Amorphous and crystalline forms of mci-1 antagonists

Disclosed herein are crystalline and amorphous forms of (1S,3'R,6'R,7'S,8'E,11'S,12'R)-6-chloro-7'-methoxy-11',12'-dimethyl-3,4-dihydro-2H,15'H-spiro[naphthalene-1,22'-[20]oxa[13]thia[1,14]diazatetracyclo[14.7.2.03,6.019,24]pentacosa[8,16,18,24]tetraen]-15'-one 13',13'-dioxide (AMG 176), and salts and hydrates thereof. Also disclosed are methods of making the crystalline and amorphous forms, and methods of treating diseases and disorders with the crystalline and amorphous forms.

Salt forms and solvates of mci-1 antagonists

Disclosed herein are salt and solvate forms of. (1S,3'R,6'R,7'S,8'E,1 TS,12'R)-6-chloro-7'-methoxy-11 ',12'- dimethyl-3,4-dihydro-2H,15'H-spiro[naphthalene-1,22'- [20]oxa[13]thia[1,14]diazatetracyclo[14.7.2.03,6.019,24]pentacosa[8,16,18,24]tetraen]-15'-one 13',13'-dioxide (AMG 176) such as crystalline salt and solvate forms thereof. Also disclosed are methods of making the salt and solvate forms, and methods of treating diseases and disorders with the salt and solvate forms.

Synthesis of vinylic alcohol intermediates

DC 107 derivatives