НЕЙРОАКТИВНЫЕ 19-АЛКОКСИ-17-ЗАМЕЩЕННЫЕ СТЕРОИДЫ И СПОСОБЫ ЛЕЧЕНИЯ С ИХ ПРИМЕНЕНИЕМ

Изобретение относится к соединению формулы (I-g) или его фармацевтически приемлемой соли, где Rвыбирают из (C-Cалкил)-O, спирооксирана, циано, =O, нитро, (C-Cалкил)C(O) и HO(C-Cалкил)C(O); Rявляется H; Rявляется H; Rозначает метил; Rявляется H; - - - означает необязательную дополнительную C-C связь, дающую C=C связь между C-C, при условии, что, если присутствует, Rне является =O или спирооксираном. Изобретение также относится к индивидуальным соединениям, к способу индукции анестезии, к способу лечения расстройств, связанных с функцией ГАМК. Технический результат: получены новые соединения формулы (I-g), которые могут быть полезны при лечении расстройств, связанных с функцией ГАМК. 9 н. и 2 з.п. ф-лы, 5 табл.

СТЕРОИДЫ, СПОСОБ ПОЛУЧЕНИЯ СТЕРОИДОВ, СПОСОБ ПОЛУЧЕНИЯ 16-МЕТИЛЕНСТЕРОИДОВ, СОЕДИНЕНИЯ

Использование: в качестве промежуточных продуктов в синтезе стероидных препаратов. Сущность: продукт - стероиды общей формулы I, приведенной в описании. Продукт получают многостадийным способом, включающим стадии тиоалкилирования и окисления тиоалкильной группы. 4с. и 11 з.п. ф-лы.

СПОСОБ ПОЛУЧЕНИЯ ФЛУМЕТАЗОНА, СОЕДИНЕНИЕ

Описывается улучшенный способ получения флуметазона (6α,9α-дифтор-11β,17α,21-тригидрокси-16α-метилпрегна-1,4-диен-3,20-диона), флуметазон 21-ацетата или его 17-карбоксил-андростенового аналога формулы I, действием хлористого бензоила в среде пиридина или его смеси с N,N'-диметилацетамидом на соединение II с получением 3-енольного сложного эфира IIIa, с последующим его взаимодействием с 1-(хлорметил)-4-фтор-1,4-диазоний-бицикло[2.2.2]октан-бис(тетрафторборатом) в среде ацетонитрила и воды с получением IIIв, после чего в положении С3 у IIIв снимают защитную группу в среде водного метабисульфита и аммиака с получением IV: после фторирования 9,11-эпоксигруппы в IV с помощью HF получают 21-ацетат флуметазона, после чего проводят необязательный гидролиз с помощью КОН в СН3ОН в присутствии или в отсутствие Н2O2 с получением I или флуметазона соответственно. 2 н. и 1 з.п. ф-лы.

ТЕРАПЕВТИЧЕСКОЕ СРЕДСТВО ДЛЯ ЛЕЧЕНИЯ ГИПЕРТЕНЗИИ

... 1. Терапевтическое средство для лечения гипертензии, содержащее в качестве активного ингредиента (7α)-21-[4-[(диэтиламино)метил]-2-метоксифенокси]-7-метил-19-норпрегна-1,3,5(10)-триен-3-ол, представленный формулой (1) ! ! или его фармацевтически приемлемую соль. ! 2. Терапевтическое средство для лечения гипертензии по п.1, которое предназначено для введения женщине в постменопаузе. ! 3. Терапевтическое средство для лечения гипертензии по п.1, которое предназначено для введения пациенту с раком молочной железы в постменопаузе. ! 4. Средство для снижения гипертензии у пациента с раком молочной железы в постменопаузе, содержащее в качестве активного ингредиента (7α)-21-[4-[(диэтиламино)метил]-2-метоксифенокси]-7-метил-19-норпрегна-1,3,5(10)-триен-3-ол, представленный формулой (1) ! ! или его фармацевтически приемлемую соль. ! 5. Способ лечения гипертензии, отличающийся тем, что способ включает введение (7α)-21-[4-[(диэтиламино)метил]-2-метоксифенокси]-7-метил-19-норпрегна-1,3,5(10)-триен-3 ...

17АЛЬФА-БЕНЗОАТ КОРТЕКСОЛОНА ДЛЯ ПРИМЕНЕНИЯ В ЛЕЧЕНИИ ОПУХОЛЕЙ

НЕЙРОАКТИВНЫЕ 19-АЛКОКСИ-17-ЗАМЕЩЕННЫЕ СТЕРОИДЫ, ИХ ПРОЛЕКАРСТВА И СПОСОБЫ ЛЕЧЕНИЯ С ИХ ПРИМЕНЕНИЕМ

Способ получения стероидов

Способ получения производных простагландина

Способ получения производных 6 @ -метилгидрокортизона

Способ получения производных 6 @ -метилгидрокортизона

Способ получения 9альфа-хлор-11бета-оксистероидов

Способ получения кортикоидов

Estrogene als Antimitotika

Androstane und Pregane zur allosterischen Modulation des GABA Rezeptors

VERFAHREN ZUR HERSTELLUNG VON DELTA-9,11 UND 21-CHLORO-STEROID-VERBINDUNGEN

Verfahren zur Herstellung von 3-Enolaethern von 6-Formyl-3-oxo-?-steroiden

Verfahren zur Herstellung von 6alpha, 9alpha-Difluor-16alpha-methylhydrocortison und -prednisolon bzw. 21-Estern derselben

21-ALKOXY-STEROID-DERIVATE.

21-HYDROXYCORTICOSTEROID ESTERS, AND COMPOSITIONS CONTAINING THEM

Verfahren zur Darstellung von ª‡-Dicarbonylverbindungen der Cyclopentanopolyhydrophenanthrenreihe

Verfahren zur Herstellung von delta 7-, delta 7,9,(11)-, delta 7,9,(11),16-, delta 7, delta 8- oder delta 8,16-Steroiden

Verfahren zur Herstellung von Steroidverbindungen

Verfahren zur Herstellung von 13-Methylverbindungen der 5alpha-oder 5beta-D-Homoandrostan-bzw. der 19-Nor-1, 3, 5-(10)-pregnatrienreihe

PROCESS FOR THE SYNTHESIS OF THE HYDROXYACETYL SIDE CHAIN OF PREGNANE STEROIDS, 21-HYDROXY 20-OXO-17 ALPHA PREGNANES AND PHARMACEUTICAL PREPARATIONS CONTAINING THEM

Verfahren zur Herstellung von in 4(5)-Stellung ungesaettigten 2-Jodsteroid-3-ketonen bzw. Steroid-3-ketonen

Verfahren zur Herstellung von therapeutisch wirksamen Steroidverbindungen

Verfahren zur Herstellung von 17ª‡-Acyloxy-20-ketosteroiden der Pregnan-, Allopregnan- und Pregnenreihe

Verfahren zur Herstellung von therapeutisch wirksamen Steroidverbindungen

Verfahren zur Herstellung eines Pregnan-3-ol-20-on-3-aethers oder -esters

Verfahren zur katalytischen Acylierung von Oxyverbindungen

9,11-EPOXY-21-HYDROXYPREGNAN-DERIVATE.

14alpha,17alpha-Methylendioxy-oestranderivate

3-Cyclopentyloxysteroide,Verfahren zu ihrer Herstellung und die Steroid-enthaltende Arzneimittel

2-chloro-delta 1,4-steroids

... 2-Chloro-DELTA1,4-steroids of formula : (where R1 is H or CH3; R2 is H, free or esterified OH; X is F, Cl or CH3; Y is H or halogen; Z is halogen of atomic wt. = Y, OH in beta-posn. or when Y is H, Z is an OH in alpha-posn.). A prefd. cpd. is 6alpha-fluoro-1alpha,2beta-dichloro-11beta-hydroxy-21-acetoxy-16a- lpha-methyl-4-pregnene-3,20-dione. Cpds. useful as anti-inflammatories.

Verfahren zur Herstellung von delta 1,4-16 alpha-Methylsteroiden

STERILISIERUNG VON BECLOMETASON-ARZNEIMITTELTEILCHEN ZUR ANWENDUNG IN DER LUNGE

17-Iodo:benzoyloxy-9-chloro-D-homo-4-pregnene-3,20-di:one derivs. - prepd. by reacting 9-unsubstituted cpds. with iodo-benzene di:chloride under UV light, used esp. as pharmaceutical intermediates

New D-homo-4-pregnene-3,20-dione derivs. are cpds. of formula (I): where C1---C2 is a C-C single or double bond, R1 is H, OH or lower acyloxy, and R2 is H,F or CF3. (I) have pharmacological, e.g. antiinflammatory activity, but they are primarily useful as intermediates for other pharmacologically active substances, particularly 11-hydroxylated cpds.

PROSTAGLANDIN-DERIVATE

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

STEREOSELEKTIVES VERFAHREN ZUR HERSTELLUNG VON 6ALPHA-FLUORPREGNANEN UND ZWISCHENPRODUKTEN

11-Substituierte Phenyl-estra-4,9-dien Derivate

Verfahren zur Herstellung von 16-Methylen-19-norprogesteronderivate der Formel I

Verfahren zur Herstellung von Hydrocortison-cyclohexylsulfamat und dessen Verwendung

VERFAHREN ZUR HERSTELLUNG VON 19AETHYLSTEROIDEN UND DIE VERBINDUNG 19AETHYL-5ALPHA-ANDROSTAN-3BETA, 17BETADIOL

Verfahren zur Herstellung neuer Steroidester der Pregnanreihe

Verfahren zur Herstellung von 3,20-Dioxo-17Alfa-hydroxy-19-nor-9Beta,10Alfa-Delta4-pregnen

VERFAHREN ZUR HERSTELLUNG VON FLUORVERBINDUNGEN DER PREGNANREIHE

Verfahren zur Herstellung von 5-Brom-6-fluorsteroiden

Delta-16 20-keto steroids prepn - by monodebrominating a 17-alpha-dibromoacetyl-17-beta-acyloxy steroid and eliminating the ac

Steroids (I) of partial formula: (where R1 is Me or Et, R2 is H or lower acyl; R3 is the residue of a steroid molecule) are prepd by partially debrominating a steroid of partial formula: with a soln of a reducing metal salt, pref. a Cr2+ or V2+ salt, and heat-treating the 17 alpha-monobromoacetyl-17 beta-acyloxy steroid thus obtd in a polar aprotic solvent in the presence of an alkali(ne earth) metal salt of a lower carboxylic acid to give the DELTA 16-21-acyloxy-20-keto steroid, and opt. removing the 21-acyl gp. The products (I) are intermediates for pharmaceuticals.

16-METHYLEN 17ALPHA-ACYLOXY-9BETA, 10ALPHA-PREGN-4-EN (ODER PREGNA-4,6-DIEN)- 3,20-DION VERBINDUNGEN, VERFAHREN ZU IHRER HERSTELLUNG SOWIE DIESE ENTHALTENDE PHARMACEUTISCHE PRAEPARATE

New steroid compounds and processes for their preparation

The invention comprises 17a -hydroxy-16a -methyl -18- norpregn -4- ene-3, 11, 20-trione derivatives having the formula: where R represents a hydrogen atom or a group convertible to a hydrogen atom by simple hydrolysis and process for the preparation thereof by hydroxylating 17a -hydroxy-16a -methyl -18- norpregn -4- ene-3, 11, 20-trione so as to introduce a hydroxyl or esterified hydroxyl group thereinto. Said hydroxylation may be effected microbiologically e.g. with Colletotrichum lindemuthianum or chemically by iodinating 17a -hydroxy -16a - methyl-18-norpregn -4- ene-3, 11, 20-trione in the presence of calcium chloride and calcium oxide to yield the corresponding 17a -hydroxy -21- diiodo -16a - methyl -18- norpregn -4- ene-3, 11, 20-trione, treating the resulting 21-diiodo derivative with an acyloxylating agent appropriate to the ester which it is sought to form, to obtain the corresponding 21-acyloxy -17a - hydroxy -16a - methyl -18- norpregn -4- ene-3, 11, 20-trione ...

Process for the manufacture of allopregnanes

A 3b ,17a -dihydroxy-16a -alkyl-allopregnan-20-one is prepared by hydrogenating a D 5:17(20)- 3b ,20-diacyloxy- 16a -alkylpregnadiene in presence of a noble metal catalyst, reacting the resulting D 17(20)-3b ,20-diacyloxy16a -alkyl-allopregnene with an organic peracid and hydrolysing the resulting oxidation product. The preferred catalyst is palladium. Suitable per-acids include peracetic, perbenzoic and mono-perphthalic and suitable hydrolysing agents include dilute sulphuric acid and alkali metal carbonates, bicarbonates, hydroxides and alcoholates. Examples of the prepartion of the 16a -methyl compound are provided. Specification 933,958 is referred to.

Process for the fluorination of steroids

Steroidal 6b -fluoro-D 4-3-ketones are prepared by reacting an enol ether or enol ester of a D 4-3-keto steroid unsubstituted in Ring B with perchloryl fluoride in an inert organic solvent, e.g. dimethylformamide or dimethylacetamide preferably mixed with a tertiary amine such as pyridine or g -collidine. The reaction is preferably conducted between -60 DEG and +60 DEG C. for from 5 minutes to 20 hours and may be applied to the preparation of compounds of the formula:- wherein R1 is hydrogen or methyl; R2 is hydrogen, a -OH, a -acyloxy, a -alkoxy, a -methyl or b -methyl; R3 is hydrogen or lower alkyl, Z is a single or double bond between C9 and C11 which may be substituted (when a single bond) at C9 by bromo, fluoro or chloro, and at C11 by a -acyloxy, a -OH, b -OH, or keto; and A is a typical androstane or pregnane substituent, e.g. oxygen, b -hydroxy, b -acyloxy, b -acetyl, a -aliphatyl-b -hydroxy, b -hydroxyacetyl, a -hydroxy-b -hydroxyacetyl, b -fluoroacetyl, ...

Unsaturated halogenated steroids and process for their manufacture

The invention comprises steroids of the general formula: wherein R1 is H, b -OH or keto, and R2 is a free or esterified group, and the corresponding 1-dehydro steroids, and a process for the preparation of steroids of the general formula: wherein Hal represents bromine or chlorine, R1 represents =O or H, H or H, b -OH, R2 represents: H or acyl, R4 represents acetyl or -COCH2R6, R5 represents acetyl or -OR3, and R6 represents a free or esterified hydroxy group, by treating 6a , 7a -oxido-steroids of the general formula: wherein R1 to R6 have the above significance, with hydrochloric or hydrobromic acid to form the corresponding 6b -halogens-7a -hydroxysteroids, and reacting these steroids with an acid dehydrating agent such as hydrochloric or hydrobromic acid. The above process may be modified in that the product is dehydrogenated to form a D 1, 4-unsaturated compound, for example, by a chemical dehydrogenating ...

NEW 11-HALOGENOSTEROIDS

... 1,240,719. 9,11# - dihalogeno - 6 - fluoro - 16-methyl steroids. SOBERING A.G. 13 Aug., 1968 [16 Aug., 1967], No. 38617/68. Heading C2U. [Also in Division A5] Novel anti-inflammatory steroids of the formula (wherein R is H or acyl; and X and Y are each a halogen atom, the atomic weight of Y being equal to or greater than that of X) are prepared by halogenation by standard procedures of the corresponding #9(11) -steroids. 21-Acylates may be hydrolysed and 21-ols acylated.

Improvements in synthesis of pregnenolone and its esters and intermediates

Pregnenolone and its esters and intermediates therefor are manufactured by any one of the following steps, or a combination thereof or of the first three: (a) heating a 3-acyloxybisnor-5-cholen-22-al with an enol esterifying agent to form a 22-enol ester; (b) treating the product of (a) with ozone to ozonize the 20 : 22 double hond without removing the enol ester grouping; (c) subjecting the product of (b) to decomposition (preferably under reductive condictions) to form a pregnenolone ester; and (d) hydrollysing this ester. Step (a) may be effected at about 60-150 DEG C., using an acid halide or preferably a mixture of a carboxylic acid anhydride and an alkali metal salt of the corresponding acid, and step (b) at a temperature below about 30 DEG C. (preferably between about -30 DEG and +10 DEG C.), advantageously in a solvent (e.g. chloroform, carbon tetrachloride, ether-chloroform mixtures, methylene chloride, glacial acetic acid or methanol). Step (c) may be effected by subjecting the ...

21-FLUORO-PREGNANES

... 1430932 21-Fluoro-pregnane compounds GLAXO LABORATORIES Ltd 4 May 1973 [5 May 1972] 21144/72 Heading C2U Novel steroids of the pregnane or 19-norpregnane series possess a 5-hydrogen atom or a 4,5-double bond, a 3-OH group, a 17-hydrogen atom, a 20-oxo group and a 21-fluorine atom. They may also possess other substituents and/or double bonds, e.g. a 2#-ethoxy group and an 11- keto group. They are prepared by reacting corresponding steroids possessing a readily eliminatable substituent at the 21-position, e.g. an iodine atom, with a source of fluoride ions, or by stereospecific reduction of corresponding 5-H- 3-keto steroids. Substituents and double bonds may be introduced into the starting materials or final products by known processes. A 2# - bromo - 3 - hydroxy - 21 - unsubstituted steroid may be converted to a #1-2-unsubstituted - 3 - hydroxy - 21 - bromo steroid by bromination in the 21-position followed, with or without keto protection, by dehydrobromination in the 1,2-position ...

í¸ -3-keto-11-hydroxy-20-cyano-21-hydroxy pregnene and its 21-acyl derivatives and preparation of same

The invention comprises a D 17:203-keto-11(b ) - hydroxy - 20 - cyano - 21 - hydroxypregnene and a 21-acyl derivative thereof and the preparation thereof by reacting a compound of the formula: wherein R is hydrogen or a acyl radical with a reagent capable of replacing the keto group in the 3 position by a substituent reconvertible into ketone, e.g. hydroxylamine, semi-carbazide an aryl hydrazine or an alkyl orthoformate thereby forming the corresponding D 17(20)-11-keto - 20 - cyano - pregnene compound, reacting this compound with an alkali metal borohydride thereby converting the keto radical in the 11-position to an 11(b )-grouping without substantially affecting the substituents attached to the 3 and 20 carbon atoms, thereby producing a D 17(20)-11(b )-hydroxy-20-cyano-pregnen compound and reacting the latter compound with a hydrolysing agent followed by acylation if R is hydrogen. As alkali metal borohydride there may be used lithium or sodium borohydride and ...

New cyclopentanophenanthrene derivatives and method for the preparation thereof

The invention comprises allopregnane3b : 11a : 17a : 21 - tetrol - 20 - one 21 - monoacetate, together with a process for the preparation of an allopregnane-17a : 21-diol3 : 11 : 20-trione 21-lower fatty acid acylate which comprises treating 22-isoallospirostan3b : 11a -diol with a lower fatty acid anhydride under pressure at a temperature of approximately 200 DEG C., to form a D 20(22)-allofurostene3b : 11a : 26-triol triacylate, thereafter oxidizing said triacylate with chromic anhydride in acetic acid, saponifying the oxidation product with alumina to form a D 16-allopregnene3b : 11a - diol-20-one diacylate, hydrogenating the D 16-compound to form the corresponding allopregnane - 3b : 11a - diol - 20 - one diacylate, enolizing the allopregnane-3b : 11a -diol-20-one diacylate to form the corresponding 20-enol acylate, oxidizing this with an aromatic per acid and saponifying the product to form allopregnane - 3b : 11a : 17a - triol - 20 - one, monobrominating this compound to form the ...

Manufacture of new compounds of the cyclopentanopolyhydrophenanthrene series

Compounds of the cyclopentanopolyhydrophenanthrene series which are unsaturated in ring C and which are substituted at least in ring A are prepared by treating a saturated or unsaturated compound of this series which is substituted in ring A and which contains in ring C a free or substituted hydroxyl group in the 12-position, with an agent which is known to be capable of splitting off such a substituent with the formation of a double bond. Parent materials may, if desired, have a side chain in the 17-position and may be substituted outside ring A for example in positions 6, 7, or 17, or in the side chain for example in positions 20 or 21. There are mentioned saturated and unsaturated androstane -3 : 12 : 12-triols, 3 : 12-diol-17-ones, and 3 : 17-dione-12-ols, the compounds may have in the 17-position in addition to a free or esterified hydroxyl group, a saturated or unsaturated hydrocarbon group, which may be substituted by alkyl alkenyl or alkinyl residues such as methyl, ethyl, diaryl-isopropyl ...

Manufacture of 11-dehydrocorticosterone and derivatives thereof

... 11-Dehydrocorticosterone or its derivatives are made by the process of the parent Specification by reacting a D 5 : 6-3-oxy-11-keto-aetiocholenic acid, of which the hydroxyl group is protected, to react with diazomethane, setting free the protected hydroxyl group in the 3-position in the resulting diazo-ketone or halogen ketone, converting the diazo-ketone group or halogen-ketone group before or after oxidation of the free 3-hydroxyl group into a free or esterified ketol group, and if desired, treating the product with a hydrolysing agent and/or an esterifying agent. A detailed example is given. Specification 612,129 is referred to.

Improvements in or relating to cyclopentanophenanthrene derivatives and methods of production thereof

The invention comprises 17a -hydroxy-21-acyloxy - and 17a : 21 - dihydroxy - D 1,2 - allopregnene-3 : 20-diones, and the preparation thereof, by bromination and dehydrobromination, followed if desired by mild hydrolysis, from 17a - hydroxy - 21 - acyloxyallopregnane - 3 : 20 - diones, which may be first prepared by the action of a mild oxidizing agent of the general formula (wherein R represents an aliphatic radical, R1 an aromatic or aliphatic radical, and X bromine or chlorine) on a 3b : 17a -dihydroxy-21-acyloxyallopregnan - 20 - one. Preferably an equimolecular proportion of the mild oxidizing agent is used, or such small excess that only an equimolecular proportion reacts, and the oxidation is effected in the presence of a weak organic base. In examples: (1) 3b : 17a - dihydroxy - 21 - acetoxyallopregnan - 20 - one is treated with N-bromoacetamide in tert.-butyl alcohol in the presence of pyridine, the resulting 3 : 20-dione is treated with bromine and hydrobromic ...

Hydrogenation of steroids

A D 4-double bond in a steroid nucleus is saturated (producing predominantly a normal configuration of hydrogen in the 5-position) by the action of hydrogen in the presence of a catalyst consisting of palladium supported on a carbonate or oxide (or mixture thereof) of a metal of group 2B of the Periodic Table. The starting materials may contain substituents such as keto, hydroxy, acyloxy, carboxy or carbalkoxy groups, e.g. in the 3, 7, 11, 12, 17, 20 and 21 positions. The reaction may be effected at 0-100 DEG C. (advantageously at room temperature), and at atmospheric or raised pressure (e.g. up to 100 lb./square inch), if desired in the presence of a solvent (preferably an alcohol), and is preferably continued until approximately one molar equivalent of hydrogen has been absorbed. The products may be purified by chromatography. Examples describe the hydrogenation of (1)-(3) 11a -hydroxyprogesterone to 11a -hydroxypregnane-3 : 20-dione (in methanol in the presence of palladium supported ...

