http://rdf.ncbi.nlm.nih.gov/pubchem/patent/GB-1436324-A
Outgoing Links
| Predicate | Object |
|---|---|
| assignee | http://rdf.ncbi.nlm.nih.gov/pubchem/patentassignee/MD5_232361c9031a709144573276863c462b |
| classificationCPCInventive | http://rdf.ncbi.nlm.nih.gov/pubchem/patentcpc/C07J43-003 |
| classificationIPCInventive | http://rdf.ncbi.nlm.nih.gov/pubchem/patentipc/C07J9-00 http://rdf.ncbi.nlm.nih.gov/pubchem/patentipc/C07J7-00 http://rdf.ncbi.nlm.nih.gov/pubchem/patentipc/C07J5-00 http://rdf.ncbi.nlm.nih.gov/pubchem/patentipc/C07J43-00 http://rdf.ncbi.nlm.nih.gov/pubchem/patentipc/C07J41-00 http://rdf.ncbi.nlm.nih.gov/pubchem/patentipc/A61K- http://rdf.ncbi.nlm.nih.gov/pubchem/patentipc/C07J31-00 http://rdf.ncbi.nlm.nih.gov/pubchem/patentipc/C07J3-00 http://rdf.ncbi.nlm.nih.gov/pubchem/patentipc/C07J17-00 http://rdf.ncbi.nlm.nih.gov/pubchem/patentipc/A61K31-57 http://rdf.ncbi.nlm.nih.gov/pubchem/patentipc/C07C- |
| filingDate | 1972-05-12-04:00^^<http://www.w3.org/2001/XMLSchema#date> |
| publicationDate | 1976-05-19-04:00^^<http://www.w3.org/2001/XMLSchema#date> |
| publicationNumber | GB-1436324-A |
| titleOfInvention | Anaesthetic 3alpha-hydroxy pregnanes |
| abstract | 1436324 21-Substituted 3α-hydroxy-pregnane compounds GLAXO LABORATORIES Ltd 11 May 1973 [12 May 1972] 22489/72 Heading C2U Novel steroids of the pregnane or 19- norpregnane series possess essentially a 3α-hydroxy group, a 5α-H atom or a #<SP>4</SP>-double bond, a 17α-H atom, a 20-oxo group and at the 21- position an alkylene or alkylidene group or at least one monovalent straight, branched or cyclic aliphatic hydrocarbon group which is either unsubstituted or substituted by at least one group or atom selected from oxo, hydroxy, etherified hydroxy, acyloxy, esterified carboxy, C-attached N-containing heterocycles, etherified mercapto, acylthio, Cl, F, aryl and di-substituted amino. Also included are acetals and 20-enol ethers of the 21-formyl compounds, and salts of the novel acidic and basic compounds. The steroids may be prepared (a) for 20-CH 2 alkyl compounds, (i) by oxidation of the corresponding 20-ols, in turn prepared by reacting 20, 21-epoxy-pregnanes with compounds furnishing an anion corresponding to the alkyl group to be introduced and a cation followed, when a metal derivative of the 20-ol is first formed, by treatment with a proton source, or (ii) by reaction of a 21-alkylidene steroid with a metal alkyl or by catalytic hydrogenation of such a steroid; (b) for 20-[(1<SP>1</SP>-di-substituted amino-alkyl)methyl] compounds, (i) by reaction of 21-unsubstituted pregnanes with NH 3 or amines and an aldehyde (under forcing conditions 21-alkylidene-21-aminoalkyl compounds are formed), or (ii) by reaction of 21-alkylidene compounds with NH 3 or amines; (c) for 20- CH 2 CHO compounds, by Claisen condensation between 21-unsubstituted compounds and alkyl formates; (d) for 20-CH 2 CH 2 OH compounds, by reduction of 21-formyl compounds; (e) for 20-(CH 2 )O acyl compounds, by acylation of the products of (d); (f) for 20-CH 2 -alk-X-Y compounds (where X is O or S and Y is an etherifying group), by reaction of 21-alkylidene compounds with YXH; for 21-alkylidene compounds, by subjecting corresponding 21-(1<SP>1</SP>- amino- or -substituted amino-alkyl) steroids to a Hoffmann elimination; (h) for 20-CH 2 S acyl compounds, by a method similar to (f) using a thioacid; (i) for 