17-ДЕЗОКСИ-1,3,5(10)-ЭСТРАТРИЕН, СПОСОБЫ ЛЕЧЕНИЯ, СПОСОБ СИНТЕЗА 7АЛЬФА-МЕТИЛЭСТРОНА, СОЕДИНЕНИЯ, ФАРМАЦЕВТИЧЕСКАЯ КОМПОЗИЦИЯ

Описываются новые антиэстрогенные соединения, которые применимы для лечения многочисленных нарушений, в частности эстрогензависимых нарушений. Предпочтительные соединения имеют 1,3,5-эстратриеновое ядро и замещены в положении С-17 или положении С-11 молекулярным фрагментом, который делает эти соединения эффективными в блокировании связывания эстрогена с его рецептором. Особенно предпочтительными соединениями являются 17-дезокси-1,3,5-эстратриены. Описаны также терапевтические способы и фармацевтические композиции. 12 c. и 9 з.п.ф-лы, 3 ил., 2 табл.

СОСТАВ НА ОСНОВЕ АБИРАТЕРОНА АЦЕТАТА

Группа изобретений относится к области фармацевтической промышленности, более конкретно, к способу получения композиции, содержащей наночастицы абиратерона ацетата, и к способу получения твердой пероральной композиции на ее основе. Также предложены фармацевтическая композиция и твердая пероральная фармацевтическая композиция, содержащие: абиратерона ацетат; измельчаемый размольный материал; агент-интенсификатор помола, выбранный из коллоидного диоксида кремния, ПАВ, полимера, стеариновой кислоты и их производных; антиоксидант, выбранный из аскорбиновой кислоты, бутилированного гидроксианизола и бутилированного гидрокситолуола; и связывающий агент, выбранный из фумаровой, винной и лимонной кислот, где [D] частиц абиратерона ацетата составляет более 100 нм и менее 1000 нм. Кроме того, предложены варианты способа лечения кастрационно-резистентного рака предстательной железы. Группа изобретений обеспечивает улучшение профиля растворения абиратерона ацетата, а также повышение стабильности композиции ...

ИНГИБИТОРЫ АРГИНАЗЫ И СПОСОБЫ ИХ ПРИМЕНЕНИЯ

Группа изобретений относится к области медицины, а именно к соединению, выбранному из:,,,,,,,,,,,,,,,,,,,,,,,или его фармацевтически приемлемой соли, к применению вышеперечисленных соединений для лечения заболеваний, выбранных из группы, состоящей из хронического инфекционного заболевания, бактериальной инфекции, паразитарной инфекции, травмы, лепры, туберкулеза, трансплантации печени, рака, фиброзных заболеваний и их комбинации, и к фармацевтической композиции, включающей вышеперечисленные соединения. Группа изобретений обеспечивает получение ингибиторов аргиназной активности, которые могут использоваться для лечения заболевания у млекопитающего, причем заболевание характеризуется либо необычно высокой аргиназной активностью, либо необычно низкими уровнями оксида азота в ткани млекопитающего. 3 н.п. ф-лы, 14 ил., 13 табл., 173 пр.

19-НОР НЕЙРОАКТИВНЫЕ СТЕРОИДЫ И СПОСОБЫ ИХ ПРИМЕНЕНИЯ

Изобретение относится к соединению формулы (I) или его фармацевтически приемлемой соли. В формуле (I)представляет собой одинарную или двойную связь, как позволяет валентность; A имеет формулу (A-1) или формулу (A-2), где точка присоединения находится в Gили Gв формуле (A-1) и точка присоединения находится в Gили Gв формуле (A-2); Gпредставляет собой N, NRили C-R, как позволяет валентность; Gпредставляет собой N или -C=N-, как позволяет валентность; Gпредставляет собой N или C-R, как позволяет валентность; Gпредставляет собой N или C-R, как позволяет валентность; Gпредставляет собой N или C-R, как позволяет валентность; Gпредставляет собой N или C-R, как позволяет валентность; и Gпредставляет собой N или C-R, как позволяет валентность; в каждом случае R, R, R, R, R, Rи Rнезависимо представляет собой водород, галоген, -CN, -ORили незамещенный Cалкил; в каждом случае Rпредставляет собой незамещенный Cалкил; в каждом случае Rнезависимо представляет собой водород, Cалкил, замещенный фтором, ...

СТЕРОИДНЫЕ СОЕДИНЕНИЯ, ПРИМЕНЕНИЕ ЭТИХ СОЕДИНЕНИЙ ДЛЯ ПОЛУЧЕНИЯ РЕГУЛИРУЮЩИХ МЕЙОЗ ЛЕКАРСТВЕННЫХ СРЕДСТВ И СПОСОБ ПОЛУЧЕНИЯ ЭТИХ СОЕДИНЕНИЙ

... 1. Стероидное соединение, имеющее общую формулу X где в фрагменте XA каждая связь между С6 и С7, между С7 и С8, между С8 и С9, между С8 и С14 и между С14 и С15 означает независимо одинарную связь или двойную связь при условии, что каждый атом углерода С6, С7, С8, С8, С14 и С15 связан с каждым соседним атомом углерода одинарной связью или, самое большее, одной двойной связью, CR3 означает а) С=O или б) CH-OR3', где R3’ выбирают из группы, включающей водород, незамещенный или замещенный, линейный или разветвленный (С1-С10)алкил и C(O)-R3’’, присоединенный к части СН-O через С(O)-группу, где R3" выбирают из группы, включающей i) замещенный или незамещенный, линейный или разветвленный (С1-С10)алкил, ii) замещенный или незамещенный, линейный или разветвленный (C1 -С10)фторалкил, iii) незамещенный или замещенный (C1-С10)арил, iv) незамещенный или замещенный (C1-С10)гетероарил, v) незамещенный или замещенный, линейный или разветвленный (C1-С10)алкилокси и vi) незамещенный или замещенный, линейный ...

КОНЪЮГАТЫ, ОБЛАДАЮЩИЕ ПРОТИВОВОСПАЛИТЕЛЬНОЙ АКТИВНОСТЬЮ

... 1. Соединение формулы:гдепредставляет собой макролидную субъединицу подструктуры:где R, R, Rи Rвыбирают независимо друг от друга из группы, состоящей из водорода, C-Cалкила, алканоила, алкоксикарбонила, арилметоксикарбонила, ароила, арилалкила, алкилсилила, алкилсилилалкоксиалкила или ковалентной связи сцепиформулыили;Rвыбирают из группы, состоящей из ковалентной связи сцепиформулыили, водорода, C-Cалкила, алканоила, алкоксикарбонила, арилметоксикарбонила, ароила, арилалкила, алкилсилила и алкилсилилалкоксиалкила; или Rпредставляет собой группу, которая может быть объединена с Rс образованием циклического карбоната или карбамата или вместе с >NRобразует циклический карбамат;Rпредставляет собой водород, C-Cалкил или ковалентную связь сцепиформулы;представляет собой цепь субструктурыили:где Xвыбирают из -CH, -CH-NH-, -C(O)-, -OC(O)-, =N-O-, -C(O)NH- или -OC(O)NH-;Xвыбирают из -NH-, -CH-, -NHC(O)-, -C(=О), -OC(O)-, -C(=O)O- или -C(O)NH-;Q представляет собой -NH- или -CH-;где каждая группа ...

НОВЫЕ СУЛЬФАТИРОВАННЫЕ ПРОИЗВОДНЫЕ ОЛИГОСАХАРИДОВ

... 1. Соединение общей формулы: ! , ! в которой каждый из X и Y представляют собой моносахаридное звено, в котором каждая гидроксильная группа, не участвующая в гликозидной связи, независимо замещена группой SO3M или Н, где М является любым фармацевтически приемлемым катионом; ! X и Y представляют собой любую D- или L-гексозу или пентозу; ! Y находится в форме замкнутого или разомкнутого цикла; ! Z представляет собой O, N, S или C, или состояния их более высокой степени окисления, или связь, и связан с аномерным атомом углерода, когда Y является восстанавливающим моносахаридом; ! R1 является линкером, выбранным из группы, включающей алкил, алкенил, алкинил, арил, гетероалкил, гетероарил, ацил, ароил, алкиламидо, алкилтиоамидо, триазолил, замещенный триазолил, или представляет собой связь; ! R2 представляет собой липофильную группу, выбранную из группы, включающей холестерил, холестанил, холат, дезоксихолат, глицирретинил, линейный алкил размером более С8, замещенный алкил размером более С8 ...

ТЕРАПЕВТИЧЕСКИ АКТИВНЫЕ ТРИАЗОЛЫ И ИХ ИСПОЛЬЗОВАНИЕ

... 1. Соединение общей формулы (I) ! , ! где А представляет собой N и В представляет собой С, или А представляет собой С ! и В представляет собой N ! n составляет 1, 2, 3, 4, 5 или 6 ! X, Y по отдельности представляют собой F, или Х и Y вместе представляют собой группу =O ! R1 выбран из группы, состоящей из: ! (a) -Н, ! (b) -(С1-С6)алкила, ! который необязательно замещен галогеном, карбонитрильной, -OR3, -SR3 или -COOR3 группами; число указанных заместителей составляет 1, 2 или 3 для галогена и 1 или 2 для любой комбинации указанных галогена, карбонитрильной, -OR3, -SR3 или -COOR3 групп, ! или который необязательно замещен арилом, где арил необязательно замещен 1 или 2 заместителями, выбранными из группы, состоящей из галогена, гидроксила и -(С1-С6)алкила, и ! (c) -фенила, который необязательно замещен галогеном, карбонитрильной, - OR3, -SR3, -COOR3 группами, или -(С1-С6)алкилом, необязательно замещенным 1, 2 или 3 галогенами, и/или необязательно замещенным 1, 2 или 3 гидроксильными группами ...

17 АЛЬФА - И 17 БЕТА - ЗАМЕЩЕННАЯ ЭСТРА-1,3,5(10)-ТРИЕН-3-КАРБОНОВАЯ КИСЛОТА, СПОСОБ ПОЛУЧЕНИЯ, ПРОМЕЖУТОЧНЫЕ ПРОДУКТЫ, ФАРМАЦЕВТИЧЕСКАЯ КОМПОЗИЦИЯ, СПОСОБ ИНГИБИРОВАНИЯ СТЕРОИДНОЙ АКТИВНОСТИ 2-РЕДУКТАЗЫ, СПОСОБ СНИЖЕНИЯ ИЛИ ПОДДЕРЖАНИЯ РАЗМЕРА ПРЕДСТАТЕЛЬНОЙ ЖЕЛЕЗЫ, СПОСОБЫ ЛЕЧЕНИЯ

Изобретение относится к имеющим ароматическое А-кольцо 17альфа- и 17бета-(замещенный ацил)-3-карбоксианалогам стероидным синтетическим соединениям, способам их получения и полупродуктам их синтеза, фармацевтическим композициям, содержащим эти соединения, и применению этих соединений для ингибирования 5а-редуктазы.

ИНГИБИТОРЫ КЛЕТОЧНОЙ ПЕРЕДАЧИ СИГНАЛОВ, ИХ СОСТАВЫ И ОТНОСЯЩИЕСЯ К НИМ СПОСОБЫ

СОЕДИНЕНИЯ, ПРОМОТИРУЮЩИЕ ОСТЕОГЕНЕЗ И/ИЛИ ИНГИБИРУЮЩИЕ КОСТНУЮ РЕЗОРБЦИЮ

Соединение представлено формулой, приведенной в описании, способно концентрироваться в костной ткани и обладает ингибирующим резорбцию и промотирующим окостенение действием.

БИОМАРКЁРЫ ДЛЯ ЛЕЧЕНИЯ НЕОПЛАСТИЧЕСКИХ ЗАБОЛЕВАНИЙ С ПРИМЕНЕНИЕМ НАЦЕЛЕННЫХ НА АНДРОГЕН МЕТОДОВ ЛЕЧЕНИЯ

АНАЛОГИ ЖЕЛЧНОЙ КИСЛОТЫ В КАЧЕСТВЕ АГОНИСТОВ FXR/TGR5 И СПОСОБЫ ИХ ПРИМЕНЕНИЯ

НОВЫЕ СТЕРОИДЫ НА ОСНОВЕ ПРЕГНАНА И ФАРМАЦЕВТИЧЕСКИЕ КОМПОЗИЦИИ, ИХ СОДЕРЖАЩИЕ

Изобретение касается новых терапевтически активных 21-аминостероидов на основе прегнана. Общая формула и значения радикалов приведены в описании изобретения.

АНТАГОНИСТЫ ПРОГЕСТЕРОНА

... 1. Соединение, имеющее структуру формулы (I)в которомRпредставляет собой атом водорода, С-Салкильную группу с прямой цепью, разветвленную С-Салкильную группу, С-Сциклоалкильную группу или атом галогена;Rпредставляет собой атом водорода, С-Салкильную группу с прямой цепью, разветвленную С-Салкильную группу, С-Сциклоалкильную группу или атом галогена; илиRи Rвместе представляют собой метиленовую группу,Rпредставляет собой атом водорода, С-Салкильную группу с прямой цепью, разветвленную С-Салкильную группу, С-Сциклоалкильную группу или атом галогена;Rпредставляет собой атом водорода, С-Салкильную группу с прямой цепью, разветвленную С-Салкильную группу, С-Сциклоалкильную группу или атом галогена; илиRи Rвместе представляют собой дополнительную связь или метиленовую группу,Rпредставляет собой радикал Y или арильный радикал, который необязательно замещен Y,Y представляет собой атом водорода, атом галогена, -OR, -NO, -N, -CN, -NRR, -NHSOR, -COR, C-Салкил, замещенный C-Салкил, C-Сциклоалкил, С-Салкенил ...

СПОСОБ ПОЛУЧЕНИЯ СУЛЬФОНИЛКАРБАМАТНЫХ ПРОИЗВОДНЫХ ЖЕЛЧНЫХ КИСЛОТ

СПОСОБ ПОЛУЧЕНИЯ ПРОИЗВОДНЫХ СТЕРИНА

... 1. Способ получения соединения формулы (I):где:пунктирная линия означает связь, являющуюся одинарной или двойной,- Rи R′одинаковые или разные, и представляют собой H или CH,- Rпредставляет собой H, CHили CH,- Rпредставляет собой -NRR′, где R и R′ одинаковые или разные, и выбраны из группы, состоящей из:-H,-(СН)n-ОН, где n представляет собой целое число от 1 до 4,-(СН)n-NHP, где n представляет собой целое число от 1 до 6, иP представляет собой H или защитную группу;-(СН)n-NP-(СН)m-NHP′, где n представляет собой целое число от 1 до 6,m представляет собой целое число от 1 до 6, иP и P′ одинаковые или разные, и представляют собой Н или защитную группу;-(СН)n-NP-(СН)m-NP′-(СН)p-NHP″,где n представляет собой целое число от 1 до 6,m представляет собой целое число от 1 до 6,p представляет собой целое число от 1 до 6, иP, P′ и P″ одинаковые или разные, и представляют собой H или защитную группу;-(CH)n-X, где n представляет собой целое число от 1 до 4, иX = имидазол, индол или фенил, необязательно ...

ИНГИБИТОРЫ CYP11B, CYP17 И/ИЛИ CYP21

... 1. Соединение формулы IX,гдеА представляет собой гетероарил, необязательно замещенный 1, 2, 3 или 4 R;каждая Rнезависимо представляет собой галоген, циано, гидроксил, алкокси, алкил, алкенил, циклоалкил, гетероциклоалкил, арил, гетероарил, -C(O)R, алкоксикарбонил, -C(O)NRR, -NRS(O)R, -NRC (О)Rили -NRR;каждая Rнезависимо представляет собой водород или алкил;каждая Rнезависимо представляет собой водород, алкил, галогеналкил, алкоксиалкил, циклоалкил, арил, арилалкил, гетероарил или гетероарилалкил;Rи Rнезависимо представляют собой водород, алкил, галогеналкил, алкоксиалкил, циклоалкил, арил, арилалкил, гетероарил или гетероарилалкил; или Rи R, взятые вместе с атомом азота, образуют 4-7-членное гетероциклическое кольцо, содержащее один или два гетероатома;Rпредставляет собой арилкарбонилокси, гетероциклоалкилкарбонилокси, гетероарилкарбонилокси, -OC(O)NRRили -ОС(О)-алкилен-NRR; где арил, гетероциклоалкил и гетероарил независимо необязательно замещены одним или двумя алкилами;Rпредставляет ...

17α-АЛКИЛ-17β-ОКСИЭСТРАТРИЕНЫ И ПРОМЕЖУТОЧНЫЕ ПРОДУКТЫ ДЛЯ ИХ ПОЛУЧЕНИЯ, ПРИМЕНЕНИЕ 17α -АЛКИЛ-17β -ОКСИЭСТРАТРИЕНОВ ДЛЯ ПОЛУЧЕНИЯ ЛЕКАРСТВЕННЫХ СРЕДСТВ, А ТАКЖЕ ФАРМАЦЕВТИЧЕСКИХ ПРЕПАРАТОВ

... 1. 17α-Алкил-17β-оксиэстратриены общей формулы I в которой Hal обозначает F или Cl и в положении 11β связан с эстратриеновым скелетом; R3 обозначает водород, С1-С4алкил, С1-С4алканоил или простой циклический С3-С7эфир с O-атомом; R17’ обозначает водород, С1-С4алкил или С1-С4алканоил; R17’’ обозначает С1-С4алкил, С1-С4алкинил, а также по меньшей мере частично фторированные алкильные остатки, при этом R17’-О в положении 17β и R17’’ в положении 17α связаны с эстратриеновым скелетом; SK обозначает группировку U-V-W-X-Y-Z-E, которая через U связана в положении 7α с эстратриеновым скелетом, где U представляет собой либо прямоцепочечный или разветвленный С1-С13алкиленовый, -алкениленовый или -алкиниленовый остаток либо группу А-В, при этом А связан с эстратриеновым скелетом и обозначает соединенный через -CH2- с эстратриеновым скелетом бензилиденовый, фениленовый или соединенный через алкильную группу с эстратриеновым скелетом C1-С3алкиларильный остаток, а В обозначает прямоцепочечный или разветвленный ...

Способ получения 8 -эстратриенов,окисленных в положении 1,3,17

Способ получения производных стероидов

Изобретение касается производных стероидов, в частности соединений общей формулы R2 В R где R, - -С -Сф-алкилдигидроиндолип, пиридинил, фенил, замещенный -алкиламиногруппой или киламино-С -С4-алкильной группой (в которых азот может быть окислен), пирролидинилом, ди-С ,-С4.-алкиламино- -С -С -алкилтио-, ди-С -С -алкиламино-С -С ,-алкилокси- или триметилси- лильной группой; R- з ОН, CHjO, этинил, карбонил, -C-NOH; Н; С2-С4.-алкенил, С -С -алкади- ен, С -С -алкинил (может быть замещен „галогеном, , (CEj)Sit низшим ал- кенилом); В и С образуют двойную связь или эпоксидную группу, которые обладают фармакологически ценными свойствами. Цель изобретения - создание новых веществ с нехарактерной для данного класса активностью. Синтез ведут из соответствующего кеталя (А - кетальная группа, которая может быть циклической или нециклической), который дегидратируют катионообменной сульфосмолой или НС1. Полз енный продукт при необходимости обрабатывают гидроксиламином или, если R, - ди-. -С,-С4-алкиламино-С ...

Способ получения 2 @ ,16 @ -диаминоандростановых производных или их солей

Neue Hydrazino und Hydroxyamino-14-beta-Hydroxyandrostan-Derivate mit kardiotonischer Aktivität, ein Verfahren zu ihrer Herstellung und pharmaceutische Präparate davon

Androstane und Pregane zur allosterischen Modulation des GABA Rezeptors

NEUE 19-NOR STEROIDE, DIE AN DER 11-BETA STELLE AN EINE THIOKOHLENSTOFFGRUPPE GEBUNDEN SIND, EIN VERFAHREN ZU IHRER HERSTELLUNG UND ZWISCHENPRODUKTE DAZU

21-HYDROXYCORTICOSTEROID ESTERS, AND COMPOSITIONS CONTAINING THEM

In 3-Position Nitro-substituierte Steroid-Derivate.

PHARMAZEUTISCHE ZUSAMMENSETZUNGEN FUER DIE PARENTERALE ANWENDUNG.

GLYKOALKALOIDE

17-ALPHA-SUBSTITUIERTE-11-BETA-SUBSTITUIERTE-4-ARYL UND 21-SUBSTITUIERTE 19-NORPREGNADIENEDIONE MIT ANTIGESTAGENER AKTIVITÄT

Luminescent conjugates for immunological analysis - comprising a complex formed between a pharmacologically, immunologically, or biochemically active ligand and a chemiluminescent cpd.

The ligand is a drug, an amino acid polypeptide or protein a steroid, intamin A, D, E or K, an antibiotic, a nucleic acid, a polynucleotide, a nucleoside, a saccharide, serotonin, spermine, galactose, phenyltartaric acid, pesticide fungicide or nematocide, a cell or cell extract, or a virus or virus particle. The chemiluminescent cpd. is tetrakis(dimethylamino) ethylene, luciferin, lucigenin, oxalyl chloride or a 2,3-dihydrophthalazine-1,4-dione of formula (I) (where R is NH2, NHMe, NHEt, NHCH2-Ph, NHCOCH2Cl, NHCOCH2NH2NHCOCH -2NHNH2, Nme2 Net2 or N(CH2Ph)2). The conjugates can be used as chemiluminescent-labeled antigens for the immunological determination of the corresp antigen (ligand) in body fluids by the competitive binding method. Antigen concns. as low as 5-25 ng/cm3 can be determined. In an example, an insulin-luminol conjugate is used to determine the insulin content of blood plasma.

KONJUGATE VON GALLENSÄURE MIT METALLBINDENDEN CHELATVERBDINGUNGEN UND DIE VERWENDUNG DAVON

Neue Glucocorticoide

Kardioaktive 17-Hydroxyiminoalkyl- und 17-Hydroxyiminomethylalkenyl-Steroid-Derivate, ein Verfahren zu ihrer Herstellung und pharmazeutische Präparate davon

Neue Hydroxyimino-5ß,14ß-androstan-Derivate, die auf das kardiovaskuläre System wirken, Verfahren zu deren Herstellung und pharmazeutische Zusammensetzungen, die dieselben enthalten

17-SUBSTITUTED STEROIDS USEFUL IN CANCER TREATMENT

Novel salt forms

Steroid intermediates in the synthesis of-hydroxyvitamin D2

This invention relates to hydroxylated derivatives of vitamin D2, to processes for preparing such compounds, to intermediates utilized in such processes and to certain isotopically labelled vitamin D2 compounds. The vitamin D2 derivatives would find application in the treatment of or prophylaxsis for various disease states characterized by calcium and phosphorous imbalances and as a substitute for vitamin D3 and its metabolites in their various applications.

Improvements in or relating to tetralol derivatives

... 1,130,051. Tetralol derivatives. G. D. SEARLE & CO. 30 Sept., 1965 [2 Oct., 1964], No. 41604/65. Heading C2C. Novel compounds of the general formula wherein R and R1 are each an alkyl radical containing from 1-6 carbon atoms, an alkanoyl radical containing from 2-6 carbon atoms, or hydrocarbon-sulphonyl radical, with the proviso that when one of R and R1 is an alkanoyl, or hydrocarbon sulphonyl radical, the other can be a hydrogen atom, and in addition, R and R1 can be combined so that they form the residue of a cycloaliphatic amine, are obtained by contacting a compound of the general formula with a vinyl organometallic reagent followed by the hydrolysis of the initial adduct to afford the desired 1-vinyl-1-tetralol.

TOPICAL PHARMACEUTICAL COMPOSITIONS CONTAINING THIAZOLIDINE-SUBSTITUTED CORTICOSTEROIDS

11A - AMINO - 3A - HYDROXYSTEROIDS

ESTRIOL DERIVATIVES

... 1452794 Estriol nicotinates THERAMEX SA 26 Feb 1975 [26 Feb 1974] 8712/74 Heading C2U The invention comprises compounds of formula (wherein R is nicotinoyl or its N-oxide; and R1 is C 3-7 aliphatic organic acyl; aromatic, alicyclic or heterocyclic organic acyl; or Me, Et, Pr, allyl, methallyl, cyclopentyl or dialkylaminoalkyl); and their preparation from estriol or its 3-ethers by esterification with nicotinoyl chloride or its N-oxide; or from estriol 16,17- dinicotinate or its N,N1-dioxide by esterification with an appropriate acylating agent. The nicotinoyl groups may be N-oxidized by reaction with per-acids. Estriol 16,17-dinicotinate is prepared by selective hydrolysis of the trinicotinate. Compounds I are credited with hypolipidaemic and anti-arteriosclerotic activity, and may be made up with carriers into pharmaceutical compositions for oral, parenteral, rectal and nasal (aerosol) administration.

COMPOUNDS

Novel 17a and 17b substituted acyl-3-carboxy 3,5-diene steroidal compounds, pharmaceutical compositions containing these compounds, and methods for using these compounds to inhibit steroid 5-a-reductase.

Invented are 17 and 17 substituted acyl-3-carboxy -3,5-diene analogues of steroidal synthetic comounds, pharmaceutical compositions containing these compounds, and methods for using these compounds to inhibit steroid 5 reductase. Also invented are intermediates and processes used in preparing these compounds.

ESTRA-1,3,5(10),16-TETRAENE-3-CARBOXAMIDES FOR INHIBITION OF 17.BETA.-HYDROXYSTEROID DEHYDROGENASE (AKR1 C3)

3-Substituted estra-1,3,5(10), 16-tetraene derivativess, methods for the production thereof, pharmaceutical preparations containing same, and use thereof for the production of medicaments

Estra-1,3,5(10), 16-tetraene-3-carboxamides for inhibition of 17 beta-hydroxysteroid dehydrogenase (AKR1 C3)

Estra-1,3,5(10),16-tetraene-3-carboxamide derivatives, process for preparation thereof, pharmaceutical preparations comprising them, and use thereof for production of medicaments

Heterocyclic aromatic esters of steroids, their preparation and pharmaceutical compositions the container.

“New 19-NOR steroids having in position 11béta a carbonaceous chain comprising a function amide or carbamate, their method of preparation and the intermediaries of this process, their application like drugs and the compositions pharmaceutical them

17a And 17b-substituted estra-1,3,5(10)-triene-3-carboxylic acid

New steroids comprising a cycle spirannic in position 17, their method and intermediaries of preparation, their application like drugs and the compositions pharmaceutical containing them.

