NZ226433A
Expired / Lapsed
NZ
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14-aminoandrostane 17-carboxylic acid ester derivatives
Assignee: Norwich Eaton Pharma
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Filing: 1988-10-03
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Granted: —
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Expires: 2008-10-03
Abstract
Abstract The invention relates to androstane-17-carboxylic acid esters, represented by general formula (I): wherein R1 represents a lower alkyl group containing 1 to 4 carbon atoms, a lower alkyl group containing 2 to 4 carbon atoms substituted by an amino group, or an aralkyl group from 6 to 12 carbon atoms, R2 and R3, which may be the same or different, represent a hydrogen atom or a lower alkyl group containing 1 to 4 carbon atoms, R4 represents a hydrogen atom, a hydroxy group or an acetoxy group, R5 represents a hydroxy or acetoxy group, or R4 and R5 represent together a divalent alkylenedioxy group, R6 represents a hydroxy group, a methoxy group, or an acetoxy group, R7 represents a methyl group or a hydroxymethyl group, R8 represents an hydrogen atom or a hydroxy group and represents either a group or a carbon atom having the double linkage in the 4- or 5-position of the steroid nucleus. Such esters are prepared by coupling reaction of the corresponding 14-azido-derivatives with a sugar, followed by a reduction. Application in therapy, especially in the treatment of heart failure.
Inventors
- 👤 Francois-Xavier Jarreau
- 👤 Jean-Jacques Koenig
Bibliographic Details
Application Number
—
Jurisdiction
NZ
Data Source
google_patents
Last Synchronized
2026-11-01 20:32
CPC Classifications
C; C07; C07J; C07J41/00; C07J41/0005; A; A61; A61K; A61K31/00; A61K31/56; A61K31/565; A61P; A61P9/00; A61P9/04
Claims Analysis
Total Claims: 15
Claim 1
Independent Claim
166 words
Androstane by general formula (I) 6IAIM0 17-carboxylic acid esters represented 10 IS ">3" RS wherein R4 represents a lower alkyl group containing 1 to 4 carbon atoms, a lower alkyl group from 2 to 4 carbon atoms substituted by an amino group, or an aralkyl group from 6 to 12 carbon atoms, R2 anc* which may be the same or different, represent a hydrogen atom or a lower alkyl group containing 1 to 4 carbon atoms, R* represents a hydrogen atom, a hydroxy group, or an acetoxy group, Rs represents a hydroxy group or an acetoxy group, or R4 and R5 represent together a divalent alky-20 lenedioxy group, Rg reprssents a-hydroxy a methoxy group or acetoxy group, R7 represents a methyl group or a hydroxymethyl group, Ro represents a hydrogen atom or a hydroxy group and i » i —Z~~ represents either a -CH- group, or a = C- carbon wher§ the double linkage is at the 4- or 3- position of the steroid 25 nucleus.
Claim 2
Dependent Claim
166 words
Androstane by general formula (I) 6IAIM0 17-carboxylic acid esters represented 10 IS ">3" RS wherein R4 represents a lower alkyl group containing 1 to 4 carbon atoms, a lower alkyl group from 2 to 4 carbon atoms substituted by an amino group, or an aralkyl group from 6 to 12 carbon atoms, R2 anc* which may be the same or different, represent a hydrogen atom or a lower alkyl group containing 1 to 4 carbon atoms, R* represents a hydrogen atom, a hydroxy group, or an acetoxy group, Rs represents a hydroxy group or an acetoxy group, or R4 and R5 represent together a divalent alky-20 lenedioxy group, Rg reprssents a-hydroxy a methoxy group or acetoxy group, R7 represents a methyl group or a hydroxymethyl group, Ro represents a hydrogen atom or a hydroxy group and i » i —Z~~ represents either a -CH- group, or a = C- carbon wher§ the double linkage is at the 4- or 3- position of the steroid 25 nucleus.
Claim 3
Dependent Claim
18 words
Androstane 17-carboxylic acid esters according to claim 1/ characterized in that Rx is a methyl &£ an-ethyl group.
Claim 4
Dependent Claim
21 words
Androstane 17-carboxylic acid esters according t9 30 claims 1 and 2, characterized in that R^ and Rg represent a hydroxy group,
Claim 5
Dependent Claim
38 words
Androstane 17-carboxylic acid esters according to any one of claims 1 and 2, characterized in that R* and Rs are combined to form an alkylenedioxy group containing 1 to 4 35 carbon atoms in the alkylene moiety thereof.