21-(1<SP>1</SP>-fluoro or chloro-alkyl) compounds, by reacting 21-alkylidene steroids with HF or HCl; (j) for 20-CH 2 R compounds, wherein R is esterified carboxyl, by Claisen condensation between 21-unsubstituted compounds and diesters of carbonic acid in presence of a base (ethoxycarbonyl products may subsequently be transesterified); (k) for 20-CH 2 acyl compounds, by similar Claisen condensation using a carboxylic acid ester. Further novel compounds may be prepared from steroids haying a readily eliminatable 21-substituent and compounds generating carbanions, e.g. R<SP>3</SP>CO.CH 2 . COR<SP>4</SP> (I) (where R<SP>3</SP> and R<SP>4</SP> are alkyl or alkoxy) or their alkali metal derivatives. (I) may also be reacted with 21-methylene steroids or with reactive derivatives of androstane 17-carboxylic acids. 21,21-Dialkyl steroids are prepared by reducing 21-(alkylidene)-21- (1<SP>1</SP>-amino- or substituted amino-alkyl)steroids. 20-Cyclopropyl or alkylcyclopropyl products are obtained from 21-alkylidene steroids and reactive methylides. 20-Alkyl enol ethers of 20-CH 2 CHO steroids are obtained by reacting 21-unsubstituted steroids with trialkyl orthoformates and strong acids. The 20-enol ethers may be transetherified. Acetals of 21-formyl steroids are prepared by reacting formyl compounds or the 20-enol ethers with an alkanol (or diol if appropriate) and a strong acid; they may be split under mild conditions. Products containing a halogen atom in the side chain (iodo compounds are prepared from the corresponding chloro compounds) may be reacted with amines (including heterocyclic amines and phthalimide) to introduce a disubstituted amino group. The novel 3α-ols may also be prepared by stereospecific reduction of the corresponding 3-ones. In the foregoing and any other processes it may be necessary to protect a 3α-OH group e.g. as a nitrate ester or THP-ether, and a 20-oxo group, e.g. as a ketal. Ring substituents and double bonds may be introduced by standard procedures (see, for example, Specifications 1,372,175; 1,376,892 and 1,380,248). Starting materials.-21-Methyl-5α-pregnane- 3,11,20-trione is prepared by method (a)(i) above from 20#, 21-epoxy-3α-nitro-oxy-5α- pregnan-11-one, in turn prepared from 21- bromo - 3α - nitro - oxy - 5α - pregnane - 11,20- dione (from the 3α-ol and nitric acid). 3α-Nitrooxy - 11 - oxo - 5α - androstane - 17# - carboxylic acid is prepared from the 3α-ol, in turn prepared from 3α - hydroxy - 5α - pregnane - 11,20- dione by oxidative degradation using sodium hypobromite. 3α-Acetoxy-20-ethoxy-21-formyl- 5α - pren - 20 - en - 11 - one is prepared from 3α - acetoxy - 5α - pregnane - 11,20 - diene and ethyl orthoformate, the starting material being prepared by acetylation of the 3α-ol. 21 - Formyl - 3α - tetrahydropyranyloxy - 5α- pregnane-11,20-dione is prepared by the action of ethyl formate on the 21-unsubstituted compound, in turn prepared from the free 3α-ol and dihydropyran. 3α - Hydroxy - 21 - iodoacetoxymethyl - 5α - pregnane - 11,20 - dione is prepared from the corresponding chloroacetoxymethyl compound and NaI. The novel steroids are anaesthetic agents and may be made up into anaesthetic compositions with suitable carriers. |
| priorityDate | 1972-05-12-04:00^^<http://www.w3.org/2001/XMLSchema#date> |
| type | http://data.epo.org/linked-data/def/patent/Publication |
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