3-Substituted estra-1,3,5(10), 16-tetraene derivativess, methods for the production thereof, pharmaceutical preparations containing same, and use thereof for the production of medicaments

Estra-1,3,5(10),16-tetraene-3-carboxamide derivatives, process for preparation thereof, pharmaceutical preparations comprising them, and use thereof for production of medicaments

3-Substituted estra-1,3,5(10), 16-tetraene derivativess, methods for the production thereof, pharmaceutical preparations containing same, and use thereof for the production of medicaments

Estra-1,3,5(10), 16-tetraene-3-carboxamides for inhibition of 17 beta-hydroxysteroid dehydrogenase (AKR1 C3)

Estra-1,3,5(10), 16-tetraene-3-carboxamides for inhibition of 17 beta-hydroxysteroid dehydrogenase (AKR1 C3)

AMPHOTERE STEROLE AND THEIR USE

17ALPHA-ALKYL-17BETA-OXY-ESTRATRIENE AND INTERMEDIATE PRODUCTS TO THEIR PRODUCTION, USE of the 17ALPHA-ALKYL-17BETA-OXY-ESTRATRIENE PREPARATIONS PHARMACEUTICAL FOR the PRODUCTION OF DRUGS AS WELL AS

PROCEDURE FOR THE PRODUCTION OF NEW CORTICOID-17 ALKYL CARBONATES

PROCEDURE FOR the PRODUCTION OF NEW ONE 4-ANDROSTEN-3-ONEN

TEST PROCEDURE WITH IMPROVED CHEMILUMINESZIERENDEN ESTERS, THIOESTERN AND AMIDES

KONJUGATE WITH ENTZÜNDUNGSHEMMENDER ACTIVITY

VERFAHREN ZUR HERSTELLUNG VON NEUEN 1,3-OXYGENIERTEN 8ALFA-OESTRATRIENEN

PROCEDURE FOR THE DETERMINATION OF AN IMMUNOLOGICALLY ACTIVE MATERIAL

PROCEDURE FOR the PRODUCTION OF NEW ONE 4-ANDROSTEN-3-ONEN

PROCEDURES FOR the PRODUCTION OF 3BETA AMINOCHOLANSÄUREDERIVATEN

NEW ANTI INFLAMMATORI 17.ALPHA. - HETERO-CYCLIC ESTERS OF 17.BETA. - CARBOTHIOAT ANDROSTAN DERIVATIVES

KARDIOAKTIVE 17-ARYL AND 17-HETEROZYKLYL-14 BETA 5ALPHA-ANDROSTANE, ANDROSTENE AND ANDROSTADIENE, a PROCEDURE FOR YOUR PRODUCTION AND PHARMACEUTICAL PRÄPERATE OF IT

C20 TO C26 AMINOSTEROIDE.

11BETA-PHENYL-14BETAH-STEROIDE.

22-ARYLSULFONYL-24,25-DIHYDROXY-CHOLESTANE AND PROCEDURE FOR YOUR PRODUCTION.

DERIVATISIERTE NUCLEINSAEURE SEQUENCE, PROCEDURE FOR THEIR PRODUCTION AS WELL AS THEIR USE FOR THE PROOF OF NUCLEINSAEUREN.

CHOLESTERIN ESTERASE FARBSUBSTRAT.

PROCEDURE FOR the PRODUCTION OF NEW ONE 1,3-OXYGENIERTEN 8ALFA-OESTRATRIENEN

PROCEDURE FOR THE PRODUCTION OF NEW TRIAMINO AND RUST ON DERIVATIVES, THEIR ACID ADDITION AND QUATERNAEREN OF SALTS

NEW STEROID INTERMEDIATE PRODUCTS AND PROCEDURES FOR YOUR PRODUCTION

KARDIOAKTIVE 17-HYDROXYIMINOALKYL AND 17 HYDROXYIMINOMETHYLALKENYL STEROID DERIVATIVES, PROCEDURE FOR YOUR PRODUCTION AND PHARMACEUTICAL PREPARATIONS OF IT

17-SUBSTITUIERTE STEROIDE, USABLE TREATMENT OF CANCER

NEW 17-HYDROXYIMINOMETHYL-5BETA, 14BETA AND RUST ON DERIVATIVES, KARDIOAKTIVES PROCEDURE TOO THEIR PRODUCTION AND PHARMACEUTICAL PREPARATIONS OF it

NEW 19-NOR STEROIDE, WHICH IS BOUND for TO of the 11-beta PLACE TO a THIOKOHLENSTOFFGRUPPE, a PROCEDURE FOR YOUR PRODUCTION AND INTERMEDIATE PRODUCTS FOR it

NEW 17 (3-IMINO-2-ALKYL-PROPENYL) - 5BETA-14BETA ANDROSTANDERIVATE, FOR the TREATMENT OF CARDIOVASCULAR ILLNESSES, A PROCEDURE TOO THEIR PRODUCTION AND PHARMACEUTICAL PREPARATIONS OF it

NEW GLUCOCORTICOIDE

NEW 19-NOR STEROIDE, SOME an AMIDE CARRYING GROUP IN 11-beta-places CREDIT, THEIR PRODUCTION, YOUR USE AS MEDICINES AND PHARMACEUTICAL PREPARATIONS OF IT

PROGESTERON DERIVATIVES, PROCEDURES FOR YOUR PRODUCTION AND PHARMACEUTICAL COMPOSITIONS.

IN POSITION STEROIDZWISCHENPRODUKTE AND PROCEDURE FOR YOUR PRODUCTION SUBSTITUTED 11.

NEW URETHANE ABSTENTION AMINOSTEROID CONNECTIONS

QUINOLIN MORE CARBOXYLSÄURESTER OF 21-HYDROXYPREGNAN DERIVATIVES AND ANTIBACTERIAL ONES AND ENTZÜDUNGSHEMMENDE PREPARATIONS OF it

DELTA 16 INSATIATED C17 HETERO-CYCLIC STEROIDE FOR USE AS STEROID C17-20 LYASE INHIBITORS

VERFARHREN FOR the PRODUCTION OF 3-ALPHA-HYDROXY, 3-BETA-SUBSTITUIERTEN PREGNAN DERIVATIVES

14BETA-H, 14 - AND 15-EN-11BETA-ARYL-4-ESTRENE

Procedure for the production of new basic 2-Androsten-17-äthern

Hydroxycholesterol immunoassay

Provided is a derivative of 22-hydroxycholesterol, 24S-hydroxycholesterol, 25-hydroxycholesterol, 26-hydroxycholesterol or 27-hydroxycholesterol. Also provided is a protein conjugated to the above derivative. Further provided is an antibody composition comprising antibodies that specifically bind to 22-hydroxycholesterol, 24S-hydroxycholesterol, 25-hydroxycholesterol, 26-hydroxycholesterol or 27-hydroxycholesterol. Additionally, a method of making antibodies that specifically bind to 22-hydroxycholesterol, 24S-hydroxycholesterol, 25-hydroxycholesterol, 26-hydroxycholesterol or 27-hydroxycholesterol is provided. Also, a method of assaying for 22-hydroxycholesterol, 24S-hydroxycholesterol, 25-hydroxycholesterol, 26-hydroxycholesterol or 27-hydroxycholesterol is provided. Additionally provided is a kit for detecting 22-hydroxycholesterol, 24S-hydroxycholesterol, 25-hydroxycholesterol, 26-hydroxycholesterol or 27-hydroxycholesterol. A method of detecting an enzyme or enzymes utilized in phase II drug metabolism is also provided. Also, a method of detecting an enzyme that synthesizes 22-hydroxycholesterol, 24S-hydroxycholesterol, 25-hydroxycholesterol, 26-hydroxycholesterol or 27-hydroxycholesterol is provided. Further provided is a method of evaluating progression of multiple sclerosis in a patient. Also provided is a method of determining whether a treatment for multiple sclerosis in a patient is effective. Further, a method of evaluating progression of Huntington's disease in a patient is provided. Additionally provided is a method of determining whether a treatment for Huntington's disease in a patient is effective.

Arginase Inhibitors and Methods of Use Thereof

The present invention includes arginase enzyme inhibitors, compositions comprising these arginase inhibitors, and methods of treating or diagnosing conditions characterized either by abnormally high arginase activity or abnormally low nitric oxide levels in a mammal, comprising administering compositions of the invention to the mammal.

Angiogenesis inhibitors

Compounds of Structural Formula I or pharmaceutically acceptable salts thereof, are effective inhibitors of angiogenesis:

PROGESTERONE RECEPTOR ANTAGONISTS

The invention relates to 17-hydroxy-17-pentafluoroethyl-estra-4,9(10)-dien-11-aryl derivatives of formula I with progesterone-antagonizing action and methods of production thereof, use thereof for the treatment and/or prevention of diseases and use thereof for producing medicinal products for the treatment and/or prevention of diseases, in particular uterine fibroids (myomata, uterine leiomyomata), endometriosis, heavy menstrual bleeding, meningiomata, hormone-dependent breast cancers and menopause-associated complaints or for fertility control and emergency contraception. 6. Compound according to in which{'sup': '9', 'Rdenotes hydrogen, methyl or ethyl and'}{'sup': '10', 'sub': 3', '2', '2', '3', '2', '2', '2', '3, 'Rdenotes —O—CH, —Cl, —COH, —COCH, —CO—NH, —SO—NH; —NH—CO—CHor —CO—NH-phenyl.'}7. A compound selected from4-[(11β,17β)-17-hydroxy-3-oxo-17-(pentafluoroethyl)estra-4,9-dien-11-yl]benzamide4-[(11β,17β)-17-hydroxy-3-oxo-17-(pentafluoroethyl)estra-4,9-dien-11-yl]-N,N-dimethylbenzamide(11β,17β)-17-hydroxy-11-{4-[(4-methylpiperazin-1-yl)carbonyl]phenyl}-17-(pentafluoroethyl)estra-4,9-dien-3-onetert-butyl-4-{4-[(11β,17β)-17-hydroxy-3-oxo-17-(pentafluoroethyl)estra-4,9-dien-11-yl]benzoyl}piperazine-1-carboxylate(11β,17β)-17-hydroxy-17-(pentafluoroethyl)-11-[4-(piperidin-1-ylcarbonyl)phenyl]estra-4,9-dien-3-onemethyl-1-{4-[(11β,17β)-17-hydroxy-3-oxo-17-(pentafluoroethyl)estra-4,9-dien-11-yl]benzoyl}piperidine-4-carboxylateN-[2-(dimethylamino)ethyl]-4-[(11β,17β)-17-hydroxy-3-oxo-17-(pentafluoroethyl)estra-4,9-dien-11-yl]benzamideN-[3-(dimethylamino)propyl]-4-[(11β,17β)-17-hydroxy-3-oxo-17-(pentafluoroethyl)estra-4,9-dien-11-yl]benzamideN-[2-(dimethylamino)ethyl]-4-[(11β,17β)-17-hydroxy-3-oxo-17-(pentafluoroethyl)estra-4,9-dien-11-yl]-N-methylbenzamidemethyl-2-({4-[(11β,17β)-17-hydroxy-3-oxo-17-(pentafluoroethyl)estra-4,9-dien-11-yl]benzoyl}amino)benzoate4-[(11β,17β)-17-hydroxy-3-oxo-17-(pentafluoroethyl)estra-4,9-dien-11-yl]-N-(pyridin-2-yl)benzamide4-[(11β,17β)- ...

METHANESULFONATE SALTS OF ABIRATERONE-3-ESTERS AND RECOVERY OF SALTS OF ABIRATER ONE-3-ESTERS FROM SOLUTION IN METHYL TERT-BUTYL ETHER

A salt of a compound of formula (I) may be made with methanesulfonic acid. The salt and salts with other acids may be prepared by recovering from methyl tert-butyl ether (MTBE). 2. A salt as claimed in in which R′ represents a lower acyloxy group.3. A salt as claimed in in which R represents a hydrogen atom.4. A process for the preparation of a salt as claimed in by recovering the salt from a solution of the free base in5. A process as claimed in in which the solvent comprises an ester or an ether.6. A process as claimed in in which the solvent comprises methyl tert-butyl ether (MTBE).8. A process as claimed in in which the acid is hydrochioric claim 7 , sulfuric or toluoyltartaric or methanesulfonic acid.9. A salt as claimed in which R′ represents a lower acyloxy group.10. A salt as claimed in in which R represents a hydrogen atom. This invention relates to novel salt forms of the esters of the compound abiraterone, or a derivative thereof, and to a process for the preparation of the compound abiraterone, or a salt or derivative thereof.Abiraterone acetate of formula:is a potent selective, orally active inhibitor of the key enzyme n testosterone synthesis, 17α-hydroxylase-C17,20-lyase, also known as steroid 17α-monooxygenase inhibitor or Human Cytochrome P450. Suppression of testosterone synthesis has been demonstrated with abiraterone acetate in patients with prostate cancer.The compound was first disclosed in WO-A-93/20097, with a further synthetic method to the compound in WO-A-95/09178 (both British Technology Group Limited). In particular, WO-A-95/09178 discloses the synthesis of a compound of formula:where the 3β substituent R′ is hydrogen or a lower acyl group having 2 to 4 carbon atoms. One of the methods disclosed makes this from the corresponding ketone via the steroidal enol triflate (trifluoromethylsulfonate):The base used in the reported route, 2,6-di-tent-butyl-4-methylpyridine (DTBMP), is expensive. The present inventors have moreover observed a ...

CERTAIN CHEMICAL ENTITIES, COMPOSITIONS, AND METHODS

Chemical entities that are bufalin derivatives, pharmaceutical compositions and methods of treatment of cancer are described. 18.-. (canceled)10. At least one chemical entity of wherein Rand Rare each independently chosen from hydrogen and optionally substituted lower alkyl.11. At least one chemical entity of wherein Rand Rare both hydrogen.12. At least one chemical entity of wherein Rand Rare joined together to form a 5- to 7-membered heterocycloalkyl ring.13. At least one chemical entity of wherein Rand Rare each independently chosen from hydrogen and optionally substituted lower alkyl.14. At least one chemical entity of wherein n is chosen from 1 claim 9 , 2 claim 9 , and 3.15. At least one chemical entity of wherein n is 1 claim 9 , and Rand Rare joined together to form a 5- to 7-membered heterocycloalkyl ring.1727.-. (canceled)28. A pharmaceutical composition comprising a pharmaceutically acceptable carrier and at least one chemical entity of .29. A pharmaceutical composition of wherein the composition is formulated in a form chosen from tablets claim 28 , capsules claim 28 , powders claim 28 , liquids claim 28 , suspensions claim 28 , suppositories claim 28 , and aerosols.30. (canceled)31. (canceled) This application is a divisional of U.S. application Ser. No. 13/007,516 filed Jan. 14, 2011, which claims the benefit of priority to U.S. Provisional Application No. 61/295,177, filed Jan. 15, 2010, which are incorporated herein by reference in their entirety.Provided are certain chemical entities and compositions thereof that may be useful in the treatment of cancer.Cancer can be viewed as a breakdown in the communication between tumor cells and their environment, including their normal neighboring cells. Signals, both growth-stimulatory and growth-inhibitory, are routinely exchanged between cells within a tissue. Normally, cells do not divide in the absence of stimulatory signals, and likewise, will cease dividing in the presence of inhibitory signals. In a ...

INHIBITION OF BACTERIAL BIOFILMS WITH ARYL CARBAMATES

Disclosure is provided for carbamate compounds that prevent, remove and/or inhibit the formation of biofilms, compositions including these compounds, devices including these compounds, and methods of using the same. 8. The compound of claim 1 , wherein n=1 to 5.9. The compound of claim 1 , wherein n=1 to 5 claim 1 , saturated.11. A composition comprising a carrier and an effective amount of the compound of .12. A composition comprising the compound of and a biocide.13. A composition comprising the compound of covalently coupled to a substrate.14. The composition of claim 13 , wherein said substrate comprises a polymeric material.15. The composition of claim 13 , wherein said substrate comprises a solid support.16. The composition of claim 13 , wherein said substrate is selected from the group consisting of a drainpipe claim 13 , glaze ceramic claim 13 , porcelain claim 13 , glass claim 13 , metal claim 13 , wood claim 13 , chrome claim 13 , plastic claim 13 , vinyl claim 13 , and laminate.17. The composition of claim 13 , wherein said substrate is selected from the group consisting of shower curtains or liners claim 13 , upholstery claim 13 , laundry claim 13 , and carpeting.18. A biofilm preventing claim 13 , removing or inhibiting coating composition claim 13 , comprising:(a) a film-forming resin;(b) a solvent that disperses said resin;{'claim-ref': {'@idref': 'CLM-00001', 'claim 1'}, '(c) an effective amount of the compound of , wherein said effective amount of said compound inhibits the growth of a biofilm thereon; and'}(d) optionally, at least one pigment.19. The coating composition of claim 18 , wherein said compound is covalently coupled to said resin.20. The coating composition of claim 18 , wherein said resin comprises a polymeric material.21. A substrate coated with the coating composition of .22. A method of controlling biofilm formation on a substrate comprising the step of contacting the compound of to said substrate in an amount effective to inhibit ...

BIVALENT MULTIFUNCTIONAL LIGANDS TARGETING A[BETA] OLIGOMERS AS TREATMENT FOR ALZHEIMER'S DISEASE

Bivalent multifunctional Aβ oligomerization inhibitors (BMAOIs) that target multiple risk factors involved in Alzheimer's disease are provided. The BMAOIs are useful for the treatment and/or prevention of Alzheimer's disease, as well as for diagnostic imaging of Aβ plaques in brain tissue. The BMAOIs comprise i) an Aβ oligomer (ApO)-inhibitor moiety which may have antioxidant activity (e.g. curcumin, curcumin derivatives, curcumin hybrids, resveratrol, etc.); ii) a cell membrane/lipid raft (CM/LR) anchoring moiety (e.g. cholesterol, cholesterylamine, a steroid, etc.); and iii) a spacer or linker moiety that stably links i) 1. A bivalent multifunctional AP oligomerization inhibitor (BMAOI) comprisingi) a multifunctional AP oligomer (AβO)-inhibitor moiety;ii) a cell membrane/lipid raft (CM/LR) anchor; andiii) a spacer moiety which forms a chemical linkage between said AβO-inhibitor moiety and said CM/LR anchor.2. The BMAOI of claim 1 , wherein said AβO-inhibitor moiety is selected from the group consisting of curcumin claim 1 , resveratrol claim 1 , and a hybrid molecule that comprises curcumin.3. The BMOI of claim 2 , wherein said hybrid molecule comprises curcumin and melatonin.4. The BMAOI of claim 1 , wherein said CM/LR anchor is selected from the group consisting of cholesterol claim 1 , a cholesterol derivative claim 1 , and a steroid.5. The BMAOI of claim 4 , wherein said cholesterol derivative is cholesterylamine.6. The BMAOI of claim 4 , wherein said steroid is diosgenin.7. The BMAOI of claim 1 , wherein said spacer moiety is 21 atoms in length.8. The BMAOI of claim 2 , wherein said AβO-inhibitor moiety is curcumin and said spacer moiety is chemically linked to carbon at position C4 of said curcumin.9. The BMAOI of claim 4 , wherein said CM/LR anchor is cholesterol and said spacer moiety is chemically linked to O attached to position C3 of said cholesterol.10. The BMAOI of claim 5 , wherein said spacer moiety is chemically linked to N attached to position C3 ...

PROGESTERONE ANALOGS AND USES RELATED THERETO

This disclosure relates to progesterone derivatives and uses related thereto. In certain embodiments, the disclosure relates to compounds disclosed herein and uses for managing inflammation resulting from traumatic brain injury or stroke. 3. The compound of claim 1 , wherein Ris alkyl substituted with a heterocyclyl further optionally substituted with one or more claim 1 , the same or different R.5. The compound of claim 4 , wherein Ris heterocyclyl or alkyl substituted with a group selected from amino and heterocyclyl claim 4 , wherein Ris optionally substituted with one or more claim 4 , the same or different claim 4 , R.7. The compound of claim 6 , wherein Rand Ris morpholinyl claim 6 , pyrrolidinyl claim 6 , piperidinyl claim 6 , or piperazinyl ring optionally substituted with one or more claim 6 , the same or different claim 6 , R.10. The compound of wherein claim 9 , Rand Ris morpholinyl claim 9 , pyrrolidinyl claim 9 , piperidinyl claim 9 , or piperazinyl ring optionally substituted with one or more claim 9 , the same or different claim 9 , R.11. The compound of selected from:17-(1-(hydroxyimino)ethyl)-10,13-dimethyl-6,7,8,9,10,11,12,13,14,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthren-3(2H)-one;17-(1-(methoxyimino)ethyl)-10,13-dimethyl-6,7,8,9,10,11,12,13,14,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthren-3(2H)-one;10,13-dimethyl-17-(1-((2-morpholinoethoxy)imino)ethyl)-6,7,8,9,10,11,12,13,14,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthren-3(2H)-one;17-(1-(acetoxyimino)ethyl)-10,13-dimethyl-6,7,8,9,10,11,12,13,14,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthren-3(2H)-one;17-(1-(((2-amino-3-methylbutanoyl)oxy)imino)ethyl)-10,13-dimethyl-6,7,8,9,10,11,12,13,14,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthren-3(2H)-one;10,13-dimethyl-17-(1-(((pyrrolidine-2-carbonyl)oxy)imino)ethyl)-6,7,8,9,10,11,12,13,14,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthren-3(2H)-one;2-((((1-(10,13-dimethyl-3-oxo-2,3,6,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a] ...

Modified drugs for use in liposomal nanoparticles

Drug derivatives are provided herein which are suitable for loading into liposomal nanoparticle carriers. In some preferred aspects, the derivatives comprise a poorly water-soluble drug derivatized with a weak-base moiety that facilitates active loading of the drug through a LN transmembrane pH or ion gradient into the aqueous interior of the LN. The weak-base moiety can optionally comprise a lipophilic domain that facilitates active loading of the drug to the inner monolayer of the liposomal membrane. Advantageously, LN formulations of the drug derivatives exhibit improved solubility, reduced toxicity, enhanced efficacy, and/or other benefits relative to the corresponding free drugs.

Conjugated Neuroactive Steroid Compositions And Methods Of Use

The present disclosure provides modified neuroactive steroids. The modified neuroactive steroids may comprise, consist of, or consist essentially of a therapeutic agent and/or a modifying moiety. The modified neuroactive steroid can have modified characteristics as compared to native neuroactive steroids that do not include a modifying moiety and/or therapeutic agent. The modified neuroactive steroid may be, for example, modified pregnenolone, pregnenolone metabolites, allopregnanolone, and/or allopregnanolone metabolites. The modified neuroactive steroids can be used to treat, prevent and/or ameliorating a phenotypic state of interest in a subject. 138-. (canceled)40. The modified neuroactive steroid of claim 39 , wherein n is an integer from 1 to 50.41. The modified neuroactive steroid of claim 39 , wherein NS is selected from the group consisting of pregnenolone claim 39 , allopregnanolone claim 39 , epiallopregnanolone claim 39 , epipregnanolone claim 39 , progesterone claim 39 , 3α-hydroxyprogesterone claim 39 , 3β-hydroxyprogesterone claim 39 , 5α-dihydroprogesterone claim 39 , 5β-dihydroprogesterone claim 39 , androsterone claim 39 , dehydroepiandrosterone claim 39 , allotetrahydrodeoxycorticosterone claim 39 , 3α claim 39 ,5α-cortisol claim 39 , 3α claim 39 ,5β-cortisol claim 39 , 3α claim 39 ,5α-11-deoxycortisol claim 39 , 3α claim 39 ,5β-11-deoxycortisol claim 39 , 5α-dihydrocortisol claim 39 , 5β-dihydrocortisol claim 39 , and pharmaceutically acceptable salts thereof claim 39 , derivatives thereof claim 39 , or combinations thereof.43. The modified neuroactive steroid of claim 39 , wherein R is a neuroactive steroid.45. The modified neuroactive steroid of claim 43 , wherein R is selected from the group consisting of pregnenolone claim 43 , allopregnanolone claim 43 , epiallopregnanolone claim 43 , epipregnanolone claim 43 , progesterone claim 43 , 3α-hydroxyprogesterone claim 43 , 3β-hydroxyprogesterone claim 43 , 5α-dihydroprogesterone claim 43 , 5β- ...

CYP11B, CYP17, AND/OR CYP21 INHIBITORS

Provided herein are inhibitors of CYP11B, CYP17, and/or CYP21 enzymes of Formula (Z), (IX), (X), (XI), (XII), (XIII), (XIV), (XV), (XVI), or (XVII). Also described herein are pharmaceutical compositions that include at least one compound described herein and the use of a compound or pharmaceutical composition described herein to treat androgen-dependent diseases, disorders and conditions. Formula (Z) 12.-. (canceled)45.-. (canceled)79.-. (canceled)1121.-. (canceled)22. A pharmaceutical composition comprising a compound of any of , and and a pharmaceutically acceptable carrier , excipient or binder.2310. A method for treating cancer in a subject comprising administering to a subject in need thereof 1) a therapeutically effective amount of a compound of any of , and or a pharmaceutically acceptable salt or solvate thereof or 2) a pharmaceutical composition comprising a therapeutically effective amount of a compound of any of , , and or a pharmaceutically acceptable salt or solvate thereof and a pharmaceutically acceptable carrier , excipient or binder.2435.-. (canceled)36. A method of treating a disease associated with hypercortisolism comprising administering to a subject in need thereof a therapeutically effective amount of a compound of , or , or a pharmaceutically acceptable salt or solvate thereof.3740.-. (canceled) Described herein are compounds, methods of making such compounds, pharmaceutical compositions and medicaments containing such compounds, and methods of using such compounds to treat androgen-dependent diseases or conditions.The 17α-hydroxylase/Clyase enzyme complex is essential for the biosynthesis of androgens. CYP17 is a bifunctional enzyme which possess both a C-lyase activity and a C17-hydroxylase activity. These two alternative enzymatic activities of CYP17 result in the formation of critically different intermediates in steroid biosynthesis and each activity appear to be differentially and developmentally regulated.In the testes and adrenal ...

Compounds and methods for treating neoplasia

The invention features compounds, pharmaceutical compositions and methods useful for the treatment of neoplasia. In particular embodiments, the compounds of the invention are useful for the treatment of multidrug resistant neoplasia.

PREPARATION METHOD OF ROCURONIUM

A method for preparing rocuronium is disclosed. 2β-(4-Morpholinyl)-16β-(1-pyrrolidinyl)-5α-androstan-3α-ol-17β-acetate is used as a starting material and is directly reacted with 3-bromopropene at ambient temperature to produce rocuronium. 2. The preparation method according to claim 1 , characterized in that claim 1 , the molar amount of 3-bromopropene is 2 to 10 equivalent amount of the acetate.3. The preparation method according to claim 1 , characterized in that claim 1 , the reaction temperature is 0 to 40° C.4. The preparation method according to claim 3 , characterized in that claim 3 , the reaction temperature is 10 to 25° C.5. The preparation method according to claim 1 , characterized in that claim 1 , the good solvent is acetonitrile claim 1 , dichloromethane claim 1 , acetone claim 1 , or a mixture thereof.6. The preparation method according to claim 1 , characterized in that claim 1 , the anti-solvent is ethyl ether claim 1 , methyl tert-butyl ether claim 1 , isopropyl ether claim 1 , isobutyl acetate claim 1 , or a mixture thereof. The present invention relates to the field of medicinal chemistry, and specifically relates to a method for preparing rocuronium bromide which is a steroidal muscle relaxant.Rocuronium bromide is a novel mono-quaternary ammonium muscle relaxant and is used as an anesthetic adjuvant drug for tracheal intubation during anesthetization and muscle relaxation in surgical operation. Rocuronium bromide is a non-depolarizing muscle relaxant used clinically with the most rapid onset. The characteristics thereof include rapid onset, rapid recovery, weak inhibitory effects on cardiovascular system, and no histamine releasing effects. This drug is the most widely used muscle relaxant internationally, and is the first-ranked muscle relaxant in consumption used in North America and most European countries. The chemical formula thereof is as follows:European patent EP 0287150 initially discloses the preparation method and use thereof, in ...