Improvements in or relating to steroids and the manufacture thereof

The invention comprises 16a -halo-6a -methyl-9a - fluoro - 11b ,17a - dihydroxy - 1,4 - pregnadiene-3,20-dione wherein the halogen is bromine or iodine, a steroid of the structure wherein R is hydrogen or acyl, wherein the acyl radical is of a hydrocarbon carboxylic acid containing from 1-12 carbon atoms inclusive; Hal is bromine or iodine; X is hydrogen or fluorine; and wherein the linkage between carbon atoms 1 and 2 is a single bond or a double bond, and in a process for the production of 16a -halo steroids wherein the halogen atom is bromine or iodine, the steps of reacting a 16(17)-oxidopregnane with hydrogen halide selected from hydrogen bromide or hydrogen iodide to obtain the corresponding 16b -bromo or 16b -iodo pregnane compound and heating the 16b -bromo or 16b -iodo pregnane with Raney nickel in a lower alkanol to obtain the corresponding 16a -halopregnane. Pharmaceutical compositions having antiinflammatory and glucocorticoid activity and containing the ...

Preparation of steroid 3-ketal derivatives

Compounds of the formula wherein R is H or an acetyl group are converted into compounds of the formula by reacting the starting compound with an excess of 2-methyl-2-ethyl-1,3-dioxolane or 2,2-dimethyldioxolane in the presence of an acid catalyst.

Pentacyclic Steroid Intermediates and Method of Preparing the same

... 1,151,209. Steroids. WARNER-LAMBERT PHARMACEUTICAL CO. 22 Aug., 1966 [23, Aug.,. 1965], No.37534/66. Heading C2U. The invention comprises compounds having the formulµ wherein R is H or CH 3 , R1 is. H, F or CH 3 , Y is H 2 , H(#-OH), or =O, Z is H or halogen, T is H 2 , H(#-CH 3 ),H(-CH 3 ), (H,#-F), (H,,F), (H,-Cl), (H,#-Cl), or =CH 2 , R3 is H or C 1-9 acyl and the C 17 carbon atom has the structure where E represents one of the groups in which n is 1 or 2 and W is CH 3 or C 2 H 5 ,. or in the first of the above formula the C 17 carbon atom has the structure where X and X1 which can be the same or different, are selected from H, OH or O Acyl containing up to 9 atoms and B is H or a saturated or unsaturated hydrocarbon radical containing up to 3 carbon, atoms, with the proviso that T is H 2 when B is other than H, and a method for the-preparation of compounds of the formula wherein R, R, T, Y, Z, and the C 17 carbon atom are as defined above for the first formula ...

Novel 5-‡-h-6-keto-steroids

... 1,145,643. 5-H-6-kete-steroid. F. HOFFMAN-LA ROCHE & CO. A.G. 12 Aug., 1966 [13 Aug., 1965; 24 March, 1966], No. 40672/68. Divided out of 1,145,641. Heading C2U. The invention comprises novel 5-H-6-keto steroids of the formula wherein R1 and R2 represent a hydroxy or acetoxy group with the proviso that R1 cannot represent an hydroxy group when R2 represents an acetoxy group and X represents a grouping of the formulµ in which Y represents a tetrahydropyran-2- yloxy group, X being grouping (a), (b), (e) or (f) when R1 represents an acetoxy group and R2 represents a hydroxy group, or grouping (b), (c), (d), (e), (f), (g), (h), (i) or (j), when R1 and R2 both represent an acetoxy group. 2# - Acetoxy - 3# - hydroxy - cholester - 6- one and 2#,3# - dihydroxy - cholester - 6 - one can be prepared by treating #2-cholester-6-one with silver acetate in the presence of glacial acetic acid and iodine and treating the resulting ...

PREPARATION OF delta< >-3-KETO STEROIDS

... 1,203,733. #5-3-oxo and #3,5-3-trichloroacetoxy steroids. ISRAEL MINISTRY OF COMMERCE & INDUSTRY, STATE OF; YEDA RESEARCH & DEVELOPMENT CO. Ltd., and Y. MAZUR. 6 March, 1968 [7 March, 1967], No. 10896/68. Heading C2U. Steroids of formula (wherein R 1 and R 2 are each H or C 1-6 alkyl, - C :D-represents the optionally substituted C and D rings of the steroid, and the dotted line signifies an optional #7-unsaturation), which compounds are novel except for 3,1 1#-bis(trichloroacetoxy) 3,5 - androstadien - 17- one,. are prepared from the corresponding #4-3-ones or #4'5-3-ones by reacting with trichloroacetic anhydride, and are convertible into #5-3-ones or #5'7-3-ones by dissolving in spectrum grade methanol or slightly basic methanol, optionally with heating, and evaporating the methanol when the conversion is complete.

Preparation of intermediate compounds in the synthesis of dehydrocorticosterone

... 3.9 - Epoxy - 11 - keto - 24,24 - diphenyl - D 23-cholene is treated with acetic anhydride and hydrogen bromide to form 3(a )-acetoxy-11-keto - 12 - bromo - 24,24 - diphenyl - D 23 - cholene which is reacted with N-bromosuccimide and dehydrobrominated to produce 3(a )-acetoxy - 11 - keto - 12 - bromo - 24,24 - diphenyl - D 20 : 22, 23 : 24 choladiene which is degraded with chromic acid to produce 3(a )-acetoxy-11,20 - diketo - 12 - bromopregnane which upon treatment with zinc yields 3(a )-acetoxy-11,20-diketopregnane.

Manufacture of pregnanes

Compounds of the pregnane series are manufactured by oxidizing a pregnane-(20) alkyl ketone by means of a per-acid (with or without the addition of an acid catalyst, e.g. sulphuric, perchloric or p-toluenesulphonic acid) to form a 20-acyloxypregnane compound, and, if desired, hydrolysing and further oxidizing this (e.g. by means of choromium trioxide, permanganates, or metal alcoholates or phenolates together with ketones) to a 20-ketopregnane. The starting materials may contain nuclear double bonds (e.g. in the 5 : 6- or 11 : 12-position), these preferably being temporarily protected (e.g. by addition of halogen or hydrogen halide, which is subsequently split off again). Nuclear substituents may also be present, e.g. an 11-keto group, or (especially in one or more of the 3-, 7-, 11- and 12-positions) a free or substituted (e.g. acylated) hydroxy group, which may be converted to a keto group by oxidation, or hydrolysis and oxidation, after the oxidation with the per-acid, either simulataneously ...

6-substituted steroids

The invention comprises steroids of the formulae (wherein R is hydrogen or C1- 6 alkyl; R1 is C1- 6 alkyl; R0 is hydrogen, hydroxy or keto; Y is a dihydroxyacetone side chain protected as a bismethylenedioxy derivative; and Z is an ethylenedioxy or bis-alkoxy radical) and the preparation of corresponding D 4,6-3-keto-6-alkyl steroids by hydroxylating a corresponding 6-unsubstituted -D 5-3-ketal to form compounds of Formula II, oxidizing these to compounds of Formula III, alkylating these with an alkyl Grignard reagent to form compounds of Formula IV and dehydrating and hydrolysing these. Hydroxylation is preferably effected with osmium tetroxide in a basic solvent, and oxidation with chromium trioxide in pyridine. If an 11-keto group is present, this is desirably reduced, e.g. with sodium borohydride, to an 11b -hydroxy group, before dehydration and hydrolysis, which may be effected with a mineral or organic acid. If a mineral ...

Process for preparing 3ª‰,5ª‰,14ª‰-trihydroxy-20(22)-cardenolide (periplogenin)

The invention comprises (1) 20-a -ethoxyethynyl - 3b ,5b ,14b ,20b ,21 - pentahydroxy-pregnane and its 3,21-diacetate, and (11) a process for preparing periplogenin from the diacetate of the invention by (a) hydrolysis to the pentaol of the invention or 3b ,5b ,14b -20-tetrahydroxy - 20(22) - dihydro - cardenolide, or a mixture of the two, followed by treatment with a dilute mineral acid, or (b) reacting the with a dilute mineral acid, or (b) reacting the diacetate of the invention with a dilute mineral acid to give 20-carbethoxymethylene-3b ,21-diacetoxy - 5b ,14b - dihydroxy - pregnane, followed by hydrolysis and cyclization. 3b ,21 - diacetoxy - 20 - a - ethoxyethynyl-5b ,14b ,20b -trihydroxy - pregnane is prepared by conversion of 14a -desoxycorticosterone to its 21-acetate, dehydration of this to 14-dehydro-desoxycorticosterone acetate, reducing this with lithium aluminium hydride to 3b ,20b ,21-trihydroxy - 4,14 - pregnadiene, converting this to its 3,20,21-triacetate, treatment with ...

Improvements in or relating to Steroid Compounds

... 1,160,552. Steroids. T. D. THREADGOLD. 29 Sept., 1966 [30 June, 1965], No. 27735/65. Heading C2U. Novel compounds having the Formula I in which the configurations at the 9- and 10-positions are 9, 10#, or 9#, 10, and the bond between positions 1 and 2 in the steroid skeleton is single or double, and in which R 17 represents a -CO-CH 3 group, and R1 17 represents hydrogen or a free, esterified or etherified hydroxy group or R 17 represents a free, esterified or etherified hydroxy group andR1 17 represents hydrogen or a lower alkyl, alkenyl or alkynyl group containing from 1-6 carbon atoms, Hal 1 represents a fluorine chlorine or bromine atom, and Hal 2 represents a fluorine, chlorine or bromine atom, are obtained by subjecting a corresponding 3 - keto - 4 - dehydro - 6 - fluoro- or -6-chloro- or -6-bromo compound to halogenation at the allylic position with respect to the 4-double bond by means of elemental chlorine or bromine, or by means of N-chloro- or N-bromo-succinimide ...

01beta-Hydroxy-12alpha-Bromo-16alpha-Methyl-5beta-Pregnanes

... 1,174,780. 12-Bromo-16-methyl-5#-preg nan-11#-ols. E. R. SQUIBB & SONS Inc. 13 Dec., 1966 [22 Dec., 1965], No. 55738/66. Heading C2V. The invention comprises compounds of formula wherein Y is H or Br and Z is H, OH or acyloxy. The compounds wherein Y is Br are prepared by bromination of the compounds wherein Y is H, and the latter are prepared from the corresponding 11,12-unsubstituted-11-enes by reaction with an N-bromo-amide or -imide. 16 - Methyl - 5# - pregn - 11 - ene - 3,20- dione (II) is prepared by the sequence: 16- methyl - 3,12 - dihydroxy - 5# - pregnan - 20- one (III) # 16 - methyl - 12 - hydroxy - 5#- pregnane - 3,20 - dione # 16 - methyl - 12- tosyloxy - 5# - pregnane - 3,20 - dione # II. 16 - Methyl - 21 - acetoxy - 5# - pregn - 11- ene - 3,20 - dione (IV) is prepared by the sequence: III # 3,12 - dihydroxy - 16- methyl - 21 - bromo - 5# - pregnan - 20 - one (V) # 3,12 - dihydroxy - 16 - methyl - 21 - iodo- 5# - pregnan - 20 - one # 3,12 - dihydroxy- 16 - methyl - 21 - acetoxy ...

03-C2-4 Alkyl-Gonane Compounds

... 1,193,951. 13-C 2-4 alkyl-gonane compounds. H. SMITH. 18 Aug., 1967 [19 May, 1966], No. 22343/66. Heading C2U. Novel steriods of the structure wherein R1 is C 2-4 alkyl; Y is CH(OH) or an ester or ether thereof or a corresponding group with the 17-hydrogen atom replaced by a substituted or unsubstituted alkyl, alkenyl or alkynyl group, CO or a ketal thereof, CH(COCH 2 OH) or an ester thereof, CH(CH.OH.CH 2 - OH) or a mono- or di-ester thereof, or CH(CO 2 H) or a halide thereof; W is CH(OH) or CO or a ketal thereof; and ring A can optionally contain at least one halogen, alkyl or ethoxalyl substituent, are prepared by reduction of the corresponding #4-, #5- or #5(10)-gonenes. This reduction may be followed by one or more of the following processes: acylation, hydrolysis, oxidation and reduction in the 17-side chain, reduction of a 3-one to a 3-ol, ketalization of a 3-one, conversion of a 2-unsubstituted-3-one to a 2-alkyl-3-one, via for example, the 2- ...

Steroid compounds

The invention comprises 16(a and b )-methyl-1,4,9(11)-pregnatriene-17a ,21-diol - 3,20 -diones and the 21-acylates thereof, and 16(a and b )-9a (bromo and chloro)-11b ,17a ,21-trihydroxy-1,4-pregnadiene-3,20-diones and the 21-acylates thereof, and a process for the preparation of the above 1,4,9(11)-pregnatriene 21-acylates by reacting 16(a and b )-methyl-1,4-pregnadiene-11b ,17a ,21-triol-3,20-dione 21-acylates with a dehydrating agent, and a process for the preparation of 16(a and b )-methyl-1,4-pregnadiene-9a (bromo or chloro)-11b ,17a ,21-triol-3,20-dione 21-acylates by treating the 1,4,9(11)-pregnatriene 21-acylates with hypobromous or hypochlorous acid respectively (the acid may be formed in situ using N-bromo- or N-chlorosuccinimide and perchloric acid in aqueous solution). The above processes may be modified by hydrolysing the formed 21-acylates to the corresponding 21-hydroxy compounds. Specifications 877,085, 877,086, 906,443 and 912,379 are referred to.

Anti inflammatory 2-Bromo-6b Fluoro-92-hals steriods of the pregna-1,4-dien-3-one series

A process for the preparation of the title compounds, which are of general formula: in which: X is an oxo group, a beta -hydroxyl group or a chlorine atom; Y is a fluorine or a chlorine atom but is not fluorine when X is a beta -chlorine atom; Z is a hydrogen atom or an alpha -hydroxyl or alpha - or beta -methyl group; R'is a hydrogen atom or an alkanoyl group having from 2 to 8 carbon atoms; and when Z is alpha -hydroxyl and R' is hydrogen, the corresponding 16 alpha , 17 alpha -acetonides and 16 alpha -alkanoyl derivatives, the alkanoyl radical having from 2 to 8 carbon atoms; and R is hydrogen or the acyl radical of a mono- or di-carboxylic organic acid having from 2 to 8 carbon atoms, of metasulfobenzoic acid or of phosphoric acid, comprises the bromination of the corresponding 2- unsubstituted- DELTA <1,4>-dienes (wherein R is C2-8 acyl) dissolved or suspended in a suitable solvent by reaction with excess of bromine in the cold, to give the corresponding 1,2-dibromo- derivative ...

A new steroid compound, processes for its preparation and pharmaceutical compositions thereof

The invention comprises 18-nor-pregn-4 - ene - 3,11,20-trione, 18-nor-pregna-3,11,20,-trione, pharmaceutical compositions thereof and processes for the preparation of 18-nor-pregn-4-ene-3,11,20-trione in which 18-nor-pregn-16-ene-3,11,20-trione is catalytically hydrogenated e.g. with palladium, to form 18-nor-pregna-3,11,20-trione, which is then brominated e.g. with free bromine, to form 4#x-bromo-18-nor-pregna-3,11,20-trione, which is dehydrobrominated e.g. with lithium bromide/lithium carbonate in N,N-dimethylformamide, to obtain the desired 18-nor-pregn-4-ene-3,11,20-trione. Said compositions having antilipaemic activity are administered orally, transcutaneously or rectally as tablets, pills, capsules, injectable solutions and suspensions, or suppositories.

Improvements in or relating to steroids

The invention comprises a compound having the general formula: wherein R1 and R11 are hydrogen, a lower alkyl radical (1-8 carbon atoms), a monocyclic aromatic radical, a monocyclic aromatic lower alkyl radical, a monocyclic heterocyclic radical or a monocyclic heterocyclic lower alkyl radical or R1 and R11 when taken together are alkylene, W is the carbonyl radical C=O or b -hydroxymethylene radical, X is hydrogen, hydroxy, acyloxy, or fluorine, Y is hydrogen or methyl, Z111 is hydrogen fluorine, chlorine bromine or iodine and the broken lines appearing inside the rings indicate D 1 and D 6-double bonds which may or may not be present provided that when X represents hydrogen or fluorine Z111 does not represent bromine or iodine, and a process for the preparation thereof which comprises treating a suspension or a solution of a steroid having the formula: wherein W, Y and Z111 are as defined above, R111 is hydrogen ...

Cyclopentanophenanthrene compounds and process for the production thereof

The invention comprises compounds of the formulae: (in which Z is a double bond or a saturated linkage between C1 and C2; R and R1 are the same or different and each represent hydrogen or an acyl group of a hydrocarbon carboxylic acid of less than 12 carbon atoms; R2 and R3 are the same or different and each represent hydrogen or a hydrocarbon group containing up to 8 carbon atoms) and processes for their preparation from 6-methyl-D 5,16-pregnadien-3b -ol-20-one by alternative routes, (a) by Oppenauer oxidation (or CrO3 oxidation followed by rearrangement of D 5-3-keto system), dehydrogenation at C6-7 with a quinone, e.g. chloranil, hydroxylation at C16 and C17 with OsO4 or KMnO4, formation of a ketal, acetal or ester at C16 and C17 and, if necessary further dehydrogenation at C1-2 with selenium dioxide; (b) by epoxidation at C16-17, Oppenauer oxidation of the resulting 6-methyl-16a , 17a -oxido-D 5-pregnen-3b -ol-20-one, dehydrogenation at C6-7, ...

Sterilisation of pharmaceuticals

Improvements in or relating to the bromination of steroid compounds

The invention comprises 21-bromo-4-fluoro-17a - hydroxy - pregn - 4 - ene - 3,11,20 - trione, 21 - bromo - 16a - methyl - pregn - 4 - ene-3,11,20-trione and a process for the preparation of a 21-bromo-4-fluoro-pregn-4-en-3,20-dione, in which a solution or suspension in a solvent medium which is essentially methanol, of a 4-fluoro - 3,20 - diketo - D 4 - steroid, the D - ring of which is of the general formula (where R1 indicates either hydrogen or a hydroxyl group) is reacted with an acidic enolizing agent and with bromine to yield the corresponding 21-bromo-4-fluoro-pregn-4-en-3,20-di-one. As acidic enolizing agents, there may be used strong organic acids, organic acid chlorides or gaseous hydrochloric or hydrobromic acids. Subsequently the 21-bromo compound may be acyloxylated e.g. with alkali metal acetate to form the corresponding 21-ester.

Novel steroid compounds and processes for their production

The invention comprises the 20-aroyloxy-5a -pregnane compounds of the general formula in which OR represents an aroyloxy group, R1 is a free or esterified hydroxy group, R2 is a hydroxy group or a 9(11) double bond, and R3 is the free or ketalized oxygen atom of a keto group, and processes for the preparation thereof by reducing a 7-ketal of a 20b -aroyloxy-3b -hydroxy - 5a - pregnane - 7,11 - dione of the general formula to form the corresponding 7-ketal of a 20b -aroyloxy - 3b ,11b - dihydroxy - 5a - pregnan-7-one, esterifying the latter to form the corresponding 3b -acyloxy or aryloxy compound, dehydrating the latter to obtain the corresponding 7-ketal of a 20b -aroyloxy-3b -acyloxy or aroyloxy - 5a - pregn - 9(11) - en - 7 - one and subjecting the latter to liberation at 7-position to obtain the corresponding 20b -aroyloxy - 3b - acyloxy or aroyloxy - 5a -pregn-9(11)-en-7-one. In the above reaction scheme reduction may be effected with potassium ...

9-halogenated 18:11-lactones of 11ª‰-hydroxy-pregnane-18-acids

The invention comprises 18, 11-lactones of 11b -hydroxy-9a - X- 20- R1-21-R2-pregnane-18-acids in which X is a fluorine, chlorine or bromine, R1 is a free or ketalized oxo group, or a hydrogen atom and a free or esterified hydroxyl group, and R2 is a hydrogen atom or a free, esterified or etherified hydroxyl group, and particularly steroids of this class having the formula and the corresponding D 5-3-ketals, and the 19-nor analogues of all these steroids. They may be prepared by treating the 18, 20b -lactones of D 4-3-oxo-9, 11b - oxido-20b -hydroxy-pregnene 18-acids with a hydrohalic acid and then translactonizing the resulting 18, 20-lactones of 9a -halogen-11b -hydroxy-pregnene-18-acids. The 9a -bromo compounds can also be prepared by direct additive combination of hypobromous acid with the 18, 20-lactone of D 4,9(11)-3-oxo-20b -hydroxy-pregnadiene-18-acid Oxidation of the so-formed 20-hydroxy compounds gives the 20-ketones, while treatment with, for example, ethylene ...

Cyclopentanophenanthrene derivatives

Fluoboric acid, HBF4, is prepared by the slow addition of boron trifluoride etherate to anhydrous hydrogen fluoride cooled in an acetone-"dry ice" bath.ALSO:6b -Fluoro-5a -hydroxy steroids of the pregnane series are prepared by reacting a 5a , 6a -oxido steroid with fluoroboric acid or with a mixture of anhydrous hydrogen fluoride and boron trifluoride etherate in a molar ratio ranging from 80:20 to 25-75, preferably in an inert solvent such as benzene or ether-benzene. Detailed examples illustrate the preparation of 6b -fluoro-pregnane-3 b , 5a -diol-20-one 3-acetate, 6b -fluoro-pregnane-3 b , 5a , 17a -triol-20-one 17-acetate, the 17, 21-diacetates of the 21-hydroxy analogue, and of 6b -fluoro-3-ethylenedioxy-pregnane-5a , 17a , 21-triol-11, 20-dione, the 16, 21-diacetate of 3-ethylene dioxy-6b , 9a -difluoro-pregnane-5a , 11 b , 16a , 17a , 21-pentol-20-one, 16a -methyl-6 b -fluoro-D 9(11)-pregnene-3 b , 5a , 17a -triol-20-one and its 17-acetate, 6b -fluoro-pregnane-3b , 5a , 11b , 17a ...

Novel steroids and process for their manufacture

The invention comprises 6-chloro- 1,4 - pregnadienes of the formula: wherein X represents hydrogen or a halogen other than iodine; Y represents O or (H,b OH); A represents a lower alkyl group and OR represents a hydroxyl or the acid radical of an organic acid having up to 12 carbon atom or of a polybasic inorganic acid and 1,2-dihydro analogues thereof, and a process for the preparation thereof by reacting with hydrogen chloride the corresponding compound of the following formula or the 1,2-dihydro analogue thereof. wherein X, Y, A and OR have the significance above. Specification 915,635 also is referred to.

Steroid compounds

The invention comprises 16b -methyl-desoxycorticosterone 21-acetate; 16a , 17a -diazomethylene-pregn-5-ene-3b , 21-diol-20-one-21-acetate; 16-methylpregna-5:16-diene-3b , 21-diol-20-one-21-acetate; and 16b -methylpregn-5-ene-3b , 21-diol-20-one 21-acetate; and a process for the preparation of 16b -methyl-desoxycorticosterone 21-acetate which may commence at any stage of the following synthesis:-pt. pregna-5:16-diene-3b , 21-diol-20-one 21-acetate is reacted with diazomethane to form 16a :17a -diazomethylenepregn-5-ene-3b , 21-diol-20-one 21-acetate, this compound is heated at 140 DEG to 170 DEG C. to form 16-methylpregna-5:16-diene-3b , 21-diol-20-one 21-acetate, this compound is hydrogenated to form 16b -methylpregn-5-ene-3b , 21-diol-20-one, and this compound is oxidized to form 16b -methyl-desoxycorticosterone, for example, by the Oppenauer type oxidation.

A new steroid compound and its formation

The invention comprises 6a -methyl-11b -hydroxy-androsta-1, 4-diene-3,17-dione, and processes for the preparation thereof by subjecting 6a - methyl-11b ,17a ,21-trihydroxy-pregna-1,4-diene-3,20-dione to the action of an oxidising agent so as thus to form the desired 6a -methyl-11b -hydroxy-androsta-1,4-diene-3,17-dione. As oxidising agents there may be used periodic acid, vanadates, lead tetracetate, cerotic nitrate, and preferably sodium bismuthate in acetic acid.