Claim 6
Dependent Claim
23 words
Androstane 17-carboxylic acid esters according to any one of claims 1 to 3, hydroxy group. characterized £n"" that 'R*4"rep£«a&its a - X3" ?264
Claim 7
Dependent Claim
40 words
6 » Androstane 17-carboxylic acid "eaters according to any one of the preceding claimst characterized in that this amino group at the 14-poaition, the eater group at the 17-position, and th® Bugar residue at the 3-positlon, have the J3 configuration.
Claim 8
Dependent Claim
32 words
Androstane 17-carboxylic acid esters accordi^ to claim 1 characterized in that they are selected from methyl a-Ii-rhamnopyranogyloxy-30 amino-14p etianate, methyl/o-L-rhaw- i • j nopyranoayloxy-3J3 methylawino-140 etianate and aethjyl o-L-rham~ nopyranosyloxy-30 amino-140 etien-4-ate.
Claim 9
Dependent Claim
127 words
A process for the preparation of the androstane 17-carboxylic acid eaters of claim 1, characterised in that it comprises carrying out a coupling reaction of a 3-hydroxy-i4j azido~androstane 17-carboxylic acid ester, represented by^t&a following general formula (II)* ~ wherein Rx and R8 are as defined in the general formula (I) of claim 1, with an activated sugar residue, thus forming a 3- pyranosyloxy-14-azido-androstane 17-carboxylic acid ester of the following general formula (III)s , • / S- . -2.4-- ~ fS .wherein R'* represents a hydrogen atom or an acetoxy group, and R'7 represents a methyl group or a -CHaOAc group, an R0 is as defined in the general formula (I), which is reduced into the derivative of general formula (I), followed if necessary by an <• aminomethylation.
Claim 10
Dependent Claim
31 words
The process of claim 8, characterized in that the coupling reaction is carried out between the 3-hydrcxy-14-azido-androstane 17-carboxylic acid eater and tri-O-acetyl -r'namnosyl bromide in the presence of mercury cyanide. jO
Claim 11
Dependent Claim
29 words
The process of claim 8, characterized in that the coupling reaction is carried cut between the 3-hydroxy-14-azido-androstane 17-carboxylic acid eater and tri-O-acetyl-digitoxoee in the presence of toluene sulfonic acid.
Claim 12
Dependent Claim
47 words
The process of any one of claims 8 to 10, characterise. zed in that the reduction of 3-pyranosyloxy-14-azido-androstan© 17-carboxylic acid ester of general formula (HI) is carried out by action of sodium borohydride in the presence of tellurium in an alcohol, followed if necessary by a deacetylation.
Claim 13
Dependent Claim
43 words
The process of any one of claims 8 to 10, characteri-2q zed in that the reduction of 3-pyranosyloxy-14-azido-androetane 17-carboxylic acid ester of general formula (HI) is carried out by hydrogenation reaction in the presence of Raney nickel, preceded if necessary by a deacetylation.
Claim 14
Dependent Claim
39 words
A pharmaceutical composition, characterized in that it 25 comprises a androstane 17-carboxylic acid ester according to any one of claims 1 to 7, as an active ingredient, combined if . necessary with 'one or several pharmacautically acceptable , carriers.
Claim 15
Dependent Claim
139 words
The use of a androstane 17-carboxylic acid e'ater ^l^cording to any one of claims 1 to 7, for the preparation of a- ''dr&g for the tieatment of heart failure. 1,5. A compound as claimed in any one of claims 1 to 7 substantially as T ^ fte&eintiefore described with reference to any example thereof. T OVv tn\\16.\ A process as claimed in any one of claims 8 to 12 when performed •4 subsjtantially as hereinbefore described with reference to any example thereof. C/7 pirepwerf <4,// 17. Asifompound of any one of claims 1 to 7 when parf-ormo4 by a process as , \ -jE aimed in any one of claims 8 to 12 and 16. 7«*r-4i— ^0^ 18 • A pharmaceutical composition as claimed in claim 13 substantially as hereinbefore described with reference to any example thereof., s ««-
References Cited (Backward Citations)
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