NOVEL IMINOSUGARS AND THEIR APPLICATIONS

Iminosugar compounds are described that have inbuilt delivery features by virtue of covalent incorporation of a tocopherol moiety, or alternative moieties that are analogues of tocopherol or select analogues of cholesterol, or its antagonist “Ezitimibe”; and are likely to have broad spectrum antiviral activity. The compounds differ from previous iminosugar compounds, even lipophillic ones, being more hydrophobic and resembling fats and oils in their partition behavior in vivo into lipid phases of lipoproteins, cellular lipid droplet organelles and biological membranes. These features confer a number of unique delivery attributes in vivo, favorable to the therapy of virus infections involving cells of the lymphoid system and the liver, in particular, but these features are also favorable in general for the treatment of virus infections of man and animals. 3. The compound of claim 1 , wherein Ris Calkyl.6. The compound of claim 5 , wherein Xare each methyl and Ris Calkyl.7. The compound of claim 1 , wherein Ware each H.11. The method of claim 9 , wherein Y is O.15. The method of claim 14 , further comprising deprotecting R—Z—Y—R—OPto form R—Z—Y—R—OH claim 14 , wherein Pis an alcohol protecting group.16. The method of claim 15 , further comprising reacting R—Z—OH with PO—R—OPto form R—Z—Y—R—OP claim 15 , wherein Pis an alcohol protecting group.21. The compound of claim 18 , wherein Z is a cholesterol derivative.22. The compound of claim 18 , wherein Z is a diacylglyceryl derivative.26. The compound of claim 23 , wherein Z is a cholesterol derivative.27. The compound of claim 23 , wherein Z is a diacylglyceryl derivative. This application claims priority from U.S. Provisional Application No. 61/656,265, filed Jun. 6, 2012, the contents of which are hereby incorporated by reference in their entirety into the present disclosure.The present application relates to novel iminosugars and their methods of making and use and in particular, to novel deoxynojimimycin based ...

NOVEL COMPOSITIONS OF TLR7 AND/OR TLR8 AGONISTS CONJUGATED TO LIPIDS

A conjugated compound of formula Q-Z—Rwherein Q is a TLR7 and/or TLR8 agonist and Z—Ris a lipid covalently linked to an amino acid or peptide coupled to a polyamine group, and a process for the manufacture of the conjugated compound, as well as a complex formed between the conjugated compound and a polyanionic molecule and a pharmaceutical composition containing the conjugated compound or complex. Also described is the use of the conjugated compound or complex in the treatment of infection, cancer or immune disorders or for use in vaccines. 5. The conjugated compound according to claim 1 , wherein Y is a single bond or —CO— claim 1 , —N(R)— claim 1 , —O— claim 1 , —S— or —S(O)— claim 1 , wherein Ris —H claim 1 , carboxyl claim 1 , —NHor a radical chosen from C-Calkyl claim 1 , C-Calkoxy claim 1 , C-Calkanoyl claim 1 , C-Caryl claim 1 , C-Cheteroaryl claim 1 , or C-Calkoxycarbonyl.6. The conjugated compound according to claim 1 , wherein X is a —(C-Carylene) claim 1 , preferably a phenylene claim 1 , a —(C-Calkylene)- claim 1 , preferably an ethylene claim 1 , a —(C-Cheteroarylene)- claim 1 , preferably a pyridinylene claim 1 , a —(C-Calkylene)-W—(C-Calkylene)- claim 1 , preferably an ethylene-W-ethylene wherein W is —O— or —NH—.7. The conjugated compound according to claim 1 , wherein s is 1.8. The conjugated compound according to claim 1 , wherein Ris —H claim 1 , —OH claim 1 , C-Calkyl claim 1 , or (C-Calkyl)-W—(C-Calkylene) claim 1 , wherein W is —O— or —NH—.9. The conjugated compound according to claim 1 , wherein A is a nitrogen atom.10. The conjugated compound according to claim 1 , wherein:{'sup': 2', '3, 'sub': 1', '6', '1', '10', '1', '10, 'A is a nitrogen atom, Ris a C-Calkylamino or C-Calkoxy-C-Calkoxy, and Ris absent or'}{'sup': 2', '3, 'sub': 6', '20, 'Rand Rform a fused C-Caryl, preferably a phenyl.'}11. The conjugated compound according to claim 1 , wherein said conjugated compound is selected from the group consisting of:bis(3,7,11,15- ...

CONTRACEPTIVE AGENTS

The invention provides compounds of formula I, II, III, or IV: 2. The compound of claim 1 , which is a compound of formula (I).3. The compound of claim 1 , which is a compound of formula (II).4. The compound of claim 1 , which is a compound of formula (III).5. The compound of claim 1 , which is a compound of formula (IV).7. The compound of claim 1 , wherein Ris H.8. The compound of claim 1 , wherein Ris H or methoxymethyl.10. The compound of claim 1 , wherein Ris H or methoxymethyl.11. The compound of claim 1 , wherein Ris H.12. The compound of claim 1 , wherein Ris H.13. The compound of claim 1 , wherein Rand Rtaken together form —C(CH)—.16. The compound of claim 1 , wherein X is O.17. The compound of claim 1 , wherein X is ═N—N═C(NH).18. The compound of claim 1 , wherein Y is O.19. The compound of claim 1 , wherein Y is ═N—N═C(NH).20. The compound of claim 1 , wherein Ris —OH claim 1 , morpholino claim 1 , or —O—C(═O)CH(NH)R; and Ris 1-methylethyl or 4-aminobutyl.22. The compound of claim 1 , wherein the compound is not one of the compounds Compound 54 claim 1 , 12 claim 1 , 1 or 1a.23. A compound comprising:a chemical structure of one of Compounds 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 55, 56, 57a, 57b, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 77a, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, or 91.24. A pharmaceutical composition comprising:{'claim-ref': {'@idref': 'CLM-00001', 'claim 1'}, 'a compound of formula I, II, III, or IV of , or a pharmaceutically acceptable salt thereof; and'}a pharmaceutically acceptable diluent or carrier having the compound.25. A method for decreasing sperm motility in a mammal comprising:{'claim-ref': {'@idref': 'CLM-00001', 'claim 1'}, 'administering the compound of formula I, II, III, or IV of , or a pharmaceutically acceptable ...

AMINOALKYLSTEROL COMPOUNDS WITH ANTITUMORAL AND NEUROPROTECTIVE ACTIVITY

Sterol derivatives of formula (I) and a method for the production of the compounds, a medicament using one of the compounds and a pharmaceutical composition comprising the medicament. 2. The sterol-based compound of formula (I) as claimed in wherein:Z is in position 5 and represents OH; andR is in position 6 and represents the substituent{'sub': 0', '1, 'claim-ref': {'@idref': 'CLM-00001', 'claim 1'}, 'of formula -QQas defined in .'}3. The sterol-based compound of formula (I) as claimed in claim 1 , wherein the bond between carbons Cand Cis a double bond claim 1 , R═NH—(CH)—NH—(CH)—NHand T=T=T=H.4. The sterol-based compound of formula (I) as claimed in wherein the bond between carbons Cand Cis a double bond claim 1 , T=T=T=H and R═NH—(CH)—NH—(CH)—NH—(CH)—NH.6. The sterol-based compound of formula (I) as claimed in wherein the bond between carbons Cand Cis a double bond claim 1 , T=T=T=H and R═—NH—(CH)—NH.7. The sterol-based compound of formula (I) as claimed in wherein the bond C-Cis a double bond claim 1 , T=T=T=H and R═—NH—(CH)—O—(CH)—O—(CH)—NH.8. The sterol-based compound of formula (I) as claimed in wherein the bond C-Cis a single bond claim 1 , Z represents OH in position 5 claim 1 , T=T=T=H and R is in position 6 and R═—NH—(CH)—NH—(CH)—NH—(CH)—NH.12. The sterol-based compound of formula (I) as claimed in wherein the bond C-Cis a single bond claim 1 , Z represents OH in position 5 claim 1 , T=T=T=H and R is in position 6 and represents R═NH—(CH)—NH—(CH)—NH.13. The sterol-based compound of formula (I) as claimed in selected from the group consisting of:cholestane-3β,5α diol-6β-N-[1-N1-(3-aminopropyl)butane-1,4-diamine];cholestane-3β,5α diol-6β-N-[N,N′-bis(3-aminopropyl)butane-1,4-diamine];cholest-7-ene-3β,5α diol-6β-N-[1-N-1-(3-aminopropyl)butane-1,4-diamine];cholest-7-ene-3β,5α diol-6β-N-[N,N′-bis(3-aminopropyl)butane-1,4-diamine];cholest-7-ene-3β,5α diol-6β-N-[2-ethylamino-(1H-imidazol-4-yl)];cholestane-3β,5α diol-6β-N-[2-ethylamino(1H-imidazol-4-yl)];cholest- ...

SYNTHESIS AND USE OF ANTI-TUMOR DRUG LQC-Y

Disclosed are the general structural formula of LQC-Y as well as the synthesis and use thereof. Pharmacological experiments demonstrated the marked antitumor effect of such compounds. Single day administration of LQC-Y3 to mice at a maximum dose of 6000 mg/kg showed no toxicity response during the 14-day continuous observation period, indicating the high safety of the compounds, and the compounds can be used to prepare medicaments for preventing and treating carcinomas such as liver cancer, lung cancer. In the general structural formula of LQC-Y, R represents steroid compounds such as cholic acid, deoxycholic acid, ursodeoxycholic acid, chenodeoxycholic acid, and hyodeoxycholic acid and so on; triterpenoid compounds such as oleanolic acid, ursolic acid, pachymic acid, glycyrrhetinic acid and glycosides thereof and so on; emodic acid, emodin and other mono-substituted or poly-substituted structures of anthraquinone parent nucleus; baicalein, baicalin and other flavonoid; shikimic acid, mono-substituted shikimic acid or poly-substituted shikimic acid; gardenia acid and other iridoid acid derivatives; paeonol, curcumin and structural derivatives thereof. 2. A method of treating a tumor disease comprising administering to a patient in need thereof an effective amount of a compound according to .4. The compound or the pharmaceutically acceptable salt thereof according to claim 3 , wherein the compound of formula 1 is an ester of R-acid with trimethyl pyrazine methanol claim 3 , and the R-acid is selected from the group consisting of cholic acid claim 3 , deoxycholic acid claim 3 , oleanolic acid claim 3 , glycyrrhetinic acid claim 3 , pachymic acid claim 3 , emodic acid and shikimic acid.5. The compound or the pharmaceutically acceptable salt thereof according to claim 3 , wherein the compound of formula 1 is an ether of R-phenol with trimethyl pyrazine methanol claim 3 , and R-phenol is one of chrysophanol or paeonol.9. The compound or the pharmaceutically acceptable ...

SYNTHESIS OF ABIRATERONE AND RELATED COMPOUNDS

The present invention relates to processes for obtaining abiraterone and derivatives thereof, such as abiraterone acetate, by means of a Suzuki coupling through a steroid borate of general formula (IV) or a C—C coupling through a steroid hydrazone of general formula (II), as well as to intermediates useful in said processes. 2. The process according to claim 1 , wherein the palladium catalyst is selected from Pd(PPh) claim 1 , Pd(dba) claim 1 , Pd(OAc) claim 1 , Pd(PPh)Cl claim 1 , Pd(dppe)Cl claim 1 , Pd(dppf)Cl claim 1 , Pd(dppf)Cl.CHCl claim 1 , Pd(dcypp)Cl claim 1 , Pd(PhCN)Cland Pd(CHCN)Cl.3. The process according to any claim 1 , wherein the base is selected from alkaline and alkaline earth metal carbonates claim 1 , bicarbonates claim 1 , phosphates claim 1 , acetates claim 1 , alkoxides claim 1 , hydroxides and halides.4. The process according to claim 1 , wherein the process is performed in the presence of a solvent or mixture of solvents selected from THF claim 1 , toluene and water; or THF and water; or water.7. The process according to claim 6 , wherein the palladium catalyst is selected from Pd(dba) claim 6 , Pd(PPh) claim 6 , Pd(dppf)Cl.CHCl claim 6 , Pd(dcypp)Cl claim 6 , PdCl(CNMe) claim 6 , Pd(OH)and Pd(OAc).8. The process according to claim 7 , further comprising the addition of a ligand to the reaction media claim 7 , said ligand being preferably selected from X-phos (2-dicyclohexylphosphino-2′ claim 7 ,4′ claim 7 ,6′-triisopropylbiphenyl) claim 7 , dppp (1 claim 7 ,4-bis(diphenylphosphino)butane) claim 7 , S-phos (2-dicyclohexylphosphino-2′ claim 7 ,6′-dimethoxybiphenyl) claim 7 , dppm (1 claim 7 ,1-bis(diphenylphosphino)-methane) claim 7 , dippe (1 claim 7 ,2-bis(diisopropylphosphino)ethane claim 7 , dmpe (1 claim 7 ,2-Bis(dimethylphosphino)ethane and dppe (1 claim 7 ,2-bis(diphenylphosphino)ethane.9. The process according to claim 6 , wherein the base is selected from alkoxides and carbonates of alkaline and alkaline earth metals claim 6 , ...

Steroids Having 7-Oxygen and 17-Heteroaryl Substitution-2

The invention relates to the use of compounds to ameliorate or treat an condition such as a cystic fibrosis, neutropenia or other exemplified conditions. Exemplary compounds that can be used include 3β-hydroxy-17β-aminoandrost-5-ene, 3β-hydroxy-16α-fluoro-17β-aminoandrost-5-ene, 3α-hydroxy-16α-fluoro-17β-aminoandrost-5-ene, 3β-hydroxy-16β-fluoro-17β-aminoandrost-5-ene, 1α,3β-dihydroxy-4α-fluoroandrost-5-ene-17-one, 1α,3β,17β-trihydroxy-4α-fluoroandrost-5-ene, 1β,3β-dihydroxy-6α-bromoandrost-5-ene, 1α-fluoro-3β,12α-dihydroxyandrost-5-ene-17-one, 1α-fluoro-3β,4α-dihydroxyandrost-5-ene and 4α-fluoro-3β,6α,17β-trihydroxyandrostane. 4. The compound of wherein the C-linked heterocycle is 2-pyridyl claim 3 , 3-pyridyl claim 3 , 4-pyridyl claim 3 , 5-pyridyl or 6-pyridyl.7. The compound of wherein Ris an N-linked heterocycle wherein the N-linked heterocycle is —N-pyrrolidine claim 6 , —N1-pyrazolone claim 6 , —N2-pyrazolone claim 6 , —N-imidazolidin-2-one claim 6 , —N1-imidazole claim 6 , —N1-4 claim 6 ,5-dihydroimidazole claim 6 , —N-morpholine claim 6 , —N-piperidine claim 6 , —N-indole claim 6 , —N-indoline claim 6 , —N-quinolidine or —N1-piperazine claim 6 , optionally substituted at N4 with alkyl claim 6 , aryl or heteroaryl.9. The compound of wherein{'sup': '1', 'sub': '3', 'Ris —OH, ═O or —NH—C(O)CH;'}{'sup': '2', 'sub': '3', 'Ris —OH or —OCH; and'}{'sup': '3', 'sub': 3', '2', '3, 'Ris —H, —OH, —O—C(O)CHor —O—C(O)CHCH; and'}{'sup': '4', 'Ris an N-linked heterocycle.'}10. The compound of claim 9 , wherein the N-linked heterocycle is —N-pyrrolidine claim 9 , —N1-pyrazolone claim 9 , —N2-pyrazolone claim 9 , —N-imidazolidin-2-one claim 9 , —N1-imidazole claim 9 , —N1-4 claim 9 ,5-dihydroimidazole claim 9 , —N-morpholine claim 9 , —N1-pyridine claim 9 , —N-piperidine or —N-piperazine.11. The compound of wherein{'sup': '1', 'sub': '3', 'Ris —OH, ═O or —NH—C(O)CH;'}{'sup': '2', 'sub': '3', 'Ris —OH or —OCH;'}{'sup': '3', 'sub': 3', '2', '3, 'Ris —H, —OH, —O—C(O)CHor —O—C(O ...

Steroids Having 7-Oxygen and 17-Heteroaryl Substitution-3

The invention relates to the use of compounds to ameliorate or treat an condition such as a cystic fibrosis, neutropenia or other exemplified conditions. Exemplary compounds that can be used include 3β-hydroxy-17β-aminoandrost-5-ene, 3β-hydroxy-16α-fluoro-17β-aminoandrost-5-ene, 3α-hydroxy-16α-fluoro-17β-aminoandrost-5-ene, 3β-hydroxy-16β-fluoro-17β-aminoandrost-5-ene, 1α,3β-dihydroxy-4α-fluoroandrost-5-ene-17-one, 1α,3β,17β-trihydroxy-4α-fluoroandrost-5-ene, 1β,3β-dihydroxy-6α-bromoandrost-5-ene, 1α-fluoro-3β,12α-dihydroxyandrost-5-ene-17-one, 1α-fluoro-3β,4α-dihydroxyandrost-5-ene and 4α-fluoro-3β,6α,17β-trihydroxyandrostane. 4. The compound of wherein the C-linked heterocycle is 2-pyridyl claim 3 , 3-pyridyl claim 3 , 4-pyridyl claim 3 , 5-pyridyl or 6-pyridyl.7. The compound of wherein Ris an N-linked heterocycle wherein the N-linked heterocycle is —N-pyrrolidine claim 6 , —N1-pyrazolone claim 6 , —N2-pyrazolone claim 6 , —N-imidazolidin-2-one claim 6 , —N1-imidazole claim 6 , —N1-4 claim 6 ,5-dihydroimidazole claim 6 , —N-morpholine claim 6 , —N-piperidine claim 6 , —N-indole claim 6 , —N-indoline claim 6 , —N-quinolidine or —N1-piperazine claim 6 , optionally substituted at N4 with alkyl claim 6 , aryl or heteroaryl.9. The compound of wherein{'sup': '1', 'sub': '3', 'Ris —OH, ═O or —NH—C(O)CH;'}{'sup': '2', 'sub': '3', 'Ris —OH or —OCH; and'}{'sup': '3', 'sub': 3', '2', '3, 'Ris —H, —OH, —O—C(O)CHor —O—C(O)CHCH; and'}{'sup': '4', 'Ris an N-linked heterocycle.'}10. The compound of claim 9 , wherein the N-linked heterocycle is —N-pyrrolidine claim 9 , —N1-pyrazolone claim 9 , —N2-pyrazolone claim 9 , —N-imidazolidin-2-one claim 9 , —N1-imidazole claim 9 , —N1-4 claim 9 ,5-dihydroimidazole claim 9 , —N-morpholine claim 9 , —N1-pyridine claim 9 , —N-piperidine or —N-piperazine.11. The compound of wherein{'sup': '1', 'sub': '3', 'Ris —OH, ═O or —NH—C(O)CH;'}{'sup': '2', 'sub': '3', 'Ris —OH or —OCH;'}{'sup': '3', 'sub': 3', '2', '3, 'Ris —H, —OH, —O—C(O)CHor —O—C(O ...

SUBSTRATE REDUCTION THERAPY

The present invention provides a compound which is an inhibitor of sphingolipid biosynthesis for use in the treatment of a disease which has a secondary Niemann-Pick type C disease like cellular phenotype. 1. A method of treating a subject having a disease which has a secondary Niemann-Pick type C disease like cellular phenotype , provided that the disease is other than mucopolysaccharidosis and other than mucolipidosis IV , wherein the method comprises selecting the subject having the disease , and administering to the subject an effective amount of an inhibitor of sphingolipid biosynthesis.26-. (canceled)10. The method of wherein the inhibitor of sphingolipid biosynthesis is selected from N-butyldeoxynojirimycin; N-nonyldeoxynojirimycin; N-butyldeoxygalactonojirimycin; N-5-adamantane-1-yl-methoxypentyl-deoxynojirimycin; alpha-homogalactonojirimycin; nojirimycin; deoxynojirimycin; N7-oxadecyl-deoxynojirimycin; deoxygalactonojirimycin; N-butyl-deoxygalactonojirimycin; N-nonyl-deoxygalactonojirimycin; N-nonyl-6deoxygalactonojirimycin; N7-oxanonyl-6deoxy-DGJ; alpha-homoallonojirimycin; beta-1-C-butyl-deoxygalactonojirimycin; 1 claim 1 ,5-dideoxy-1 claim 1 ,5-imino-D-glucitol claim 1 , 1 claim 1 ,5-(Butylimino)-1 claim 1 ,5-dideoxy-D-glucitol; 1 claim 1 ,5-(Methylimino)-1 claim 1 ,5-dideoxy-D-glucitol; 1 claim 1 ,5-(Hexylimino)-1 claim 1 ,5-dideoxy-D-glucitol; 1 claim 1 ,5-(Nonylylimino)-1 claim 1 ,5-dideoxy-D-glucitol; 1 claim 1 ,5-(2-Ethylbutylimino)-1 claim 1 ,5-dideoxy-D-glucitol; 1 claim 1 ,5-(2-Methylpentylimino)-1 claim 1 ,5-dideoxy-D-glucitol; 1 claim 1 ,5-(Benzyloxycarbonylimino)-1 claim 1 ,5-dideoxy-D-glucitol claim 1 , tetraacetate; 1 claim 1 ,5-(Phenylacetylimino)-1 claim 1 ,5-dideoxy-D-glucitol claim 1 , tetraacetate; 1 claim 1 ,5-(Benzoylimino)-1 claim 1 ,5-dideoxy-D-glucitol claim 1 , tetraacetate; 1 claim 1 ,5-(Butylimino)-1 claim 1 ,5-dideoxy-D-glucitol claim 1 , tetraacetate; 1 claim 1 ,5-(Ethyl malonylimino)-1 claim 1 ,5-dideoxy-D-glucitol claim 1 , ...

INHIBITORS OF 17Beta-HSD1, 17Beta-HSD3 AND 17Beta-HSD10

The present application discloses 17β hydroxy steroid dehydrogenase (17β HSD) type 1, 3, 10 inhibitors and use thereof (alone and in combination) in the treatment of cancer and other afflictions. 17β HSD1 inhibitors include estradiol derivatives with a nieta-carbamoylbenzyl substituent at C 16. 17β HSD3/HSD10 inhibitors include androsterone derivatives substituted at the C3 position with a sulfonamide piperazine. Also disclosed are compounds that are inhibitors of both 17β HSD1 and 17β HSD3 that have a spiro-morpholine substituent at C20.

Androgen receptor down-regulating agents and uses thereof

The present disclosure provides the design and synthesis of novel steroidal compounds that cause down-regulation of the androgen receptor (AR), both full length and splice variant. The compounds are potential agents for the treatment of all forms of prostate cancer and other diseases that depend on functional AR.

C7, c12, and c16 substituted neuroactive steroids and their methods of use

Described herein are neuroactive steroids of Formula (I), Formula (V), or Formula (IX) or a pharmaceutically acceptable salt thereof; wherein each instance of R2, R3, R4, R5, R6, R7, R11a, R11b, R12, R16, R17, R19, and are as defined herein. Such compounds are envisioned, in certain embodiments, to behave as GABA modulators. Also provided are pharmaceutical compositions comprising a compound described herein and methods of use and treatment, e.g., such as for inducing sedation and/or anesthesia.

NOVEL COMPOSITIONS AND METHODS FOR TREATING PROSTATE CANCER

Described herein are compounds, methods of making such compounds, pharmaceutical compositions, and medicaments comprising such compounds, and methods of using such compounds to treat androgen receptor mediated diseases or conditions. In some embodiments, the solid matrix comprises a polymer. In some embodiments, the polymer is soluble in an aqueous solution. In particular embodiments, the aqueous solution is water. In other embodiments, the aqueous solution has a pH of 5.0 or greater. 1204-. (canceled)206. The pharmaceutical composition of claim 205 , wherein said compound is substantially in a non-crystalline form after storage of the composition for at least about one week.207. The pharmaceutical composition of claim 205 , wherein said compound is substantially in a non-crystalline form after storage of the composition for at least about one month.208. The pharmaceutical composition of claim 206 , wherein said composition is stored at about 25-40° C. and/or about 60-75% relative humidity.209. The pharmaceutical composition of claim 207 , wherein said composition is stored at about 25-40° C. and/or about 60-75% relative humidity.210. The pharmaceutical composition of claim 205 , wherein said composition is spray dried. This application claims the benefit of U.S. Provisional Application No. 61/508,823, filed Jul. 18, 2011, which application is incorporated herein by reference.Cancer represents a significant burden on human health, accounting for an estimated 13% of all deaths each year. In particular, several common cancers and diseases are associated with androgen hormone signaling, such as, for example, prostate cancer, breast cancer, ovarian cancer, polycystic ovary disease. For example, prostate cancer is the most common cancer in men. The majority of prostate cancer deaths are due to the development of metastatic disease that is unresponsive to conventional androgen deprivation therapy. Androgen deprivation therapy has been the standard of care in subjects with ...

Tetrazolones as a Carboxylic Acid Bioisosteres

The present disclosure provides compounds that include a tetrazolone derivative of a carboxyl group of an active agent. This disclosure also relates to pharmaceutical compositions that include these compounds, methods of using these compounds in the treatment of various diseases and disorders, and processes for preparing these compounds. 1. A compound comprising a tetrazolone derivative of a carboxyl group of an active agent.2. The compound of claim 1 , wherein the tetrazolone derivative comprises a tetrazolone or a substituted tetrazolone.4. The compound of claim 3 , wherein Ris hydrogen or alkyl.5. The compound of claim 1 , wherein the active agent is a therapeutically effective active agent.6. The compound of claim 1 , wherein the tetrazolone derivative is produced from the carboxyl group of the active agent.8. A pharmaceutical composition comprising a compound of and a pharmaceutically acceptable carrier.9. The pharmaceutical composition of claim 8 , further comprising a second active agent.10. A compound comprising a tetrazolone or substituted tetrazolone produced from a carboxyl group of an active agent.11. A method of treating a disease or disorder in a subject in need of treatment claim 8 , the method comprising administering to the subject a compound comprising a tetrazolone derivative of a carboxyl group of an active agent.12. The method of claim 11 , wherein the tetrazolone derivative comprises a tetrazolone or a substituted tetrazolone.14. The method of claim 13 , wherein Ris hydrogen or alkyl.15. The method of claim 11 , wherein the active agent is a therapeutically effective active agent.16. The method of claim 11 , wherein the tetrazolone derivative is produced from the carboxyl group of the active agent. This application claims priority pursuant to 35 U.S.C. §119(e) to the filing date of U.S. Provisional Application No. 62/107,948, filed Jan. 26, 2015, the disclosure of which is herein incorporated by reference.Tetrazole is an organic heterocyclic ...