New steroid compounds

The invention comprises steroids of the general formula wherein R represents hydrogen or a halogen of a free or a carboxylic esterified hydroxy group, R1 represents an aliphatic, cycloaliphatic or arylaliphatic hydrocarbon group containing from 4 to 7 carbon atoms, X represents hydrogen, fluorine or chlorine or the methyl group, Y is hydrogen or the methyl group, and Z represents hydrogen or the methyl or a free or a carboxylic esterified hydroxy group with the limitation that X, Y and Z do not all represent hydrogen except when R represents a halogen, but when one of these symbols is other than hydrogen the other two symbols represent hydrogen, and the preparation thereof by reacting a corresponding D 4-3-keto-steroid with an alcohol of the formula R1OH wherein R1 has the above significance, in the presence of an acid catalyst and a lower alkyl orthoformate in solution in an organic solvent. A preferred method of preparation comprises reacting the D 4-3-keto-steroid ...

Process for the preparation of drospirenone

A process is described for the preparation of drospirenone, a synthetic steroid with progestogenic, antimineralocorticoid and antiandrogenic activity, useful for preparing pharmaceutical compositions with contraceptive action; comprising the oxidation of 17α-(3-hydroxypropyl)-6β,7β,15β,16β-dimethylene-5β-androstane-3β,5,17β-triol.

Preparation method of drospirenone

The present invention discloses the preparation method of drospirenone. 3β,5-dyhydroxy-6β,7β,15β,16β-dimethylene-5β-androstane-17,20-epoxy is taken as the raw material. It is subject to oxidization of the hydroxyl at the 3 rd position, ketalization of 3-ketone group, condensation reaction and deesterification to obtain carboxylic acid lactone, sulfonation of the hydroxyl at the 5 th position, and deketalization and desulphonation in the reaction system of glacial acetic acid and sodium acetate to produce the 3-keto-4-alkenyl compound, thus obtaining drospirenone. The preparation method of the invention has high intensification, reaction specificity, less by-products and high yield of products in each step, thus overcoming the disadvantages of low yield and unstable quality.

Chemoselective enrichment for compound isolation

Chemoselective isolation of hydroxyl group-containing and carboxyl group-containing compounds is accomplished via formation of polymeric silyl ethers and polymeric siloxyl esters, respectively. Preparation of chemoselective polymeric reagents for capture of hydroxyl group containing compounds and carboxyl group containing compounds is described.

Method for producing silylenol ethers

The invention relates to a method for producing silyl enol ether compound (3) by reacting ketone or aldehyde compound (1) with allylsilane compound (2) in the presence of a base and 0.00001 to 0.5 equivalents of an acid catalyst relative to ketone or aldehyde compound (1).

NON-HORMONAL STEROID MODULATORS OF NF-kB FOR TREATMENT OF DISEASE

The present invention relates to compounds and methods which may be useful as treatments of neuromuscular diseases such as muscular dystrophy, and as inhibitors of NF-κB for the treatment or prevention of muscular wasting disease, including muscular dystrophy. 2. The method as recited in wherein said disease is muscular dystrophy claim 1 , asthma claim 1 , chronic obstructive pulmonary disease claim 1 , traumatic brain injury claim 1 , spinal cord injury claim 1 , amyotrophic lateral sclerosis claim 1 , and Sjogren's syndrome.3. The method as recited in claim 2 , wherein said disease is muscular dystrophy.4. The method as recited in claim 3 , wherein said muscular dystrophy is Duchenne muscular dystrophy.5. The method as recited in claim 2 , wherein said disease is asthma.6. The method as recited in claim 2 , wherein said disease is chronic obstructive pulmonary disease.7. The method as recited in claim 2 , wherein said disease is arthritis.8. The method as recited in claim 2 , wherein said disease is traumatic brain injury.9. The method as recited in claim 2 , wherein said disease is spinal cord injury.10. The method as recited in claim 2 , wherein said disease is amyotropc lateral sclerosis.11. The method as recited in claim 2 , wherein said disease is Sjogren's syndrome. This application is a divisional of application Ser. No. 13/327,628, filed Dec. 15, 2011, which is a divisional of application Ser. No. 12/473,921, filed May 28, 2009, issued as U.S. Pat. No. 8,207,151 on Jun. 26, 2012, which claims the benefit of priority of U.S. provisional application No. 61/056,715, filed May 28, 2008, the disclosures of which are hereby incorporated by reference as if written herein in their entireties.This invention was made with support from the U.S. Government under Contract No. DOD 05118004 and NIH No. 1U54HD053177-01A1. The U.S. Government has certain rights to this invention.Disclosed herein are new non-hormonal steroid compounds and compositions and their application ...

Derivatives of 3-O-(3',3'-dimethylsuccinyl)-betulinic acid

The present invention relates to compounds of the following formula (I): 2. The compound according to claim 1 , characterized in that R represents a (C-C)alkyl group substituted with one or more claim 1 , preferably one or two claim 1 , groups chosen from COOH and NHR.3. The compound according to or claim 1 , characterized in that R represents a group —(CHR)—(CHR)—X claim 1 , in which:n represents 0 or 1,{'sup': '1', 'X represent a group COOH or NHR, and'}{'sup': 2', '3', '1, 'sub': 1', '8', '1', '4, 'Rand Rrepresent, independently of each other, a hydrogen atom or a (C-C)alkyl group, preferably a (C-C)alkyl group, optionally substituted with a group COOH or NHR,'}{'sup': 2', '3, 'preferably at least Ror Rrepresenting a hydrogen atom.'}4. The compound according to any of to claim 1 , characterized in that Rrepresents a hydrogen atom or a —C(O)O-Alk group claim 1 , in particular a hydrogen atom or a tert-butyloxycarbonyl group.6. A compound according to any of to as a medicine.7. A compound according to any of to for use in the treatment of an infection with a retrovirus such as HIV claim 1 , and in particular HIV-1.8. A pharmaceutical composition comprising at least one compound according to any of to and at least one pharmaceutically acceptable vehicle. The present invention relates to derivatives of 3-O-(3′,3′-dimethylsuccinyl)-betulinic acid, a method for preparing them and their use in the treatment of an infection with a retrovirus such as HIV.Most of the anti-HIV-1 drug inhibitors target the enzymatic activities catalyzed by the reverse transcriptase (RT), the integrase (IN) or the protease (PR) and have caused the emergence of multidrug-resistant HIV-1 strains. Thus, the scientific community has been involved in the discovery of new targets to fight AIDS and in the development of new molecules directed against these targets. The assembly of the HIV-1 Gag precursor (Pr55Gag) and the maturation steps of the virus replication represent attractive targets for the ...

VEGF Production Promoter

Provided are a VEGF production promoter, a hair quality improver, and an external preparation for skin, each of which has a VEGF production promoting activity and can be used as a pharmaceutical agent, a cosmetic, a food, or a material therefor. The VEGF production promoter, the hair quality improver, and the external preparation for skin each comprises, as an active ingredient, a cycloartane-type glycoside represented by the following general formula (1) (where R represents a xylose residue or an arabinose residue, and the ring D moiety represents any one of the following moieties a to f (where R 1 represents a hydrogen atom or a methyl group, R 2 represents a hydrogen atom or an acetyl group, R 3 represents a hydrogen atom or a hydroxyl, group, R 4 represents a hydrogen atom or a hydroxyl group, and Ac represents an acetyl group)).

New Steroids Having Increased Water Solubility and Resistance Against Metabolism and Methods For Their Production

Steroid compounds having increased resistance against metabolism and increased water solubility are disclosed, together with methods for their production. These substances are suitable for the manufacture of pharmaceuticals for the treatment of steroid related or steroid induced CNS disorders and for use in methods of prevention, alleviation or treatment of such disorders.

Pharamceutical compositions and methods of use 4-pregenen-11beta-17-21-triol-3,20-dione derivatives

The present invention relates to pharmaceutical compositions comprising 4-pregenen-11β-17-21-triol-3,20-dione derivatives, and their use as pharmaceuticals as modulators of the glucocorticoid receptors (GR) and/or the mineralocorticoid receptors (MR). The invention relates specifically to the use of these compounds and their pharmaceutical compositions to treat ocular conditions associated with the glucocorticoid receptors (GR) and/or the mineralocorticoid receptors (MR).

Process for Production of Triterpene Alcohol

A process for producing triterpene alcohol, comprising sequentially conducting the following steps (A) to (C): 1. A process for producing triterpene alcohol , comprising sequentially conducting the following steps (A) to (C):(A) subjecting γ-oryzanol to alkaline hydrolysis;(B) mixing the alkaline hydrolysate with a low polarity organic solvent, and extracting triterpene alcohol to obtain a triterpene alcohol-containing low polarity organic solvent; and(C) adding water to the triterpene alcohol-containing low polarity organic solvent thus obtained, removing the low polarity organic solvent, and then melting triterpene alcohol in hot water, followed by cooling.2. The process for producing triterpene alcohol according to claim 1 , wherein the low polarity organic solvent is hexane.3. The process for producing triterpene alcohol according to claim 1 , wherein the amount of water added to the triterpene alcohol-containing low polarity organic solvent is 5 to 100 times by weight of the initial amount of γ-oryzanol.4. The process for producing triterpene alcohol according to claim 1 , wherein the amount of water added to the triterpene alcohol-containing low polarity organic solvent is 5 to 20 times by weight of the initial amount of γ-oryzanol.5. The process for producing triterpene alcohol according to claim 1 , wherein the amount of water added to the triterpene alcohol-containing low polarity organic solvent is 8 to 15 times by weight of the initial amount of γ-oryzanol.6. The process for producing triterpene alcohol according to claim 1 , wherein the temperature of the hot water for melting triterpene alcohol is from 85 to 100° C.7. The process for producing triterpene alcohol according to claim 1 , wherein the temperature of the hot water for melting triterpene alcohol is from 90 to 100° C.8. The process for producing triterpene alcohol according to claim 1 , comprising conducting adsorption treatment for exposing the triterpene alcohol-containing low polarity ...

Substituted 16,17-annellated steroid compounds for use in womens health

The present invention relates to substituted steroid compounds having the formula Wherein R 1 is H or halogen; R 2 is H, (1C-4C)alkyl, (1C-4C)acyl, glucuronyl or sulfamoyl; R 3 is H or halogen; R 4 is H, (1C-4C)alkyl, (2C-4C)alkenyl or (2C-4C)alkynyl; R 5 is methyl or ethyl; R 6 is H or methyl; R 7 is H or methyl; R 8 is H or acyl for use in the treatment and prevention of endometriosis, for contraception, for hormonal therapy in perimenopausal and post-menopausal women, for the treatment of osteoporosis and for the treatment uterine fibroids and other menstrual-related disorders, such as dysfunctional uterine bleeding.

METHODS FOR INHIBITING MUSCLE ATROPHY

In one aspect, the invention relates methods for inhibiting or preventing muscle atrophy or increasing muscle mass by providing to a subject in need thereof an effective amount of ursolic acid, a derivative thereof, or an analog of the ursane scaffold. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present invention. 2. The method of claim 1 , wherein the mammal has been diagnosed with a need for treatment of muscle atrophy prior to the administering step.3. The method of claim 1 , wherein the compound is not ursolic acid claim 1 , boswellic acid claim 1 , corosolic acid claim 1 , betulinic acid claim 1 , or UA0713.4. The method of claim 1 , wherein the compound is ursolic acid claim 1 , boswellic acid claim 1 , corosolic acid claim 1 , betulinic acid claim 1 , or UA0713.5. The method of claim 1 , wherein the compound is ursolic acid.6. The method of claim 1 , wherein the compound is not administered as a foodstuff.7. The method of claim 1 , wherein administration increases muscle mass and/or muscular strength in the animal.17. The method of claim 16 , wherein AA is a phenylalanine residue claim 16 ,19. A pharmaceutical composition comprising at least one compound as defined in .20. A pharmaceutical composition comprising at least one compound as defined in . This application claims the benefit of U.S. Applications No. 61/346,813, filed on May 20, 2010, and No. 61/445,488, filed on Feb. 22, 2011, which are hereby incorporated by reference in entirety.This invention was made with government support under grant VA Career Development Award-2 to Christopher M. Adams, and support from a VA Research Enhancement Award Program to Steven D. Kunkel. The United States government has certain rights in the invention.Skeletal muscle atrophy is characteristic of starvation and a common effect of aging. It is also a nearly universal consequence of severe human illnesses, including cancer, ...

C-3 CYCLOALKENYL TRITERPENOIDS WITH HIV MATURATION INHIBITORY ACTIVITY

Compounds having drug and bio-affecting properties, their pharmaceutical compositions and methods of use are set forth. In particular, C-3 cycloalkenyl triterpenoids that possess unique antiviral activity are provided as HIV maturation inhibitors, as represented by compounds of Formulas I, II, III and IV: 2. The compound as claimed in claim 1 , wherein said compound has the Formula I.3. The compound as claimed in claim 1 , wherein said compound has the Formula II.4. The compound as claimed in claim 1 , wherein said compound has the Formula III.5. The compound as claimed in claim 2 , wherein Ris isopropenyl.6. The compound as claimed in claim 5 , wherein X is selected from the group of Ccycloalkenyl claim 5 , Cspirocycloalkyl claim 5 , and Cspirocycloalkenyl.7. The compound as claimed in claim 6 , wherein Y is —COOR.8. The compound as claimed in claim 7 , wherein Y is —COOH.9. The compound as claimed in claim 6 , wherein A is —H.12. A pharmaceutical composition which comprises an antiviral effective amount of one or more of the compounds as claimed in claim 1 , together with one or more pharmaceutically acceptable carriers claim 1 , excipients or diluents.13. A pharmaceutical composition which comprises an antiviral effective amount of one or more of the compounds as claimed in claim 10 , together with one or more pharmaceutically acceptable carriers claim 10 , excipients or diluents.14. pharmaceutical composition which comprises an antiviral effective amount of one or more of the compounds as claimed in claim 11 , together with one or more pharmaceutically acceptable carriers claim 11 , excipients or diluents.15. The pharmaceutical composition of claim 12 , useful for treating infection by HIV claim 12 , which additionally comprises an antiviral effective amount of an AIDS treatment agent selected from the group consisting of: (a) an AIDS antiviral agent; (b) an anti-infective agent; (c) an immunomodulator; and (d) another HIV entry inhibitor.16. A method for ...

(11beta, 17alpha)-11-(4-(2-11C-ACETYL)PHENYL)-17,23-EPOXY-19,24-DINORCHOLA-4,9,20-TRIEN-3-ONE

The present invention relates to (11β,17α)-11-(4-(2-C-acetyl)phenyl)-17,23-epoxy-19,24-dinorchola-4,9,20-trien-3-one, an C-labelled ORG 33628; a process for the preparation thereof, intermediates used in this process and the use of this compound as a PET tracer for the detection of breast cancer. 1. (canceled)48-. (canceled)9. The process according to wherein the acid treatment is combined with the previous reaction step.10. The process according to wherein in step b the base is a Grignard reagent.11. The process according to wherein the Grignard reagent is isopropylmagnesium bromide.12. The process according to wherein the [C]methyllithium is prepared by reacting [C]methyl halide with (C3-6)alkyl-lithium.13. A method of diagnosing or monitoring breast cancer or a breast cancer state in mammals comprising the steps of:a. administering an effective amount of the compound according to Formula 1 to a subject;b. imaging said mammal, performing a PET scan on the subject to generate PET scan images and diagnosing or monitoring said breast cancer or breast cancer state.1415-. (canceled) The present invention relates to (11β,17α)-11-(4-(2-C-acetyl)phenyl)-17,23-epoxy-19,24-dinorchola-4,9,20-trien-3-one, an C-labelled ORG 33628; a process for the preparation thereof, intermediates used in this process and the use of this compound as a PET tracer for the detection of breast cancer.Breast cancer is a common cause of death among women and, although less common, also in men. Breast cancer is a well known example of a hormone dependent cancer in which steroid hormone receptors play a key role in tumor proliferation and disease progression. Steroid hormone receptors, more specifically estrogen receptors and progesterone receptors, are often expressed in breast tumor tissue.ORG 33628 is a highly selective progesterone receptor modulator (PRM) with a predominant anti-progestagenic profile. Two main indications for the use of PRMs are the treatment of breast cancer and fertility ...

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.

Triterpene-containing oleogel-forming agent, triterpene-containing oleogel and method for producing a triterpene-containing oleogel

The invention relates to an oleogel-forming agent which comprises at least one highly dispersed triterpene. The invention also relates to an oleogel which comprises a nonpolar liquid in an amount ranging from 80% by weight to 99% by weight based on the total weight of the oleogel and an oleogel-forming agent comprising a highly dispersed triterpene in an amount ranging from 1% by weight to 20% by weight based on the total weight of the oleogel. The invention also relates to a method for producing an oleogel.

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.

COMBINATION THERAPEUTIC NANOPARTICLES

Nanoparticles that include a chemotherapeutic agent and an anti-inflammatory are particularly cytotoxic to prostate cancer cells. 17-. (canceled)8. A method for treating prostate cancer in a subject in need thereof , comprising:administering a therapeutically effective amount of a nanoparticle comprising a chemotherapeutic agent and an anti-inflammatory agent to the subject.9. A method according to claim 8 , wherein the nanoparticle comprises a hydrophilic core and a hydrophilic layer surrounding the core.10. A method according to claim 8 , wherein the chemotherapeutic agent and the anti-inflammatory agent are attached to the core.11. A method according to claim 8 , wherein the chemotherapeutic agent is cisplatin.12. A method according to claim 11 , wherein the anti-inflammatory agent is aspirin.13. A method according to claim 8 , wherein the prostate cancer is castration resistant prostate cancer.14. A use according to claim 8 , wherein the nanoparticle is more cytotoxic to prostate cancer cells than a combination of a comparable dose of the free chemotherapeutic agent and the free anti-inflammatory agent.15. A nanoparticle claim 8 , comprising:a hydrophobic nanoparticle core, wherein the hydrophobic polymer that forms at least a part of the core is selected from the group consisting of a polymer comprising polylactic acid (PLA) and a polymer comprising polylactic-co-glycolic acid (PLGA);a hydrophilic layer surrounding the core, wherein the hydrophilic polymer moiety is attached to the core via a hydrophobic polymer moiety that forms at least a part of the core;an anti-inflammatory agent attached to the core; anda chemotherapeutic agent attached to the core.16. A nanoparticle according to claim 15 , wherein the anti-inflammatory agent is a corticosteroid or a non-steroidal anti-inflammatory drug.17. A nanoparticle according to claim 15 , the anti-inflammatory agent is aspirin.18. A nanoparticle according to claim 15 , the anti-inflammatory agent is prednisone.19. A ...

CRYSTALLINE SOLVATE FORMS OF A PHARMACEUTICAL

Described herein are solid state 17α-ethynylandrost-5-ene-3β,7β,17β-triol including amorphous and crystalline forms and specific polymorphic forms thereof, and use of solid state 17α-ethynylandrost-5-ene-3β,7β,17β-triol in treating numerous diseases and disorders, including hyperglycemic conditions, such as type 2 diabetes and metabolic syndrome, autoimmune conditions, such as rheumatoid arthritis, ulcerative colitis and type 1 diabetes, among other inflammation related conditions, and neurodegenerative conditions in subjects or human patients. 1. (canceled)2. (canceled)3. (canceled)4. (canceled)5. (canceled)6. (canceled)7. (canceled)8. (canceled)9. (canceled)10. (canceled)11. (canceled)12. A method to treat an inflammation condition comprising administering to a human or mammal in need thereof an effective amount of a formulation comprising a solid state form of 17α-ethynylandrost-5-ene-3β ,7β ,17β-triol and at least one pharmaceutically acceptable excipient.13. The method of claim 12 , wherein the inflammation condition is an inflammatory bowel condition.14. The method of claim 12 , wherein the inflammation condition is an inflammatory lung condition.15. The method of claim 14 , wherein the inflammatory lung condition is cystic fibrosis claim 14 , asthma claim 14 , bronchitis or chronic obstructive pulmonary disease.16. The method of claim 12 , wherein the solid state form of 17α-ethynylandrost-5-ene-3β claim 12 ,7β claim 12 ,17β-triol is crystalline solvate 17α-ethynylandrost-5-ene-3β claim 12 ,7β claim 12 ,17β-triol.17. The method of claim 16 , wherein the crystalline solvate is crystalline methanolate 17α-ethynylandrost-5-ene-3β claim 16 ,7β claim 16 ,17β-triol.18. The method of claim 16 , wherein the crystalline solvate is crystalline ethanolate 17α-ethynylandrost-5-ene-3β claim 16 ,7β claim 16 ,17β-triol.19. (canceled)20. The method of claim 16 , wherein the crystalline solvate is Form III 17α-ethynylandrost-5-ene-3β claim 16 ,7β claim 16 ,17β-triol.21. ( ...

FLUORINATED AND ALKYLATED BILE ACIDS

The present invention relates to fluorinated and alkylated bile acids. 3. The compound according to wherein X claim 2 , X claim 2 , Xand Xare all —F.4. The compound according to wherein any three of X claim 2 , X claim 2 , Xand Xare —F.5. The compound according to wherein any two of X claim 2 , X claim 2 , Xand Xare —F.6. The compound according to wherein one of X claim 2 , X claim 2 , Xand Xis —F.10. The compound according to claim 9 , wherein Xand Xare all alkylated.11. The compounds according to claim 9 , wherein any one of Xand Xare alkylated.13. A method of treating or preventing a disease that is selected from the group consisting of neurological disease claims 1 , diabetes claims 1 , ocular disorders claims 1 , spinal cord injury claims 1 , kidney injury or metabolic syndrome in a subject claims 1 , said method comprising administering to said subject a therapeutically effective amount of a compound according to claims 1 ,14. The method according to claim 13 , wherein the disease is a neurological disease selected from the group consisting of Alzheimer's claim 13 , Parkinson's claim 13 , Huntington's claim 13 , and amyotrophic lateral sclerosis (ALS).15. The method according to claim 13 , wherein the disease is type 2 diabetes.16. The method according to claim 13 , wherein the disease is acute kidney injury.17. The method according to claim 13 , wherein the disease is an ocular disorder selected from macular degeneration (MD) and diabetic retinopathy. This application is a divisional of U.S. patent application Ser. No. 15/556768, filed Sep. 8, 2017, which is a U.S. National Stage Application filed under 35 U.S.C. § 371 from International Application Serial No. PCT/US2016/021809, filed on Mar. 10, 2016, and published as WO 2016/145216 on Sep. 15, 2016, which claims the benefit of priority to U.S. Provisional Application Ser. No. 62/130,931, filed on Mar. 10, 2015 and U.S. Provisional Application Ser. No. 62/141,506, filed on Apr. 1, 2015, which applications ...