AMINOSTEROID DERIVATIVES AND PROCESS FOR PRODUCING SAME

Estrane-based and androstane-based aminosteroid derivatives are described herein. More specifically, the following piperazinyl-steroid compounds of Formula I, Formula II, Formula III, and Formula IV are described. The compounds display cytotoxicity on a variety of cancer cell lines. A process for producing the compounds and their use in the manufacture of pharmaceutical formulations and/or combinations is also disclosed. 521.-. (canceled)2627.-. (canceled)36. A pharmaceutical composition comprising a pharmaceutically acceptable amount of the aminosteroid derivative according to and a pharmaceutically acceptable carrier.37. A pharmaceutical combination comprising an aminosteroid derivative according to and one or more agents selected from a taxane claim 1 , an epothitone claim 1 , an anti-androgen and a platinum derivative.38. The pharmaceutical combination of claim 37 , wherein the one or more agents are at least one of docetaxel claim 37 , paclitaxel claim 37 , taxol claim 37 , ixabepitone claim 37 , patupitone claim 37 , sagopitone; mitoxantrone; predinisotone; dexamethasone; estramustin; vinblastin; vincristin; doxorubicin; adriamycin; idarubicin; daunorubicin; bleomycin; etoposide; cyctophosphamide; ifosfamide; procarbazine; metphalan; 5-fluorouracil; capecitabine; fludarabine; cytarabine; ara-C; 2-chloro-2″-deoxyadenosine claim 37 , thioguanine claim 37 , flutamide claim 37 , cyproterone acetate claim 37 , bicatutamide claim 37 , bortezomib claim 37 , cisplatin claim 37 , carboplatin; chlorambucil; methotrexate or rituximab.3947.-. (canceled)48. A method of treating a disease in a subject comprising administering to the subject an aminosteroid derivative according to .49. The method of claim 48 , wherein the aminosteroid derivative is administered intravenously claim 48 , intra-arterially claim 48 , subcutaneously claim 48 , topically claim 48 , or intramuscularly.50. The method of claim 48 , wherein the aminosteroid derivative is administered systemically ...

INHIBITORS OF GLUCOCORTICOID RECEPTOR

The present invention relates generally to compositions and methods for treating cancer and hypercortisolism. Provided herein are substituted steroidal derivative compounds and pharmaceutical compositions comprising said compounds. The subject compounds and compositions are useful for inhibition of glucocorticoid receptors. Furthermore, the subject compounds and compositions are useful for the treatment of cancer and hypercortisolism. 2. The compound of or a pharmaceutically acceptable salt claim 1 , solvate claim 1 , or prodrug thereof claim 1 , wherein Ris hydrogen claim 1 , alkyl claim 1 , haloalkyl claim 1 , hydroxy claim 1 , halo claim 1 , carbocyclyl claim 1 , or heteroalkyl.3. The compound of either of or or a pharmaceutically acceptable salt claim 1 , solvate claim 1 , or prodrug thereof claim 1 , wherein Ris Calkyl or hydrogen.4. The compound of any one of - or a pharmaceutically acceptable salt claim 1 , solvate claim 1 , or prodrug thereof claim 1 , wherein Ris methyl.5. The compound of any one of - or a pharmaceutically acceptable salt claim 1 , solvate claim 1 , or prodrug thereof claim 1 , wherein Ris methyl and Rand Rare H.6. The compound of any one of - or a pharmaceutically acceptable salt claim 1 , solvate claim 1 , or prodrug thereof claim 1 , wherein Ris H.7. The compound of any one of - or a pharmaceutically acceptable salt claim 1 , solvate claim 1 , or prodrug thereof claim 1 , wherein R claim 1 , R claim 1 , and Rare H.8. The compound of any one of - or a pharmaceutically acceptable salt claim 1 , solvate claim 1 , or prodrug thereof claim 1 , wherein ring A is monocyclic heteroaryl or monocyclic aryl.9. The compound of any one of - or a pharmaceutically acceptable salt claim 1 , solvate claim 1 , or prodrug thereof claim 1 , wherein ring A is phenyl claim 1 , pyridinyl claim 1 , pyrimidinyl claim 1 , pyrazinyl claim 1 , or pyridazinyl.10. The compound of any one of - or a pharmaceutically acceptable salt claim 1 , solvate claim 1 , or ...

CHEMILUMINESCENT ANDROSTENEDIONE CONJUGATES

Chemiluminescent androstenedione conjugates are disclosed. These chemiluminescent androstenedione conjugates may be used as chemiluminescent tracers in immunoassays for the quantification and identification of certain analytes.

PROCESS FOR THE PREPARATION OF ABIRATERONE AND INTERMEDIATES THEREOF

The present invention provides intermediates for preparing abiraterone, and processes for preparing abiraterone and intermediates thereof. The intermediates include a compound of formula (IV): 3. The process according to or , wherein the hydroxy-protecting group is selected from the group consisting of trimethylsilyl (TMS) , tert-butyldimethylsilyl (TBS) , tetrahydropyranyl (THP) , triethylsilyl (TES) , triisopropylsilyl (TIPS) , dimethylphenylsilyl , diphenylmethylsilyl , tert-butyldiphenylsilyl (TBDPS) and triphenylmethyl (trityl , Tr).4. The process of claim 3 , wherein the hydroxy-protecting group is trimethylsilyl (TMS).5. The process according to claim 2 , wherein the triflating agent is selected from the group consisting of N-phenyl-bis(trifluoromethanesulfonimide) claim 2 , N-(5-chloro-2-pyridyl)triflimide or N-(2-pyridyl)triflimide.6. The process of claim 5 , wherein the triflating agent is N-phenyl-bis(trifluoromethanesulfonimide).7. (canceled)8. The process of claim 2 , wherein the strong base is an amide based organometallic reagent selected from the group consisting of sodium hexamethyldisilazide (NaHMDS) claim 2 , potassium hexamethyldisilazide (KHMDS) claim 2 , lithium hexamethyldisilazide (LiHMDS) and lithium diisopropylamide (LDA).9. The process of claim 8 , wherein the amide based organometallic reagent is sodium hexamethyldisilazide (NaHMDS).10. The process of claim 2 , wherein X has the formula —BY claim 2 , wherein Y is selected from alkyl claim 2 , alkoxy or hydroxy group.11. The process of claim 10 , wherein Y is selected from the group consisting of ethyl and hydroxy.12. The process of claim 2 , wherein step (d) is performed in the presence of a palladium catalyst selected from the group consisting of bis(triphenylphosphine)palladium(II) dichloride (PdCl(PPh)) claim 2 , tetrakis(triphenylphosphine)palladium (Pd(PPh)) claim 2 , tris(dibenzylideneacetone)dipalladium (Pd(dba)) claim 2 , palladium acetate (Pd(OAc)) claim 2 , dichloro(1 claim 2 ,2 ...

STEROID DERIVATIVE REGULATORS, METHOD FOR PREPARING THE SAME, AND USES THEREOF

Steroid derivative regulators, a method for preparing the same, and uses thereof are described. Specifically, a compound as shown in formula (I), a preparation method therefor, a pharmaceutical composition containing the compound, and uses thereof as a regulator of GABA A receptor for treating depression, convulsion, Parkinson's disease, and nervous system diseases are described, wherein the substituents of the formula (I) are as defined in the description. 16. The compound of formula (I) claim 5 , the stereoisomer thereof claim 5 , or the pharmaceutically acceptable salt thereof according to claim 5 , wherein Rselected from the group consisting of hydrogen atom claim 5 , cyano claim 5 , halogen claim 5 , nitro claim 5 , Calkyl claim 5 , Calkynyl claim 5 , Calkoxy claim 5 , Chaloalkyl claim 5 , Ccycloalkyl claim 5 , Chydroxyalkyl claim 5 , 5 to 10 membered heterocyclyl claim 5 , 5 to 10 membered heteroaryl claim 5 , —(CH) claim 5 ,10R claim 5 , —(CH)SR claim 5 , —(CH)C(O)R claim 5 , —(CH)C(O)NRR claim 5 , —(CH)C(O)ORand —(CH)S(O)R claim 5 , wherein the Calkyl claim 5 , Calkoxy claim 5 , Chaloalkyl claim 5 , Ccycloalkyl claim 5 , Chydroxyalkyl claim 5 , wherein the 5 to 10 membered heterocyclyl and 5 to 10 membered heteroaryl are each optionally substituted by one or more substituents selected from the group consisting of hydrogen atom claim 5 , Calkyl claim 5 , halogen claim 5 , cyano claim 5 , hydroxy claim 5 , Ccycloalkyl claim 5 , Chydroxyalkyl claim 5 , 5 to 10 membered heterocyclyl and 5 to 10 membered heteroaryl;{'sub': 23', '24', '1-6, 'Rand Rare each independently selected from the group consisting of hydrogen atom, Calkyl and 3 to 8 membered heterocyclyl.'}17. The compound of formula (I) claim 5 , the stereoisomer thereof claim 5 , or the pharmaceutically acceptable salt thereof according to claim 5 ,wherein:{'sub': 2', '2', '2', '2', '2, 'Z is selected from the group consisting of —CH—, —CHNH—, —CHO—, —CH—, —NH— and —NHSO—;'}{'sub': 3a', '1-6', '1-6', '1-6 ...

Cleavable Lipids

Disclosed herein are novel compounds, pharmaceutical compositions comprising such compounds and related methods of their use. The compounds described herein are useful, e.g., as liposomal delivery vehicles to facilitate the delivery of encapsulated polynucleotides to target cells and subsequent iransfection of said target cells, and in certain embodiments are characterized as having one or more properties that afford such compounds advantages relative to other similarly classified lipids. 2. (canceled)3. The nanoparticle of claim 1 , wherein Ris imidazole.4. The nanoparticle of claim 1 , wherein{'sub': '1', 'Ris imidazole;'}andn is 1.5. The nanoparticle of claim 1 , wherein Ris guanidinium.6. The nanoparticle-of claim 1 , wherein{'sub': '1', 'Ris guanidinium;'}andn is 1.723.-. (canceled)2629.-. (canceled)30. The nanoparticle of claim 1 , further comprising one or more compounds selected from the group consisting of a cationic lipid claim 1 , a PEG-modified lipid claim 1 , a non-cationic lipid and a helper lipid.31. (canceled)32. The nanoparticle of claim 1 , wherein one or more of the polynucleotides comprises a chemical modification.33. The nanoparticle of claim 1 , wherein the one or more polynucleotides is selected from the group consisting of an antisense oligonucleotide claim 1 , siRNA claim 1 , miRNA claim 1 , snRNA claim 1 , snoRNA and combinations thereof.34. (canceled)35. The nanoparticle of claim 1 , wherein the one or more polynucleotides comprise DNA.36. The nanoparticle of claim 1 , wherein the one or more polynucleotides comprise RNA.37. (canceled)38. The nanoparticle of claim 36 , wherein the RNA encodes an enzyme.39. The nanoparticle of claim 38 , wherein the enzyme is selected from the group consisting of agalsidase alfa claim 38 , alpha-L-iduronidase claim 38 , iduronate-2-sulfatase claim 38 , N-acetylglucosamine-1-phosphate transferase claim 38 , N-acetylglucosaminidase claim 38 , alpha-glucosaminide acetyltransferase claim 38 , N- ...

SYNTHESIS OF THERAPEUTIC AND DIAGNOSTIC DRUGS CENTERED ON REGIOSELECTIVE AND STEREOSELECTIVE RING OPENING OF AZIRIDINIUM IONS

Stereoselective and regioselective synthesis of compounds via nucleophilic ring opening reactions of aziridinium ions for use in stereoselective and regioselective synthesis of therapeutic and diagnostic compounds. 2. The method of claim 1 , further comprising:converting a substituted β amino alcohol to a substituted alkylating agent;converting the substituted alkylating agent to the substituted aziridinium ion; andstereoselectively or regioselectively reacting the aziridinium ion with a nucleophile to obtain the compound.4. The method of claim 2 , further comprising:{'sub': 4', '2', '3', '3', '6', '4, 'converting the substituted alkylating agent to the aziridinium ion in the presence of halosequestering agent comprising AgClO, AgOTf, AgCO, AgOTs, AgNO, AgSbF, or AgBF; and'}stereoselectively or regioselectively reacting the aziridinium ion in situ with a nucleophile to obtain the compound.6. The method of claim 5 , further comprising:{'sub': 4', '2', '3', '3', '6', '4, 'converting the substituted alkylating agent to the aziridinium ion in the presence of halosequestering agent comprising AgClO, AgOTf, AgCO, AgOTs, AgNO, AgSbF, or AgBF; and'}stereoselectively or regioselectively reacting the aziridinium ion in situ with the nucleophile in the presence of a base to obtain the compound.7. The method of claim 5 , further comprising:converting a substituted β amino alcohol to a substituted alkylating agent;converting the substituted alkylating agent to the substituted aziridinium ion; andstereoselectively or regioselectively reacting the aziridinium ion with a nucleophile to obtain the compound, wherein the reaction occurs without isolation of any intermediate compound.9. The method of claim 8 , further comprising removing a protecting group comprising an amino claim 8 , a carboxyl claim 8 , or a hydroxyl protecting group from the compound using a deprotection reaction.10. The method of claim 9 , further comprising converting a nitro group in the compound to an amino ...

Mammalian metabolites of steroids

Described herein, in certain embodiments, are steroidal derivatives, methods of making such compounds, pharmaceutical compositions and medicaments comprising such compounds, and methods of using such compounds to treat androgen receptor mediated diseases or conditions.

COMPOUNDS AND METHODS FOR TRANS-MEMBRANE DELIVERY OF MOLECULES

A conjugate for delivery of drugs, such as genetic drugs, [e.g., siRNA, dsiRNA, or antisense oligonucleotides (ASO)]across biological membranes is provided. The conjugates of the Invention are capable of delivering drugs in both presence and absence of plasma proteins. 2. The conjugate according to claim 1 , wherein in E claim 1 , E′ claim 1 , or E″ moiety claim 1 , W is a nucleoside claim 1 , selected from natural or modified adenine claim 1 , cytosine claim 1 , thymine and uracil claim 1 , and the sugar moiety is ribose or 2′-deoxyribose.3. The conjugate according to claim 2 , wherein in E claim 2 , E′ claim 2 , or E″ moiety claim 2 , W is 2′-deoxyuridine.4. The conjugate according to claim 1 , wherein in E claim 1 , E′ claim 1 , or E″ moiety claim 1 , W has the structure set forth in Formula (II′) claim 1 , wherein J is —CH—.24. The conjugate according to claim 1 , comprising E claim 1 , E′ or E″ moiety according to any of Formulae (II) claim 1 , (III) claim 1 , (IVa) claim 1 , (IVb) claim 1 , (IVc) claim 1 , (Va′) claim 1 , (Va″) claim 1 , (Va′″) claim 1 , (Vb′) claim 1 , (Vb″) claim 1 , (Vb′″) claim 1 , (Vc′) claim 1 , (Vc″) or (Vc′″) claim 1 , linked to a drug.25. The conjugate according to claim 24 , wherein the drug is a macromolecule drug.26. The conjugate according to claim 25 , wherein the macromolecule drug is an oligonucleotide drug (OD) claim 25 , comprising natural or modified oligonucleotide chains claim 25 , and selected from siRNA claim 25 , dsiRNA claim 25 , mRNA claim 25 , microRNA claim 25 , and antisense oligonucleotide (ASO).27. A pharmaceutical composition claim 24 , comprising the conjugate according to claim 24 , and a pharmaceutically-acceptable salt or carrier.28. The conjugate according to claim 26 , wherein the OD is linked to either one claim 26 , two claim 26 , three claim 26 , or more than three of E claim 26 , E′ claim 26 , or E″ moieties.29. The conjugate according to claim 26 , wherein the OD is a Dicer substrate claim 26 , being ...

PREGNANE-OXIMINO-AMINOALKYLETHERS AND PROCESS FOR PREPARATION THEREOF, USEFUL AS ANTIDIABETIC AND ANTIDYSLIPIDEMIC AGENTS

The present invention relates to the synthesis of pregnane-oximino-aminoalkyl-ethers and their antidiabetic and antidyslipidemic activities. More particularly, the invention relates to the synthesis of compounds of formula 3 and biological profile thereof. Further the invention relates to compounds of formula 3 and pharmaceutically acceptable salts thereof. 2. The compound as claimed in claim 1 , selected from the group consisting of:3β-Hydroxy-pregna-5,16-dien-20-one-O-n-butyl-oxime (10a),3β-Hydroxy-pregna-5,16-dien-20-one-O-benzyl-oxime (10b),3β-Hydroxypregna-5,16-dien-20-one-O-(2-piperidinyl-ethyl)-oxime (11a),3β-Hydroxypregna-5,16-dien-20-one-O-(2-azepan-1-yl-ethyl)-oxime (11b),3β-Hydroxypregna-5,16-dien-20-one-O-(2-morpholin-4-yl-ethyl)-oxime (11c),3β-Hydroxypregna-5,16-dien-20-one-O-(2-diethylamino-ethyl)-oxime (11d),3β-Hydroxy-pregna-5,16-dien-20-one-O-[3-{2-hydroxy-3-(4-(2-methoxy-phenyl-piperazinyl)-propyl)}]-oxime (13a),3β-Hydroxy-pregna-5,16-dien-20-one-O[3-(2-hydroxy-3-(4-phenyl-piperazinyl)-propyl)]-oxime (13b),3β-Hydroxy-pregna-5-en-20-one-O-(2-pyrrolidin-1-yl-ethyl)-oxime (14a),3β-Hydroxy-pregna-5-en-20-one-O-(2-piperidin-1-yl-ethyl)-oxime (14b),3β-Hydroxy-pregna-5-en-20-one-O[2-hydroxy-3-iso-propylamino-propyl)-oxime (16a),3β-Hydroxy-pregna-5-en-20-one-O-[2-hydroxy-3-tert.-butylamino-propyl]-oxime (16b),3β-Hydroxy-pregna-5-en-20-one-O-[2-hydroxy-3-(4-phenyl-piperazin-1-yl)-propyl]-oxime (16c),3β-Hydroxy-pregna-5-en-20-one-O-{2-hydroxy-3-[4-(2-methoxyphenyl)-piperzin-1-yl]-propyl}-oxime (16d),3β-Hydroxy-pregna-5-en-20-one-O[2-hydroxy-3-(2-pyridyl-piperazin-1-yl)-propyl]-oxime (16f),3β-Hydroxy-pregna-5-en-2-one-O-[2-hydroxy-3-pipridinyl-propyl)-oxime (16g),3β-Hydroxy-pregna-5-en-20-one-O-[2-hydroxy-3-(4-methyl-piperazin-1-yl)-propyl]-oxime (16h),3β-Hydroxy-pregna-5-en-20-one-O-[2-hydroxy-3-diisopropylamino-propyl)-oxime (16i), and3β-Hydroxy-pregna-5-en-20-one-O-[2-hydroxy-3-diethylamino-propyl)-oxime (16j).3. The compound as claimed in claim 1 , ...

BERBERINE-URSODEOXYCHOLIC ACID CONJUGATE FOR TREATING THE LIVER

The present invention is a method and compound for treating liver cancer. The invention treats liver cancer by directing a cancer-fighting drug into the liver hepatoportal circuit. The cancer-fighting drug is attached to a natural produced molecule which functions primarily in the hepatoportal circuit and has organotropism for the hepatoportal circuit. 2. The compound of claim 1 , wherein said R is a hydrogen atom.3. The compound of claim 1 , wherein said R is a functional group.4. The compound of claim 1 , wherein said R is an ethyl group.6. The method of synthesizing a molecule of claim 5 , further comprising the steps:cooling said first synthesized compound; andrecrystallizing said first synthesized compound to create a crystalized solid.7. The method of synthesizing a molecule of claim 6 , further comprising the steps:mixing said crystallized solid with a first solvent and adding 1,6-dibromohexane to create a first mixture;heating said first mixture;diluting with a first precipitation solvent to create a first precipitate; andfiltering said first precipitate and washing said first precipitate with a first washing solvent to create a first crude compound.8. The method of synthesizing a molecule of claim 7 , further comprising the steps:purifying said first crude compound to create a first purified compound.9. The method of synthesizing a molecule of claim 8 , further comprising the steps:dissolving said first purified compound in a second solvent;adding aqueous ammonia and ammonium chloride; andstirring to create a second mixture.10. The method of synthesizing a molecule of claim 9 , further comprising the steps:evaporating said second mixture to create a second crude compound.11. The method of synthesizing a molecule of claim 10 , further comprising the steps:purifying said second crude compound to create a second purified compound.12. The method of synthesizing a molecule of claim 11 , further comprising the steps:mixing said second purified compound and ...

OXYSTEROLS AND METHODS OF USE THEREOF

Compounds are provided according to Formula (A): and pharmaceutically acceptable salts thereof, and pharmaceutical compositions thereof; wherein R, R, R, R, R, R, and Rare as defined herein. Compounds of the present invention are contemplated useful for the prevention and treatment of a variety of conditions. 140-. (canceled)4243-. (canceled)44. The pharmaceutical composition of claim 41 , wherein Ris substituted or unsubstituted C-Calkyl.45. The pharmaceutical composition of claim 41 , wherein Ris —CH claim 41 , —CF claim 41 , —CHCH claim 41 , or —CHOR claim 41 , wherein Ris substituted or unsubstituted C-Calkyl.4647-. (canceled)48. The pharmaceutical composition of claim 41 , wherein each of Rand Ris independently hydrogen or substituted or unsubstituted alkyl.49. (canceled)50. The pharmaceutical composition of claim 41 , wherein each of Rand Ris independently hydrogen claim 41 , —CF claim 41 , or —CH.51. (canceled)52. The pharmaceutical composition of claim 41 , wherein Rand R claim 41 , together with the carbon atom to which they are attached form an oxo group.5354-. (canceled)55. The pharmaceutical composition of claim 41 , wherein Rand Rare hydrogen.56. The pharmaceutical composition of claim 41 , wherein Ris substituted or unsubstituted aryl or substituted or unsubstituted heteroaryl and Ris hydrogen.57. The pharmaceutical composition of claim 41 , wherein Ris substituted or unsubstituted carbocyclyl or substituted or unsubstituted heterocyclyl and Ris hydrogen.5859-. (canceled)6193-. (canceled)95. The pharmaceutical composition of claim 94 , wherein Ris substituted or unsubstituted C-Calkyl.96. The pharmaceutical composition of claim 94 , wherein Ris —CH claim 94 , —CF claim 94 , —CHCH claim 94 , or —CHOR claim 94 , wherein Ris substituted or unsubstituted C-Calkyl.97. The pharmaceutical composition of claim 94 , wherein each of Rand Ris independently hydrogen or substituted or unsubstituted alkyl.98. The pharmaceutical composition of claim 94 , wherein each ...

METHODS TO INDUCE TARGETED PROTEIN DEGRADATION THROUGH BIFUNCTIONAL MOLECULES

The present application provides bifunctional compounds which act as protein degradation inducing moieties. The present application also relates to methods for the targeted degradation of endogenous proteins through the use of the bifunctional compounds that link a cereblon-binding moiety to a ligand that is capable of binding to the targeted protein which can be utilized in the treatment of proliferative disorders. The present application also provides methods for making compounds of the application and intermediates thereof. 2. The compound of wherein X is C(CH).3. The compound of claim 1 , wherein X is C(CHCH).4. The compound of claim 1 , wherein Ris H or deuterium.5. The compound of claim 1 , wherein each Ris independently selected from methoxy claim 1 , ethoxy claim 1 , and propoxy.6. The compound of claim 1 , wherein m is 0.7. The compound of claim 1 , wherein m is 1.8. The compound of claim 1 , wherein n is 0.9. The compound of claim 1 , wherein each Ris independently methyl claim 1 , methoxy claim 1 , ethoxy claim 1 , or propoxy.13. A method of treating a proliferative disease claim 1 , comprising administering to a subject in need thereof a therapeutically effective amount of a compound of .14. A pharmaceutical composition comprising a therapeutically effective amount of a compound of or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable excipient.19. A method of treating a proliferative disease claim 15 , comprising administering to a subject in need thereof a therapeutically effective amount of a compound of .20. A pharmaceutical composition comprising a therapeutically effective amount of a compound of or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable excipient. This application is a continuation of International Application No. PCT/US2015/000274, filed in the Patent Cooperation Treaty, U.S. Receiving Office on Dec. 23, 2015, which claims the benefit of and priority to U.S. Provisional Application ...

TANDEM FACIAL AMPHIPHILES

The invention provides tandem facial amphiphiles for biochemical manipulations and characterization of membrane proteins, such as intrinsic membrane proteins. Members of this new family display favorable behavior with several membrane proteins. These amphiphiles can form relatively small micelles, and small changes in amphiphile chemical structures can result in large changes in their physical properties. The tandem facial amphiphiles can be used to aid the solubilization, isolation, purification, stabilization, crystallization, and/or structural determination of membrane proteins. 2. The compound of wherein each Ris (C-C)alkyl.3. The compound of wherein Y is a direct bond.4. The compound of wherein at least two of R claim 1 , Rand Rare O-Sac and each Sac is a disaccharide.15. The compound of wherein a plurality of the compounds form a micelle in water comprising about 6 to about 15 molecules of the compound.1620-. (canceled) This application is a continuation of U.S. patent application Ser. No. 13/669,198, filed Nov. 5, 2012, which claims priority under 35 U.S.C. §119(e) to U.S. Provisional Patent Application No. 61/556,625, filed Nov. 7, 2011, all of which are incorporated herein by reference.This invention was made with government support under GM075913 awarded by the National Institutes of Health. The government has certain rights in the invention.Membrane proteins (MPs) play crucial roles in biology, but these proteins are difficult to handle and analyze because of their physical properties. The native conformations of MPs display extensive nonpolar surfaces. The display of these nonpolar surfaces is necessary for residence in a lipid bilayer but leads to denaturation and/or aggregation in an aqueous medium. Detergents such as dodecyl-β--maltoside (DDM) are typically employed to render MPs soluble by coating the nonpolar protein surfaces. However, only some MPs can be maintained in native-like conformations when solubilized with conventional detergents (Serrano ...

Protected Linker Compounds

The invention features protected linker compounds which comprise at one terminus a protected amino group and at another other terminus a phosphorous activating group, such as a phosphoramidite group. These protected linker compounds are introduced chemically at the 5′-end of oligonucleotides for the purpose of preparing 5′-amino modified oligonucleotides. After deprotection, the thereby introduced amino group then allows further modification (e.g. attachment of dyes) or immobilization (on surfaces or beads) of the oligonucleotide. Specifically, the presented amino protecting group is designed to provide such protected linker compounds in a solid form, which facilitates efficient purification by precipitation or crystallization and aliquoting for distribution and storage.

FATTY ACID CONJUGATES OF STATIN AND FXR AGONISTS: COMPOSITIONS AND METHODS OF USE

The invention relates to fatty acid statin conjugates and fatty acid FXR agonist conjugates; compositions comprising an effective amount of a fatty acid statin conjugate or a fatty acid FXR agonist conjugate; and methods for treating or preventing a metabolic disease comprising the administration of an effective amount of a fatty acid statin conjugate or a fatty acid FXR agonist conjugate.

SOLID SUPPORTS AND PHOSPHORAMIDITE BUILDING BLOCKS FOR OLIGONUCLEOTIDE CONJUGATES

Novel non-nucleoside solid supports and phosphoramidite building blocks for preparation of synthetic oligonucleotides containing at least one non-nucleosidic moiety conjugated to a ligand of practical interest and synthetic processes for making the same are disclosed. Furthermore, oligomeric compounds are prepared using said solid supports and phosphoramidite building blocks, preferably followed by removal of protecting groups to provide oligonucleotides conjugated to ligands of interest. 2. The compound of wherein one of R and Ris selected from tris-(4-methoxyphenyl)methyl protecting group claim 1 , bis-(4-methoxyphenyl)phenylmethyl protecting group claim 1 , 9-phenylxanthen-9-yl protecting group claim 1 , or 9-(4-methoxyphenyl)xanthen-9-yl protecting group and the other of R and Ris selected from a residue of succinic acid optionally further attached to a solid phase material W via the second carboxylic function or a residue of diglycolic acid optionally further attached to a solid phase material W via the second carboxylic function.3. The compound of wherein one of R and Ris selected from tris-(4-methoxyphenyl)methyl protecting group claim 1 , bis-(4-methoxyphenyl)phenylmethyl protecting group claim 1 , 9-phenylxanthen-9-yl protecting group claim 1 , or 9-(4-methoxyphenyl)xanthen-9-yl protecting group and the other of R and Ris a phosphoramidite moiety PA.4. The compound of wherein each Rand Ris isopropyl group or Rand Rtogether with the nitrogen they are attached to form a cycle so that R+R=—(CH)— claim 3 , R+R=—(CH)— claim 3 , or R+R=—(CH)—O—(CH)—.5. The compound of wherein each A and Ais independently selected from —CH— or —(CH)—.6. The compound of wherein each E and Eis independently selected from —CH— claim 1 , —OCH— claim 1 , —(CH)— claim 1 , or —O(CH)—.7. The compound of wherein G is selected from an atom of hydrogen claim 1 , an alkyl group claim 1 , a trifluoroacetyl group claim 1 , (9H-fluoren-9-yl)methoxycarbonyl (Fmoc) group claim 1 , 6-( ...

PRO-DRUG FORMING COMPOUNDS

Various prodrug compounds having the general structure: Active agent-(acid)-(linker)-SONRRare described herein. Compounds having this general structure were shown to be more orally active than the unmodified parent molecule. 2. The compound of claim 1 , wherein the active agent is an androgen.3. The compound of claim 1 , wherein the active agent is testosterone.4. The compound of claim 1 , wherein the active agent is 7α claim 1 ,11β-dimethyl-estra-4 claim 1 ,9-dien-17β-ol5. The compound of claim 1 , wherein the active agent is an estrogen.6. The compound of claim 1 , wherein the active agent is estradiol.7. The compound of claim 1 , wherein the active agent is estriol.8. The compound of claim 1 , wherein the active agent is a progestin.9. The compound of claim 1 , wherein the active ingredient is trimesgestone.10. The compound of claim 1 , wherein Rand Rare linked together to form a cycloalkyl or a 3-7 membered ring with up to one heteroatom.11. The compound of claim 10 , wherein n is 1; m is 0; L is 1; hAr is aryl; Rand Rare H claim 10 , and Y and X are H.12. The compound of claim 10 , wherein n is 1; m is 1; L is 0; hAr is aryl; Rand Rare H claim 10 , and Y and X are H.13. The compound of claim 1 , wherein Ris alkyl.14. The compound of claim 13 , wherein n is 1; Ris H; m is 0; L is 1; hAr is aryl; Y and X are H; and Rand Rare H.15. The compound of claim 13 , wherein Ris isopropyl.14. The compound of claim 13 , wherein Ris methyl.15. A pharmaceutical composition comprising a compound as described in and one or more pharmaceutically acceptable carriers.17. The compound of claim 16 , wherein the active agent is an androgen.18. The compound of claim 16 , wherein the active agent is testosterone.19. The compound of claim 16 , wherein the active agent is 7α claim 16 ,11β-dimethyl-estra-4 claim 16 ,9-dien-17β-ol20. The compound of claim 16 , wherein the active agent is an estrogen.21. The compound of claim 16 , wherein the active agent is estradiol.22. The compound of ...

19-NOR C3, 3-DISUBSTITUTED C21-C-BOUND HETEROARYL STEROIDS AND METHODS OF USE THEREOF

Provided herein are 19-nor C3,3-disubstituted steroids of Formula (I): 127-. (canceled)30. The method of claim 28 , wherein Ris —CH claim 28 , —CHCH claim 28 , —CHF claim 28 , —CHF claim 28 , —CF claim 28 , —CHOCH claim 28 , or substituted or unsubstituted cyclopropyl.31. The method of claim 30 , wherein Ris —CH.32. The method of claim 28 , wherein Ris hydrogen.33. The method of claim 28 , wherein Rand Rare both hydrogen.34. The method of claim 28 , wherein represents a single bond claim 28 , and both of Rand Rare hydrogen.35. The method of claim 28 , wherein represents a single bond claim 28 , and both of Rand Rare fluoro.36. The method of claim 28 , wherein at least one of R claim 28 , R claim 28 , R claim 28 , R claim 28 , and Ris substituted or unsubstituted Calkyl claim 28 , —COR claim 28 , —C(═O)R claim 28 , —CN claim 28 , —NO claim 28 , or halogen claim 28 , wherein Ris substituted or unsubstituted Calkyl.37. The method of claim 36 , wherein at least one of R claim 36 , R claim 36 , R claim 36 , R claim 36 , and Ris substituted or unsubstituted —CH.38. The method of claim 28 , wherein R claim 28 , R claim 28 , R claim 28 , R claim 28 , and Rare hydrogen.42. The method of claim 28 , wherein the human subject has a CNS-related disorder.43. The method of claim 42 , wherein the CNS-related disorder is a sleep disorder claim 42 , a mood disorder claim 42 , a schizophrenia spectrum disorder claim 42 , a convulsive disorder claim 42 , a disorder of memory and/or cognition claim 42 , a movement disorder claim 42 , a personality disorder claim 42 , autism spectrum disorder claim 42 , pain claim 42 , traumatic brain injury claim 42 , a vascular disease claim 42 , a substance abuse disorder and/or withdrawal syndrome claim 42 , or tinnitus.44. The method of claim 43 , wherein the mood disorder is depression.45. The method of claim 44 , wherein the depression is postnatal depression.46. The method of claim 43 , wherein the sleep disorder is insomnia.47. The method of ...

METHODS TO INDUCE TARGETED PROTEIN DEGRADATION THROUGH BIFUNCTIONAL MOLECULES

The present application provides bifunctional compounds which act as protein degradation inducing moieties. The present application also relates to methods for the targeted degradation of endogenous proteins through the use of the bifunctional compounds that link a cereblon-binding moiety to a ligand that is capable of binding to the targeted protein which can be utilized in the treatment of proliferative disorders. The present application also provides methods for making compounds of the application and intermediates thereof. 145.-. (canceled)48. The compound of claim 47 , wherein W is O or CH.49. The compound of claim 47 , wherein Q is —CHC(O)NH—.50. The compound of claim 46 , wherein Tis CH.51. The compound of claim 50 , wherein Rgis C(O)Rg.52. The compound of claim 51 , wherein Rgis C-Calkoxy.53. The compound of claim 46 , wherein Tis CHCH.54. The compound of claim 53 , wherein Rgis C(O)Rg.55. The compound of claim 54 , wherein Rgis C-Calkoxy.56. The compound of claim 46 , wherein two R claim 46 , together with the carbon atom to which they are attached claim 46 , form C(O).58. The compound of claim 57 , wherein X is C(O).59. The compound of claim 57 , wherein X is C(R).60. The compound of claim 46 , wherein Rand Rare H.61. The compound of claim 46 , wherein m is 0.62. The compound of claim 46 , wherein nn10 is 2.64. A pharmaceutical composition comprising a therapeutically effective amount of the compound or stereoisomer or pharmaceutically acceptable salt thereof of claim 46 , and a pharmaceutically acceptable carrier.65. A method for the treatment of a disease mediated by FKBP12 claim 46 , comprising administering a therapeutically effective amount of the compound or stereoisomer or pharmaceutically acceptable salt thereof of claim 46 , optionally in a pharmaceutically acceptable carrier claim 46 , to a human in need thereof. This application is a continuation of U.S. Ser. No. 15/816,646, filed Nov. 17, 2017, which is a continuation of U.S. Ser. No. 15/148, ...

TRIFLUOROMETHOXYLATION OF ARENES VIA INTRAMOLECULAR TRIFLUOROMETHOXY GROUP MIGRATION

The present invention provides a process of producing a trifluoromethoxylated aryl or trifluoromethoxylated heteroaryl having the structure: 19-. (canceled)11. The process of claim 10 , wherein the second suitable solvent is chloroform claim 10 , dichloromethane claim 10 , nitromethane claim 10 , dimethylforamide claim 10 , diethyl ether claim 10 , tetrahydrofuran claim 10 , dioxane claim 10 , dichloroethane claim 10 , or hexane.12. The process of claim 10 , wherein step (b) is carried out at room temperature.13. The process of claim 10 , wherein step (b) is carried out at a temperature of 50-140° C.14. The process of claim 10 , wherein the compound is maintained in the second suitable solvent for 10-50 hours.15. The process of claim 10 , wherein A is a phenyl or pyridine.16. The process of claim 10 , wherein A is a furan claim 10 , thiophene claim 10 , pyrrole claim 10 , thiazole claim 10 , imidazole claim 10 , pyrazole claim 10 , isooxazole claim 10 , isothiazole claim 10 , naphthalene claim 10 , anthracene claim 10 , pyrimidine claim 10 , pyrazine claim 10 , pyridazine claim 10 , indole claim 10 , indoline claim 10 , benzofuran claim 10 , benzothiophene claim 10 , or quinolone.2037-. (canceled) This application claims priority of U.S. Provisional Application Nos. 62/192,789, filed Jul. 15, 2015; 62/192,462, filed Jul. 14, 2015; 62/063,246, filed Oct. 13, 2014; and 62/062,508, filed Oct. 10, 2014, the contents of each of which are hereby incorporated by reference.Throughout this application various publications are referenced. The disclosures of these documents in their entireties are hereby incorporated by reference into this application in order to more fully describe the state of the art to which this invention pertains.Fluorine atoms are often introduced into organic molecules to enhance their pharmacological properties such as solubility, metabolic and oxidative stability, lipophilicity, and bioavailability. Among the fluorine containing functional groups, ...

COMPOSITIONS AND METHODS FOR TREATING CNS DISORDERS

Described herein are neuroactive steroids of the Formula (II): or a pharmaceutically acceptable salt thereof; wherein A, R, R, R, R, R, R, R, R, Rand are as defined herein. Such compounds are envisioned, in certain embodiments, to behave as GABA modulators. The present invention also provides pharmaceutical compositions comprising a compound of the present invention and methods of use and treatment, e. g., such for inducing sedation and/or anesthesia. 164-. (canceled)74. The method of claim 66 , wherein A is a 5-10-membered ring.75. The compound of claim 74 , wherein A is phenyl claim 74 , naphthyl claim 74 , furan claim 74 , thiophene claim 74 , thiazole claim 74 , pyrrole claim 74 , imidazole claim 74 , pyrazole claim 74 , or triazole.77. The method of claim 65 , wherein the CNS-related disorder is a sleep disorder claim 65 , a mood disorder claim 65 , a schizophrenia spectrum disorder claim 65 , a convulsive disorder claim 65 , a disorder of memory claim 65 , a disorder of cognition claim 65 , a movement disorder claim 65 , a personality disorder claim 65 , autism spectrum disorder claim 65 , pain claim 65 , traumatic brain injury claim 65 , a vascular disease claim 65 , a substance abuse disorder claim 65 , a substance abuse withdrawal syndrome claim 65 , a neurodegenerative disorder claim 65 , or tinnitus.78. The method of claim 77 , wherein the CNS-related disorder is tremor.79. The method of claim 78 , wherein the tremor is essential tremor.80. The method of claim 66 , wherein the CNS-related disorder is a sleep disorder claim 66 , a mood disorder claim 66 , a schizophrenia spectrum disorder claim 66 , a convulsive disorder claim 66 , a disorder of memory claim 66 , a disorder of cognition claim 66 , a movement disorder claim 66 , a personality disorder claim 66 , autism spectrum disorder claim 66 , pain claim 66 , traumatic brain injury claim 66 , a vascular disease claim 66 , a substance abuse disorder claim 66 , a substance abuse withdrawal syndrome claim ...

INHIBITORS OF GLUCOCORTICOID RECEPTOR

The present invention relates generally to compositions and methods for treating cancer and hypercortisolism. Provided herein are substituted steroidal derivative compounds and pharmaceutical compositions comprising said compounds. The subject compounds and compositions are useful for inhibition of glucocorticoid receptors. Furthermore, the subject compounds and compositions are useful for the treatment of cancer. 2. The compound of or a pharmaceutically acceptable salt claim 1 , solvate claim 1 , or prodrug thereof claim 1 , wherein R is hydrogen claim 1 , alkyl claim 1 , haloalkyl claim 1 , hydroxy claim 1 , halo claim 1 , carbocyclyl claim 1 , or heteroalkyl.3. The compound of or or a pharmaceutically acceptable salt claim 1 , solvate claim 1 , or prodrug thereof claim 1 , wherein Ris Calkyl or hydrogen.4. The compound of any one of - or a pharmaceutically acceptable salt claim 1 , solvate claim 1 , or prodrug thereof claim 1 , wherein Ris methyl.5. The compound of any one of - or a pharmaceutically acceptable salt claim 1 , solvate claim 1 , or prodrug thereof claim 1 , wherein Ris H.6. The compound of any one of - or a pharmaceutically acceptable salt claim 1 , solvate claim 1 , or prodrug thereof claim 1 , wherein ring A is monocyclic heteroaryl or monocyclic aryl.7. The compound of any one of - or a pharmaceutically acceptable salt claim 1 , solvate claim 1 , or prodrug thereof claim 1 , wherein ring A is phenyl claim 1 , pyridinyl claim 1 , pyrimidinyl claim 1 , pyrazinyl claim 1 , or pyridazinyl.8. The compound of any one of - or a pharmaceutically acceptable salt claim 1 , solvate claim 1 , or prodrug thereof claim 1 , wherein ring A is phenyl.9. The compound of any one of - or a pharmaceutically acceptable salt claim 1 , solvate claim 1 , or prodrug thereof claim 1 , wherein Ris Calkyl.10. The compound of any one of - or a pharmaceutically acceptable salt claim 1 , solvate claim 1 , or prodrug thereof claim 1 , wherein Ris Calkyl.11. The compound of any ...

INHIBITORS OF GLUCOCORTICOID RECEPTOR

The present invention relates generally to compositions and methods for treating cancer and hypercortisolism. Provided herein are substituted steroidal derivative compounds and pharmaceutical compositions comprising said compounds. The subject compounds and compositions are useful for inhibition of glucocorticoid receptors. Furthermore, the subject compounds and compositions are useful for the treatment of cancer and hypercortisolism. 25.-. (canceled)6. The compound of claim 1 , or a pharmaceutically acceptable salt claim 1 , solvate claim 1 , or prodrug thereof claim 1 , wherein each Ris independently —NRR claim 1 , halo claim 1 , alkyl claim 1 , carbocyclyl claim 1 , alkoxy claim 1 , or —CN.7. (canceled)8. The compound of claim 1 , or a pharmaceutically acceptable salt claim 1 , solvate claim 1 , or prodrug thereof claim 1 , wherein Rand Rare each independently —H claim 1 , alkyl claim 1 , or —S(O)R.9. The compound of claim 1 , or a pharmaceutically acceptable salt claim 1 , solvate claim 1 , or prodrug thereof claim 1 , wherein{'sup': 4', '5', '6, 'sub': '2', 'Rand Rattached to the same N atom are taken together with the N atom to which they are attached to form a substituted or unsubstituted 4-, 5-, or 6-membered ring heterocycle additionally containing 0-3 heteroatoms selected from the group consisting of —O—, —NH—, —NR—, —S—, and —S(O)—; and'}{'sup': '6', 'Ris alkyl.'}10. The compound of claim 1 , or a pharmaceutically acceptable salt claim 1 , solvate claim 1 , or prodrug thereof claim 1 , wherein Ris alkyl claim 1 , carbocyclyl claim 1 , or fluoroalkyl.11. The compound of claim 1 , or a pharmaceutically acceptable salt claim 1 , solvate claim 1 , or prodrug thereof claim 1 , wherein Ris alkyl claim 1 , carbocyclyl claim 1 , optionally substituted aryl claim 1 , optionally substituted aralkyl claim 1 , or optionally substituted heterocyclyl.1213.-. (canceled)14. The compound of claim 1 , or a pharmaceutically acceptable salt claim 1 , solvate claim 1 , or ...

METHOD FOR MEASURING AN ABILITY OF HIGH-DENSITY LIPOPROTEIN TO UPTAKE CHOLESTEROL

Provided is a monoclonal antibody or antigen-binding fragment thereof which binds to a peptide consisting of 51st to 110th amino acid sequence or a peptide consisting of 201st to 267th amino acid sequence of an amino acid sequence of SEQ ID NO: 1, and is capable of binding to high-density lipoproteins of (1) to (3) below; 2. The method according to claim 1 , wherein the monoclonal antibody or antigen-binding fragment thereof binds to a peptide consisting of 91st to 110th amino acid sequence of the amino acid sequence of SEQ ID NO: 1 and does not bind to a range of 101st to 160th of the amino acid sequence of SEQ ID NO: 1.3. The method according to claim 1 , wherein the monoclonal antibody or antigen-binding fragment thereof binds to non-denatured high-density lipoprotein present in a sample under non-denatured conditions.4. The method according to claim 1 , wherein the monoclonal antibody or antigen-binding fragment thereof comprises HCDR1 claim 1 , HCDR2 claim 1 , HCDR3 claim 1 , LCDR1 claim 1 , LCDR2 and LCDR3 comprising amino acid sequences that are respectively same as amino acid sequences of HCDR1 claim 1 , HCDR2 claim 1 , HCDR3 claim 1 , LCDR1 claim 1 , LCDR2 and LCDR3 of monoclonal antibody produced from a hybridoma of accession No. NITE BP-02442 or accession No. NITE BP-02443 or its progeny claim 1 , and wherein HCDR represents a heavy chain complementarity determining region and LCDR represents a light chain complementarity determining region.5. The method according to claim 1 , wherein the monoclonal antibody contains a heavy chain variable region and a light chain variable region consisting of amino acid sequences that are respectively same as amino acid sequences of a heavy chain variable region and a light chain variable region of monoclonal antibodies produced from a hybridoma of accession No. NITE BP-02442 or accession No. NITE BP-02443 or its progeny.6. The method according to claim 1 , wherein the monoclonal antibody contains an amino acid sequence ...

ESTRA-1,3,5(10),16-TETRAENE-3-CARBOXAMIDES FOR INHIBITION OF 17.BETA.-HYDROXYSTEROID DEHYDROGENASE (AKR1 C3)

The invention relates to AKR1C3 inhibitors of formula (I) and to processes for preparation thereof, to the use thereof for treatment and/or prophylaxis of diseases and to the use thereof for production of medicaments for treatment and/or prophylaxis of diseases, especially of bleeding disorders and endometriosis. 2. The compound of claim 1 ,whereinX is carbon substituted by hydrogen,{'sup': '2', 'Y is carbon or nitrogen, where the carbon may be substituted by R,'}{'sup': '2', 'sub': '3', 'Ris hydrogen, fluorine, chlorine, nitrile, methoxy, ethoxy, trifluoromethoxy, methyl, ethyl, trifluoromethyl, —(C═O)CH,'}{'sup': '3', 'Ris hydrogen or fluorine,'}{'sup': '4', 'Ris hydrogen, methyl, ethyl, isopropyl, propyl, butyl, cyclopropyl or 2,2,2-trifluoroethyl,'}{'sup': '5', 'claim-text': 'or', 'Ris hydrogen, methyl, ethyl, propyl, 2,2,2-trifluoroethyl, 3,3,3-trifluoropropyl, 2-fluoroethyl, 2-sulphamoylethyl, 3-sulphamoylpropyl, (1S,2R)-2-hydroxycyclopentyl, 3-hydroxy-2,2-dimethylpropyl, (1S,2S)-2-hydroxycyclopentyl, (3R)-4-hydroxy-3-methylbutyl, 1-(hydroxymethyl)cyclopentyl, (2S)-1-hydroxybutan-2-yl, (2R)-1-hydroxy-3-methylbutan-2-yl, 3-hydroxybutan-2-yl, 2-hydroxyethyl, 3,3,3-trifluoro-2-hydroxypropyl, 2-(1H-tetrazol-5-yl)ethyl, 1H-tetrazol-5-ylmethyl, 2-(methylsulphamoyl)ethyl, 3-amino-3-oxopropyl, 3-(methylamino)-3-oxopropyl, 2-methyl-2-[(methylsulphonyl)amino]propyl, (2S)-2,3-dihydroxypropyl, 3-hydroxypropyl, 4-hydroxybutyl, (2RS)-2,3-dihydroxypropyl, (2R)-2,3-dihydroxypropyl, 2,3-dihydroxybutyl, 2-(methylsulphinyl)ethyl, 3-(methylsulphinyl)propyl, 2-(methylsulphonyl)ethyl, 3-(methylsulphonyl)propyl, 2-(S-methylsulphonimidoyl)ethyl, (2R)-2-hydroxypropyl, (2S)-1-hydroxypropan-2-yl, 2-methoxyethyl, 3-methoxypropyl, 2-(isopropylsulphonyl)ethyl, (3-methyloxetan-3-yl)methyl, (2S)-2-hydroxypropyl, 2-(2-hydroxyethoxy)ethyl,'}{'sup': 4', '5, 'Rand Rtogether with the directly joining nitrogen atom are piperidinyl, pyrrolidinyl, morpholinyl, N-methylpiperazinyl, 1- ...

STRUCTURAL MODIFICATION OF 19-NORPROGESTERONE I: 17-ALPHA-SUBSTITUTED-11-BETA-SUBSTITUTED-4-ARYL AND 21-SUBSTITUTED 19-NORPREGNADIENEDIONE AS NEW ANTIPROGESTATIONAL AGENTS

Disclosed are compounds having the general formula: 160-. (canceled)62. The compound in accordance with claim 61 , wherein Ris a member selected from the group consisting of —N(CH) claim 61 , —NCH claim 61 , —NCHO claim 61 , —C(O)CH claim 61 , —O(CH)N(CH) claim 61 , —O(CH)NCH claim 61 , and —O(CH)NCH.63. The compound in accordance with claim 61 , wherein Ris a member selected from the group consisting of hydrogen claim 61 , alkyloxy claim 61 , alkoxy claim 61 , —SAc claim 61 , —SCN claim 61 , —OC(O)CHN(CH) claim 61 , and —OC(O)R claim 61 , wherein Ris a member selected from the group consisting of alky claim 61 , alkoxy ester and alkoxy.64. The compound in accordance with claim 63 , wherein Ris —OC(O)Rand Ris a member selected from the group consisting of-CHCH claim 63 , —CHOCH claim 63 , and —OCH.65. The compound in accordance with claim 61 , wherein Ris an alkoxy selected from the group consisting of methoxy claim 61 , ethoxy claim 61 , vinyloxy claim 61 , ethynyloxy and cyclopropyloxy.66. The compound in accordance with claim 61 , wherein Ris a member selected from the group consisting of alkyl claim 61 , alkoxy claim 61 , acyloxy and hydroxy.67. The compound in accordance with claim 61 , wherein Ris alkyl.68. The compound in accordance with claim 61 , wherein X is ═O.69. The compound in accordance with claim 61 , wherein X is ═N—OR.70. The compound in accordance with claim 61 , wherein Ris acyloxy selected from the group consisting of —OC(O)H claim 61 , —OC(O)CHCHand —OC(O)CH.71. The compound in accordance with claim 61 , wherein the compound is:{'sup': '1', 'sub': 3', '2, 'Ris —N(CH);'}{'sup': '2', 'Ris hydrogen;'}{'sup': '3', 'Ris methoxymethyl;'}{'sup': '4', 'Ris methyl; and'}X is ═O;{'sup': '1', 'sub': 4', '8, 'Ris —NCH;'}{'sup': '2', 'Ris hydrogen;'}{'sup': '3', 'Ris acetoxy;'}{'sup': '4', 'Ris methyl; and'}X is ═O;{'sup': '1', 'sub': 5', '10, 'Ris —NCH;'}{'sup': '2', 'Ris hydrogen;'}{'sup': '3', 'Ris acetoxy;'}{'sup': '4', 'Ris methyl; and'}X is ═O;{'sup': ...

ESTRA-1,3,5(10)-TRIENE COMPOUNDS CONDENSED IN POSITION 16(17) WITH A PYRAZOLE RING AS INHIBITORS OF 17-HSD1

The invention relates to compounds of formula (I) and pharmaceutically acceptable salts thereof 3. The compound according to claim 1 , whereinR1 is selected from the group consisting of H, F and Cl,R2 is selected from the group consisting of H, F and Cl, and{'claim-ref': {'@idref': 'CLM-00001', 'claim 1'}, 'R3, R4 and R5 are as defined in ,'}or a pharmaceutically acceptable salt thereof.4. The compound according to claim 1 , whereinR1 is selected from the group consisting of H, F and Cl,R2 is H or F, and{'claim-ref': {'@idref': 'CLM-00001', 'claim 1'}, 'R3, R4 and R5 are as defined in ,'}or a pharmaceutically acceptable salt thereof.5. The compound according to claim 1 , whereinR1 is HR2 is F, and{'claim-ref': {'@idref': 'CLM-00001', 'claim 1'}, 'R3, R4 and R5 are as defined in ,'}or a pharmaceutically acceptable salt thereof.7. The compound according to claim 1 , whereinthe 1 to 3 heteroatoms of the 5 membered unsubstituted unsaturated or aromatic heterocycle are independently selected from nitrogen and oxygen,the 1 to 3 heteroatoms of the 5 membered unsubstituted unsaturated or aromatic heterocycle are independently selected from 2 nitrogens and 1 sulphur, orthe 1 to 3 heteroatoms of the 5 membered unsubstituted unsaturated or aromatic heterocycle are independently selected from 2 nitrogens and 1 oxygen,or a pharmaceutically acceptable salt thereof.8. The compound according to claim 1 , whereinR3 is H,{'sub': '2', 'R4 is a 5 membered unsaturated or aromatic heterocycle with 1 to 3 heteroatoms selected from the group consisting of nitrogen, and oxygen, optionally substituted with one or two substituent(s) selected from the group consisting of CN, C1-4-alkyl, C1-3-alkoxy, halogen and C(O)N(C1-3-alkyl),'}or a pharmaceutically acceptable salt thereof.11. The compound according to claim 1 , whereinR1 is H,R2 is H or F,R3 is H,{'sub': '2', 'R4 is a 6 membered aromatic heterocycle with 1 to 3 heteroatoms selected from the group consisting of nitrogen, oxygen and sulfur, ...