Process for the Preparation of Drospirenone

A process is described wherein, by employing 17α-(3-hydroxypropyl) -63,7β3;15β,16β-dimethylene-5β-androstane-3β,5,17β-triol (II) as starting product, in a single stage reaction there is obtained drospirenone, (I), whereby the reaction is achieved using gaseous oxygen as the stoichiometric oxidant in the presence of a catalytic system containing (i) TEMPO or a derivative thereof (ii) a ferric salt (Fe3+) and (iii) NaCl. The product drospirenone is a known synthetic steroid with progestogenic, antimineralocorticoid and antiandrogenic action, that is useful for preparing pharmaceutical compositions with contraceptive action. 2. The process according to claim 1 , wherein the oxygen is employed in the form of pure oxygen claim 1 , air or mixtures of inert gas and oxygen.3. The process according to claim 1 , wherein the derivative of 2 claim 1 ,2 claim 1 ,6 claim 1 ,6-tetramethylpiperidine-1-oxyl radical is selected from the group consisting of 4-hydroxy-2 claim 1 ,2 claim 1 ,6 claim 1 ,6-tetramethylpiperidine-1-oxyl radical claim 1 , 4-methoxy-2 claim 1 ,2 claim 1 ,6 claim 1 ,6-tetramethylpiperidine-1-oxyl radical claim 1 , 4-(benzoyloxy)-2 claim 1 ,2 claim 1 ,6 claim 1 ,6-tetramethylpiperidine-1-oxyl radical claim 1 , 4-acetamido-2 claim 1 ,2 claim 1 ,6 claim 1 ,6-tetramethylpiperidine-1-oxyl radical and 4-amino-2 claim 1 ,2 claim 1 ,6 claim 1 ,6-tetramethylpiperidine-1-oxyl radical.4. The process according to claim 1 , wherein said acid is selected from the group consisting of acetic acid claim 1 , anhydrous or hydrated oxalic acid claim 1 , citric acid claim 1 , anhydrous or hydrated para toluene sulphonic acid claim 1 , formic acid claim 1 , sulphuric acid claim 1 , perchloric acid claim 1 , hydrochloric acid claim 1 , phosphoric acid claim 1 , nitric acid claim 1 , hydrobromic acid claim 1 , fumaric acid claim 1 , maleic acid claim 1 , xinafoic acid claim 1 , benzoic acid and substitution derivatives thereof on the aromatic ring claim 1 , or alkali metal and ...

BUFALIN PHOSPHATE PRODRUGS AND METHODS OF USE THEREOF

Bufalin phosphate prodrugs are provided herein, as well as methods for their use as small molecule inhibitors of steroid receptor coactivator (SRC) family proteins. Methods for using bufalin phosphate prodrugs in treating or preventing cancer are also provided herein. 5. The compound of claim 4 , wherein the cation is a metal cation.6. The compound of claim 5 , wherein the metal cation is an alkali metal cation or an alkaline earth metal cation.7. The compound of claim 4 , wherein X is selected from the group consisting of Na claim 4 , K claim 4 , Li claim 4 , and NH.10. A composition comprising a compound of and a pharmaceutically acceptable carrier.11. (canceled)12. A method of treating or preventing a steroid receptor coactivator-related disease in a subject claim 1 , comprising:{'claim-ref': {'@idref': 'CLM-00001', 'claim 1'}, 'administering to the subject an effective amount of a compound of .'}13. The method of claim 12 , wherein the steroid receptor coactivator-related disease is cancer claim 12 , obesity claim 12 , or human immunodeficiency virus.14. The method of claim 13 , wherein the steroid receptor coactivator-related disease is cancer and the cancer is a poor prognosis or invasive cancer claim 13 , breast cancer claim 13 , pancreatic cancer claim 13 , glioblastoma claim 13 , liver cancer claim 13 , lung cancer claim 13 , pancreatic cancer claim 13 , or prostate cancer.15. (canceled)16. The method of claim 14 , wherein the cancer is breast cancer and the breast cancer is triple negative breast cancer.17. (canceled)18. (canceled)19. The method of claim 14 , wherein the cancer is glioblastoma and the glioblastoma is a glioblastoma multiforme tumor.20. The method of claim 19 , wherein the glioblastoma multiforme tumor is a pediatric glioblastoma multiforme tumor.21. (canceled)22. (canceled)23. (canceled)24. (canceled)25. The method of claim 12 , further comprising administering a second compound or composition.26. The method of claim 25 , wherein the ...

NOVEL PROCESS FOR PREPARATION OF GLUCOCORTICOID STEROIDS

The present invention discloses a process for the preparation of 16, 17-acetals of pregnane derivatives having formula I 3. The process as claimed in step (i) of claim 1 , wherein dihydroxylation of compound of formula (II) is carried out with an oxidizing agent claim 1 , selected from group comprising potassium permanganate claim 1 , potassium dichromate claim 1 , chromic acid claim 1 , peroxyacids or mixtures thereof claim 1 , preferably claim 1 , potassium permanganate claim 1 , formic acid and sodium metabisulphite to form compound of formula (III).4. The process as claimed in step (ii) of claim 1 , wherein compound of formula (III) is brominated with a brominating agent claim 1 , selected from the group comprising dibromantin claim 1 , N-bromosuccinamide claim 1 , preferably claim 1 , dibromatin to form compound of formula (IV) in presence of organic solvent claim 1 , selected from the group comprising tetrahydrofuran claim 1 , acetone claim 1 , N claim 1 ,N-dimethyl formamide claim 1 , DMSO claim 1 , methanol claim 1 , methylene dichloride claim 1 , acetonitrile claim 1 , ethyl acetate claim 1 , diethyl ether claim 1 , 1-butanol claim 1 , methylethyl ketone claim 1 , 1-propanol claim 1 , formamide claim 1 , preferably claim 1 , tetrahydrofuran.5. The process as claimed in step (iii) of claim 1 , wherein compound of formula (IV) is debrominated to form compound of formula (V) in presence of catalyst claim 1 , Rt---SH (VIII) with an aprotic solvent at appropriate temperature claim 1 , wherein{'br': None, 'sub': 't', 'R—SH\u2003\u2003 Formula VIII'}{'sub': t', '2', '2', '2', 't', '2, 'wherein Ris —CHCOOH or —CHCHCOOH preferably Ris —CHCOOH.'}6. The process as claimed in claim 5 , wherein catalyst is selected from the group comprising chromous or chromium sulfate claim 5 , chromous or chromium chloride or its hydrate claim 5 , preferably claim 5 , chromium chloride hexahydrate.7. The process as claimed in claim 5 , wherein aprotic solvent is selected from the ...

Methods for Preparing Bile Acids

The present disclosure provides methods of preparing cholic acid, deoxycholic acid, or chenodeoxycholic acid, an ester thereof, or a pharmaceutically or cosmetically acceptable salt thereof, and novel and useful synthetic intermediates, for example, as described for methods 1, 1A, 1B, 2, 3, 3A, and 4. The method can start with a plant derived steroid as a starting material, such as dehydroepiandrosterone (DHEA) or Acetyl-dehydroepiandrosterone (Ac-DHEA). Also provided are pharmaceutical or cosmetic compositions and uses thereof, which comprise one or more of cholic acid, deoxycholic acid, or chenodeoxycholic acid, an ester thereof, or a pharmaceutically or cosmetically acceptable salt thereof, which is of high purity, for example, free of animal derived impurities. 176.-. (canceled)78. The compound of claim 77 , wherein Ris H claim 77 , and Rand Rare each independently a hydroxyl protecting group.79. The compound of claim 78 , wherein the hydroxyl protecting group is acetyl.82. The method of claim 80 , wherein Ris H claim 80 , and Rand Rare each independently a hydroxyl protecting group.83. The method of claim 82 , wherein the hydroxyl protecting group is acetyl. This application is a continuation of U.S. application Ser. No. 16/636,260, which is a 35 U.S.C. § 371 national phase of PCT/CN2018/098535, having an international filing date of Aug. 3, 2018, which claims priority to PCT/CN2017/095784, filed on Aug. 3, 2017, the contents of which are herein incorporated by reference in their entirety.The present disclosure is generally related to the field of steroid synthesis, e.g., methods of preparing a bile acid (e.g., cholic acid, deoxycholic acid, or chenodeoxycholic acid) from a plant derived steroid, and novel synthetic intermediates. The present disclosure is also related to pharmaceutical or cosmetic compositions comprising a bile acid (e.g., cholic acid, deoxycholic acid, or chenodeoxycholic acid) or its ester(s) or salt(s), and pharmaceutical or cosmetic uses ...

ANXIOLYTIC MARCGRAVIACEAE COMPOSITIONS CONTAINING BETULINIC ACID, BETULINIC ACID DERIVATIVES, AND METHODS

Pharmaceutical compositions for preventing or treating anxiety, comprising betulinic acid or derivatives thereof are provided. Methods for preventing or treating anxiety with betulinic acid or derivatives thereof are also provided. The invention further provides betulinic-acid containing preparations of plants of the family Marcgraviaceae having anxiolytic activity and methods for making such extracts and using them to prevent or treat anxiety in a subject. 1. A betulinic acid-containing composition obtained from of a plant of the family Marcgraviaceae.2. The composition of claim 1 , wherein the composition is an extract of Marcgraviaceae claim 1 , prepared by a method comprising:(a) contacting a Marcgraviaceae plant, or part thereof, with a first solvent in which betulinic acid is soluble, to form a betulinic acid-containing extract; and(b) recovering the betulinic acid-containing extract from the first solvent, thereby preparing a betulinic acid-containing composition.3. The composition of claim 2 , wherein (b) further comprises:(a) filtering the betulinic acid-containing extract from (a); and(b) evaporating the first solvent.4. The composition of claim 2 , wherein (b) further comprises:(a) filtering the betulinic acid-containing extract from (a),(b) evaporating the solvent,(c) extracting by stirring with a second solvent; and(d) evaporating the second solvent.5. The composition of claim 1 , comprising at least about 0.1% to 90% by weight betulinic acid.6. The composition of claim 1 , comprising at least about 0.5% by weight betulinic acid.7. The composition of claim 1 , comprising at least about 1% by weight betulinic acid.8. The composition of claim 1 , comprising at least about 5% by weight betulinic acid.9Marcgraviastrum, Norantea, Ruyschia, Sarcopera, Marcgravia, Pseudosarcopera, SouroubeaSchwartzia.. The composition of claim 1 , wherein the plant is of a genus selected from the group consisting of claim 1 , or10Souroubea. The composition of claim 1 , wherein ...

Process for the preparation of 17-(3-hydroxypropyl)-17-hydroxysteroids

The present invention relates to a process for the preparation of 17α-(3-hydroxypropyl)-17β-hydroxysteroids of the formula I starting from 17-ketosteroids of the formula III via the intermediates of the formula V wherein the radicals R 3 , R 5 , R 6 , R 7 , R 10 , R 13 , R 15 , R 16 , R 40 , R 41 and R 42 have the meaning indicated in the description.

PROCESS FOR ALKYNYLATING 16-SUBSTITUTED-17-KETO STEROIDS

A process ethynylates 16-methylene-17-keto steroids to the corresponding 16-methylene-17α-ethynyl-17β-hydroxy steroids by treatment with silyl-protected lithium acetylides followed by further desilylation. The resulting products are useful intermediates in the preparation of several pharmaceutically active agents, such as e.g. Nestorone® or melengestrol acetate. 4. Process according to claim 2 , wherein{'sup': 3', '1', '1, 'sub': 1', '3, 'Ris selected from O or —OR, wherein Ris a C-Calkyl;'}{'sup': '6', 'Ris selected from H, F, methyl and methylene;'}{'sup': '9', 'Ris selected from H and F;'}{'sup': 11', '9', '11, 'sub': 9', '11, 'Ris selected from H and OH, or there is a double bond between Cand Cand Rand Rare absent;'}{'sup': '18', 'Ris selected from methyl and ethyl;'}{'sup': '19', 'Ris selected from H and methyl.'}6. Process according to claim 1 , wherein each R is independently selected from C-Calkyl and phenyl.7. Process according to claim 1 , wherein the compound of formula (I) is lithium trimethylsilylacetylene.8. Process according to claim 1 , wherein desilylation step (b) is performed by treatment with potassium carbonate.9. Process according to claim 1 , wherein the ethynylated product is further converted to a compound selected from the group formed by Nestorone® claim 1 , nestorone alcohol and melengestrol acetate.15. Process for the preparation of a compound selected from the group formed by Nestorone® claim 12 , nestorone alcohol and melengestrol acetate claim 12 , said process comprising the use of a compound as defined in .16. Process according to claim 2 , comprising one of the following conditions (a) to (d):{'sub': 1', '3, '(a) wherein each R is independently selected from C-Calkyl and phenyl;'}(b) wherein the compound of formula (I) is lithium trimethylsilylacetylene;(c) wherein desilylation step (b) is performed by treatment with potassium carbonate;(d) wherein the ethynylated product is further converted to a compound selected from the group ...

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 ...

Commands and method of treating cancer via RHO pathway

Lanosterol derivatives useful as anti-cancer agent, which can inhibit the growth of lung cancer cells, liver cancer cells, mammary cancer cells, brain cancer cells and pancreatic cancer cells, possibly by acting on the RHO pathway. These lanosterol derivatives are represented by compound LD030:

Methods and compounds for modulating the secretion or expression of adhesion proteins or angiopoietins of cells

This invention provides methods, processes, compounds and compositions for modulating the gene expression or secretion of adhesion proteins, angiopoietins or their receptors to cure diseases, for anti-angiogenesis and for treating parasites, wherein the adhesion proteins or receptors comprise fibronectin, integrins family, myosin, vitronectin, collagen, laminin, glycosylation cell surface proteins, polyglycans, cadherin, heparin, tenascin, CD 54, CAM, elastin and FAK; wherein the angiopoietins comprise angiopoietin 1, angiopoietin 2, angiopoietin 3, angiopoietin 4, angiopoietin 5, angiopoietin 6, angiopoietin 7, angiopoietin-like 1, angiopoietin-like 2, angiopoietin-like 3, angiopoietin-like 4, angiopoietin-like 5, angiopoietin-like 6, and angiopoietin-like 7; wherein the cancers comprise breast cancer, leukocyte cancer, liver cancer, ovarian cancer, bladder cancer, prostate cancer, skin cancer, bone cancer, brain cancer, leukemia cancer, lung cancer, colon cancer, CNS cancer, melanoma cancer, renal cancer, cervical cancer, esophageal cancer, testicular cancer, spleenic cancer, kidney cancer, lymphatic cancer, pancreas cancer, stomach cancer and thyroid cancer.

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.

NON-HORMONAL STEROID MODULATORS OF NF-kB FOR TREATMENT OF DISEASE

The present invention relates to compounds and methods which may be useful as treatments of neuromuscular diseases such as muscular dystrophy, and as inhibitors of NF-κB for the treatment or prevention of muscular wasting disease, including muscular dystrophy. 1. (canceled)3. The pharmaceutical composition of claim 2 , wherein said disease is atherosclerosis.4. The pharmaceutical composition of claim 2 , wherein said disease is hypercholesterolemia.5. The pharmaceutical composition of claim 2 , wherein said disease is heart disease.6. The pharmaceutical composition of claim 2 , wherein said disease is chronic heart failure.7. The pharmaceutical composition of claim 2 , wherein said disease is ischemia/reperfusion.8. The pharmaceutical composition of claim 2 , wherein said disease is angina pectoris.9. The pharmaceutical composition of claim 2 , wherein said disease is myocarditis.10. The pharmaceutical composition of claim 2 , wherein said pharmaceutical composition comprises a tablet or a capsule.11. The pharmaceutical composition of claim 3 , wherein said pharmaceutical composition comprises a tablet or a capsule.12. The pharmaceutical composition of claim 4 , wherein said pharmaceutical composition comprises a tablet or a capsule.13. The pharmaceutical composition of claim 5 , wherein said pharmaceutical composition comprises a tablet or a capsule.14. The pharmaceutical composition of claim 6 , wherein said pharmaceutical composition comprises a tablet or a capsule.15. The pharmaceutical composition of claim 7 , wherein said pharmaceutical composition comprises a tablet or a capsule.16. The pharmaceutical composition of claim 8 , wherein said pharmaceutical composition comprises a tablet or a capsule.17. The pharmaceutical composition of claim 9 , wherein said pharmaceutical composition comprises a tablet or a capsule. This application is a continuation of application Ser. No. 15/229,947, filed Aug. 5, 2016, which is a continuation of application Ser. No. 14/164, ...

SYNTHESIS OF ENT-PROGESTERONE AND INTERMEDIATES THEREOF

The present invention relates to the synthesis of ent-progesterone and intermediates thereof.

GANAXOLONE DERIVATIVES FOR TREATMENT OF CENTRAL NERVOUS SYSTEMS DISORDERS

The present invention is directed to Ganaxolone prodrugs with increased aqueous solubility and oral bioavailability relative to Ganaxolone and that enable development of stable extended release formulations which offer a significant therapeutic advantage and improved patience compliance by enabling treatments with lower doses over prolonged periods of time. 223-. (canceled)25. A compound according to claim 24 , wherein Xis selected from the group consisting of:{'sup': 2', '1', '2', '1', '2', '−', '+', '2', '2', '1', '2', '2', '2, 'sub': 2', '2', '2', '2', '2', '2', '2', '2', '2', '2', '2', '2', '2', '2', '2, '(C═O)—OC(R)O(C═O)R, (C═O)—OC(R)O(C═O)OR, (C═O)—OC(R)O(P═O)—(OM), (C═O)—OC(R)O(P═O)—(OC(R)O(C═O)YR), (C═O)—OC(R)O(C═O)(CHR)N(R), (C═O)—OC(R)O(C═O)N(R), and (C═O)—OC(R)O(C═O)N(CHCOR).'}26. A compound according to claim 24 , wherein Xis selected from the group consisting of:{'sup': 1', '−', '+', '−', '+', '4', '+', '−', '1', '−', '+', '2', '1, 'sub': 2', 'n', '2', '2', 'n', '2', '2', 'm', '2', 'n', '2', '2', '2', 'n', '2', '2', 'n', '2', '2', 'p', '2', '2', '3', '2', '2', '2', '2', '2', '2, '(C═O)R, (C═O)—(CH)COM, (C═O)—(CH)COR, (C═O)—(CH)O(C═O)R, (C═O)—(CH)OR, (C═O)—CH═CH—COR, (C═O)—CH═CH—COM, (C═O)—(CH)N(R), (C═O)—(CH)(C═O)N(R), (C═O)—(CH)N(C═O)R, (C═O)—(CHR)N(R), (C═O)—(CH)NRA, (C═O)OR, (P═O)—(OM), (P═O)—(OC(R)O(C═O)YR), and (C═O)—N(CHCOR).'}27. A compound according to claim 24 , wherein Xis selected from the group consisting of:{'sup': 2', '1', '2', '1', '2', '−', '+', '2', '2', '1', '2', '2', '2, 'sub': 2', '2', '2', '2', '2', '2', '2', '2', '2', '2', '2', '2', '2', '2', '2, 'C(R)O(C═O)R, C(R)O(C═O)OR, C(R)O(P═O)—(OM), C(R)O(P═O)—(OC(R)O(C═O)YR), C(R)O(C═O)(CHR)N(R), C(R)O(C═O)N(R), and C(R)O(C═O)N(CHCOR).'}28. A compound according to wherein R is hydrogen.29. A compound according to wherein R is methyl.30. (canceled)31. A compound according to wherein Ris alkyl.32. (canceled)33. (canceled)34. (canceled)35. A compound according to wherein Ris hydrogen36. A ...

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, ...

C-3 AND C-17 MODIFIED TRITERPENOIDS AS HIV-1 INHIBITORS

Compounds having drug and bio-affecting properties, their pharmaceutical compositions and methods of use are set forth. In particular, betulinic acid derivatives that possess unique antiviral activity are provided as HIV maturation inhibitors, as represented by compounds of Formula I: 3. The compound of claim 2 , wherein Ris isopropenyl.4. The compound of claim 3 , wherein Y is —COOR.5. The compound of claim 4 , wherein Ris H.6. The compound of claim 1 , wherein Ris —Calkyl-Q.7. The compound of claim 6 , wherein Qis —NRR.9. The compound of claim 8 , wherein Rand Rare each selected from the group of —H and —Calkyl.10. The compound of claim 1 , wherein Qis —CN.14. A composition which comprises an HIV ameliorating amount of one or more compounds as claimed in claim 1 , together with one or more pharmaceutically acceptable carriers claim 1 , excipients claim 1 , and/or diluents.15. A composition which comprises an HIV ameliorating amount of one or more compounds as claimed in claim 11 , together with one or more pharmaceutically acceptable carriers claim 11 , excipients claim 11 , and/or diluents.16. A composition which comprises an HIV ameliorating amount of one or more compounds as claimed in claim 12 , together with one or more pharmaceutically acceptable carriers claim 12 , excipients claim 12 , and/or diluents.17. A composition which comprises an HIV ameliorating amount of one or more compounds as claimed in claim 13 , together with one or more pharmaceutically acceptable carriers claim 13 , excipients claim 13 , and/or diluents.18. A method for treating a mammal infected with the HIV virus comprising administering to said mammal an HIV ameliorating amount of a compound as claimed in claim 1 , together with one or more pharmaceutically acceptable carriers claim 1 , excipients claim 1 , and/or diluents.19. A method for treating a mammal infected with the HIV virus comprising administering to said mammal an HIV ameliorating amount of a compound as claimed in claim 12 ...

COMBINATION THERAPEUTIC NANOPARTICLES

Nanoparticles that include a chemotherapeutic agent and an anti-inflammatory are particularly cytotoxic to prostate cancer cells. 17-. (canceled)8. A method for treating prostate cancer in a subject in need thereof , comprising:administering a therapeutically effective amount of a nanoparticle comprising a chemotherapeutic agent and an anti-inflammatory agent to the subject.9. A method according to claim 8 , wherein the nanoparticle comprises a hydrophilic core and a hydrophilic layer surrounding the core.10. A method according to claim 8 , wherein the chemotherapeutic agent and the anti-inflammatory agent are attached to the core.11. A method according to claim 8 , wherein the chemotherapeutic agent is cisplatin.12. A method according to claim 11 , wherein the anti-inflammatory agent is aspirin.13. A method according to claim 8 , wherein the prostate cancer is castration resistant prostate cancer.14. A use according to claim 8 , wherein the nanoparticle is more cytotoxic to prostate cancer cells than a combination of a comparable dose of the free chemotherapeutic agent and the free anti-inflammatory agent.15. A nanoparticle claim 8 , comprising:a hydrophobic nanoparticle core, wherein the hydrophobic polymer that forms at least a part of the core is selected from the group consisting of a polymer comprising polylactic acid (PLA) and a polymer comprising polylactic-co-glycolic acid (PLGA);a hydrophilic layer surrounding the core, wherein the hydrophilic polymer moiety is attached to the core via a hydrophobic polymer moiety that forms at least a part of the core;an anti-inflammatory agent attached to the core; anda chemotherapeutic agent attached to the core.16. A nanoparticle according to claim 15 , wherein the anti-inflammatory agent is a corticosteroid or a non-steroidal anti-inflammatory drug.17. A nanoparticle according to claim 15 , the anti-inflammatory agent is aspirin.18. A nanoparticle according to claim 15 , the anti-inflammatory agent is prednisone.19. A ...

NON-HORMONAL STEROID MODULATORS OF NF-kB FOR TREATMENT OF DISEASE

The present invention relates to compounds and methods which may be useful as treatments of neuromuscular diseases such as muscular dystrophy, and as inhibitors of NF-κB for the treatment or prevention of muscular wasting disease, including muscular dystrophy. 2. The use as recited in claim 1 , wherein{'sub': 7', '8', '2', '3', '7', '8', '3-6, 'Rand Rare independently selected from the groups consisting of hydrogen, unsubstituted C-Calkyl, or Rand Rcan be taken together to form Csaturated cycloalkyl;'}{'sub': '9', 'Ris selected from the group consisting of hydrogen, acyl, and alkyl, said acyl and alkyl being optionally substituted with one or more substituents selected from the group consisting of acyl, alkenyl, alkoxy, alkyl, alkylamino, alkylthio, alkynyl, amino, aryl, aryloxy, aroyl, carbamate, cyano, cycloalkyl, halogen, haloalkoxy, haloalkyl, heteroalkyl, heterocycloalkyl, heteroaryl, hydrazinyl, hydroxy, mercaptyl, perhaloalkoxy, sulfonate, alkylsulfonyl, N-sulfonamido, S-sulfonamido, and thiol;'}{'sub': 1', '2', '2', '3', '4', '5', '7', '8', '6', '9', '1', '5, 'if Ris hydrogen, methyl, —CHF, or fluoro, R, R, R, R, R, and Rare each hydrogen, and Ris hydroxyl, then Ris not hydrogen, formyl, unsubstituted C-Calkylacyl, or benzoyl;'}{'sub': 1', '2', '2', '3', '4', '7', '8', '5', '6', '9', '1', '5, 'if Ris hydrogen, methyl, —CHF, or fluoro, R, R, R, R, and Rare each hydrogen, Ris methyl, and Ris hydroxyl, then Ris not hydrogen, formyl, unsubstituted C-Calkylacyl, trifluoroacetyl, —C(O)-adamantyl, or benzoyl;'}{'sub': 1', '2', '3', '4', '6', '7', '8', '5', '9', '1', '5, 'if Ris hydrogen, methyl, fluoro, or chloro, R, R, R, R, R, and Rare each hydrogen, and Ris methyl, then Ris not hydrogen, unsubstituted C-Calkylacyl, or benzoyl;'}{'sub': 1', '2', '3', '4', '7', '8', '5', '6', '9, 'if said dashed line indicates a double bond, R, R, R, R, R, and Rare each hydrogen, and Rand Rare each methyl, then Ris not hydrogen, acetyl, or benzoyl;'}{'sub': 1', '2', '3', '4', '5', ...

Process and intermediates for the production of 17(20)-ene b-seco steroids

The invention pertains to a process for producing a compound of formula (11) wherein R7 and R8 are each independently selected from H, halogen, alkyl, aryl, or alkylaryl, R42 is H or a protective group, R43 is H or R3, wherein R3 is a protective group, by contacting a compound of formula (10) with an olefmation reagent, wherein compound of formula (10) comprises a counter acid X1 when R42═H and R43═H.

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.

PROCESS FOR THE PREPARATION OF DROSPIRENONE

A process is disclosed wherein, using either 17a-(3-hydroxypropyl)-6p,7p;15p,16p-dimethylene-5p-androstane-3p,5,17p-triol (II) or 3β,5̂iÎκ̂-6β,7β;15β,16β-dimethylene-5β,17α-pregnane-21,17-carbolactone (III) as starting material, through a single-step reaction it is obtained drospirenone (I), a synthetic steroid with progestogenic, antimineralocorticoid and antiandrogenic activity, useful for preparing pharmaceutical compositions with contraceptive action. 2. The process according to claim 1 , wherein oxygen is used in form of pure oxygen claim 1 , air claim 1 , or mixtures of an inert gas and oxygen at a pressure between 1 and 10 bar.3. The process according to claim 1 , wherein said palladium compound is selected from acetate (Pd(CHO)) claim 1 , acetylacetonate (Pd(CHO)) claim 1 , trifluoroacetate (Pd(COF)) claim 1 , hexafluoroacetylacetonate (Pd(CHOF)) claim 1 , propionate (Pd(CHO)) claim 1 , chloride (PdCl) claim 1 , bromide (PdBr) claim 1 , iodide (PdI) claim 1 , cyanide (Pd(CN)) claim 1 , nitrate (Pd(NO)) claim 1 , sulfide (PdS) claim 1 , oxide (PdO) and hydroxide (Pd(OH)).4. The process according to claim 1 , wherein said palladium compound is used in amounts by weight ranging from 1% to 100% with respect to compound (II) or compound (III).5. The process according to claim 1 , wherein said organic base is selected from pyridine and its alkyl derivatives claim 1 , triethylamine claim 1 , aniline claim 1 , pyrrolidine claim 1 , DBU (1 claim 1 ,8-Diazabicyclo[5.4.0]undec-7-ene) claim 1 , DBN (1 claim 1 ,5-Diazabicyclo[4.3.0]non-5-ene) claim 1 , and cyclic compounds containing two or more nitrogen atoms claim 1 , both aromatic and non-aromatic.6. The process according to claim 1 , wherein said organic base is used in amount by weight equal to or greater than 0.5 times the amount of palladium compound used.7. The process according to claim 6 , wherein the amount by weight of organic base is between 0.5 and 25 times as much as the amount of palladium compound used. ...

EPOXY-(METH)ACRYLATE MONOMERS AND POLYMERS AND METHODS OF MAKING AND USING THE SAME

The present invention relates to the unexpected discovery of novel monomer compounds capable of crosslinking interpenetrating polymer networks (IPNs). In certain embodiments, the monomer compounds of the invention each comprise at least one methacrylate functionality capable of forming polymeric bonds with other methacrylate and vinyl functionalities, and at least one epoxide functionality capable of forming polymeric bonds with epoxide functionalities, amine functionalities, and/or reactive oxygen species. 2. The compound of claim 1 , wherein m is 1 and n is 1.3. A composition comprising at least one monomer of .4. The composition of claim 3 , further comprising at least one polymerization initiator.5. The composition of claim 4 , wherein the polymerization initiator is at least one selected from the group consisting of photoinitiators claim 4 , thermal initiators claim 4 , and redox initiators claim 4 , with and/or without an accelerator.6. The composition of claim 3 , further comprising at least one additional compound comprising at least one selected from the group consisting of an epoxide functionality claim 3 , a methacrylate functionality claim 3 , a vinyl functionality claim 3 , an acrylate functionality claim 3 , an allylic functionality claim 3 , a cyclic carbonate functionality claim 3 , a thiol functionality claim 3 , an amine functionality claim 3 , an aniline functionality claim 3 , an anhydride functionality claim 3 , a carboxylic acid functionality claim 3 , and an unsaturated polyester.7. The composition of claim 6 , wherein the at least one additional compound is selected from the group consisting of bisphenol A diglycidyl ether claim 6 , bisphenol F diglycidyl ether claim 6 , bisguaiacol diglycidyl ether claim 6 , novolac epoxies claim 6 , glycidyl ethers of hydrogenated bisphenols and epoxides claim 6 , di(cyclohexane epoxidemethyl)ether claim 6 , epoxy cyclohexyl methyl-epoxy cyclohexane carboxylate claim 6 , 4 claim 6 ,4′- ...

4-pregenen-11beta-17-21-triol-3,20-dione derivatives

The present invention relates to novel 4-pregenen-11β-17-21-triol-3,20-dione derivatives, processes for preparing them, pharmaceutical compositions containing them and their use as pharmaceuticals, as modulators of glucocorticoid or mineralocorticoid receptors. The invention relates specifically to the use of these compounds and their pharmaceutical compositions to treat disorders associated with glucocorticoid or mineralocorticoid receptor modulation.

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 ...

NON-HORMONAL STEROID MODULATORS OF NF-kB FOR TREATMENT OF DISEASE

The present invention relates to compounds and methods which may be useful as treatments of neuromuscular diseases such as muscular dystrophy, and as inhibitors of NF-κB for the treatment or prevention of muscular wasting disease, including muscular dystrophy.

CRYSTALLINE FORMS OF DEXAMETHASONE DIMERS AND USES THEREOF

The disclosure features polymorphs of a prodrug dimer of dexamethasone linked at the 21-C and 21′-C carbons via a carbonate-triethylene glycol-carbonate linker. Also disclosed are pharmaceutical compositions and articles comprising said polymorphs, and the use thereof in the treatment of a disease or condition, e.g. via the extended or controlled release of dexamethasone from said articles. 1. A solid crystalline form of Compound 1 characterized by a powder X-ray diffraction (PXRD) diffractogram obtained using Cu(λ=1.54 Å) radiation comprising peaks expressed in degrees 2θ (±0.2°) at: 3.8° , 7.6° , and 12.1°.2. The solid crystalline form of claim 1 , wherein said solid crystalline form characterized by a PXRD diffractogram obtained using Cu(λ=1.54 Å) radiation further comprising peaks expressed in degrees 2θ (±0.2°) at: 8.7° claim 1 , 9.7° claim 1 , 10.6° claim 1 , 13.3° claim 1 , and 14.6°.3. A solid crystalline form of Compound 1 characterized by a powder X-ray diffraction (PXRD) diffractogram obtained using Cu(λ=1.54 Å) radiation comprising peaks expressed in degrees 2θ (±0.2°) at: 3.9° claim 1 , 7.9° claim 1 , 11.9° claim 1 , and 15.8°.4. The solid crystalline form of claim 3 , wherein said solid crystalline form characterized by a PXRD diffractogram obtained using Cu(λ=1.54 Å) radiation further comprising peaks expressed in degrees 2θ (±0.2°) at: 4.8° claim 3 , 5.7° claim 3 , 6.6° claim 3 , 8.6° claim 3 , 9.7° claim 3 , 13.4° claim 3 , 14.5° claim 3 , and 17.2°.5. A solid crystalline form of Compound 1 characterized by a powder X-ray diffraction (PXRD) diffractogram obtained using Cu(λ=1.54 Å) radiation comprising peaks expressed in degrees 2θ (±0.2°) at: 8.0° claim 3 , 9.8° claim 3 , 12.1° claim 3 , and 13.8°.6. The solid crystalline form of claim 5 , wherein said solid crystalline form characterized by a PXRD diffractogram obtained using Cu(λ=1.54 Å) radiation further comprising peaks expressed in degrees 2θ (±0.2°) at: 3.9° claim 5 , 15.0° claim 5 , 16.1° ...

ANTAGONISTS OF CB1 RECEPTOR

The invention relates to an antagonist of CB1 receptor for use in the treatment of a pathologic condition or disorder selected from the group consisting of bladder and gastrointestinal disorders; inflammatory diseases; cardiovascular diseases; nephropathies; glaucoma; spasticity; cancer; osteoporosis; metabolic disorders; obesity; addiction, dependence, abuse and relapse related disorders; psychiatric and neurological disorders; neurodegenerative disorders; autoimmune hepatitis and encephalitis; pain; reproductive disorders and skin inflammatory and fibrotic diseases. 130-. (canceled)32. The method according to claim 31 , wherein said compound is not substantially converted into active pregnenolone down stream derivatives after administration to a subject.34. The pregnenolone derivative compound according to claim 33 , wherein said compound is 17α-Methylprogesterone or 17α-Benzylprogesterone.36. The method according to claim 35 , wherein said compound is 5-pregnen-3β-O-benzyl-20-one claim 35 , 3β-Aminopregnenolone or 5-pregnen-3β-azido-20-one.38. The method according to claim 37 , wherein said compound is 17α-Allyl-3β-methoxypregnenolone claim 37 , 17α-Benzyl-3β-fluoropregnenolone claim 37 , 3β-Fluoro-17α-methylpregnenolone claim 37 , 3β-Methoxy-17α-methylpregnenolone claim 37 , 17α-Benzyl-3β-methoxypregnenolone claim 37 , 3β-Benzyloxy-17α-methylpregnenolone or 17α-Benzyl-3β-benzyloxypregnenolone.40. The method according to claim 39 , wherein said compound is 17α-Benzylpregnenolone claim 39 , 17α-Ethylpregnenolone claim 39 , 17α-Methylpregnenolone or 17-Methoxypregnenolone.42. The method according to claim 41 , wherein said compound is 20-Deoxypregnenolone or 20-Methylamino-5-pregnen-3β-ol.44. The method according to wherein said compound is 5 claim 43 ,16-Pregnadien-20-one.45. The method according to wherein the bladder and gastrointestinal disorder is selected from the group consisting of liver fibrosis; liver steatosis; non-alcoholic steatohepatitis (NASH); liver ...

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.

ENZYMATIC PROCESS FOR OBTAINING 17 ALPHA-MONOESTERS OF CORTEXOLONE AND/OR ITS 9,11-DEHYDRODERIVATIVES

The present invention refers to a new enzymatic process for obtaining 17α-monoesters of cortexolone and/or its 9,11-dehydroderivatives starting from the corresponding 17α,21-diesters which comprises an enzymatic alcoholysis reaction. Furthermore, the present invention refers to new crystalline forms of cortexolone-17α-propionate and 9,11-dehydro-cortexolone 17α-butanoate. 1. Crystalline form I of cortexolone-17α-propionate characterized by an IR as shown in .2. Crystalline form I of cortexolone-17α-propionate according to claim 1 , wherein the crystalline form is further characterized by a DSC as shown in .3. Crystalline form I of cortexolone-17α-propionate according to claim 1 , prepared by a process comprising crystallizing cortexolone-17α-propionate from tert-butylmethylether.4. Crystalline form I of cortexolone-17α-propionate according to claim 3 , wherein the process further comprises crystallizing cortexolone-17α-propionate at a concentration of 0.9 to 1.1 g of cortexolone-17α-propionate in 9 to 11 ml tert-butylmethylether.5. A pharmaceutical composition comprising at least one physiologically acceptable excipient and crystalline form I of cortexolone-17α-propionate according to .6. The composition of claim 5 , wherein the at least one physiologically acceptable excipient is propylene glycol claim 5 , cetylic alcohol claim 5 , glyceryl monostearate claim 5 , liquid paraffin claim 5 , or a combination of any of the foregoing.7. The composition of claim 5 , further comprising mixed tocopherols claim 5 , polysorbate 80 claim 5 , or a combination thereof.8. The composition of claim 5 , wherein the composition is in the form of a tablet claim 5 , capsule claim 5 , powder claim 5 , pellet claim 5 , suspension claim 5 , emulsion claim 5 , cream claim 5 , gel claim 5 , ointment claim 5 , lotion claim 5 , or paste.9. The composition of claim 5 , wherein the composition is in the form of a solid claim 5 , semi-solid claim 5 , or a paste.10. The composition of claim 8 , ...

Synthesis of a substituted indene derivative

This invention is directed to methods of preparing AQX-1125 having the formula: This invention is also directed to intermediates utilized in the methods of preparing AQX-1125.

Polyethylene Glycol-Conjugated Glucocorticoid Prodrugs and Compositions and Methods Thereof

Polyethylene glycol (PEG)-conjugated glucocorticoid prodrugs, methods of preparation, and use for the treatment of diseases and disorders are disclosed. In particular, PEG-conjugated dexamethasone compounds and methods of using them for treating inflammatory and autoimmune diseases, including but not limited to lupus, are disclosed. 2. The pharmaceutical composition of claim 1 , wherein E is a linker comprising a branched structure capable of covalently bonding to two or more Rgroups claim 1 , said linker optionally comprising one or more heteroatoms independently selected from the group consisting of O claim 1 , S claim 1 , and N.3. The pharmaceutical composition of claim 1 , wherein Z is a linker comprising a branched structure capable of covalently bonding to two or more dexamethasone moieties claim 1 , said linker optionally comprising one or more heteroatoms independently selected from the group consisting of O claim 1 , S claim 1 , and N.17. The pharmaceutical composition of claim 1 , wherein n is 40 to 50.18. The pharmaceutical composition of claim 1 , wherein the composition is in oral claim 1 , nasal claim 1 , topical claim 1 , buccal claim 1 , sublingual claim 1 , rectal claim 1 , vaginal claim 1 , intravenous claim 1 , intramuscular claim 1 , intraperitoneal claim 1 , or other parenteral form.19. The pharmaceutical composition of in vaporization-ready claim 1 , nebulization-ready claim 1 , nanoparticle formulation claim 1 , or liposomal formulation.20. The pharmaceutical composition of claim 1 , further comprising a second therapeutic agent selected from the group consisting of a NSAID (e.g. Aspirin claim 1 , Naproxen claim 1 , Celebrex) claim 1 , a Glucocorticoid (e.g. Dexamethasone claim 1 , Prednisone claim 1 , Betamethasone) claim 1 , and a DMARD (e.g. Methotrexate claim 1 , Leflunomide claim 1 , Sulfasalazine claim 1 , Hydroxychoroquine) claim 1 , and a biologic drug.21. A method of treating an autoimmune disease and/or inflammatory disorder claim 1 ...

CERTAIN CHEMICAL ENTITIES, COMPOSITIONS, AND METHODS

Chemical entities that are bufalin derivatives, pharmaceutical compositions and methods of treatment of cancer are described. 131.-. (canceled)32. A compound selected from the group consisting of:(R)-(3S,5R,8R,9S,10S,13R,14S,17R)-14-hydroxy-10,13-dimethyl-17-(2-oxo-2H-pyran-5-yl)hexadecahydro-1H-cyclopenta[a]phenanthren-3-yl 2-aminopropanoate;(S)-(3S,5R,8R,9S,10S,13R,14S,17R)-14-hydroxy-10,13-dimethyl-17-(2-oxo-2H-pyran-5-yl)hexadecahydro-1H-cyclopenta[a]phenanthren-3-yl 2-aminopropanoate;(R)-(3S,5R,8R,9S,10S,13R,14S,17R)-14-hydroxy-10,13-dimethyl-17-(2-oxo-2H-pyran-5-yl)hexadecahydro-1H-cyclopenta[a]phenanthren-3-yl 2-amino-3-methylbutanoate;(S)-(3S,5R,8R,9S,10S,13R,14S,17R)-14-hydroxy-10,13-dimethyl-17-(2-oxo-2H-pyran-5-yl)hexadecahydro-1H-cyclopenta[a]phenanthren-3-yl 2-amino-3-methylbutanoate;(R)-(3S,5R,8R,9S,10S,13R,14S,17R)-14-hydroxy-10,13-dimethyl-17-(2-oxo-2H-pyran-5-yl)hexadecahydro-1H-cyclopenta[a]phenanthren-3-yl 2-amino-4-methylpentanoate;(S)-(3S,5R,8R,9S,10S,13R,14S,17R)-14-hydroxy-10,13-dimethyl-17-(2-oxo-2H-pyran-5-yl)hexadecahydro-1H-cyclopenta[a]phenanthren-3-yl 2-amino-4-methylpentanoate;(3S,5R,8R,9S,10S,13R,14S,17R)-14-hydroxy-10,13-dimethyl-17-(2-oxo-2H-pyran-5-yl)hexadecahydro-1H-cyclopenta[a]phenanthren-3-yl (2-(pyrrolidin-1-yl)ethyl) carbonate;(3S,5R,8R,9S,10S,13R,14S,17R)-14-hydroxy-10,13-dimethyl-17-(2-oxo-2H-pyran-5-yl)hexadecahydro-1H-cyclopenta[a]phenanthren-3-yl (2-morpholinoethyl) carbonate;(3S,5R,8R,9S,10S,13R,14S,17R)-14-hydroxy-10,13-dimethyl-17-(2-oxo-2H-pyran-5-yl)hexadecahydro-1H-cyclopenta[a]phenanthren-3-yl (2-(pyrrolidin-1-yl)ethyl)carbamate;(3S,5R,8R,9S,10S,13R,14S,17R)-14-hydroxy-10,13-dimethyl-17-(2-oxo-2H-pyran-5-yl)hexadecahydro-1H-cyclopenta[a]phenanthren-3-yl (2-morpholinoethyl)carbamate;(3S,5R,8R,9S,10S,13R,14S,17R)-14-hydroxy-10,13-dimethyl-17-(2-oxo-2H-pyran-5-yl)hexadecahydro-1H-cyclopenta[a]phenanthren-3-yl piperazine-1-carboxylate;4-(((((3S,5R,8R,9S,10S,13R,14S,17R)-14-hydroxy-10,13-dimethyl-17-(2-oxo-2H-pyran-5- ...

NEUROACTIVE STEROIDS, COMPOSITIONS, AND USES THEREOF

Described herein are steroids of Formula (I): 2. The method of claim 1 , wherein Ris methyl.3. The method of claim 1 , wherein both Rand Rare hydrogen.4. The method of claim 1 , wherein Ris C-Calkyl claim 1 , C-Calkenyl claim 1 , C-Calkynyl claim 1 , carbocyclyl claim 1 , heterocyclyl claim 1 , C(O)R claim 1 , —C(O)OR claim 1 , or —C(O)NRR.5. The method of claim 4 , wherein Ris —C(O)NRR.6. The method of claim 1 , wherein Ris hydrogen claim 1 , C-Calkyl claim 1 , or —OH.7. The method of claim 6 , wherein Ris hydrogen.8. The method of claim 1 , wherein both Rand Rare hydrogen claim 1 , the between —CRand —CRRis a single bond claim 1 , and both Rand Rare hydrogen.9. The method of claim 1 , wherein Z is —CH—.10. The method of claim 1 , wherein Ris hydrogen and Ris C-Calkyl.12. The method of claim 11 , wherein Ris methyl.13. The method of claim 11 , wherein Ris C-Calkyl claim 11 , C-Calkenyl claim 11 , C-Calkynyl claim 11 , carbocyclyl claim 11 , heterocyclyl claim 11 , —C(I)R claim 11 , —C(O)OR claim 11 , or —C(O)NRR.14. The method of claim 11 , wherein Ris C-Calkyl.15. The method of claim 11 , wherein Ris hydrogen.16. The method of claim 11 , wherein both Rand Rare hydrogen and both Rand Rare hydrogen.19. The method of claim 18 , wherein Ris methyl.20. The method of claim 18 , wherein Ris C-Calkyl claim 18 , C-Calkenyl claim 18 , C-Calkynyl claim 18 , carbocyclyl claim 18 , heterocyclyl claim 18 , —C(O)R claim 18 , —C(O)OR claim 18 , or —C(O)NRR.21. The method of claim 18 , wherein Ris C-Calkyl.22. The method of claim 20 , wherein Ris —C(O)NRR.23. The method of claim 18 , wherein Ris —OH.24. The method of claim 18 , wherein Ris hydrogen.25. The method of claim 18 , wherein both Rand Rare hydrogen and both Rand Rare hydrogen.27. (canceled)28. (canceled)29. (canceled)30. The method of claim 1 , wherein the CNS-related disorder is a major depressive disorder.31. The method of claim 1 , wherein the CNS-related disorder is tremor.32. The method of claim 31 , wherein the ...

17A-MONOESTERS AND 17A,21-DIESTERS OF CORTEXOLONE FOR USE IN THE TREATMENT OF TUMORS

The present invention relates to certain cortexolone derivatives of formula (I) 2. The method of claim 1 , wherein the disease is a tumor disease.3. The method of claim 2 , wherein the tumor disease is a malignant neoplasia or metastasis.4. The method of or claim 2 , wherein the tumor disease is a solid tumor.5. The method of claim 4 , wherein the solid tumor is an epithelial tumor.6. The method of claim 5 , wherein the epithelial tumor is prostate carcinoma claim 5 , mammary carcinoma claim 5 , uterine carcinoma claim 5 , pancreatic carcinoma claim 5 , lung carcinoma claim 5 , gastro-intestinal tract carcinoma claim 5 , kidney cancer claim 5 , thyroid carcinoma claim 5 , uterine carcinoma or adrenal carcinoma.7. The method of claim 6 , wherein the epithelial tumor is prostate carcinoma claim 6 , pancreatic carcinoma claim 6 , exocrine pancreatic carcinoma claim 6 , gastro-intestinal tract carcinoma or mammary carcinoma.8. The method of claim 7 , wherein the prostate carcinoma is or becomes resistant to anti-androgen targeted therapy.9. The method of claim 8 , wherein the anti-androgen targeted therapy is enzalutamide.10. The method of claim 7 , wherein the mammary carcinoma is triple negative breast cancer.11. The method of claim 10 , wherein the subject is relapsed or a non-responder to conventional therapy.12. The method of claim 7 , wherein the gastro-intestinal tract carcinoma is colon carcinoma.13. The method of claim 1 , wherein:{'sub': '1', 'R is C(O)—R;'}{'sub': 1', '2', '3, 'Ris hydrogen or CHCH;'}{'sub': 2', '3', '3, 'R′ is —(CH)—CHor a phenyl group; and'}{'sub': '1', 'wherein Rand R′ are not the same.'}14. The method of claim 13 , wherein the compound is cortexolone 17α-valerate-21-propionate.15. The method of claim 1 , further comprising administering at least one other chemotherapeutic active ingredient to said subject.17. The method of claim 16 , wherein:{'sub': '1', 'R is C(O)—R;'}{'sub': 1', '2', '3, 'Ris hydrogen or CHCH; and'}{'sub': 2', '3', '3, ...