INHIBITORS OF GLUCOCORTICOID RECEPTOR

The present invention relates generally to compositions and methods for treating cancer and hypercortisolism. Provided herein are substituted steroidal derivative compounds and pharmaceutical compositions comprising said compounds. The subject compounds and compositions are useful for inhibition of glucocorticoid receptors. Furthermore, the subject compounds and compositions are useful for the treatment of cancer and hypercortisolism. 2. The compound of or a pharmaceutically acceptable salt claim 1 , solvate claim 1 , or prodrug thereof claim 1 , wherein{'sup': 1', '3', '6', '3', '3', '4', '3', '6', '3', '3', '4', '3', '3', '4', '3', '4', '6, 'sub': 2', '2', '2', '2', '2', '2, 'Ris —NRS(O)R, —NRS(O)NRR, -alkyNRS(O)R, -alkyNRS(O)NRR, —NRaralkyl, —C(O)NRR, —S(O)NRR, or —S(O)R;'}{'sup': 3', '4', '10', '6, 'sub': 2', '2, 'Rand Rare each independently —H, optionally substituted alkyl, fluoroalkyl, optionally substituted carbocyclyl, optionally substituted carbocyclylalkyl, optionally substituted aryl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heteroaryl, —C(O)N(R), or —S(O)R;'}{'sup': 3', '4, 'or Rand Rattached to the same N atom are taken together with the N atom to which they are attached to form a substituted or unsubstituted 3-, 4-, 5-, or 6-membered heterocycle;'}{'sup': '5', 'Ris optionally substituted alkyl, fluoroalkyl, optionally substituted carbocyclyl, or optionally substituted heterocyclyl;'}{'sup': '6', 'Ris optionally substituted alkyl, fluoroalkyl, optionally substituted carbocyclyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted heterocyclyl, or optionally substituted heteroaryl;'}{'sup': 7', '8', '5', '3', '4', '3', '4, 'Rand Rare each independently —H, optionally substituted alkyl, fluoroalkyl, halo, —OR, —NRR, —C(O)NRR, —CN, optionally substituted carbocyclyl, or optionally substituted carbocyclylalkyl;'}{'sup': 7', '8', '6, 'sub': '2', 'or Rand Rare taken ...

COMPOSITIONS AND METHODS FOR TREATING CNS DISORDERS

Described herein are neuroactive steroids of the Formula (I); or a pharmaceutically acceptable salt thereof, wherein, R, R, R, Rand A are as defined herein. Such compounds are envisioned, in certain embodiments, to behave as GABA modulators. The present invention also provides pharmaceutical compositions comprising a compound of the present invention and methods of use and treatment, e.g., such for inducing sedation and/or anesthesia. 151-. (canceled)53. The process of claim 52 , wherein the process is performed in a solvent.54. The process of claim 52 , wherein the solvent is tetrahydrofuran.55. The process of claim 52 , wherein the process occurs at room temperature. This application claims priority to Provisional Application No. 62/064,957, filed Oct. 16, 2014, the entire contents of which are incorporated herein by reference.Brain excitability is defined as the level of arousal of an animal, a continuum that ranges from coma to convulsions, and is regulated by various neurotransmitters. In general, neurotransmitters are responsible for regulating the conductance of ions across neuronal membranes. At rest, the neuronal membrane possesses a potential (or membrane voltage) of approximately −70 mV, the cell interior being negative with respect to the cell exterior. The potential (voltage) is the result of ion (K, Na, Cl, organic anions) balance across the neuronal semipermeable membrane. Neurotransmitters are stored in presynaptic vesicles and are released under the influence of neuronal action potentials. When released into the synaptic cleft, an excitatory chemical transmitter such as acetylcholine will cause membrane depolarization, e.g., a change of potential from −70 mV to −50 mV. This effect is mediated by postsynaptic nicotinic receptors which are stimulated by acetylcholine to increase membrane permeability to Na ions. The reduced membrane potential stimulates neuronal excitability in the form of a postsynaptic action potential.In the case of the GABA ...

Neuroactive steroids, compositions, and uses thereof

Described herein are neuroactive steroids of the Formula (I): or a pharmaceutically acceptable salt thereof; wherein R 1 , R 2 , R a , G, X, Y, Z, and n are as defined herein. Such compounds are envisioned, in certain embodiments, to behave as GABA modulators. Also provided are pharmaceutical compositions comprising a compound described herein and methods of use and treatment, e.g., such for inducing sedation and/or anesthesia.

CERTAIN CHEMICAL ENTITIES, COMPOSITIONS, AND METHODS

Chemical entities that are novel compounds, pharmaceutical compositions and methods of treatment of cancer are described. 2. (canceled)3. (canceled)4. The compound of claim 1 , wherein R claim 1 , R claim 1 , R claim 1 , R claim 1 , R claim 1 , R claim 1 , R claim 1 , Rand Rare independently chosen from hydrogen claim 1 , hydroxy claim 1 , and methyl.5. The compound of claim 1 , wherein Ris hydroxy.6. (canceled)7. The compound of claim 1 , wherein Rand Rare joined together with any intervening atoms to form an oxirane ring.8. (canceled)9. (canceled)10. The compound of claim 1 , wherein Ris chosen from hydrogen and —OCOCH.11. The compound of claim 1 , wherein Rand Ware independently chosen from hydrogen and optionally substituted alkyl.12. (canceled)13. The compound of claim 1 , wherein Ris chosen from hydrogen claim 1 , methyl claim 1 , and hydroxymethyl.1417.-. (canceled)18. The compound of claim 1 , wherein represents a single bond.19. The compound of claim 1 , wherein represents a double bond.2931.-. (canceled)32. The compound of claim 1 , wherein Ris chosen from 2-morpholinoethyl claim 1 , 2-(pyrrolidin-1-yl)ethyl claim 1 , and 2-(3-oxopiperazin-1-yl)ethyl.3340.-. (canceled)41. The compound of claim 1 , wherein the compound is selected from:(1R,2aR,3aS,3bR,5aR,7S,9aS,9bS,11aR)-9a,11a-dimethyl-1-(2-oxo-2H-pyran-5-yl)hexadecahydronaphtho[1′,2′:6,7]indeno[1,7a-b]oxiren-7-yl (2-(pyrrolidin-1-yl)ethyl) carbonate,(1R,2aR,3aS,3bR,5aR,7S,9aS,9bS,11aR)-9a,11a-dimethyl-1-(2-oxo-2H-pyran-5-yl)hexadecahydronaphtho[1′,2′:6,7]indeno[1,7a-b]oxiren-7-yl (2-morpholinoethyl) carbonate,(1R,2R,2aR,3aS,3bR,5aR,7S,9aS,9bS,11aR)-9a,11a-dimethyl-1-(2-oxo-2H-pyran-5-yl)-7-(((2-(pyrrolidin-1-yl)ethoxy)carbonyl)oxy)hexadecahydronaphtho[1′,2′:6,7]indeno[1,7a-b]oxiren-2-yl acetate,(1R,2R,2aR,3aS,3bR,5aR,7S,9aS,9bS,11aR)-9a,11a-dimethyl-7-(((2-morpholinoethoxy)carbonyl)oxy)-1-(2-oxo-2H-pyran-5-yl)hexadecahydronaphtho[1′,2′:6,7]indeno[1,7a-b]oxiren-2-yl acetate,(1R,2R,2aR,3aS,3bR,5aS,7S,9aR, ...

HYDROXYSTEROID COMPOUNDS, THEIR INTERMEDIATES, PROCESS OF PREPARATION, COMPOSITION AND USES THEREOF

The present invention relates to novel steroidal compounds of formula (I), process for preparation of the same and composition comprising these compounds. 4. (canceled)5. The compound of claim 3 , wherein the compound is selected from the group consisting of:xiii. (10R,11S,13S,17S)-11-hydroxy-10,13-dimethyl-3-oxo-6,7,8,9,10,11,12,13,14,15,16,17-dodecahydro-3H-cyclopenta[a]phenanthrene-17-carboxylic acid;xiv. (10R,11S,13S,17S)-11-hydroxy-N,N,10,13-tetramethyl-3-oxo-6,7,8,9,10,11,12,13,14,15,16,17-dodecahydro-3H-cyclopenta[a]phenanthrene-17-carboxamide;xv. (10R,11S,13S,17S)-17-acetyl-1-hydroxy-10,13-dimethyl-6,7,8,9,10,11,12,13,14,15,16,17-dodecahydro-3H-cyclopenta[a]phenanthren-3-one;xvi. (10R,11S,13S,17S)-11-hydroxy-17-((R)-1-hydroxyethyl)-10,13-dimethyl-6,7,8,9,10,11,12,13,14,15,16,17-dodecahydro-3H-cyclopenta[a]phenanthren-3-one;xxxiii. (10R,11S,13S,17S)-11,17-dihydroxy-10,13-dimethyl-6,7,8,9,10,11,12,13,14,15,16,17-dodecahydro-3H-cyclopenta[a]phenanthren-3-one;xxxiv. (10R,11S,13S)-11-hydroxy-10,13-dimethyl-7,8,9,10,11,12,13,14,15,16-decahydro-3H-cyclopenta[a]phenanthrene-3,17(6H)-dione;xli. (10R,11S,13S,17S)-11-hydroxy-10,13-dimethyl-3-oxo-6,7,8,9,10,11,12,13,14,15,16,17-dodecahydro-3H-cyclopenta[a]phenanthrene-17-carboxamide;xlii. (10R,11S,13S,17S)-11-hydroxy-17-(hydroxymethyl)-10,13-dimethyl-6,7,8,9,10,11,12,13,14,15,16,17-dodecahydro-3H-cyclopenta[a]phenanthren-3-one;xliii. (10R,11S,13S,17S)-17-((dimethylamino)methyl)-11-hydroxy-10,13-dimethyl-6,7,8,9,10,11,12,13,14,15,16,17-dodecahydro-3H-cyclopenta[a]phenanthren-3-one;lvi. (8S,9S,10R,11S,13S,14S,Z)-11-hydroxy-17-(hydroxyimino)-10,13-dimethyl-6,7,8,9,10,11,12,13,14,15,16,17-dodecahydro-3H-cyclopenta[a]phenanthren-3-one;lvii. (8S,9S,10R,11S,13S,14S)-17-amino-11-hydroxy-10,13-dimethyl-6,7,8,9,10,11,12,13,14,15,16,17-dodecahydro-3H-cyclopenta[a]phenanthren-3-one;lviii. (8S,9S,10R,11S,13S,14S)-11-hydroxy-10,13-dimethyl-6,7,8,9,10,11,12,13,14,15,16,17-dodecahydro-3H-cyclopenta[a]phenanthren-3-one; andlix. (8S,9S, ...

INHIBITORS OF CYP17A1

Compounds according to formula I or II are provided. Such compounds are useful in treating cancers, such as leukemia, colon cancer, breast cancer, or prostate cancer by beneficially inhibiting CYP17A1. Pharmaceutical compositions and methods including the compounds are also provided. 2. The compound of claim 1 , wherein Zand Zare each N.4. The compound of claim 3 , wherein Z claim 3 , Z claim 3 , and Zare each independently N.5. The compound of claim 3 , wherein{'sup': '1', 'Yis O or a bond;'}{'sup': '2', 'Yis a bond; and'}{'sup': 1', '2', '16', '17', '18, 'Xand Xare each independently C(O)NRR, C(O)OR, nitro, or cyano.'}6. The compound of claim 3 , wherein Rand Rare each independently H claim 3 , OH claim 3 , NRR claim 3 , or trifluoromethoxy; or Rand Rtogether are ═O or ═N—OH.8. The compound of claim 7 , wherein the compound of formula II is a compound according to formula VI.10. A pharmaceutical composition claim 2 , comprising an effective amount of the compound of and a pharmaceutically acceptable carrier.11. A method comprising inhibiting CYP17A1 by administration of the compound of .12. The method of claim 11 , comprising inhibiting CYP17A1 by administration of a pharmaceutical composition wherein the pharmaceutical composition comprises an effective amount of the compound and a pharmaceutically acceptable carrier.13. The method of claim 11 , wherein administration of the compound selectively inhibits CYP17A1.14. The method of claim 13 , wherein administration of the compound selectively inhibits CYP17A1 over CYP21A2.16. A method of treating a biological condition comprising administering to a subject suffering from a biological condition selected from leukemia claim 2 , colon cancer claim 2 , breast cancer claim 2 , or prostate cancer claim 2 , an effective amount of the compound of .17. The method of claim 16 , wherein the method comprises administering a pharmaceutical composition claim 16 , wherein the pharmaceutical composition comprises the effective ...

CRYSTAL FORM OF ABIRATERONE PROPIONATE AND PREPARATION METHOD THEREFOR

The present invention relates to the field of pharmaceutical chemistry, and particularly to a crystal form of Abiraterone propionate and a preparation method therefor. Characteristic diffraction peaks occur at positions, where the 2θ value is 5.7°, 11.9°, 12.4°, 14.9°, 15.8°, 16.7°, 18.5°, 19.1°, 21.7°, 22.4°, and 39.9°±0.2°, in an X-ray powder diffraction spectrum of the crystal form of Abiraterone propionate. 1. A crystal form A of Abiraterone propionate , wherein X-ray powder diffraction pattern thereof has characteristic diffraction peaks at 2θ±0.2° , and the 2θ is 5.7° , 11.9° , 12.4° , 14.9° , 15.8° , 16.7° , 18.5° , 19.1° , 21.7° , 22.4° , and 39.9°.2. The crystal form A of claim 1 , wherein the X-ray powder diffraction pattern has a diffraction peaks at 2θ±0.2° claim 1 , and the 2θ is 5.3° claim 1 , 5.7° claim 1 , 11.9° claim 1 , 12.4° claim 1 , 14.2° claim 1 , 14.9° claim 1 , 15.8° claim 1 , 16.7° claim 1 , 17.0° claim 1 , 18.5° claim 1 , 19.1° claim 1 , 20.3° claim 1 , 21.7° claim 1 , 22.4° claim 1 , 22.9° claim 1 , 23.4° claim 1 , 24.9° claim 1 , 25.7° claim 1 , 26.9° claim 1 , 27.6° claim 1 , 27.9° claim 1 , 28.2° claim 1 , 30.0° claim 1 , 32.4° claim 1 , 34.6° claim 1 , 37.1° claim 1 , 37.8° claim 1 , 39.1° claim 1 , and 39.9°.3. A method for preparing the crystal form A of Abiraterone propionate claim 1 , comprising the following steps:a) dissolving Abiraterone propionate in an organic solvent;b) performing cooling crystallization under stirring and/or crystallization by adding a poor solvent; andc) separating solid.4. The method according to claim 3 , wherein the organic solvent is selected from methanol claim 3 , ethanol claim 3 , isopropanol claim 3 , acetone claim 3 , ethyl acetate claim 3 , methyl acetate claim 3 , dichloromethane claim 3 , chloroform claim 3 , acetonitrile claim 3 , tetrahydrofuran and n-heptane claim 3 , or a mixture thereof.5. The method according to claim 3 , wherein the temperature at which Abiraterone propionate is dissolved ...

Novel c-17-heteroaryl steroidal cyp17 inhibitors/antiandrogens, in vitro biological activities, pharmacokinetics and antitumor activity

Described are steroidal C-17 benzoazoles, pyrimidinoazoles (azabenzoazoles) and diazines. Methods for their synthesis are also described, which include methods having a step of nucleophilic vinylic “addition-elimination” substitution reaction of 3β-acetoxy-17-chloro-16-formylandrosta-5,16-diene or analogs thereof and benzoazole or pyrimidinoazole nucleophiles and methods having a palladium catalyzed cross-coupling reaction of 17-iodoandrosta-5,16-dien-3β-ol or analogs thereof with tributylstannyl diazines. The compounds are potent inhibitors of human CYP17 enzyme as well as potent antagonists of both wild type and mutant androgen receptors (AR). The compounds are useful for the treatment of human prostate cancer.

Arginase Inhibitors and Methods of Use Thereof

The present invention includes arginase enzyme inhibitors, compositions comprising these arginase inhibitors, and methods of treating or diagnosing conditions characterized either by abnormally high arginase activity or abnormally low nitric oxide levels in a mammal, comprising administering compositions of the invention to the mammal.

CERTAIN CHEMICAL ENTITIES, COMPOSITIONS, AND METHODS

Chemical entities that are novel compounds, pharmaceutical compositions and methods of treatment of cancer are described. 2. The compound of claim 1 , wherein R claim 1 , R claim 1 , R claim 1 , R claim 1 , R claim 1 , R claim 1 , R claim 1 , R claim 1 , Rand Rare independently chosen from hydrogen claim 1 , hydroxy claim 1 , optionally substituted alkyl claim 1 , optionally substituted alkoxy claim 1 , optionally substituted aminocarbonyloxy claim 1 , optionally substituted acyloxy claim 1 , optionally substituted alkoxycarbonyloxy claim 1 , and optionally substituted amino.3. The compound of claim 2 , wherein R claim 2 , R claim 2 , R claim 2 , R claim 2 , R claim 2 , R claim 2 , R claim 2 , R claim 2 , Rand Rare independently chosen from hydrogen claim 2 , hydroxy claim 2 , and optionally substituted alkyl.4. (canceled)5. The compound of claim 1 , wherein Ris hydroxy.6. The compound of claim 1 , wherein Rand Rare joined together with any intervening atoms to form an optionally substituted 3- to 8-membered heterocycloalkyl ring.7. (canceled)8. The compound of claim 1 , wherein Ris chosen from hydrogen claim 1 , hydroxy claim 1 , optionally substituted alkoxy claim 1 , optionally substituted aminocarbonyloxy claim 1 , optionally substituted acyloxy claim 1 , optionally substituted alkoxycarbonyloxy claim 1 , and optionally substituted amino.9. (canceled)10. The compound of claim 1 , wherein Ris chosen from hydrogen and —OCOCH.11. The compound of claim 1 , wherein Rand Ware independently chosen from hydrogen and optionally substituted alkyl.12. (canceled)13. The compound of claim 1 , wherein Ris chosen from hydrogen claim 1 , methyl claim 1 , and hydroxymethyl.14. The compound of claim 1 , wherein Y is chosen from O claim 1 , NH and NCH.15. (canceled)16. The compound of claim 1 , wherein Ris chosen from cyano claim 1 , halo claim 1 , hydroxy claim 1 , carboxy claim 1 , sufonyl claim 1 , optionally substituted alkoxy claim 1 , optionally substituted alkoxycarbonyl ...

Neuroactive steroids, compositions, and uses thereof

Described herein are neuroactive steroids of the Formula (I): or a pharmaceutically acceptable salt thereof; wherein R 1 , R 2 , R a , G, X, Y, Z, and n are as defined herein. Such compounds are envisioned, in certain embodiments, to behave as GABA modulators. Also provided are pharmaceutical compositions comprising a compound described herein and methods of use and treatment, e.g., such for inducing sedation and/or anesthesia.

STEROIDAL COMPOUND, COMPOSITION CONTAINING THE SAME AND USE THEREOF

Disclosed are a steroidal compound as shown in formula (I) and a drug composition containing the same, or a crystal form, a pharmaceutically acceptable salt, a hydrate or solvate, a stereoisomer, a prodrug, a metabolite or an isotopic variant thereof. The compound can be used as a CYP17 enzyme inhibitor, and has better pharmacokinetic parameters, which can improve drug concentration of the compound in an animal, thereby improving the efficacy and safety of the drug, and in turn the compound may be applied in the preparation of the drug for treating CYP17 enzyme-related diseases (such as prostate cancer). 114-. (canceled)16. The compound according to claim 15 , wherein R claim 15 , R claim 15 , R claim 15 , and Rare each independently deuterium or hydrogen.17. The compound according to claim 15 , wherein at least one of R claim 15 , R claim 15 , R claim 15 , and Ris deuterium.18. The compound according to claim 15 , wherein R claim 15 , R claim 15 , R claim 15 , R claim 15 , R claim 15 , R claim 15 , R claim 15 , R claim 15 , R claim 15 , Rand Rare each independently deuterium or hydrogen.19. The compound according to claim 15 , wherein Ris deuterium.20. The compound according to claim 19 , wherein Y is an acetyl group substituted with three deuteriums.21. The compound according to claim 15 , wherein Xand Xare independently selected from a methyl or an ethyl group claim 15 , which are substituted with one or more deuteriums.22. The compound according to claim 15 , wherein Y is selected from hydrogen claim 15 , deuterium claim 15 , and an acetyl group substituted with one or more deuteriums.23. The compound according to claim 15 , wherein Xand Xare a methyl group substituted with three deuteriums.24. The compound according to claim 15 , wherein Y is an acetyl group substituted with three deuteriums.28. A pharmaceutical composition comprising:{'claim-ref': {'@idref': 'CLM-00015', 'claim 15'}, 'the compound according to or a pharmaceutically acceptable salt thereof; and ...

Compounds that are Analogs of Squalamine, Used as Antibacterial Agents

The invention relates to compounds of formula (I), to the pharmaceutical compositions comprising same, and to the use thereof in the treatment of bacterial, fungal, viral and parasitic infections or in the treatment of cancer in humans or animals. In formula (I), R1 and R2 are as defined in claim 1.

PROCEDURE FOR THE PREPARATION OF ABIRATERONE ACETATE AND INTERMEDIATES THEREOF

Disclosed is a process for the preparation of abiraterone and abiraterone acetate with high yields and purity. A key element of the method is the isolation of a crystalline intermediate that makes the process particularly suitable for implementation on an industrial scale. 1. The compound of formula (14). This non-provisional application is a continuation of U.S. Ser. No. 15/114,089, filed on Jul. 26, 2016, which is a U.S. National Stage of PCT/IB2015/050613, filed on 27 Jan. 2015, which claims priority to and the benefit of Italian Application No. MI2014A000111 filed on 28 Jan. 2014, the contents of which are all incorporated by reference in their entireties.The present invention relates to a process for the preparation of abiraterone and abiraterone acetate with high yields and purity. A key element of the process is the isolation of a crystalline intermediate that makes the process particularly suitable for implementation on an industrial scale.Abiraterone acetate, the chemical name of which is (3β)-17-(3-pyridinyl)androsta-5,16-dien-3-yl acetate of formula (1), is the prodrug of the active metabolite abiraterone (2), a selective inhibitor of enzyme CYP17.Abiraterone acetate forms the basis of the novel medicament Zytiga®, a tablet formulation containing 250 mg of active ingredient, which is administered orally at a single daily dose. When combined with prednisone or prednisolone it is indicated for the treatment of metastatic, castration-resistant prostate cancer in adult males in whom the disorder appears during or after a chemotherapy regimen based on docetaxel.Numerous processes are reported in the literature for the preparation of abiraterone or derivatives thereof. In most cases the starting product is prasterone (dehydroepiandrosterone).The preparation of abiraterone acetate was originally disclosed in EP0633893. Its synthesis involves conversion of the carbonyl at the 17 position of dehydroepiandrosterone-3-acetate (prasterone acetate, 3) to the ...

SELECTIVE GLUCOCORTICOID RECEPTOR LIGANDS

Described herein are certain steroid derivative compounds, for example of formula (I): wherein X, X, XL, and Ar are as defined herein, pharmaceutical compositions comprising such compounds, the use of such compounds and compositions to specifically target glucocorticoid action, and the use of such compounds and compositions in the treatment of acute and chronic inflammatory conditions, in particular rheumatoid arthritis, haematological and other malignancies, and for causing immunosuppression in the prevention or treatment of transplant rejection, as well as methods of preparing such compounds. 3. The compound of claim 1 , wherein Ar is independently selected from phenyl claim 1 , pyridinyl claim 1 , thiazolyl claim 1 , pyrrolyl claim 1 , furanyl claim 1 , benzothiazolyl claim 1 , and benzoxazolyl claim 1 , optionally substituted with one or more substituents R.4. The compound of claim 1 , wherein Ar is independently phenyl or pyridinyl claim 1 , optionally substituted with one or more substituents R.5. The compound of claim 1 , wherein Ris independently selected from —F claim 1 , —OMe claim 1 , and —COMe.6. The compound of claim 1 , wherein L is L.7. The compound of claim 1 , wherein Lis -L-O— claim 1 , wherein -L- is independently saturated Calkylene.8. The compound of claim 1 , wherein Lis —CHCH— or —CHCHCH—.9. The compound of wherein Ris —H.1112.-. (canceled)13. A method of treating a medical condition selected from an inflammatory condition claim 1 , a rheumatoid disease claim 1 , a malignancy claim 1 , a vascular disease or a lung disease claim 1 , comprising administering to a subject in need thereof a therapeutically effective amount of the compound of .14. The method of wherein treating the medical condition comprises one or more of (i) inducing apoptosis in target cells in the subject (ii) causing immunosuppression in the subject and (iii) preventing or treating transplant rejection in the subject.15. The method of wherein the medical condition is selected ...