Progesterone Phosphate Analogs and Uses Related Thereto

This disclosure relates to progesterone phophate derivatives and uses related thereto. In certain embodiments, the disclosure relates to compounds disclosed herein and uses for managing inflammation such as those resulting from traumatic brain injury or stroke. 2. The method of claim 1 , wherein X is N—OCRROPZ(OR)and Y is O.3. The method of claim 1 , wherein Y is N—OCRROPZ(OR)and X is O.4. The method of claim 1 , wherein Rand Rare hydrogen or alkyl.5. The method of claim 1 , wherein Rand Rform a cyclopropyl ring.6. The method of claim 1 , wherein Ris phosphate ion claim 1 , hydrogen claim 1 , alkanoyl claim 1 , or alkyl.9. A method of treating or preventing inflammation or CNS injury comprising administering an effective amount of a pharmaceutical composition comprising (E)-(((1-(10 claim 1 ,13-dimethyl-3-oxo-2 claim 1 ,3 claim 1 ,6 claim 1 ,7 claim 1 ,8 claim 1 ,9 claim 1 ,10 claim 1 ,11 claim 1 ,12 claim 1 ,13 claim 1 ,14 claim 1 ,15 claim 1 ,16 claim 1 ,17-tetradecahydro-1H-cyclopenta[a]phenanthren-17-yl)ethylidene)amino)oxy)methyl dihydrogen phosphate or salts thereof claim 1 , to a subject in need thereof.10. The method of claim 1 , wherein the pharmaceutical composition is administered to a subject that incurred trauma to the head or other organ or tissue.11. The method of claim 1 , wherein the pharmaceutical composition is administered after a medical procedure.12. The method of claim 1 , wherein the pharmaceutical composition is administered in combination with a second anti-inflammatory agent.13. A method of treating stroke or traumatic brain injury comprising administering an effective amount of a pharmaceutical composition of to a subject in need thereof.14. A method of treating a neurodegenerative disease or condition comprising administering an effective amount of a pharmaceutical composition of to a subject in need thereof.15. The method of claim 14 , wherein the neurodegenerative disease or condition is selected from Alzheimer's disease claim 14 , ...

Process and new intermediates for the preparation of 11-methylene steroids

The invention relates to a process for the preparation of 11-methylene steroids through selective olefination of the ketone at position 11. The resulting products are useful intermediates in the preparation of several pharmaceutically active agents, such as Etonogestrel and Desogestrel.

OXYSTEROLS AND METHODS OF USE THEREOF

Compounds are provided according to Formula (I) and pharmaceutically acceptable salts thereof, and pharmaceutical compositions thereof; wherein 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. 1. (canceled)3. The compound or pharmaceutically acceptable salt thereof claim 2 , of claim 2 , wherein Rand Rare not both hydrogen.45.-. (canceled)6. The compound or pharmaceutically acceptable salt thereof claim 2 , of claim 2 , wherein each of Rand Ris independently hydrogen claim 2 , —P(O)(R) claim 2 , —S(O)R claim 2 , —C(O)R claim 2 , —C(O)OR claim 2 , —C(O)N(R) claim 2 , —(CH)C(O)N(R) claim 2 , —(CH)OP(O)(R) claim 2 , —(CH)OS(O)R claim 2 , —(CH)OC(O)R claim 2 , or —(CH)C(O)OR;{'sup': a', 'b', 'd, 'each of Rand Ris independently selected from —ORor substituted or unsubstituted alkyl;'}{'sup': 'c', 'each Ris independently substituted or unsubstituted alkyl;'}{'sup': 'd', 'each Ris independently hydrogen or substituted or unsubstituted alkyl;'}each x is independently 1 or 2; andeach of n, m, p is independently 1, 2, 3, or 4.7. (canceled)8. The compound or pharmaceutically acceptable salt thereof claim 2 , of claim 2 , wherein Ris substituted or unsubstituted Calkyl.9. The compound or pharmaceutically acceptable salt thereof claim 2 , of claim 2 , wherein Ris hydrogen.1011.-. (canceled)12. The compound or pharmaceutically acceptable salt thereof claim 2 , of claim 2 , wherein each of Rand Ris independently hydrogen claim 2 , methyl claim 2 , —CF claim 2 , ethyl claim 2 , isopropyl claim 2 , cyclopropyl claim 2 , or butyl.13. The compound or pharmaceutically acceptable salt thereof claim 2 , of claim 2 , wherein Ris a moiety cleavable under biological conditions and Ris hydrogen.14. The compound or pharmaceutically acceptable salt thereof claim 2 , of claim 2 , wherein Ris hydrogen and Ris a moiety cleavable under biological conditions.15. The compound or ...

Compounds and methods for managing cancer through immune system

The present disclosure relates to methods of managing cancer by modulating/inhibiting cap methyltransferase enzyme. The modulation/inhibition is carried out by pharmacological or biological inhibitors, including but not limited to compounds of formula (VIII) or Compound A or A-1. Thus, the present disclosure relates to such inhibitors including compounds of formula (VIII) and their use for management of cancer. In some aspects, the compound of formula (VIII) is Compound 1. The present disclosure also relates to methods of activating B cells or T cells via modulation of cap methyltransferases. The present disclosure also relates to methods of managing cancer with a molecule or biologic that generates unmethylated RNA. The generation of unmethylated RNA activates B cells and presents the RNA to B-cell receptor (BCR). The present disclosure therefore also relates to management of cancer by activating B cells and then adoptively transferring the B cells to exert an anticancer effect.

COMPOUNDS AND METHODS FOR TRANS-MEMBRANE DELIVERY OF MOLECULES

A novel delivery system for drugs, and especially macromolecules such as proteins or oligonucleotides through biological membranes is provided, and specifically delivery of siRNA The delivery system comprises conjugation of the macromolecule drug to a moiety that enables effective passage through the membranes. Respectively, novel compounds and pharmaceutical compositions are provided, utilizing said delivery system. In one aspect of the invention, the compounds may be utilized in medical practice, for example, in delivery of siRNA or antisense oligonucleotides across biological membranes for the treatment of medical disorders. 4. (canceled)610.-. (canceled)11. The Conjugate according to claim 5 , as set forth in Formula (XIV) claim 5 , wherein s is 2 or 4.12. (canceled)13. (canceled)14. The Conjugate according to claim 5 , as set forth in Formula (XVI) claim 5 , wherein t is 2 or 4.15. A Conjugate as claimed in claim 3 , according to general Formula (I) claim 3 , where E claim 3 , E′ or E″ has the structure as set forth in any of Formulae II claim 3 , VII claim 3 , VIII or VIIIa claim 3 , attached to a drug.16. The Conjugate according to claim 15 , wherein the drug is a macromolecule claim 15 , selected from the group consisting of siRNA claim 15 , ASO and a therapeutic protein.17. The Conjugate according to claim 16 , wherein the therapeutic protein comprises a CRISPR protein.18. The Conjugate according to claim 17 , wherein the CRISPR protein is Cas9 protein.19. The pharmaceutical composition claim 15 , comprising a Conjugate according to and a pharmaceutically-acceptable salt or carrier.20. A method for delivery of a drug into biological cells claim 15 , wherein said cells are in culture claim 15 , or in a living animal or a human subject; the method comprising contacting the cells with a Conjugate according to .21. A method for treatment of a medical disorder claim 19 , said method comprising administration to a patient in need claim 19 , therapeutically ...

19-NOR C3, 3-DISUBSTITUTED C21-N-PYRAZOLYL STEROIDS AND METHODS OF USE THEREOF

Provided herein are 19-nor C3,3-disubstituted C21-pyrazolyl steroids of Formula (I), and pharmaceutically acceptable salts thereof; wherein-, R, R, R, R, R, R, R, R, and Rare as defined herein. Such compounds are contemplated useful NI 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. 2. The compound of Formula (I) of claim 1 , wherein Ris Calkyl optionally substituted with alkoxy or one to two halo groups claim 1 , and at least one of R claim 1 , R claim 1 , and Ris halogen claim 1 , —NO claim 1 , —CN claim 1 , —OR claim 1 , —N(R) claim 1 , —C(═O)R claim 1 , —C(═O)OR claim 1 , SR claim 1 , —S(O)R claim 1 , e.g. claim 1 , —S(═O)R claim 1 , —S(═O)R claim 1 , —S(═O)OR claim 1 , —OS(═O)R claim 1 , —S(═O)N(R) claim 1 , substituted or unsubstituted Calkyl claim 1 , wherein Ris substituted or unsubstituted Calkyl.5. The compound of claim 1 , wherein Ris unsubstituted Calkyl.6. The compound of claim 1 , wherein Ris a Calkyl optionally substituted with alkoxy.7. The compound of claim 1 , wherein Ris a Calkyl optionally substituted with one or two halo.8. The compound of claim 1 , wherein Ris —CH claim 1 , —CHCH claim 1 , —CHF claim 1 , —CHF claim 1 , —CHO CHCH claim 1 , or —CHOCH.9. The compound of claim 8 , wherein Ris —CH.10. The compound of claim 1 , wherein Ris —OH claim 1 , —OCH claim 1 , —OCHCH claim 1 , —OCHCHCH claim 1 , —CH claim 1 , —CHCH claim 1 , —CHCHCH claim 1 , substituted or unsubstituted cyclopropyl claim 1 , fluoro claim 1 , or chloro.11. The compound of claim 10 , wherein Ris —CHor —OCH.12. The compound of claim 11 , wherein Ris —OCH.13. The compound of claim 1 , wherein Ris hydrogen.14. The ...

Compositions for the prevention and treatment of parkinson's disease

Methods of preventing or retarding or reversing or abolishing the onset of Parkinson's and other neurodegenerative diseases are discussed.

NOVEL BETULINIC ACID DERIVATIVES AS HIV INHIBITORS

The invention relates to novel betulinic acid derivatives and related compounds, and pharmaceutical compositions useful for therapeutic treatment of viral diseases and particularly HIV mediated diseases. 3. A compound selected from the group consisting of:(1R,3aS,5aR,5bR,7aR,9S,11aR,11bR,13aR,13bR)-9-((1S,3R)-3-(carboxymethyl)-2,2-dimethylcyclopropanecarbonyloxy)-5a,5b,8,8,11a-pentamethyl-1-(prop-1-en-2-yl)icosahydro-1H-cyclopenta[a]chrysene-3a-carboxylic acid,2-((1R,3S)-2,2-dimethyl-3-(((1R,3aS,5aR,5bR,7aR,9S,11aR,11bR,13aR,13bR)-5a,5b,8,8,11a-pentamethyl-3a-(piperidine-1-carbonyl)-1-(prop-1-en-2-yl)icosahydro-1H-cyclopenta[a]chrysen-9-yloxy)carbonyl)cyclopropyl)acetic acid,2,2-dimethyl-4-oxo-4-((1R,3aS,5aR,5bR,7aR,9S,11aR,11bR,13aR,13bR)-5a,5b,8,8,11a-pentamethyl-1-(1-methylcyclopropyl)-3a-(piperidine-1-carbonyl)icosahydro-1H cyclopenta[a]chrysen-9-yloxy)butanoic acid,4-((1R,3aS,5aR,5bR,7aR,9S,11aR,11bR,13aR,13bR)-3a-(2,2-dimethyl-3-(piperidine-1-carbonyl)cyclobutylcarbamoyl)-5a,5b,8,8,11a-pentamethyl-1-(1-methylcycloprop yl)icosahydro-1H-cyclopenta[a]chrysen-9-yloxy)-2,2-dimethyl-4-oxobutanoicacid,2-((1R,3S)-2,2-dimethyl-3-(((1R,3aS,5aR,5bR,7aR,9S,11aR,11bR,13aR,13bR)-5a,5b,8,8,11a-pentamethyl-3a-(5-phenyl-1,3,4-oxadiazol-2-yl)-1-(prop-1-en-2-yl)icosa hydro-1H-cyclopenta[a]chrysen-9-yloxy)carbonyl)cyclopropyl)acetic acid,2-((1R,3S)-2,2-dimethyl-3-(((1R,3aS,5aR,5bR,7aR,9S,11aR,11bR,13aR,13bR)-5a,5b,8,8,11a-pentamethyl-1-(prop-1-en-2-yl)-3a-(5-(pyridin-3-yl)-1,3,4-oxadiazol-2-yl)icosahydro-1H-cyclopenta[a]chrysen-9-yloxy)carbonyl)cyclopropyl)aceticacid,4-((1R,3aS,5aR,5bR,7aR,9S,11aR,11bR,13aR,13bR)-3a-(4-(1-methylethyl-2,2,2,1′,1′,1′-D6)piperazine-1-carbonyl)-5a,5b,8,8,11a-pentamethyl-1-(prop-1-en-2-yl)icosahydro-1H-cyclopenta[a]chrysen-9-yloxy)-2,2-dimethyl-4-oxobutanoic acid,4-((1R,3aS,5aR,5bR,7aR,9S,11aR,11bR,13aR,13bR)-3a-((1R,3S)-3-(4-(1-methylethyl-2,2,2,1′,1′,1′-D6)piperazine-1-carbonyl)-2,2-dimethylcyclobutylcarbamoyl)-5a,5b,8,8,11a-pentamethyl-1-(prop-1-en ...

DERIVATIVES OF BETULIN

The present invention relates to compounds characterized by having a structure according to the following formula I: 2. The compound of claim 1 , wherein Land Lare both [C(RR′)].3. The compound of claim 1 , wherein Land Lare both —CH—.4. The compound of claim 1 , wherein each instance of q is independently 1 claim 1 , 2 claim 1 , or 3.5. The compound of claim 1 , wherein q is 1.6. The compound of claim 1 , wherein W is O.7. The compound of claim 1 , wherein W is a bond.8. The compound of claim 1 , wherein when W is a bond claim 1 , then Ris —H.9. The compound of claim 1 , wherein when W is O claim 1 , then Ris —H.10. The compound of claim 1 , wherein Qin the A group is absent and in the A group is —CH— and the Q in the Formula I structure is —C(═O)—.11. The compound of claim 1 , wherein Ris —H.12. The compound of claim 1 , wherein Ris —(CH)NRR.13. The compound of claim 1 , wherein Ris (dimethylamino)ethyl.14. The compound of claim 1 , wherein each instance of r is independently 0 claim 1 , 1 claim 1 , 2 claim 1 , or 3.15. The compound of claim 1 , wherein r is 2.17. The compound of claim 1 , wherein X is a monocyclic (C-C)aryl.18. The compound of claim 1 , wherein X is phenyl.19. The compound of claim 1 , wherein Ris —H.20. The compound of claim 1 , wherein each instance of m is independently 0 or 1.21. The compound of claim 1 , wherein m is 0.22. The compound of claim 1 , wherein m is 1.23. The compound of claim 1 , wherein n is 1.24. The compound of claim 1 , wherein Rand R′ are both —H.25. The compound of claim 1 , wherein Rand Rare both (C-C)alkyl.26. The compound of claim 1 , wherein Ris methyl.27. The compound of claim 1 , wherein Ris methyl.28. The compound of claim 1 , wherein Rand Rare both methyl.29. The compound of claim 1 , wherein Ris halo.30. The compound of claim 1 , wherein Ris selected from chloro claim 1 , bromo claim 1 , or fluoro.31. The compound of claim 1 , wherein Ris chloro.32. The compound of claim 1 , wherein Ris absent.33. The compound of ...

Compounds and methods for trans-membrane delivery of molecules

A novel delivery system for drugs, and especially macromolecules such as proteins or oligonucleotides through biological membranes is provided, and specifically delivery of siRNA. The delivery system comprises conjugation of the macromolecule drug to a moiety that enables effective passage through the membranes. Respectively, novel compounds and pharmaceutical compositions are provided, utilizing said delivery system. In one aspect of the invention, the compounds may be utilized in medical practice, for example, in delivery of siRNA or antisense oligonucleotides across biological membranes for the treatment of medical disorders.

METHODS FOR INHIBITING MUSCLE ATROPHY

In one aspect, the invention relates methods for inhibiting or preventing muscle atrophy or increasing muscle mass by providing to a subject in need thereof an effective amount of ursolic acid, a derivative thereof, or an analog of the ursane scaffold. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present invention. 2. The method of claim 1 , wherein the ursolic acid or pharmaceutically acceptable salt claim 1 , hydrate claim 1 , or solvate thereof is administered to the animal in an amount of greater than or equal to 100 mg per day.3. The method of claim 1 , wherein the animal is a mammal.4. The method of claim 1 , wherein the animal is a human.5. The method of claim 1 , wherein the animal is selected from the group consisting of a dog claim 1 , cat claim 1 , pig claim 1 , cow claim 1 , horse claim 1 , goat claim 1 , bison claim 1 , sheep claim 1 , chicken claim 1 , turkey claim 1 , duck claim 1 , goose claim 1 , and domesticated fish.6. The method of claim 1 , wherein the ursolic acid is present as a pharmaceutically acceptable salt selected from salts derived from aluminum claim 1 , ammonium claim 1 , calcium claim 1 , copper (-ic and -ous) claim 1 , ferric claim 1 , ferrous claim 1 , lithium claim 1 , magnesium claim 1 , manganese claim 1 , potassium claim 1 , sodium claim 1 , or zinc; salts of primary claim 1 , secondary claim 1 , and tertiary amines; and salts derived from arginine claim 1 , betaine claim 1 , caffeine claim 1 , choline claim 1 , N claim 1 ,N′-dibenzylethylenediamine claim 1 , diethylamine claim 1 , 2-diethylaminoethanol claim 1 , 2-dimethylaminoethanol claim 1 , ethanolamine claim 1 , ethylenediamine claim 1 , N-ethylmorpholinc claim 1 , N-ethylpiperidine claim 1 , glucamine claim 1 , glucosamine claim 1 , histidine claim 1 , hydrabamine claim 1 , isopropylamine claim 1 , lysine claim 1 , methylglucamine claim 1 , morpholine claim 1 , piperazine claim 1 , ...

Dexamethasone prodrug compositions and uses thereof

The disclosure features dexamethasone prodrug dimers of dexamethasone and pharmaceutical compositions thereof useful for, e.g., the extended release of a drug and for the treatment of a disease or condition.

NEUROACTIVE 19-ALKOXY-17-SUBSTITUTED STEROIDS, PRODRUGS THEREOF, AND METHODS OF TREATMENT USING SAME

The present disclosure is generally directed to neuroactive 19-alkoxy-17-substituted steroids as referenced herein, and pharmaceutically acceptable salts thereof, for use as, for example, an anesthetic, and/or in the treatment of disorders relating to GABA function and activity. The present disclosure is further directed to pharmaceutical compositions comprising such compounds. 153-. (canceled)55. The compound of claim 54 , wherein the Rgroup is selected from the group consisting of H claim 54 , methyl claim 54 , and trifluoromethyl.56. The compound of claim 54 , wherein Ris selected from the group consisting of H claim 54 , methoxy claim 54 , ethoxy claim 54 , and an optionally substituted morpholinyl ring.57. The compound of claim 54 , wherein Ris H.58. The compound of claim 54 , wherein each instance of - - - between C-Cand C-Cis absent and C—H is in the alpha position.59. The compound of claim 54 , wherein each instance of - - - between C-Cand C-Cis absent and C—H is in the beta position.60. The compound of claim 54 , wherein each instance of - - - between C-Cis absent and Ris in the beta position.61. The compound of claim 54 , wherein Ris ═O claim 54 , methoxy or H.62. The compound of claim 54 , wherein Ris methyl.63. The compound of claim 54 , wherein Ris beta-methoxy.64. The compound of claim 54 , wherein Ris beta-spirooxirane.65. The compound of claim 54 , wherein Ris beta-cyano.66. The compound of claim 54 , wherein Ris ═O.67. The compound of claim 54 , wherein Ris beta-nitro.68. The compound of claim 54 , wherein Ris beta-CHC(O)—.69. The compound of claim 54 , wherein Ris beta-HOCHC(O)—.73. The method of claim 72 , wherein the disorder is selected from the group consisting of insomnia claim 72 , mood disorders claim 72 , convulsive disorders claim 72 , anxiety claim 72 , or symptoms of ethanol withdrawal. This application is a continuation application and claims priority to U.S. patent application Ser. No. 15/459,492, filed on Mar. 15, 2017, which claims ...

CERTAIN CHEMICAL ENTITIES, COMPOSITIONS, AND METHODS

Chemical entities that are bufalin derivatives, pharmaceutical compositions and methods of treatment of cancer are described. 131.-. (canceled)33. The method of claim 32 , wherein the subject is a human.34. The method of claim 32 , wherein the compound or the pharmaceutically acceptable salt is administered orally claim 32 , subcutaneously claim 32 , intravenously claim 32 , intranasally claim 32 , transdermally claim 32 , intraperitoneally claim 32 , intramuscularly claim 32 , intrapulmonary claim 32 , vaginally claim 32 , rectally claim 32 , or intraocularly.35. The method of claim 32 , wherein the compound or the pharmaceutically acceptable salt is administered intravenously.36. The method of claim 32 , wherein the compound or the pharmaceutically acceptable salt is administered orally.37. The method of claim 32 , further comprising administering to the subject an additional anti-cancer and/or cytotoxic agent.38. The method of claim 37 , wherein the additional anti-cancer and/or cytotoxic agent is administered simultaneously with the compound or the pharmaceutically acceptable salt.39. The method of claim 32 , wherein the amount of the compound or the pharmaceutically acceptable salt administered is in the range of 0.01 mg to 100 mg per kilogram body weight of the subject.40. The method of claim 32 , wherein amount of the compound of Formula I administered is in the range of about 0.01 mg to 1000 mg.41. The method of claim 32 , wherein Rand Rare each independently chosen from hydrogen and optionally substituted lower alkyl.42. The method of claim 32 , wherein Rand Rare both hydrogen.43. The method of claim 32 , wherein Rand Rare joined together to form a 5- to 7-membered heterocycloalkyl ring.44. The method of claim 32 , wherein each Rand Ris independently chosen from hydrogen and optionally substituted lower alkyl.45. The method of claim 32 , wherein n is chosen from 1 claim 32 , 2 claim 32 , and 3.46. The method of claim 32 , wherein n is 1 claim 32 , and Rand ...

METATHESIS CATALYSTS AND METHODS THEREOF

The present application provides, among other things, compounds and methods for metathesis reactions. In some embodiments, the present disclosure provides methods for preparing alkenyl halide with regioselectivity and/or stereoselectivity. In some embodiments, the present disclosure provides methods for preparing alkenyl halide with regioselectivity and Z-selectivity. In some embodiments, the present disclosure provides methods for preparing alkenyl halide with regioselectivity and E-selectivity. In some embodiments, provided technologies are particularly useful for preparing alkenyl fluorides. In some embodiments, a provided compound useful for metathesis reactions has the structure of formula II-a. In some embodiments, a provided compound useful for metathesis reactions has the structure of formula II-b. 120-. (canceled)22. The compound of claim 21 , wherein M is Mo. This application is a divisional application of U.S. patent application Ser. No. 14/933,741, filed Nov. 5, 2015, which claims priority to U.S. Provisional Application No. 62/075,315, filed Nov. 5, 2014, the entirety of each of which is incorporated herein by reference.This invention was made with government support under Grant No. GM59426 awarded by the National Institute of Health and Grant No. CHE-1362763 awarded by the National Science Foundation. The U.S. government has certain rights in the invention.The present invention generally relates to metathesis reactions.Catalytic metathesis has transformed chemical synthesis and offers exceptionally efficient pathways for the synthesis of many commercially important chemicals including biologically active molecules, oleochemicals, renewables, fine chemicals, and polymeric materials. There remains an unmet need for improved methods and catalysts for metathesis reactions, for example, in terms of better catalyst stability and/or activity, efficiency and stereoselectivity.Among other things, the present disclosure recognizes that it is particularly ...

NON-HORMONAL STEROID MODULATORS OF NF-kB FOR TREATMENT OF DISEASE

Provided herein is a pharmaceutical composition comprising a compound having the structural formula 2. The pharmaceutical composition of claim 1 , wherein the therapeutically effective amount is between 10 mg to 200 mg of the compound.3. (canceled)4. (canceled)5. The pharmaceutical composition of claim 1 , wherein the compound is administered as a tablet or capsule.6. (canceled)7. The pharmaceutical composition of claim 1 , wherein the suspension further comprises a flavoring agent.8. The pharmaceutical composition of claim 24 , wherein the muscular dystrophy is chosen from Duchenne muscular dystrophy claim 24 , Becker muscular dystrophy claim 24 , limb girdle muscular dystrophy claim 24 , congenital muscular dystrophy claim 24 , facioscapulohumeral muscular dystrophy claim 24 , myotonic muscular dystrophy claim 24 , oculopharyngeal muscular dystrophy claim 24 , distal muscular dystrophy claim 24 , and Emery-Dreifuss muscular dystrophy.9. The pharmaceutical composition of claim 8 , wherein the muscular dystrophy is Duchenne muscular dystrophy.10. The pharmaceutical composition of claim 8 , wherein the muscular dystrophy is Becker muscular dystrophy.11. The pharmaceutical composition of claim 8 , wherein the muscular dystrophy is limb girdle muscular dystrophy.12. The pharmaceutical composition of claim 8 , wherein the muscular dystrophy is congenital muscular dystrophy.13. The pharmaceutical composition of claim 8 , wherein the muscular dystrophy is facioscapulohumeral muscular dystrophy.14. The pharmaceutical composition of claim 8 , wherein the muscular dystrophy is myotonic muscular dystrophy.15. The pharmaceutical composition of claim 8 , wherein the muscular dystrophy is oculopharyngeal muscular dystrophy.16. The pharmaceutical composition of claim 8 , wherein the muscular dystrophy is distal muscular dystrophy.17. The pharmaceutical composition of claim 8 , wherein the muscular dystrophy is Emery-Dreifuss muscular dystrophy.19. The method of claim 18 , wherein ...

Boron-based prodrug strategy for increased bioavailability and lower-dosage requirements for drug molecules containing at least one phenol (or aromatic hydroxyl) group

Boron-based prodrugs of phenol- or aromatic hydroxyl group-containing therapeutic molecules (“original drugs”), uses thereof, and methods of making the same, are provided for achieving, for example, improved bioavailability, prolonged retention (e.g., in a circulatory system) and, in particular, significantly lowered therapeutically effective dosage in order to reduce adverse effects while maintaining the desired therapeutic effects of the original drugs.

ENZYMATIC PROCESS FOR OBTAINING 17 ALPHA-MONOESTERS OF CORTEXOLONE AND/OR ITS 9,11-DEHYDRODERIVATIVES

The present invention refers to a new enzymatic process for obtaining 17α-monoesters of cortexolone and/or its 9,11-dehydroderivatives starting from the corresponding 17α,21-diesters which comprises an enzymatic alcoholysis reaction. Furthermore, the present invention refers to new crystalline forms of cortexolone-17α-propionate and 9,11-dehydro-cortexolone 17α-butanoate. 120-. (Canceled)2160. A topical composition comprising crystalline cortexolone-17 -propionate in at least two crystalline forms selected from the group consisting of crystalline Form I , crystalline Form II , crystalline Form III , and crystalline Form IV.22. The topical composition of claim 21 , wherein the composition comprises crystalline Form I and any of crystalline Forms II claim 21 , III claim 21 , or IV claim 21 , or any combination thereof.23. The topical composition of claim 21 , wherein the composition comprises crystalline Form II and any of crystalline Forms I claim 21 , III claim 21 , or IV claim 21 , or any combination thereof.24. The topical composition of claim 21 , wherein the composition comprises crystalline Form III and any of crystalline Forms I claim 21 , II claim 21 , or IV claim 21 , or any combination thereof.25. The topical composition of claim 21 , wherein the composition comprises crystalline Form IV and any of crystalline Forms I claim 21 , II claim 21 , or III claim 21 , or any combination thereof.26. The topical composition of claim 21 , wherein cortexolone-17α-propionate is present in the formulation in a total amount ranging from 0.1 to 2% by weight.27. The topical composition of claim 22 , wherein crystalline Form I is characterized by a DRX with at least peaks at about: 7.6 claim 22 , 8.4 claim 22 , 17.0 claim 22 , and 20.1 degrees 2theta.28. The topical composition of claim 23 , wherein crystalline Form II is characterized by a DRX with at least peaks at about: 10.8 claim 23 , 13.3 claim 23 , 16.5 claim 23 , and 21.9 degrees 2theta29. The topical composition of ...

PHARMACEUTICALLY ACCEPTABLE SALTS OF NOVEL BETULINIC ACID DERIVATIVES

The present invention relates to certain novel salts of Betulinic acid derivatives, to process for preparing such compounds, to use the compounds in treating diseases or disorders mediated by HIV infection, to methods for their therapeutic use and to pharmaceutical compositions containing them. 2. A salt of a compound selected from the group consisting of:Arginine salt of 4-((1R,3aS,5aR,5bR,9S,1aR)-3a-((1R,3S)-2,2-dimethyl-3-(piperidine-1-carbonyl)cyclobutylcarbamoyl)-5a,5b,8,8,11a-pentamethyl-1-(prop-1-en-2-yl)icosahydro-1H-cyclopenta[a]chrysen-9-yloxy)-2,2-dimethyl-4-oxobutanoic acid (Compound 1),Amino guanidine salt of 4-((1R,3aS,5aR,5bR,9S,11aR)-3a-((1R,3S)-2,2-dimethyl-3-(piperidine-1-carbonyl)cyclobutylcarbamoyl)-5a,5b,8,8,11a-pentamethyl-1-(prop-1-en-2-yl)icosahydro-1H-cyclopenta[a]chrysen-9-yloxy)-2,2-dimethyl-4-oxobutanoic acid (Compound 2),Calcium salt of 4-((1R,3aS,5aR,5bR,9S,11aR)-3a-((1R,3S)-2,2-dimethyl-3-(piperidine-1-carbonyl)cyclobutylcarbamoyl)-5a,5b,8,8,11a-pentamethyl-1-(prop-1-en-2-yl)icosahydro-1H-cyclopenta[a]chrysen-9-yloxy)-2,2-dimethyl-4-oxobutanoic acid (Compound 3),Choline salt of 4-((1R,3aS,5aR,5bR,9S,11aR)-3a-((1R,3S)-2,2-dimethyl-3-(piperidine-1-carbonyl)cyclobutylcarbamoyl)-5a,5b,8,8,11a-pentamethyl-1-(prop-1-en-2-yl)icosahydro-1H-cyclopenta[a]chrysen-9-yloxy)-2,2-dimethyl-4-oxobutanoic acid (Compound 4),Dicyclohexylamine salt of 4-((1R,3aS,5aR,5bR,9S,11aR)-3a-((1R,3S)-2,2-dimethyl-3-(piperidine-1-carbonyl)cyclobutylcarbamoyl)-5a,5b,8,8,11a-pentamethyl-1-(prop-1-en-2-yl)icosahydro-1H-cyclopenta[a]chrysen-9-yloxy)-2,2-dimethyl-4-oxobutanoic acid (Compound 5),Diethanolamine salt of 4-((1R,3aS,5aR,5bR,9S,11aR)-3a-((1R,3S)-2,2-dimethyl-3-(piperidine-1-carbonyl)cyclobutylcarbamoyl)-5a,5b,8,8,11a-pentamethyl-1-(prop-1-en-2-yl)icosahydro-1H-cyclopenta[a]chrysen-9-yloxy)-2,2-dimethyl-4-oxobutanoic acid (Compound 6),2,6-dimethyl piperazine salt of 4-((1R,3aS,5aR,5bR,9S,1aR)-3a-((1R,3S)-2,2-dimethyl-3-(piperidine-1-carbonyl)cyclobutylcarbamoyl ...

Compound for treating metabolic diseases and preparation method and use thereof

Provided are a compound for treating metabolic diseases having the structure as shown in formula (I) or formula (II), or a racemate, stereoisomer, geometric isomer, tautomer, solvate, hydrate, metabolite, pharmaceutically acceptable salt or prodrug thereof. The compound is an activator of FXR and/or a TGR5 receptor, and thus has the activity of activating FXR and/or a TGR5 receptor, and can be used in the preparation of drugs for treating chronic liver diseases, metabolic diseases or portal hypertension.

DIMER COMBINATIONS AND USES THEREOF

The present invention is directed towards articles comprising a steroid material comprising a steroid dimer and at least one therapeutic agent distributed throughout the steroid material and the use of such articles in sustained release delivery systems. Said article may be fibers, fiber meshes, woven fabrics, non-woven fabrics, films, pellets, cylinders, microparticles, nanoparticles, shaped articles or coatings on a substrate (such as an implant). Control of the release profile of the at least one therapeutic agent can be achieved via selection of the steroids within the steroid dimer, the linker conjugating the steroids within the dimer, the linkage groups between the steroids and the linker, the surface area of the article, the location of the at least one therapeutic agent within the article and the amount of the at least one therapeutic agent within the article. 127-. (canceled)28. An article comprising a steroid material and at least one therapeutic agent , the steroid material comprising a compound of formula (A-I):{'br': None, 'D1-L-D2\u2003\u2003(A-I)'}or a pharmaceutically acceptable salt thereof, (i) each of D1 and D2 is, independently, a steroid radical; and L is a linker covalently linking D1 to D2; and', '(ii) the at least one therapeutic agent is distributed throughout the steroid material., 'wherein29. The article of claim 28 , wherein the steroid material is free of a controlled release excipient.30. The article of claim 28 , wherein the article comprises 45% to 99% (w/w) of the compound of formula (A-I).31. The article of claim 30 , wherein the article comprises more than or equal to 90% (w/w) of the compound of formula (A-I).32. The article of claim 28 , wherein the article comprises 1% to 55% (w/w) of the at least one therapeutic agent.33. The article of claim 32 , wherein the article comprises less than or equal to 10% (w/w) of the at least one therapeutic agent.34. The article of claim 28 , wherein the article has a (w/w) ratio of the compound ...

Platform drug delivery system utilizing crystal engineering and theanine dissolution

A platform drug delivery system and a method of improving the delivery of low solubility pharmaceuticals utilizing crystal engineering and Theanine dissolution resulting in enhanced bioactivity, dissolution rate, and solid state stability.

PHARMACEUTICAL COMPOSITIONS AND METHODS OF USE OF 4-PREGENEN-11BETA-17-21-TRIOL-3,20-DIONE DERIVATIVES

The present invention relates to pharmaceutical compositions comprising 4-pregenen-11β-17-21-triol-3,20-dione derivatives, and their use as pharmaceuticals as modulators of the glucocorticoid receptors (GR) and/or the mineralocorticoid receptors (MR). The invention relates specifically to the use of these compounds and their pharmaceutical compositions to treat ocular conditions associated with the glucocorticoid receptors (GR) and/or the mineralocorticoid receptors (MR). 114.-. (canceled)15. A method of treating an ocular condition associated with glucocorticoid and or mineralocorticoid receptor modulation which comprises topically administering to a patient in need thereof , a pharmaceutical composition comprising a therapeutically effective amount of at least one compound selected from:(8S,9S,10R,11S,13S,14S,17R)-17-glycoloyl-11-hydroxy-10,13-dimethyl-3-oxo-2,3,6,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-17-yl phenylacetate;(8S,9S,10R,11S,13S,14S,17R)-17-glycoloyl-11-hydroxy-10,13-dimethyl-3-oxo-2,3,6,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-17-yl butyrate;(8S,9S,10R,11S,13S,14S,17R)-17-glycoloyl-11-hydroxy-10,13-dimethyl-3-oxo-2,3,6,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-17-yl propionate;(8S,9S,10R,11S,13S,14S,17R)-17-glycoloyl-11-hydroxy-10,13-dimethyl-3-oxo-2,3,6,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-17-yl octanoate;(8S,9S,10R,11S,13S,14S,17R)-17-Glycoloyl-11-hydroxy-10,13-dimethyl-3-oxo-2,3,6,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-17-yl hexanoate;(8S,9S,10R,11S,13S,14S,17R)-17-glycoloyl-11-hydroxy-10,13-dimethyl-3-oxo-2,3,6,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-17-yl benzoate;(8S,9S,10R,11S,13S,14S,17R)-17-glycoloyl-11-hydroxy-10,13-dimethyl-3-oxo-2,3,6,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-17-yl heptanoate;(8S,9S,10R,11S,13S, ...

Cholic acid derivative, and preparation method and medical use thereof

The present invention relates to a cholic acid derivative, and a preparation method and a medical use thereof. In particular, the present invention relates to a cholic acid derivative of formula (I), a stereoisomer, or a pharmaceutically acceptable salt thereof. The series of compounds can be used to treat FXR mediated diseases, including cardiovascular disease, atherosclerosis, arteriosclerosis, hypercholesterolemia, hyperlipidemia and chronic hepatitis diseases, chronic liver diseases, gastrointestinal diseases, nephrosis, heart vascular diseases, metabolic diseases, cancer (for example colorectal cancer) or neurological diseases, such as strokes and other diseases, with a wide range of medical applications, and are expected to develop into a new generation of FXR agonists.

Intermediates for the Synthesis of Bile Acid Derivatives, in Particular of Obeticholic Acid

The present invention relates to compounds which are intermediates in the synthesis of bile acid derivatives with pharmacological activity. The invention relates to compounds of general formula (I): wherein: , R 1 , R 2 , R 3 , R 4 , R 5 , R 6 and Y are as defined herein. The compounds are intermediates in the synthesis of synthetic bile acids which are useful in the treatment of conditions such as liver disease. In addition, the invention relates to a method of synthesizing these intermediates and a method of preparing obeticholic acid and obeticholic acid analogues from the compounds of the invention.

Crystalline solvate forms of a pharmaceutical

The invention provides and describes solid state 17α-ethynyl-androst-5-ene-3β,7β,17β-triol including amorphous and crystalline forms and specific polymorphic forms thereof. Anhydrates and solvates of 17α-ethynyl-androst-5-ene-3β,7β,17β-triol include Form I anhydrate and Form IV and Form V solvates. The invention further relates to solid and suspension formulations containing 17α-ethynyl-androst-5-ene-3β,7β,17β-triol in a described solid state form and use of the formulations to treat hyperglycemic conditions, such as type 2 diabetes and metabolic syndrome, and autoimmune conditions, such as rheumatoid arthritis, ulcerative colitis and type 1 diabetes, among other inflammation related conditions in subjects or human patients. The invention also relates to methods to make liquid formulations from solid state forms of 17α-ethynyl-androst-5-ene-3β,7β,17β-triol and uses of such formulations in treating the described conditions.

NEUROACTIVE 19-ALKOXY-17-SUBSTITUTED STEROIDS, PRODRUGS THEREOF, AND METHODS OF TREATMENT USING SAME

The present disclosure is generally directed to neuroactive 19-alkoxy-17-substituted steroids as referenced herein, and pharmaceutically acceptable salts thereof, for use as, for example, an anesthetic, and/or in the treatment of disorders relating to GABA function and activity. The present disclosure is further directed to pharmaceutical compositions comprising such compounds. 2. (canceled)3. The compound of claim 1 , wherein the Rgroup is selected from the group consisting of H claim 1 , methyl claim 1 , and trifluoromethyl.4. (canceled)5. The compound of claim 1 , wherein Ris H.6. The compound of claim 1 , wherein Ris substituted methyl.7. The compound of claim 1 , wherein the C—H is in the alpha position.8. The compound of claim 1 , wherein the C—H is in the beta configuration and Rgroup is in the beta configuration.9. The compound of claim 1 , wherein Ris H.10. The compound of claim 1 , wherein Ris ═O claim 1 , methoxy or H.11. The compound of claim 1 , wherein Ris methyl.13. The compound of wherein Ris methyl.14. The compound of claim 12 , wherein Ris beta-methoxy.15. (canceled)16. The compound of claim 12 , wherein Ris beta-cyano.17. The compound of claim 12 , wherein Ris ═O.18. (canceled)19. The compound of claim 12 , wherein Ris beta-CHC(O)—.20. The compound of claim 12 , wherein Ris beta-HOCHC(O)—.22. The compound of claim 21 , wherein Ris methyl.2350-. (canceled)53. (canceled) This application claims priority benefit of U.S. Provisional Patent Application Ser. No. 61/738,822, filed on Dec. 18, 2012, the entire content of which is incorporated herein by reference.The claimed subject matter was developed with Government support under NIH Grant #GM47969, awarded by the National Institute of Health. Accordingly, the Government has certain rights in the claimed subject matter.The present disclosure is generally directed to novel compounds having utility as an anesthetic and/or in the treatment of disorders relating to GABA function and activity. More ...

NEUROACTIVE 19-ALKOXY-17-SUBSTITUTED STEROIDS, PRODRUGS THEREOF, AND METHODS OF TREATMENT USING SAME

The present disclosure is generally directed to neuroactive 19-alkoxy-17-substituted steroids as referenced herein, and pharmaceutically acceptable salts thereof, for use as, for example, an anesthetic, and/or in the treatment of disorders relating to GABA function and activity. The present disclosure is further directed to pharmaceutical compositions comprising such compounds. 2. The compound of claim 1 , wherein one or both of Ror R claim 1 , when present and other than H claim 1 , are in the beta configuration.3. The compound of claim 1 , wherein the Rgroup is selected from the group consisting of H claim 1 , methyl claim 1 , and trifluoromethyl.4. The compound of claim 1 , wherein Ris selected from the group consisting of H claim 1 , methoxy claim 1 , ethoxy claim 1 , and an optionally substituted morpholinyl ring.5. The compound of claim 1 , wherein Ris H.6. The compound of claim 1 , wherein Ris substituted methyl.7. The compound of claim 1 , wherein the C—H is in the alpha position.8. The compound of claim 1 , wherein the C—H is in the beta configuration and Rgroup is in the beta configuration.9. The compound of claim 1 , wherein Ris H.10. The compound of claim 1 , wherein Ris ═O claim 1 , methoxy or H.11. The compound of claim 1 , wherein Ris methyl.13. The compound of wherein Ris methyl.14. The compound of claim 12 , wherein Ris beta-methoxy.15. The compound of claim 12 , wherein Ris beta-spirooxirane.16. The compound of claim 12 , wherein Ris beta-cyano.17. The compound of claim 12 , wherein Ris ═O.18. The compound of claim 12 , wherein Ris beta-nitro.19. The compound of claim 12 , wherein Ris beta-CHC(O)—.20. The compound of claim 12 , wherein Ris beta-HOCHC(O)—.22. The compound of claim 21 , wherein Ris methyl.2324-. (canceled)26. The compound of claim 25 , wherein Ris OH in the beta configuration.27. The compound of claim 25 , wherein Ris ═O.28. The compound of claim 25 , wherein Ris selected from the group consisting of H claim 25 , methoxy claim 25 , ...

Compounds and methods involving sterols

Compounds and methods of synthesizing oxysterols are provided. The compounds and methods provided allow the oxysterol to be safely produced at a high yield. The compounds and methods provided can produce the oxysterol in a stereoselective manner.

PROGESTERONE ANTAGONISTS

Described herein are compounds which either act as pure antiprogestins or as antiprogestins with partial agonistic activity and methods of treating cancer using such compounds. 19-. (canceled)11. (canceled)12. The method of claim 10 , wherein:{'sup': '7', 'sub': 3', '2', '2', '2', '2, 'Ris —CH═CH—CF, —CH—CF═CF, or —CF—CH═CH.'}1314-. (canceled)16. (canceled)18. (canceled) The present application is a divisional of U.S. patent application Ser. No. 13/193,426, filed Jul. 28, 2011, which is incorporated herein by reference.The present invention relates to the identification of a class of compounds that behave either as pure antiprogestins or as antiprogestins with partial agonistic activity, also called mesoprogestins. Pure antiprogestins has been known to suppress the growth of cancer and other proliferative diseases, whereas mesoprogestins has been shown to be useful in the treatment of fibroids and endometriosis etc. The present invention also relates to processes of preparation and the use in therapy of such novel compounds.In the past, progesterone antagonists have been postulated to be of potential benefit in the treatment of breast cancer where the primary lesion contains both estrogen and progesterone receptors. In a recent study of an in vivo rat model of progesterone receptor positive breast cancer, it was shown that the administration of a new antiprogestin (Proellex, CDB-4124) resulted in a regression of tumor size as well as a decrease in the development of new tumors. shows a series of selected progesterone receptor modulators that have been shown to be effective in vitro and in vivo. The prototype antagonist, Mifepristone (see ), is characterized by the 19-nor-4,9-diene steroid nucleus, the 17α-propynyl-17β-hydroxy functionality, and the 11β-(4-dimethylamino)phenyl functional group which is believed to be responsible for its antagonistic activity. While Mifepristone is a potent progesterone antagonist, its long-term clinical use is limited due to its ...

Preparation and Uses of Obeticholic Acid

The present invention relates to obeticholic acid: or a pharmaceutically acceptable salt, solvate or amino acid conjugate thereof. Obeticholic acid is useful for the treatment or prevention of a FXR mediated disease or condition, cardiovascular disease or cholestatic liver disease, and for reducing HDL cholesterol, for lowering triglycerides in a mammal, or for inhibition of fibrosis. The present invention also relates to processes for the synthesis of obeticholic acid.

C-3 alkyl and alkenyl modified betulinic acid derivatives

Compounds having drug and bio-affecting properties, their pharmaceutical compositions and methods of use are set forth. In particular, alkyl and alkenyl C-3 modified betulinic acid derivatives that possess unique antiviral activity are provided as HIV maturation inhibitors, as represented by compounds of Formulas I, II, III and IV: a compound of Formula I a compound of Formula II a compound of Formula III and a compound of Formula IV These compounds are useful for the treatment of HIV and AIDS.

PENTACYCLIC TRITERPENE COMPOUNDS AND USES THEREOF

Disclosed herein is a PEGylated bis pentacyclic triterpene, compositions comprising the PEGylated bis pentacyclic triterpene, methods of preparing the PEGylated bis pentacyclic triterpene, and a method of treating or preventing a fungal disease in a plant using the compounds and compositions disclosed herein. The PEGylated bis pentacyclic triterpene has the formula A-P-B, wherein A is a first pentacyclic triterpene; B is a second pentacyclic triterpene; and P is a polyethylene glycol (PEG) molecule. 1. A PEGylated bis pentacyclic triterpene having the formula:{'br': None, 'A-P-B,'}wherein,A is a first pentacyclic triterpene;B is a second pentacyclic triterpene; andP is a polyethylene glycol (PEG) molecule, for use in preventing or treating a fungal disease in a plant.2. The PEGylated bis pentacyclic triterpene of claim 1 , wherein the first and second pentacyclic triterpenes are each independently betulin claim 1 , betulinic acid claim 1 , lupeol claim 1 , or an analogue or derivative thereof.3. The PEGylated bis pentacyclic triterpene of claim 1 , wherein the first and second pentacyclic triterpenes are each betulin.4. The PEGylated bis pentacyclic triterpene of claim 1 , wherein the PEG molecule has a molecular weight of about 1500 Da to about 8 claim 1 ,000 Da.5. The PEGylated bis pentacyclic triterpene of claim 4 , wherein the PEG molecule has a molecular weight of about 3 claim 4 ,000 Da.6. The PEGylated bis pentacyclic triterpene of claim 1 , wherein the PEG molecule is α claim 1 ,ω biscarboxymethyl PEG.7. The PEGylated bis pentacyclic triterpene of claim 3 , wherein the PEG molecule is covalently bound via a first ester linkage to C3 or C28 of the first pentacyclic triterpene and via a second ester linkage to C3 or C28 of the second pentacyclic triterpene.8. The PEGylated bis pentacyclic triterpene of claim 1 , wherein the fungal disease is blight.9Phytophthora infestans, Phytophthora infestansBotrytis cinerea.. The PEGylated bis pentacyclic triterpene of ...