NOVEL STEROIDAL CYP17 INHIBITORS/ANTIANDROGENS

Steroidal C-17 nitrogen-containing heterocycles of Formula I: 2. The compound of claim 1 , wherein each position of the ABC ring structure is independently optionally substituted with one or more of alkyl claim 1 , halogenated alkyl claim 1 , alkenyl claim 1 , halogenated alkenyl claim 1 , halogen claim 1 , amino claim 1 , aminoalkylene claim 1 , hydroxyimino claim 1 , and hydroxy.3. The compound of claim 2 , wherein X is optionally substituted with one or more of halogen claim 2 , amino claim 2 , aminoalkylene claim 2 , hydroxy claim 2 , —SH claim 2 , —S-alkyl claim 2 , alkyl and halogenated C-C-alkyl.4. The compound of claim 3 , wherein Y is OH.6. The compound of claim 3 , wherein Y is a physiological precursor of a 3-hydroxyl group.7. The compound of claim 6 , wherein Y is O-acetyl claim 6 , O-propionyl claim 6 , O-betaine claim 6 , O-carnitine claim 6 , an amino acid group claim 6 , or a peptidyl group.10. The compound of claim 9 , wherein the EF group is 1-azaazulene claim 9 , 2-alkylindazole claim 9 , pyrazolo-[1 claim 9 ,5-a]-pyridine claim 9 , imidazo-[1 claim 9 ,2-a]-pyridine claim 9 , pyrrolo-[2 claim 9 ,3-a]-pyrimidine claim 9 , pyrrolo-[2 claim 9 ,3-c]-pyrimidine claim 9 , imidazo-[1 claim 9 ,2-c]-pyrimidine claim 9 , imidazo-[1 claim 9 ,2-a]-pyrimidines4-alkylpyrazolo-[1 claim 9 ,5-a]imidazole claim 9 , 2 claim 9 ,1-benzoxazoles claim 9 , 2 claim 9 ,1-benzthiazole claim 9 , imidazo[2 claim 9 ,1-b][1 claim 9 ,3]oxazole claim 9 , imidazo[2 claim 9 ,1-b][1 claim 9 ,3]thiazole claim 9 , imidazo-[2 claim 9 ,1-b][1 claim 9 ,2]isoxazole claim 9 , or cyclopenta[b]pyrrole claim 9 , any of which is optionally substituted with halogen claim 9 , amino claim 9 , aminoalkylene claim 9 , hydroxy claim 9 , —SH claim 9 , —S-alkyl claim 9 , alkyl and halogenated C-C-alkyl.11. A pharmaceutical composition comprising a therapeutically-effective amount of one or more compounds of and one or more pharmaceutically-acceptable excipients claim 1 , bulking agents claim 1 , ...

BIMODAL LIGANDS WITH MACROCYCLIC AND ACYCLIC BINDING MOIETIES, COMPLEXES AND COMPOSITIONS THEREOF, AND METHODS OF USING

Substituted 1,4,7-triazacyclononane-N,N′,N″-triacetic acid and 1,4,7,10-tetraazacycicododecane-N,N′,N″,N′″-tetraacetic acid compounds with a pendant amino or hydroxyl group, metal complexes thereof, compositions thereof, and methods of making and use in diagnostic imaging and treatment of cellular disorders. 2. A complex comprising the compound of and a metal ion claim 1 , a radioactive isotope of the metal ion claim 1 , or a radioactive isotope of carbon claim 1 , nitrogen claim 1 , iodine claim 1 , fluorine claim 1 , oxygen claim 1 , or helium.3. A conjugate comprising the complex of and a targeting moiety claim 2 , a fluorescence moiety claim 2 , or a nanoparticle.4. The complex of claim 2 , wherein the metal ion is selected from the group consisting of Ac claim 2 , Al claim 2 , Bi claim 2 , Pb claim 2 , Y claim 2 , Mn claim 2 , Cr claim 2 , Fe claim 2 , Co claim 2 , Zn claim 2 , Ni claim 2 , Tc claim 2 , Gd claim 2 , In claim 2 , Ga claim 2 , Cu claim 2 , Re claim 2 , Sm claim 2 , Pm claim 2 , Ho claim 2 , Zr claim 2 , Ra claim 2 , Sr claim 2 , Cs claim 2 , Th claim 2 , Am claim 2 , U claim 2 , an alkali metal claim 2 , an alkaline earth metal claim 2 , a transition metal claim 2 , a lanthanide claim 2 , and an actinide.5. A conjugate comprising the complex of and a targeting moiety claim 4 , a fluorescence moiety claim 4 , or a nanoparticle.6. A conjugate comprising the compound of and a targeting moiety claim 1 , a fluorescence moiety claim 1 , a ligand claim 1 , or a nanoparticle.7. The conjugate according to claim 6 , comprising the targeting moiety claim 6 , wherein the targeting moiety comprises a biomolecule selected from a hormone claim 6 , a bile acid claim 6 , an amino acid claim 6 , a peptide claim 6 , a peptidomimetic claim 6 , a protein claim 6 , a deoxyribonucleic acid (DNA) claim 6 , a ribonucleic acid (RNA) claim 6 , a lipid claim 6 , an albumin claim 6 , a receptor molecule claim 6 , a receptor binding molecule claim 6 , a hapten claim 6 , a ...

Progesterone analogs and uses related thereto

This disclosure relates to progesterone derivatives and uses related thereto. In certain embodiments, the disclosure relates to compounds disclosed herein and uses for managing inflammation resulting from traumatic brain injury or stroke.

PROCESS FOR THE PURIFICATION OF ABIRATERONE ACETATE

The invention relates to a process for the purification of crude abiraterone acetate by treatment with polymer resins in aqueous solvent. The purified product is recovered by simple concentration and filtration. 1. A process for the purification of abiraterone acetate starting from crude products , which comprisespreparing a solution of the crude product, adsorbing it on a polymer resin andeluting abiraterone acetate from the resin using a mixture of water/aqueous buffer and a polar solvent as eluent.2. A process according to wherein the polymer resin is a resin suitable for hydrophobic interaction chromatography.3. A process according to wherein the resins are selected from resins with an acrylic or styrene-divinyl benzene matrix free from functional groups.4. A process according to wherein the resin has a particle size distribution ranging from 50 to 600 μm claim 2 , preferably from 60 to 200 μm.5. A process according to wherein the crude abiraterone acetate is dissolved in methanol claim 1 , ethanol claim 1 , isopropanol claim 1 , n-propanol claim 1 , acetonitrile claim 1 , dimethylsulphoxide claim 1 , tetrahydrofuran or acetone or in a mixture of said solvents with water.6. A process according to wherein the eluent used for eluting the resin is a mixture of water or aqueous buffering agents with one or more solvents selected from methanol claim 1 , isopropanol claim 1 , ethanol claim 1 , acetonitrile claim 1 , acetone or a mixture thereof.7. A process according to wherein the isocratic or gradient elution is carried out with mixtures with increasing solvent concentrations.8. (canceled) The invention relates to a process for the purification of crude abiraterone acetate by treatment with polymer resins in aqueous solvent. The purified product is recovered by simple concentration and filtration.Abiraterone acetate, the chemical name of which is (3β)-17-(3-pyridinyl)androsta-5,16-dien-3-yl acetate, is the prodrug of the active metabolite abiraterone, a selective ...

Radiolabeled cationic steroid antimicrobials and diagnostic methods

The disclosure provides compounds, methods, and kits for diagnosis, detection, screening, and imaging of a disease condition (e.g., infection, cancer, tumor, neoplasia), in vitro, ex vivo, and/or in vivo. Certain embodiments include administering a cationic steroid antimicrobial “CSA” or “ceragenin”), the CSA including a steroidal backbone and a heterocyclic ring separated from the steroidal backbone by at least 4 atoms (and up to 24 atoms or more), to a subject having or at risk of having a disease condition in an amount effective to diagnose, detect, screen for or image the disease condition in the subject.

CYCLIN-DEPENDENT KINASE DEGRADERS AND METHODS OF USE

The present application provides bifunctional compounds of Formula (Ia): (Ia), or an enantiomer, diastereomer, stereoisomer, or pharmaceutically acceptable salt thereof, which act as protein degradation inducing moieties for one or mor of cyclin-dependent kinase 8 (CDK8) and cyclin-dependent kinase 19 (CDK19). The present application also relates to methods for the targeted degradation of CDK8 and/or CDK19 through the use of the bifumtional compounds that link a ubiquitin ligase-binding moiety to a ligand that is capable of binding to CDK8 and/or CDK19 which can be utilized in the treatment of disorders modulated by CDK8 and/or CDK19. 45.-. (canceled)7. (canceled)8. The bifunctional compound of claim 2 , wherein X is —O— claim 2 , —NR— claim 2 , or -Het- claim 2 , wherein{'sub': '5', 'Ris methyl and'}{'sub': '2', 'Hetis selected from aziridine, azetidine, pyrrolidine, dihydropyrrole, piperidine, piperazine, dihydropyridine, tetrahydropyridine, azepane, oxaziridine, oxazetidine, isoxazoline, isoxazolidine, oxazoline, oxazolidine, thiazoline, thiazolidine, isothiazoline, isothiazolidine, pyrazoline, pyrazolidine, imidazoline, imidazolidine, morpholine, oxazinane, thiomorpholine, thiazinane, and triazole.'}913.-. (canceled)14. The bifunctional compound of claim 8 , wherein Hetis morpholine claim 8 , or iperazine.1516.-. (canceled)17. The bifunctional compound of claim 2 , wherein Hetis 6-isoquinolinyl claim 2 , 7-isoquinolinyl claim 2 , 6-quinazolinyl claim 2 , 6-phthalazinyl claim 2 , 6-indazolyl claim 2 , 6-indazolyl-3-amine claim 2 , or 5-indazolyl.18. (canceled)2023.-. (canceled)25. The bifunctional compound of claim 24 , whereinp2 is 0,p3 is 2,each W is O,{'sub': '3', 'Zis C(O), and'}Q is absent.27. (canceled)29. The bifunctional compound of claim 28 , wherein{'sub': 1', '2', '1', '2', '1', '2', '2, 'at least one of Zand Z is C(O), or wherein Zis C(O), or wherein Zand Zare each is C(O), or wherein Zis C(O) and Zis CH.'}3032.-. (canceled)33. The bifunctional ...

19-NOR NEUROACTIVE STEROIDS AND METHODS OF USE THEREOF

Provided herein are 3,3-disubstituted 19-nor-steroidal compounds according to Formula (1): and pharmaceutical compositions thereof. Such compounds are contemplated useful for the prevention and treatment of a variety of CNS-related conditions, for example, treatment of sleep disorders, mood disorders, schizophrenia spectrum disorders, disorders of memory and/or cognition, movement disorders, personality disorders, autism spectrum disorders, pain,traumatic brain injury, vascular diseases, substance abuse disorders and/or withdrawal syndromes, tinnitus, and status epilepticus. 141-. (canceled)60. The method of claim 42 , wherein the method is a method of treating a sleep disorder.61. The method of claim 60 , wherein the sleep disorder is insomnia.62. The method of claim 42 , wherein the method is a method of treating a mood disorder.63. The method of claim 42 , wherein the mood disorder is depression.64. The method of claim 63 , wherein the depression is postnatal depression.65. The method of claim 64 , wherein the compound or pharmaceutical composition is administered orally. Brain excitability is defined as the level of arousal of an animal, a continuum that ranges from coma to convulsions, and is regulated by various neurotransmitters. In general, neurotransmitters are responsible for regulating the conductance of ions across neuronal membranes. At rest, the neuronal membrane possesses a potential (or membrane voltage) of approximately −70 mV, the cell interior being negative with respect to the cell exterior. The potential (voltage) is the result of ion (K, Na, organic anions) balance across the neuronal semipermeable membrane. Neurotransmitters are stored in presynaptic vesicles and are released under the influence of neuronal action potentials. When released into the synaptic cleft, an excitatory chemical transmitter such as acetylcholine will cause membrane depolarization (change of potential from −70 mV to −50 mV). This effect is mediated by postsynaptic ...

19-NOR NEUROACTIVE STEROIDS AND METHODS OF USE THEREOF

Provided herein are 3,3-disubstituted 19-nor-steroidal compounds according to Formula (1): and pharmaceutical compositions thereof. Such compounds are contemplated useful for the prevention and treatment of a variety of CNS-related conditions, for example, treatment of sleep disorders, mood disorders, schizophrenia spectrum disorders, disorders of memory and/or cognition, movement disorders, personality disorders, autism spectrum disorders, pain, traumatic brain injury, vascular diseases, substance abuse disorders and/or withdrawal syndromes, tinnitus, and status epilepticus. 237-. (canceled)39. The method of claim 38 , wherein the CNS-related disorder is a sleep disorder claim 38 , a mood disorder claim 38 , a schizophrenia spectrum disorder claim 38 , a convulsive disorder claim 38 , a disorder of memory and/or cognition claim 38 , a movement disorder claim 38 , a personality disorder claim 38 , autism spectrum disorder claim 38 , pain claim 38 , traumatic brain injury claim 38 , a vascular disease claim 38 , a substance abuse disorder and/or withdrawal syndrome claim 38 , tinnitus claim 38 , or status epilepticus.40. The method of or wherein the compound is administered orally claim 38 , subcutaneously claim 38 , intravenously claim 38 , or intramuscularly.41. The method of or wherein the compound is administered chronically. Brain excitability is defined as the level of arousal of an animal, a continuum that ranges from coma to convulsions, and is regulated by various neurotransmitters. In general, neurotransmitters are responsible for regulating the conductance of ions across neuronal membranes. At rest, the neuronal membrane possesses a potential (or membrane voltage) of approximately −70 mV, the cell interior being negative with respect to the cell exterior. The potential (voltage) is the result of ion (K, Na, Cl, organic anions) balance across the neuronal semipermeable membrane.Neurotransmitters are stored in presynaptic vesicles and are released under the ...

PROCESS FOR ABIRATERONE ACETATE

The present invention provides a novel process for the preparation of abiraterone. The present invention also provides a novel process for the preparation of abiraterone acetate. 1. A process for the preparation of abiraterone , which comprises:a) reacting dehydroepiandrosterone-3-acetate in a chlorinated solvent with trifluoromethanesulfonic anhydride in the presence of a base selected from the group consisting of n-methylpyrrolidone, N-methylpiperidine or tetramethylethylenediamine in a chlorinated solvent;b) concentrating the reaction mass to obtain a residual mass;c) reacting the residual mass obtained in step (b) in an ether solvent with diethyl(3-pyridyl)borane in the presence of bis(triphenylphosphine)pailadium(II) chloride;d) adding a base and water to the reaction mass;e) concentrating the reaction mass to obtain a residual mass;f) adding a base and an alcoholic solvent to the residual mass obtained in step);g) adding water to the reaction mass;h) pH of the reaction mass was adjusted with hydrochloric acid;i) adding chlorinated solvent to the reaction mass;j) removing the solvent from the reaction mass to obtain a residual solid;k) slurring the residual solid obtained in step (j) with a hydrocarbon solvent; andl) isolating the abiraterone.2. The process as claimed in claim 1 , wherein the chlorinated solvent used in step (a) and (i) is a solvent or a mixture of solvents selected from methylene chloride claim 1 , chloroform claim 1 , carbontetrachloride and ethylene dichloride.3. The process as claimed in claim 1 , wherein the ether solvent used in step (c) is a solvent or a mixture of solvents selected from tetrahydrofuran claim 1 , methyl tetrahydrofuran claim 1 , methyl tert-butyl ether claim 1 , ethyl tert-butyl ether claim 1 , 1 claim 1 ,4-dioxane claim 1 , diisopropyl ether claim 1 , diethyl ether and tetrahydropyran.4. The process as claimed in claim 1 , wherein the base used in step (d) and (f) is organic base or inorganic base.5. The process as ...

Conjugate of Estradiol and Applications Thereof

The present invention relates to conjugate of 17-β estradiol with an analogue of indocyanine green dye for the detection of cancers. The invention also provides a method of preparation of the conjugate and method of detection of cancer cells.

FLUORINATED BILE ACIDS

Compounds of general formula (1): 2. (canceled)4. A compound according to which is a compound of general formula (IA).5. A compound according to which is a compound of general formula (IB).6. A compound according to claim 1 , wherein both Rand Rare F.7. (canceled)8. A compound according to claim 1 , wherein Y is —CHCH—.9. (canceled)10. A compound according to claim 1 , wherein{'sup': ['12', '16', '10', '11'], '#text': 'Ris selected from H methyl, and ethyl, and is optionally substituted with Ror N(R)(R); or'}{'sup': ['3', '12', '13', '12', '13', '12', '15', '16', '12', '12', '15', '16', '12'], 'sub': ['2', '2', 'n', '2', 'n'], '#text': 'Ris selected from C(O)NRS(O)R, NHC(O)NRS(O)R, C(O)NR[CH(R)]R, and C(O)NRC(O)CHNR[CH(R)]R; and Ris H or methyl; and/or'}{'sup': ['13', '16', '13', '16'], '#text': 'Ris a 5- or 6-membered carbocyclic ring or heterocyclic ring optionally substituted with Ror ═O; or Ris phenyl optionally substituted with R; or'}{'sup': ['3', '12', '13', '12', '13', '12', '13', '16'], 'sub': '2', '#text': 'Ris selected from C(O)NRRand S(O)NRRand Rand Rtogether with the nitrogen atom to which they are attached form a 5- or 6-membered heterocyclic ring optionally substituted with one or more substituents selected from Rand ═O and optionally comprising one or more further heteroatoms selected from O, N and S; and/or'}{'sup': '16', 'sub': ['2', '2', '1-6', '2'], '#text': 'Ris selected from C(O)OH, S(O)OH, S(O)(Calkyl), and OS(O)OH; or'}{'sup': '16', 'sub': ['2', '2', '2'], '#text': 'Ris selected from C(O)OH, S(O)OH, OS(O)OH and P(O)(OH), and the compound is in the form of a pharmaceutically acceptable salt.'}1112-. (canceled)13. A compound according to wherein Ris C(O)NR[CH(R)]Ror a pharmaceutically acceptable salt thereof claim 1 ,{'sup': ['12', '16'], '#text': 'wherein Ris H, methyl or methyl substituted with R;'}{'sup': '16', 'sub': ['2', '2', '1-6', '2'], '#text': 'where Ris C(O)OH, S(O)OH, S(O)(Calkyl) or OS(O)OH.'}1415-. (canceled)16. A compound ...

ORGANIC COMPOUNDS

The invention relates to particular prodrugs and analogs of (3α,5α)-3-hydroxy-21-(1H-imidazol-1-yl)-3-methoxymethyl)-pregnan-20-one, in free or pharmaceutically acceptable salt and/or substantially pure form as described herein, pharmaceutical compositions thereof, and methods of use as sedatives, hypnotics, anxiolytics, and/or anesthetics, and methods for treatment of depression, anxiety, insomnia, epilepsy, and other central nervous system disorders, as well as to combinations with other agents. 2. A compound according to claim 1 , wherein X is H.3. A compound according to claim 1 , wherein X is selected from —(C═O)—R claim 1 , —CH—(C═O)—O—R claim 1 , and —CH—(C═O)—N(R)(R).4. A compound according to claim 1 , wherein X is —(C═O)—R.5. A compound according to claim 1 , wherein X is —CH—(C═O)—O—R.6. A compound according to claim 1 , wherein X is CH—(C═O)—N(R)(R).7. A compound according to claim 1 , wherein X is CH—(C═O)—N(R)(R) and Ris H.8. A compound according to claim 1 , wherein Ris CH.9. A compound according to claim 1 , wherein Ris CD.10. A compound according to claim 1 , wherein any one or two or three or four of Rto Ris D.11. A compound according to claim 1 , wherein Rand Rare D.12. A compound according to claim 1 , wherein Rto Rare D.13. A compound according to claim 1 , wherein any one claim 1 , two or three of Rto Rare D.15. A compound according to claim 1 , in the salt form claim 1 , e.g. claim 1 , in the form of a pharmaceutically acceptable salt.16. A compound according to claim 1 , having greater than 50% incorporation of deuterium at one or more of the indicated positions of the structure (i.e. claim 1 , greater than 50 atom % D) claim 1 , e.g. claim 1 , greater than 60% claim 1 , or greater than 70% claim 1 , or greater than 80% claim 1 , or greater than 90% or greater than 95% claim 1 , or greater than 96% claim 1 , or greater than 97% claim 1 , or greater than 98% claim 1 , or greater than 99%.17. A pharmaceutical composition comprising a compound ...

NEUROACTIVE STEROIDS, COMPOSITIONS, AND USES THEREOF

Described herein are neuroactive steroids of the Formula (I): or a pharmaceutically acceptable salt thereof; wherein -------, R, R, R, A and L are as defined herein. Such compounds are envisioned, in certain embodiments, to behave as GABA modulators. The present invention also provides pharmaceutical compositions comprising a compound of the present invention and methods of use and treatment, e.g., such for inducing sedation and/or anesthesia. 190-. (canceled)92. The compound of claim 91 , wherein each is a single bond and Ris hydrogen.93. The compound of claim 92 , wherein Ris methyl claim 92 , ethyl claim 92 , or isopropyl claim 92 , each of which is unsubstituted.94. The compound of claim 93 , wherein Ris unsubstituted methyl or unsubstituted ethyl.95. The compound of claim 91 , wherein Ris unsubstituted Calkyl.96. The compound of claim 91 , wherein Ris methyl or —CF.99. The compound of claim 91 , wherein ring A is an optionally substituted 5-membered or 6-membered monocyclic heteroaryl claim 91 , wherein the heteroaryl of ring A comprises 2 claim 91 , 3 claim 91 , or 4 nitrogen atoms and wherein the heteroaryl of ring A is linked through a nitrogen atom.103. The compound of claim 100 , wherein n is 1 or 2 claim 100 , and each Ris independently cyano claim 100 , halo claim 100 , Calkyl claim 100 , Calkoxy claim 100 , —C(O)R claim 100 , or —S(O)R.104. The compound of claim 103 , wherein n is 1 claim 103 , and Ris —C(O)CH claim 103 , —S(O)CH claim 103 , cyano claim 103 , halo claim 103 , or Calkyl.108. The compound of claim 105 , wherein n is 1 or 2 claim 105 , and each Ris independently cyano claim 105 , halo claim 105 , Calkyl claim 105 , Calkoxy claim 105 , —C(O)R claim 105 , or —S(O)R.109. The compound of claim 108 , wherein n is 1 claim 108 , and Ris —C(O)CH claim 108 , —S(O)CH claim 108 , cyano claim 108 , halo claim 108 , or Calkyl.113. The compound of claim 110 , wherein n is 1 or 2 claim 110 , and each Ris independently cyano claim 110 , halo claim 110 , ...

NEUROACTIVE STEROIDS, COMPOSITIONS, AND USES THEREOF

Provided herein are 19-nor C3,3-disubstituted steroids of Formula (I): 134-. (canceled)36. The method of claim 35 , wherein step (a) is performed at a temperature of about 60° C.38. The method of any one of - claim 35 , wherein the solvent of step (a) is THF.41. The method of claim 39 , wherein the solvent system comprises CHClsaturated with water.42. The method of or claim 39 , wherein the reaction of step (d) is performed under stirring conditions.44. The method of claim 43 , wherein the solvent of step (e) is DMSO.45. The method of or claim 43 , wherein step (e) is performed under stirring conditions at room temperature.47. The method of claim 46 , wherein the HCl of step (f) is reacted at a concentration of 2M.48. The method of or claim 46 , wherein step (f) is performed under stirring conditions for about 12 hours.49. The method of any one of - claim 46 , wherein step (f) is performed at room temperature.51. The method of claim 50 , wherein step (g) is performed in the presence of NaOH.52. The method of claim 51 , wherein the NaOH is provided as about 10% aqueous NaOH.53. The method of or claim 51 , wherein step (g) is performed in the presence of HO.54. The method of claim 53 , wherein the HOis provided as an about 30% aqueous solution of HO.56. The method of claim 55 , wherein step (a) is performed at a temperature of about 60° C.; and the solvent of step (a) is THF. This application is a continuation of U.S. Ser. No. 15/314,565 filed Nov. 29, 2016, which is a national stage application under 35 U.S.C. § 371 of International Application No. PCT/CN2015/080216, filed May 29, 2015, published as International Publication No. WO2015/180679 on Dec. 3, 2015, which claims priority to international application No. PCT/CN2014/078820, filed May 29, 2014, the entire contents of each of which are incorporated herein by reference in their entirety.Brain excitability is defined as the level of arousal of an animal, a continuum that ranges from coma to convulsions, and is ...

NEUROACTIVE STERIODS, COMPOSITIONS, AND USES THEREOF

Provided herein are 19-nor C3,3-disubstituted steroids of Formula (I): 134-. (canceled) This application is a continuation of U.S. Ser. No. 15/314,565 filed Nov. 29, 2016, which is a national stage application under 35 U.S.C. § 371 of International Application No. PCT/CN2015/080216, filed May 29, 2015, published as International Publication No. WO2015/180679 on Dec. 3, 2015, which claims priority to international application No. PCT/CN2014/078820, filed May 29, 2014, the entire contents of each of which are incorporated herein by reference in their entirety.Brain excitability is defined as the level of arousal of an animal, a continuum that ranges from coma to convulsions, and is regulated by various neurotransmitters. In general, neurotransmitters are responsible for regulating the conductance of ions across neuronal membranes. At rest, the neuronal membrane possesses a potential (or membrane voltage) of approximately −70 mV, the cell interior being negative with respect to the cell exterior. The potential (voltage) is the result of ion (K, Na, Cl, organic anions) balance across the neuronal semipermeable membrane. Neurotransmitters are stored in presynaptic vesicles and are released under the influence of neuronal action potentials. When released into the synaptic cleft, an excitatory chemical transmitter such as acetylcholine will cause membrane depolarization (change of potential from −70 mV to −50 mV). This effect is mediated by postsynaptic nicotinic receptors which are stimulated by acetylcholine to increase membrane permeability to Na ions. The reduced membrane potential stimulates neuronal excitability in the form of a postsynaptic action potential.In the case of the GABA receptor complex (GRC), the effect on brain excitability is mediated by GABA, a neurotransmitter. GABA has a profound influence on overall brain excitability because up to 40% of the neurons in the brain utilize GABA as a neurotransmitter. GABA regulates the excitability of individual ...

SULFATED OLIGOSACCHARIDE DERIVATIVES

The invention relates to novel compounds that have utility as inhibitors of heparan sulfate-binding proteins; compositions comprising the compounds, and use of the compounds and compositions thereof for the antiangiogenic, antimetastatic, anti-inflammatory, antimicrobial, anticoagulant and/or antithrombotic treatment of a mammalian subject. 2. The pharmaceutical or veterinary composition according to claim 1 , wherein in said at least one compound Ris cholestanyl.3. The pharmaceutical or veterinary composition according to claim 1 , wherein in said at least one compound Ris propylstearamide.4. The pharmaceutical or veterinary composition according to claim 1 , wherein said at least one compound is selected from the group consisting of:{'smallcaps': D', 'D', 'D', 'D, '3β-cholestanyl-2,3,4,6-tetra-O-sodium sulfonato-α--glucopyranosyl-(1→4)-2,3,6-tri-O-sodium sulfonato-α--glucopyranosyl-(1→4)-2,3,6-tri-O-sodium sulfonato-α--glucopyranosyl-(1→4)-2,3,6-tri-O-sodium sulfonato-β--glucopyranoside (compound 65);'}{'smallcaps': D', 'D', 'D, '4-(cholestan-3β-yl-oxymethyl)[1,2,3]triazol-1-yl-2,3,4,6-tetra-O-sodium sulfonato-α--glucopyranosyl-(1→4)-2,3,6-tri-O-sodium sulfonato-α--glucopyranosyl-(1→4)-1-deoxy-2,3,6-tri-O-sodium sulfonato-β--glucopyranoside (compound 70);'}{'smallcaps': D', 'D', 'D, '4-(cholestan-3β-yl-oxymethyl)[1,2,3]triazol-1-yl-2,3,4,6-tetra-O-sodium sulfonato-α--glucopyranosyl-(1→4)-2,3,6-tri-O-sodium sulfonato-α--glucopyranosyl-(1→4)-1-deoxy-2,3,6-tri-O-sodium sulfonato-β--glucopyranoside (compound 76);'}{'smallcaps': D', 'D', 'D, '3β-cholestanyl-2,3,4,6-tetra-O-sodium sulfonato-α--glucopyranosyl-(1→4)-2,3,6-tri-O-sodium sulfonato-α--glucopyranosyl-(1→4)-2,3,6-tri-O-sodium sulfonato-β--glucopyranoside (compound 87);'}{'smallcaps': D', 'D', 'D, '3-stearamidopropyl-2,3,4,6-tetra-O-sulfo-α--glucopyranosyl-(1→4)-2,3,6-tri-O-sulfo-α--glucopyranosyl-(1→4)-2,3,6-tri-O-sulfo-β--glucopyranoside, decasodium salt (compound 123); and'}{'smallcaps': D', 'D', 'D', 'D, '3- ...