NEUROACTIVE STEROIDS AND COMPOSITIONS AND METHODS THEREOF

The invention provides novel neuroactive steroids and pharmaceutical compositions thereof, as well as methods of their preparation and use, in therapy of various diseases and conditions, for example, various neurological or brain diseases. 2. The compound of claim 1 , wherein at least one of Rand Ris a halogen.3. (canceled)4. The compound of claim 2 , wherein the halogen is F.5. The compound of claim 1 , wherein each of Rand Ris H6. The compound of claim 1 , wherein Ris CH.7. The compound of claim 1 , wherein Ris H.8. The compound of claim 1 , wherein Ris an unsubstituted C-Calkyl.9. The compound of claim 8 , wherein Ris an unsubstituted methyl.10. The compound of claim 8 , wherein Ris a substituted C-Calkyl.11. The compound of claim 10 , wherein Ris a substituted methyl which is substituted with a heterocyclic or heterobicyclic group.12. (canceled)14. The compound of claim 13 , wherein X is CH.15. The compound of claim 13 , wherein X is N.16. The compound of claim 13 , wherein each of X claim 13 , X claim 13 , Xand Xis CH.17. The compound of claim 13 , wherein Ris CN claim 13 , F claim 13 , is C═O(NH claim 13 , O(CHCHO)CHor CHO(CHCHO)CH.1821-. (canceled)24. A pharmaceutical composition comprising a compound according to claim 1 , effective to treat or reduce one or more diseases or disorders claim 1 , in a mammal claim 1 , including a human claim 1 , and a pharmaceutically acceptable excipient claim 1 , carrier claim 1 , or diluent.2531-. (canceled)32. A unit dosage form comprising a pharmaceutical composition of .33. (canceled)3548-. (canceled) This application claims the benefit of priority to U.S. Provisional Application No. 62/944,006, filed Dec. 5, 2019, the entire content of which is incorporated herein by reference for all purposes.The invention generally relates to pharmaceuticals and therapeutic methods. More particularly, the invention provides novel neuroactive steroids and pharmaceutical compositions thereof, as well as methods of their preparation and ...

C-20 STEROID COMPOUNDS, COMPOSITIONS AND USES THEREOF TO TREAT TRAUMATIC BRAIN INJURY (TBI), INCLUDING CONCUSSIONS

The present invention relates to C-20 steroid compounds, compositions and methods of use thereof to treat, minimize and/or prevent traumatic brain injury (TBI), including severe TBI, moderate TBI and mild TBI, including concussions. 5. The compound of wherein claim 1 , the composition of Formula I possesses the stereochemical configuration of natural steroids.6. The compound of wherein claim 1 , the composition of Formula I is racemic.7. The compound of wherein claim 1 , the composition of Formula I possesses a stereochemical configuration that is opposite to that of natural steroids.27. The pharmaceutical composition of wherein said pharmaceutical composition further comprises an additional therapeutic agent selected from the classes comprising small molecules claim 27 , antibodies claim 27 , proteins and enzymes.28. The pharmaceutical composition of wherein said additional therapeutic agent is a neuroprotective agent claim 28 , an anti-inflammatory agent claim 28 , an anti-amyloid agent or an anti-Tau agent.29. The pharmaceutical composition of claim 27 , wherein said pharmaceutical composition is a formulation selected from the list comprising a tablet claim 27 , capsule claim 27 , gelcap claim 27 , caplet claim 27 , powder claim 27 , solution claim 27 , suspension claim 27 , eyedrop claim 27 , cream claim 27 , lotion claim 27 , gel and suppository.30. The pharmaceutical composition of wherein said formulation is a powder claim 30 , a gel or a solution.32. The method of claim 32 , wherein said animal is a human.33. The method of - claim 32 , wherein said injury or disease is severe or moderate TBI.34. The method of - claim 32 , wherein said injury or disease is mild traumatic brain injury (MTBI).35. The method of - claim 32 , wherein said injury or disease is a concussion. This application claims priority to and the benefit of U.S. Application No. 62/051,898, filed on Sep. 17, 2014 and of U.S. Application No. 62/052,457 filed Sep. 18, 2014, which are both hereby ...

ENZYMATIC PROCESS FOR OBTAINING 17 ALPHA-MONOESTERS OF CORTEXOLONE AND/OR ITS 9,11-DEHYDRODERIVATIVES

The present invention refers to a new enzymatic process for obtaining 17α-monoesters of cortexolone and/or its 9,11-dehydroderivatives starting from the corresponding 17α,21-diesters which comprises an enzymatic alcoholysis reaction. Furthermore, the present invention refers to new crystalline forms of cortexolone-17α-propionate and 9,11-dehydro-cortexolone 17α-butanoate. 1. A composition comprising:{'figref': [{'@idref': 'DRAWINGS', 'FIG. 7, 10'}, {'@idref': 'DRAWINGS', 'FIG. 8, 11'}, {'@idref': 'DRAWINGS', 'FIG. 9, 12'}], 'b': 13', '14', '15, 'a) crystalline form III of cortexolone-17α-propionate characterized by a DRX spectrum as represented in , or , or a DRX spectrum with at least peaks at about: 6.2, 12.6, 14.1, 14.3, 16.0, 22.4, and 23.7 degrees 2theta, or a DSC spectrum as represented in , or , or an IR spectrum as shown in , or ; and'}{'figref': {'@idref': 'DRAWINGS', 'FIG. 28'}, 'b) crystalline form IV of cortexolone-17α-propionate characterized by a DRX spectrum as represented in , or a DRX spectrum with at least peaks at about: 4.8, 12.9, 14.4, 15.8, 16, 19.3, and 19.5 degrees 2theta.'}2. The composition of claim 1 , further comprising at least one physiologically acceptable excipient.3. The composition of claim 2 , wherein the at least one physiologically acceptable excipient is propylene glycol claim 2 , cetylic alcohol claim 2 , glyceryl monostearate claim 2 , liquid paraffin claim 2 , or a combination of any of the foregoing.4. The composition of claim 2 , further comprising mixed tocopherols claim 2 , polysorbate 80 claim 2 , or a combination thereof.5. The composition of claim 2 , wherein the composition is in the form of a tablet claim 2 , capsule claim 2 , powder claim 2 , pellet claim 2 , suspension claim 2 , emulsion claim 2 , cream claim 2 , gel claim 2 , ointment claim 2 , lotion claim 2 , or paste.6. The composition of claim 2 , wherein the composition is in the form of a solid claim 2 , semi-solid claim 2 , or a paste.7. The composition of ...

19-NOR C3, 3-DISUBSTITUTED C21-N-PYRAZOLYL STEROIDS AND METHODS OF USE THEREOF

Provided herein are 19-nor C3,3-disubstituted C21-pyrazolyl steroids of Formula (I): 147-. (canceled)49. The method of claim 48 , wherein the compound is administered orally claim 48 , subcutaneously claim 48 , intravenously claim 48 , or intramuscularly.50. The method of claim 48 , wherein the compound is administered chronically.51. The method of claim 49 , wherein the compound is administered orally.52. The method of claim 49 , wherein the compound is administered intravenously.54. The method of claim 53 , wherein the compound is administered orally claim 53 , subcutaneously claim 53 , intravenously claim 53 , or intramuscularly.55. The method of claim 53 , wherein the compound is administered chronically.56. The method of claim 54 , wherein the compound is administered orally.57. The method of claim 54 , wherein the compound is administered intravenously.59. The method of claim 58 , wherein the pharmaceutical composition is administered orally claim 58 , subcutaneously claim 58 , intravenously claim 58 , or intramuscularly.60. The method of claim 58 , wherein the pharmaceutical composition is administered chronically.61. The method of claim 59 , wherein the pharmaceutical composition is administered orally.62. The method of claim 59 , wherein the pharmaceutical composition is administered intravenously. This application is a divisional of U.S. Ser. No. 16/020,641 filed Jun. 27, 2018, which is a divisional of U.S. Ser. No. 15/297,845 filed Oct. 19, 2016, which is a divisional of U.S. Ser. No. 14/785,171, which issued as U.S. Pat. No. 9,512,165, filed Oct. 16, 2015, which is a national stage application under U.S.C. § 371 of International Application No. PCT/CN2014/075594, filed Apr. 17, 2014, published as International Publication No. WO2014/169833 on Oct. 23, 2014, which claims priority to International Application No. PCT/CN2013/074323, filed Apr. 17, 2013, the contents of each of which is incorporated herein by reference in its entirety.Brain excitability is ...

Preparation comprising hexose-6-phosphate-modified cholesterol derivative

Provided is a compound represented by the general formula (1) (where: G represents a hexose-6-phosphate residue; and L represents a divalent linker group).

Treatment Methods Using Pharmaceutical Solid State Forms

The invention provides and describes solid state 17α-ethynyl-androst-5-ene-3β,7β,17β-triol including amorphous and crystalline forms and specific polymorphic forms thereof. Anhydrates and solvates of 17α-ethynyl-androst-5-ene-3β,7β,17β-triol include Form I anhydrate and Form IV and Form V solvates. The invention further relates to solid and suspension formulations containing 17α-ethynyl-androst-5-ene-3β,7β,17β-triol in a described solid state form and use of the formulations to treat hyperglycemic conditions, such as type 2 diabetes and metabolic syndrome, and autoimmune conditions, such as rheumatoid arthritis, ulcerative colitis and type 1 diabetes, among other inflammation related conditions in subjects or human patients. The invention also relates to methods to make liquid formulations from solid state forms of 17α-ethynyl-androst-5-ene-3β,7β,17β-triol and uses of such formulations in treating the described conditions.

METHOD FOR THE SEPARATION OF THE ISOPRENIC CONSTITUENTS OF GUAYULE

Method for the separation of at least one isoprenic constituent from the resin of a plant of guayule and/or of the guayule type comprising the steps of: a) providing a defatted resin of guayule and/or of the guayule type; b) subjecting the defatted resin to partitioning of the liquid-liquid type with solvents that are immiscible in each other thus obtaining an apolar extract containing the isoprenic constituents guayulin A, guayulin B and argentatin B; and a polar extract containing the isoprene constituents argentatin A, argentatin C and argentatin D; and c) separating at least one isoprenic constituent from said polar extract and/or from the apolar extract thus obtained, wherein step c) comprises a step in which the polar extract is subjected to partitioning of the liquid-liquid type with solvents immiscible in each other and/or a step in which the apolar extract is subjected to partitioning of the solid-liquid type. 1. A method for separating at least one isoprenic constituent from a resin of a guayule and/or of the guayule type plant , the method comprising:a) forming a defatted resin of a guayule, a guayule-type plant, or both;b) liquid-liquid partitioning the defatted resin with solvents that are immiscible in each other to obtain: an apolar extract comprising the isoprenic constituents guayulin A, guayulin B and argentatin B; and a polar extract comprising the isoprenic constituents argentatin A, argentatin C and argentatin D; andc) separating at least one isoprenic constituent from the polar extract, the apolar extract, or both 'liquid-liquid partitioning the polar extract with solvents that are immiscible in each other,', 'wherein the separating c) comprisessolid-liquid partitioning the apolar extract,or a combination thereof.2. The method according to claim 1 , wherein the at least one isoprenic constituent is selected from the group consisting of guayulin A claim 1 , guayulin B claim 1 , argentatin A claim 1 , argentatin B claim 1 , argentatin C claim 1 , ...

NEUROACTIVE STEROIDS, COMPOSITIONS, AND USES THEREOF

Described herein are steroids of Formula (I): 2. The method of claim 1 , wherein Ris methyl.3. The method of claim 1 , wherein both Rand Rare hydrogen.4. The method of claim 1 , wherein Ris C-Calkyl claim 1 , C-Calkenyl claim 1 , C-Calkynyl claim 1 , carbocyclyl claim 1 , heterocyclyl claim 1 , C(O)R claim 1 , —C(O)OR claim 1 , or —C(O)NRR.5. The method of claim 4 , wherein Ris —C(O)NRR.6. The method of claim 1 , wherein Ris hydrogen claim 1 , C-Calkyl claim 1 , or —OH.7. The method of claim 6 , wherein Ris hydrogen.8. The method of claim 1 , wherein both Rand Rare hydrogen claim 1 , the between —CRand —CRRis a single bond claim 1 , and both Rand Rare hydrogen.9. The method of claim 1 , wherein Z is —CH—.10. The method of claim 1 , wherein Ris hydrogen and Ris C-Calkyl.12. The method of claim 11 , wherein Ris methyl.13. The method of claim 11 , wherein Ris C-Calkyl claim 11 , C-Calkenyl claim 11 , C-Calkynyl claim 11 , carbocyclyl claim 11 , heterocyclyl claim 11 , —C(O)R claim 11 , —C(O)OR claim 11 , or —C(O)NRR.14. The method of claim 11 , wherein Ris C-Calkyl.15. The method of claim 11 , wherein Ris hydrogen.16. The method of claim 11 , wherein both Rand Rare hydrogen and both Rand Rare hydrogen.19. The method of claim 18 , wherein Ris methyl.20. The method of claim 18 , wherein Ris C-Calkyl claim 18 , C-Calkenyl claim 18 , C-Calkynyl claim 18 , carbocyclyl claim 18 , heterocyclyl claim 18 , —C(O)R claim 18 , —C(O)OR claim 18 , or —C(O)NRR.21. The method of claim 18 , wherein Ris C-Calkyl.22. The method of claim 20 , wherein Ris —C(O)NRR.23. The method of claim 18 , wherein Ris —OH.24. The method of claim 18 , wherein Ris hydrogen.25. The method of claim 18 , wherein both Rand Rare hydrogen and both Rand Rare hydrogen.27. The method of claim 1 , wherein the CNS-related disorder is a sleep disorder claim 1 , a mood disorder claim 1 , a schizophrenia spectrum disorder claim 1 , a convulsive disorder claim 1 , a disorder of memory and/or cognition claim 1 , a ...

SELECTIVE METAL-MEDIATED ARYLATION OF DICHALCOGENIDES IN BIOMOLECULES

Disclosed are methods of selective cysteine and selenocysteine modification on peptide/protein molecules under physiologically relevant conditions. The methods feature several advantages over existing methods of peptide modification, such as specificity towards thiols and selenols over other nucleophiles (e.g., amines, hydroxyls), excellent functional group tolerance, and mild reaction conditions, including completely aqueous reaction conditions. Also disclosed are methods of preparing palladium complexes in the presence of oxygen. 2. The method of claim 1 , wherein the biopolymer is a peptide claim 1 , an oligopeptide claim 1 , a polypeptide claim 1 , a protein claim 1 , an antibody claim 1 , an antibody fragment claim 1 , an oligonucleotide claim 1 , a polynucleotide claim 1 , an oligosaccharide claim 1 , or a polysaccharide.3. (canceled)5. (canceled)713-. (canceled)1520-. (canceled)21. The method of claim 4 , wherein the solvent comprises an aqueous buffer.23. (canceled)24. The method of claim 22 , wherein the compound containing a thiol moiety or a selenol moiety is a biomolecule selected from the group consisting of a natural or unnatural amino acid claim 22 , a plurality of natural or unnatural amino acids claim 22 , a peptide claim 22 , an oligopeptide claim 22 , a polypeptide claim 22 , and a protein.2544-. (canceled)4647-. (canceled)4960-. (canceled)61. The method of claim 45 , wherein Aris (C-C)carbocyclic aryl claim 45 , (C-C)heteroaryl claim 45 , (C-C)polycyclic aryl claim 45 , or alkenyl; and Aris optionally substituted by one or more substituents independently selected from the group consisting of halide claim 45 , acyl claim 45 , azide claim 45 , isothiocyanate claim 45 , alkyl claim 45 , aralkyl claim 45 , alkenyl claim 45 , alkynyl or protected alkynyl claim 45 , alkoxyl claim 45 , arylcarbonyl claim 45 , cycloalkyl claim 45 , formyl claim 45 , haloalkyl claim 45 , hydroxyl claim 45 , amino claim 45 , nitro claim 45 , sulfhydryl claim 45 , amido ...

17ALPHA-MONOESTERS OF CORTEXOLONE FOR USE IN THE TREATMENT OF TUMORS

The present invention provides certain cortexolone derivatives, and the same for use as antitumor active ingredients for the curative or adjuvant, or neoadjuvant or palliative treatment of precancerous lesions, dysplasias, metaplasias and tumor diseases, including malignant neoplasias and metastasis. The present invention also provides pharmaceutical compositions comprising the cortexolone derivatives as active ingredients and at least one physiologically acceptable excipient, and to the use of said pharmaceutical compositions as antitumor medicinal products. 2. The pharmaceutical composition of claim 1 , comprising at least one other active ingredient.3. The pharmaceutical composition of claim 2 , wherein the other active ingredient is a chemotherapeutic active ingredient.6. The method of claim 5 , wherein the disease or disorder is a precancerous lesion claim 5 , dysplasia claim 5 , metaplasias or tumor disease.7. The method of claim 6 , wherein the tumor disease is a solid tumor.8. The method of claim 7 , wherein the solid tumor is an epithelial tumor.9. The method of claim 8 , wherein the epithelial tumor is uterine carcinoma; lung carcinoma; gastrointestinal tract carcinoma claim 8 , kidney cancer; thyroid carcinoma; or adrenal carcinoma.10. The method of claim 5 , wherein the pharmaceutical composition comprises at least one other active ingredient.11. The method of claim 5 , wherein the compound or pharmaceutical composition is administered with a second composition comprising at least one other active ingredient.12. The method of claim 11 , wherein the second composition is suitable for simultaneous claim 11 , separate or sequential administration. The instant application is a division of U.S. patent application Ser. No. 15/517,659, filed on 7 Apr. 2017 as a national stage filing under 35 U.S.C. § 371 of PCT/EP2015/073176, filed on 7 Oct. 2015, and claims the benefit of priority to European Patent Application No. 14188063.3, filed 8 Oct. 2014. Each ...

NOVEL PROCESS FOR PREPARATION OF CORTICOSTEROIDS

The present invention discloses a process for the preparation of pregnadiene derivatives having formula I, their stereoisomer and intermediate thereof. Formula I wherein each substituent is independently, Rand Ris hydrogen or C-Cstraight, branched alkyl chain, saturated or unsaturated cycloalkyl; Ris hydrogen or wherein Rrepresents C-Cstraight, branched alkyl chain or cycloalkyl; Ris hydrogen or halogen; Ris hydrogen or halogen; 3. The process as claimed in claim 1 , wherein the compound of Formula (1) isi. (1S,2S,4R,8S,9S,11S,12R,13S,19S)-12,19-difluoro-11-hydroxy-8-(2-hydroxyacetyl)-6,6,9,13-tetramethyl-5,7-dioxapentacyclo[10.8.0.02,9.04,8.013,18]icosa-14,17-dien-16-one;ii. 6α,9-difluoro-11β,16α,17,21-tetrahydroxypregna-1,4-diene-3,20-dione, cyclic 16,17-acetal with acetone,21-acetate;iii. 1S,2S,4R,8S,9S,11S,12S,13R,19S)-19-fluoro-11-hydroxy-8-(2-hydroxyacetyl)-6,6,9,13-tetramethyl-5,7-dioxapentacyclo[10.8.0.02,9.04,8.013,18]icosa-14,17-dien-16-one;iv. ((16,17-(butylidenebis(oxy))-11,21-dihydroxy-, (11-β,16-α)-pregna-1,4-diene-3,20-dionev. 2-[(1S,2S,4R,8S,9S,11S,12S,13R)-6-cyclohexyl-11-hydroxy-9, 13-dimethyl-16-oxo-5, 7-dioxapentacyclo [10.8.0.02,9.04, 8.013,18] icosa-14, 17-dien-8-yl]-2-oxoethyl 2-methylpropanoate.vi. (1S,2S,4R,8S,9S,11S,12S,13R)-11-hydroxy-8-(2-hydroxyacetyl)-6,6,9,13-tetramethyl-5,7-dioxapentacyclo[10.8.0.02,9.04,8.013,18]icosa-14,17-dien-16-onevii. (4aS,4bR,5S,6aS,6bS,9aR,10aS,10bS)-4b-fluoro-6b-glycoloyl-5-hydroxy-4a,6a,8,8-tetramethyl-4a,4b,5,6,6a,6b,9a,10,10a,10b,11,12-dodecahydro-2H-naphtho[2′,1′:4,5]indeno[1,2-d][1,3]dioxol-2-oneviii. 2-[(1S,2S,4R,8S,9S,11S,12R,13S)-12′-fluoro-11′-hydroxy-9′,13′-dimethyl-16′-oxo-5′,7′-dioxaspiro[cyclopentane-1,6′ pentacyclo[10.8.0.02,9.04,8.013,18]icosane]-14′,17′-dien-8′-yl]-2-oxoethyl acetate;ix. (11β,16α)-9-Fluoro-11,16,17,21-tetrahydroxypregna-1,4-diene-3,20-dione;x. (11β,16α)-21-(3,3-Dimethyl-1-oxobutoxy)-9-fluoro-11-hydroxy-16,17-((1-methylethylidene)bis(oxy))pregna-1,4-diene-3,20-dione4. The ...

CYCLOPENTANOPERHYDROPHENANTHRENE FRAMEWORK COMPOUNDS AND PREPARATION METHOD THEREFOR

The present invention pertains to the field of pharmaceutical chemistry, and relates to compounds having cyclopentanoperhydrophenanthrene skeletons and preparation methods therefore. The compounds have some physiological activity, and are useful as synthons/intermediates for further synthesizing some compounds having specific structures. These compounds and salts thereof are useful as lead compounds for synthesizing pharmaceuticals, pesticides and new materials. From this, further screen and preparation by chemical, biological and medical means offer new compounds that are more valuable and have important applications, achieving the object of inventing and creating new drugs. The present invention relates to compounds having cyclopentanoperhydrophenanthrene skeletons and preparation methods therefore. The compounds may have some physiological activity, and are useful as synthons/intermediates for further synthesizing some compounds having specific structures.Cyclopentanoperhydrophenanthrene compounds exist widely in plants and animals, and play an important role in their life processes. Biologically active cyclopentanoperhydrophenanthrene compounds have long been a hot research area, and nowadays these compounds still play an important role in community, offering great social and economic benefits.In pharmaceutical chemistry, natural endogenous compounds from plants and animals are studied in order to find physiologically active and effective ingredients as well as lead compounds for synthesizing pharmaceuticals, pesticides and new materials. From this, further screen and preparation by chemical, biological and medical means offer new compounds that are more valuable and have important applications, achieving the object of inventing and creating new drugs. In order to enrich compound libraries, reveal biological relations of compounds, and provide new skeletons and new lead compounds for the screen of active compounds, we synthesized compounds having ...