CERTAIN CHEMICAL ENTITIES, COMPOSITIONS, AND METHODS

Chemical entities that are bufalin derivatives, pharmaceutical compositions and methods of treatment of cancer are described. 2. At least one chemical entity of wherein Z is OR.3. At least one chemical entity of wherein Ris chosen from optionally substituted alkyl claim 2 , optionally substituted cycloalkyl claim 2 , and optionally substituted heterocycloalkyl.4. At least one chemical entity of wherein Z is NRR.5. At least one chemical entity of wherein Ris chosen from hydrogen claim 4 , optionally substituted alkyl claim 4 , optionally substituted cycloalkyl claim 4 , and optionally substituted heterocycloalkyl claim 4 , and Ris chosen from optionally substituted alkyl claim 4 , optionally substituted cycloalkyl claim 4 , and optionally substituted heterocycloalkyl.6. At least one chemical entity of wherein Ris hydrogen and Ris chosen from optionally substituted alkyl.7. At least one chemical entity of wherein Rand Rare joined together to form a 5- to 7-membered heterocycloalkyl ring.8. At least one chemical entity chosen from compounds I-a-I-f and pharmaceutically acceptable salts thereof.10. At least one chemical entity of wherein Rand Rare each independently chosen from hydrogen and optionally substituted lower alkyl.11. At least one chemical entity of wherein Rand Rare both hydrogen.12. At least one chemical entity of wherein Rand Rare joined together to form a 5- to 7-membered heterocycloalkyl ring.13. At least one chemical entity of any one of to wherein Rand Rare each independently chosen from hydrogen and optionally substituted lower alkyl.14. At least one chemical entity of any one of to wherein n is chosen from 1 claim 9 , 2 claim 9 , and 3.15. At least one chemical entity of wherein n is 1 claim 9 , and Rand Rare joined together to form a 5- to 7-membered heterocycloalkyl ring.16. At least one chemical entity chosen from compounds II-a-II-h and pharmaceutically acceptable salts thereof.18. At least one chemical entity of wherein Ris chosen from hydrogen ...

19-NOR NEUROACTIVE STEROIDS AND METHODS OF USE THEREOF

Provided herein are 3,3-disubstituted 19-nor-steroidal compounds according to Formula (I): and pharmaceutical compositions thereof. Such compounds are contemplated useful for the prevention and treatment of a variety of CNS-related conditions, for example, treatment of sleep disorders, mood disorders, schizophrenia spectrum disorders, disorders of memory and/or cognition, movement disorders, personality disorders, autism spectrum disorders, pain, traumatic brain injury, vascular diseases, substance abuse disorders and/or withdrawal syndromes, tinnitus, status epilepticus. 6. The compound of claim 5 , wherein Ris substituted or unsubstituted hydrogen claim 5 , substituted or unsubstituted Calkyl claim 5 , —C(═O)R claim 5 , —C(═O)OR claim 5 , —C(═O)N(R) claim 5 , or —S(═O)R.9. The compound of claim 1 , wherein e is 1.10. The compound of claim 1 , wherein Ris substituted or unsubstituted Calkyl.11. The compound of claim 1 , wherein Ris —CH.12. The compound of claim 1 , wherein Ris ORwherein Ris hydrogen or substituted or unsubstituted Calkyl.13. The compound of claim 1 , wherein Ris OH.14. The compound of claim 1 , wherein Ris —S(═O)Rwherein Ris substituted or unsubstituted Calkyl.15. The compound of claim 1 , wherein Ris —S(═O)CH.16. The compound of claim 1 , wherein Ris —C(═O)Rwherein Ris substituted or unsubstituted Calkyl.17. The compound of claim 1 , wherein Ris —C(═O)CH.18. The compound of claim 1 , wherein Ris —C(═O)N(R)wherein Ris hydrogen or substituted or unsubstituted Calkyl.19. The compound of claim 1 , wherein Ris —C(═O)NHCH.20. The compound of claim 1 , wherein between C5 and C6 is a double bond and Ris absent.21. The compound of claim 1 , wherein between C5 and C6 is a single bond.23. A pharmaceutical composition comprising a pharmaceutically acceptable carrier and a compound of claim 1 , or a pharmaceutically acceptable salt thereof.24. A method for treating a CNS-related disorder in a subject in need thereof claim 1 , comprising administering to the ...

NOVEL 17B-HETEROARYL-SUBSTITUTED STEROIDS AS MODULATORS OF GABAA RECEPTORS

The invention is directed to novel 17β-heteroaryl substituted steroids of Formula I, pharmaceutical compositions thereof, and their use as modulators of GABAreceptors. 1518-. (canceled)19. A compound of claim 1 , wherein R claim 1 , R claim 1 , R claim 1 , R claim 1 , R claim 1 , R claim 1 , R claim 1 , R claim 1 , R claim 1 , and Rare hydrogen claim 1 , Ris selected from the group Calkyl claim 1 , and Chaloalkyl; each Ris independently hydrogen claim 1 , halogen claim 1 , optionally substituted Calkyl claim 1 , and Chaloalkyl; C1 to C2 claim 1 , C4 to C5 claim 1 , and C11 to C12 are single bonds claim 1 , or a pharmaceutically acceptable salts claim 1 , solvates claim 1 , or prodrugs thereof.2021-. (canceled)22. A compound of wherein R claim 1 , R claim 1 , R claim 1 , R claim 1 , R claim 1 , R claim 1 , R claim 1 , R claim 1 , R claim 1 , and Rare hydrogen; Ris selected from the group consisting of Calkyl claim 1 , Calkenyl claim 1 , Calkynyl claim 1 , and Chaloalkyl; Ris hydrogen or methyl; each Ris independently hydrogen claim 1 , halogen claim 1 , Calkyl claim 1 , optionally substituted with hydroxy claim 1 , and halogen; HET is selected from the group consisting of 5-isoxazolyl claim 1 , 3-isoxazolyl claim 1 , 2-oxazolyl claim 1 , 4-oxazolyl and 5-oxazolyl claim 1 , all optionally substituted with 1 to 2 Rgroups; C1 to C2 claim 1 , C4 to C5 claim 1 , and C11 to C12 are single bonds claim 1 , a*d or a pharmaceutically acceptable salts claim 1 , solvates claim 1 , or prodrugs thereof.23. A compound of wherein Ris methyl; Ris a 5α-hydrogen atom; Ris methyl; each Ris independently hydrogen claim 22 , Calkyl and hydroxymethyl; or a pharmaceutically acceptable salts claim 22 , solvates claim 22 , or prodrugs thereof.24. A compound of wherein R claim 1 , R claim 1 , R claim 1 , R claim 1 , R claim 1 , R claim 1 , R claim 1 , R claim 1 , R claim 1 , and Rare hydrogen; Ris selected from the group consisting of Calkyl claim 1 , Calkenyl claim 1 , Calkynyl claim 1 , and ...

METHODS TO INDUCE TARGETED PROTEIN DEGRADATION THROUGH BIFUNCTIONAL MOLECULES

The present application provides bifunctional compounds which act as protein degradation inducing moieties. The present application also relates to methods for the targeted degradation of endogenous proteins through the use of the bifunctional compounds that link a cereblon-binding moiety to a ligand that is capable of binding to the targeted protein which can be utilized in the treatment of proliferative disorders. The present application also provides methods for making compounds of the application and intermediates thereof. 6. The compound of claim 5 , wherein n is 0 claim 5 , Ris H claim 5 , each Ris H claim 5 , and two R claim 5 , together with the carbon atom to which they are attached claim 5 , form C(O).7. The compound of claim 6 , wherein X is C(O).8. The compound of claim 7 , wherein Y is a O claim 7 , NH claim 7 , or NR claim 7 ,10. The compound of claim 9 , wherein n is 0 claim 9 , Ris H claim 9 , each Ris H claim 9 , and two R claim 9 , together with the carbon atom to which they are attached claim 9 , form C(O).11. The compound of claim 10 , wherein X is C(O).12. The compound of claim 2 , wherein n is 0 claim 2 , Ris H claim 2 , each Ris H claim 2 , and two R claim 2 , together with the carbon atom to which they are attached claim 2 , form C(O).14. The compound of claim 13 , wherein n is 0 claim 13 , Ris H claim 13 , and two R claim 13 , together with the carbon atom to which they are attached claim 13 , form C(O).15. The compound of claim 14 , wherein X—Xis C(R)═N.17. The compound of claim 16 , wherein n is 0 claim 16 , Ris H claim 16 , and two R claim 16 , together with the carbon atom to which they are attached claim 16 , form C(O).18. The compound of claim 17 , wherein X—Xis C(R)═N.19. A pharmaceutical composition comprising a therapeutically effective amount of a compound of claim 1 , or an enantiomer claim 1 , diastereomer claim 1 , stereoisomer claim 1 , or pharmaceutically acceptable salt thereof claim 1 , and a pharmaceutically acceptable ...

TETRAZOLONE SUBSTITUTED STEROIDS AND USE THEREOF

The present disclosure relates to compounds of formula (AI), (I), (AII), and (II), or a pharmaceutically acceptable salt, solvate, stereoisomer, or tautomer thereof, a pharmaceutical composition comprising a compound of formula (AI), (I), (AII), and (II), and use thereof, wherein R2, R3, R4, R5, R6, R7, R10, R11a, R11b, R12, R16, R19a, R19b, and R20 are described herein. Such compounds are envisioned useful for the prevention and treatment of a variety of CNS-related conditions, for example, treatment of sleep disorders, mood disorders, movement disorders, convulsive disorders, schizophrenin spectrum disorders, disorders of memory and/or cognition, personality disorders, autism spectrum disorders, pain, traumatic brain injury, vascular diseases, substance abuse disorders and/or withdrawal syndromes, or tinnitus etc. 3. The compound of or , wherein the substituents are selected from fluoro , chloro , bromo , cyano , nitro , hydroxy , methoxy , ethoxy , propoxy , isopropoxy , methyl , ethyl , propyl , isopropyl , butyl , i-butyl , s-butyl , t-butyl , —CHCN , —CHCHCN , —CHF , —CHF , —CF , —CHOCH , —CHSCH , -methylhydroxy , morpholine , pyrrolidine , piperidine , piperazine , phenyl , benzyl , pyridine , pyrimidine , oxazole , pyrazole , cyclopropyl , cyclobutyl , cyclopentyl , cyclohexyl , —OCHF , —OCHF , —OCF , -ethylmethoxy , -methylcyclopropyl , —OR , —C(═O)R , —C(═O)OR , —OC(═O)R , —OC(═O)OR , —C(═O)NRR , —NRR , —NRC(═O)R , —OC(═O)NRR , —NRC(═O)OR , —NRC(═O)NRR , —SR , —S(═O)R , —S(═O)R , —S(═O)OR , —OS(═O)R , —S(═O)NRR , or —NRS(═O)R , wherein Ris independently hydrogen , methyl , ethyl , propyl , isopropyl , cyclopropyl , cyclobutyl , cyclopentyl , cyclohexyl , —CHF , —CHF , —CF , phenyl , benzyl , pyridine , pyrimidine , -ethylmethoxy , or -methylcyclopropyl , or two Rgroups can be taken together with the atoms to which they are attached to , to form a heterocylyl or heteroaryl ring.4. The compound of any one of - , wherein Ris hydrogen , —OH , —OCH , —OCHCH , — ...

SALTS AND CRYSTAL FORMS OF GABA-A POSITIVE ALLOSTERIC MODULATOR

The invention relates to salts of Compound 1, crystalline forms thereof, methods of their preparation, pharmaceutical compositions thereof and methods of their use 191.-. (canceled)93. The citrate salt of claim 92 , wherein the Form A exhibits an XRPD pattern comprising peaks at about 5.7±0.2; 20.1±0.2 and 20.3±0.2 degrees two-theta.94. The citrate salt of claim 92 , wherein the Form A exhibits an XRPD pattern substantially similar to .95. The citrate salt of claim 92 , wherein the Form A is defined by unit cell parameters substantially similar to the following:a=8.9 Åb=12.2 Åc=16.5 Åα=73.7°β=76.6°γ=83.2°Space group P1,Molecules/asymmetric unit 2,wherein the crystalline form is at about 120 K.96. The citrate salt of claim 92 , wherein the Form A exhibits a differential scanning calorimetry thermogram having a peak value at about 89.0±2.0° C. or about 139.5±2.0° C.97. A pharmaceutical composition comprising the citrate salt of and a pharmaceutically acceptable carrier.98. The pharmaceutical composition of claim 97 , wherein the composition is a tablet.100. The hydrobromide salt of claim 99 , wherein the Form A exhibits an XRPD pattern comprising peaks at about 15.2±0.2 claim 99 , 15.5±0.2 claim 99 , and 16.3±0.2 degrees two-theta.101. The hydrobromide salt of claim 99 , wherein the Form A exhibits an XRPD pattern substantially similar to .102. The hydrobromide salt of claim 99 , wherein the Form A exhibits a differential scanning calorimetry thermogram having a peak value at about 243.1±2.0° C.103. A pharmaceutical composition comprising the hydrobromide salt of and a pharmaceutically acceptable carrier.104. The pharmaceutical composition of claim 103 , wherein the composition is a tablet.106. The hydrobromide salt of claim 105 , wherein the Form E exhibits an XRPD pattern comprising peaks at about 15.2±0.2 and 16.3±0.2 degrees two-theta.107. The hydrobromide salt of claim 105 , wherein the Form E exhibits an XRPD pattern substantially similar to .108. The ...

PROCESS AND INTERMEDIATES FOR THE PREPARATION OF ABIRATERONE ACETATE

The present invention relates to a process for the synthesis of (3beta)17-(3-pyridinyl)androsta-5,16-dien-3-yl acetate (Abiraterone acetate) represented by the structure of formula (1), and salts thereof, especially salts with pharmaceutically acceptable acids. The present invention further relates to certain intermediates in such processes. 120-. (canceled)22. The process according to claim 21 , wherein the hydroxyl protecting group PG is selected from the group consisting of acetate (Ac) claim 21 , benzyl (Bzl) claim 21 , Si(R) claim 21 , tetrahydropyranyl (THP) and trityl (Trt) claim 21 , wherein Ris a substituted or unsubstituted alkyl claim 21 , cycloalkyl claim 21 , alkylaryl or aryl.23. The process according to claim 21 , wherein M is Li or MgX claim 21 , wherein X is Cl claim 21 , Br or I.24. The process according to claim 21 , wherein step (a) is carried out by reacting compound (10) with 3-Py-Li in an organic solvent at a temperature of about −70° C. to about 0° C. claim 21 , in the absence or presence of one or more additives.25. The process according to claim 24 , wherein step (a) is carried out in the presence of an additive selected from the group consisting of: (i) an amine; (ii) an amide; (iii) an inorganic salt; (iv) a rare earth element salt; and (v) salt mixtures or complex salts.26. The process according to claim 25 , wherein(i) the amine is N,N′-tetramethylethylenediamine;(ii) the amide is 1,3-Dimethyl-3,4,5,6-tetrahydro-2(1H)-pyrimidinone (DMPU);(iii) the inorganic salt is selected from lithium chloride, lithium perchlorate, cadmium chloride, magnesium chloride, zinc chloride and ferric chloride;(iv) the rare earth element salt is a lanthanide salt selected from lathanium chloride and cerium chloride;{'sub': 3', '3', '3', '3', '3', '3, '(v) the salt mixtures of complex salts are selected from YCl.2LiCl, CeCl.2LiCl, NdCl.2LiCl, PrCl.2LiCl, DyCl.2LiCl and ErCl.2LiCl.'}27. The process according to claim 26 , wherein the additive is lithium ...

Process for producing a solid form of abiraterone acetate

The present invention relates to a process for the preparation of 17-substituted steroids and, more particularly, to an improved method of preparing micro size abiraterone or derivatives thereof in high yield and purity by means of a spherical agglomeration process.

19-nor c3, 3-disubstituted c21-c-bound heteroaryl steroids and methods of use thereof

Provided herein are 19-nor C3,3-disubstituted steroids of Formula (I): and pharmaceutically acceptable salts thereof; wherein, , R 1 , R 2 , R 3a , R 3b , R 4a , and R 4b are as defined herein, and A is a carbon bound substituted or unsubstituted 5- to 6-membered heteroaryl ring as defined herein. Such compounds are contemplated useful for the prevention and treatment of a variety of CNS-related conditions, for example, treatment of sleep disorders, mood disorders, schizophrenia spectrum disorders, convulsive disorders, disorders of memory and/or cognition, movement disorders, personality disorders, autism spectrum disorders, pain, traumatic brain injury, vascular diseases, substance abuse disorders and/or withdrawal syndromes, and tinnitus.

19-NOR NEUROACTIVE STEROIDS AND METHODS OF USE THEREOF

Provided herein are 3,3-disubstituted 19-nor-steroidal compounds according to Formula (I): and pharmaceutical compositions thereof. Such compounds are contemplated useful for the prevention and treatment of a variety of CNS-related conditions, for example, treatment of sleep disorders, mood disorders, schizophrenia spectrum disorders, disorders of memory and/or cognition, movement disorders, personality disorders, autism spectrum disorders, pain, traumatic brain injury, vascular diseases, substance abuse disorders and/or withdrawal syndromes, tinnitus, and status epilepticus. 2. (canceled)2434-. (canceled)37. A pharmaceutical composition comprising a pharmaceutically acceptable carrier and a compound of claim 1 , or a pharmaceutically acceptable salt thereof.38. A method for treating a CNS-related disorder in a subject in need thereof claim 1 , comprising administering to the subject an effective amount of a compound claim 1 , or a pharmaceutically acceptable salt thereof.39. The method of claim 38 , wherein the CNS-related disorder is a sleep disorder claim 38 , a mood disorder claim 38 , a schizophrenia spectrum disorder claim 38 , a convulsive disorder claim 38 , a disorder of memory and/or cognition claim 38 , a movement disorder claim 38 , a personality disorder claim 38 , autism spectrum disorder claim 38 , pain claim 38 , traumatic brain injury claim 38 , a vascular disease claim 38 , a substance abuse disorder and/or withdrawal syndrome claim 38 , tinnitus claim 38 , or status epilepticus.4041-. (canceled) Brain excitability is defined as the level of arousal of an animal, a continuum that ranges from coma to convulsions, and is regulated by various neurotransmitters. In general, neurotransmitters are responsible for regulating the conductance of ions across neuronal membranes. At rest, the neuronal membrane possesses a potential (or membrane voltage) of approximately −70 mV, the cell interior being negative with respect to the cell exterior. The potential ( ...

THERAPEUTICALLY ACTIVE ESTRATRIENTHIAZOLE DERIVATIVES AS INHIBITORS OF 17.BETA-HYDROXY-STEROID DEHYDROGENASE, TYPE 1

The invention relates to compounds of formula (I) and pharmaceutically acceptable salts thereof wherein R2, R3, R4, R7 and R8 are as defined in the claims. The invention further relates to their use as inhibitors of 17β-HSD1 and in treatment or prevention of steroid hormone dependent diseases or disorders, such as steroid hormone dependent diseases or disorders requiring the inhibition of the 17β-HSD1 enzyme and/or requiring the lowering of the endogenous estradiol concentration. The present invention also relates to the preparation of the aforementioned compounds and to pharmaceutical compositions comprising as an active ingredient(s) one or more of the aforementioned compounds or pharmaceutically acceptable salts thereof. 4. A compound as claimed in claim 2 , wherein R8 is selected from the group consisting of C-alkyl claim 2 , C-haloalkyl claim 2 , C-perhaloalkyl claim 2 , (CH)CN claim 2 , (CH)OH claim 2 , (CH)N(R′) claim 2 , (CH)C(O)OR′ claim 2 , C(O)N(R′) claim 2 , and (CH)C(O)NH.5. A compound as claimed in claim 3 , wherein R8 is selected from the group consisting of C-alkyl claim 3 , C-haloalkyl claim 3 , C-perhaloalkyl claim 3 , (CH)CN claim 3 , (CH)OH claim 3 , (CH)N(R′) claim 3 , (CH)C(O)OR′ claim 3 , C(O)N(R′) claim 3 , and (CH)C(O)NH.7. A compound as claimed in claim 1 , wherein R2 and R4 are each independently selected from the group consisting of H claim 1 , halogen claim 1 , C-alkyl claim 1 , C-haloalkyl claim 1 , C-perhaloalkyl claim 1 , CN claim 1 , NO claim 1 , N claim 1 , N(R′) claim 1 , (CH)N(R′) claim 1 , OR′ claim 1 , (CH)OR′ claim 1 , COR′ claim 1 , CONHR′ claim 1 , COR″ claim 1 , NHCOR″ claim 1 , SCOR′ claim 1 , or COR′″; and{'sub': 1-6', '1-3', '1-3', '2', '2', 'n', '2', '2', 'n', '3', '3', '3', '2', 'n', '2', '2', '2', '2', '2', '2', '2', 'n', '2, 'R3 is selected from the group consisting of H, halogen, C-alkyl, C-haloalkyl, C-perhaloalkyl, N(R′), (CH)NH, (CH)OR % N, and OR′, wherein R′ is selected from the group consisting of R′, benzyl, ...

THERAPEUTICALLY ACTIVE 17-NITROGEN SUBSTITUTED ESTRATREINTHIAZOLE DERIVATIVES AS INHIBITORS OF 17.BETA-HYDROXYSTEROID DEHYDROGENASE

The invention relates to compounds of formula (I) and pharmaceutically acceptable salts thereof wherein R2 to R7 are as defined in the claims. The invention further relates to their use as inhibitors of 17β-HSD and in treatment or prevention of steroid hormone de-pendent diseases or disorders, such as steroid hormone dependent diseases or disorders requiring the inhibition of the 17β-HSD1 enzyme and/or requiring the lowering of the endogenous estradiol concentration. The present invention also relates to the preparation of the aforementioned compounds and to pharmaceutical compositions comprising as an active ingredient(s) one or more of the afore-mentioned compounds or pharmaceutically acceptable salts thereof. 3. A compound as claimed in claim 2 , wherein R7′ is selected from the group consisting of H claim 2 , methyl claim 2 , ethyl claim 2 , allyl claim 2 , and carboxymethylenyl.4. A compound as claimed in claim 1 , wherein R5 and R6 are both H.8. A compound as claimed in claim 1 , wherein{'sub': 1-6', '1-3', '1-3', '2', '3', '2', '2', 'n', '2, '(i-a) R2 and R4 are each independently selected from the group consisting of H, halogen, C-alkyl, C-haloalkyl, C-perhaloalkyl, CN, NO, N, N(R′), (CH)(R′), C(═N—OH)R″, and C(═N—OMe)R″.'}9. A compound as claimed in claim 1 , wherein{'sub': 1-6', '1-3', '2', '3, 'R3 is selected from a group consisting of H, C-alkyl, C-perhaloalkyl, N(R′), N, and OR′.'}10. A compound as claimed in claim 9 , wherein R3 is H or OR′.11. A compound as claimed in claim 1 , wherein R2 and R3 or R3 and R4 claim 1 , together with the ring carbon atoms to which they are attached claim 1 , form an oxazolone or 1 claim 1 ,3-oxazole ring claim 1 , optionally substituted with methyl.12. A compound as claimed in claim 11 , wherein R4 or R2 claim 11 , respectively claim 11 , is selected from the group consisting of H claim 11 , F claim 11 , Cl claim 11 , Br claim 11 , and I.13. A compound as claimed in claim 1 , wherein{'sub': 1-6', '1-3', '1-3', '2', '3', ...

COMPOSITIONS AND METHODS FOR TREATING CNS DISORDERS

Provided herein is a compound of Formula (I) 2. The compound of claim 1 , wherein Ris C-Calkyl substituted with 0-7 independent occurrences of deuterium or X—OX claim 1 , wherein Xis C-Calkylene substituted with 0-7 independent occurrences of deuterium and Xis C-Calkylene substituted with 0-7 independent occurrences of deuterium.3. The compound of or claim 1 , wherein if Ris —CH claim 1 , then at least one of R claim 1 , R claim 1 , R claim 1 , R claim 1 , R claim 1 , R claim 1 , R claim 1 , and Ris deuterium claim 1 , or if all of R claim 1 , R claim 1 , R claim 1 , R claim 1 , R claim 1 , R claim 1 , R claim 1 , and Rare hydrogen claim 1 , then Ris a methyl group substituted with 1-3 independent occurrences of deuterium.4. The compound of claim 1 , wherein Ris selected from the group consisting of —CHand CD.5. The compound of or claim 1 , wherein Ris —CH.6. The compound of or claim 1 , wherein Ris —CD.7. The compound any one of - claim 1 , wherein at least one of R claim 1 , R claim 1 , R claim 1 , R claim 1 , R claim 1 , R claim 1 , R claim 1 , R claim 1 , R claim 1 , R claim 1 , R claim 1 , R claim 1 , R claim 1 , R claim 1 , R claim 1 , R claim 1 , R claim 1 , R claim 1 , R claim 1 , R claim 1 , and Ris deuterium.8. The compound of claim any one of - claim 1 , wherein at least one of R claim 1 , R claim 1 , R claim 1 , R claim 1 , R claim 1 , R claim 1 , R claim 1 , and Ris deuterium.9. The compound of any one of - claim 1 , wherein Ris —CHand at least one of R claim 1 , R claim 1 , R claim 1 , R claim 1 , R claim 1 , R claim 1 , R claim 1 , R claim 1 , R claim 1 , R claim 1 , R claim 1 , R claim 1 , R claim 1 , R claim 1 , R claim 1 , R claim 1 , R claim 1 , R claim 1 , R claim 1 , R claim 1 , and Ris deuterium.10. The compound of any one of - claim 1 , wherein Ris —CHand at least one of R claim 1 , R claim 1 , R claim 1 , R claim 1 , R claim 1 , R claim 1 , R claim 1 , and Ris deuterium.11. The compound of any one of - claim 1 , wherein Rand Rare hydrogen.12. ...