11α-Amino-androstanes

Claim 2

Compounds of the formula: ##STR4## wherein: R 1 is a C 1-8 alkyl group or a C 3-7 cycloalkyl group; R 2 is a hydrogen atom, a C 1-6 alkoxy group or a C 2-5 alkanoyloxy group; and R 3 is a C 1-8 alkyl group or a C 3-7 cycloalkyl group; provided that when the compounds contain a 5β-hydrogen atom, R 2 is a hydrogen atom, and the D-homo analogues thereof having the group --CO 2 R 3 (wherein R 3 is as defined above) at the 17aβ-position, and acid addition salts thereof.

Claim 3

Compounds as claimed in claim 1 wherein: R 1 is an isopentyl, hexyl, isohexyl, neohexyl, cyclopentyl or cyclohexyl group, R 2 is a hydrogen atom or a methoxy, ethoxy or propoxy group and R 3 is a methyl or ethyl group, having a 5α-hydrogen atom and wherein ring D has 5 members.

Claim 4

Compounds as claimed in either of claims 1 and 2 in the form of physiologically acceptable acid addition salts.

Claim 5

Compounds as claimed in claim 3 in the form of hydrochlorides, hydrobromides, phosphates, sulphates, p-toluenesulphonates, methanesulphonates, citrates, tartrates, acetates, ascorbates, lactates, maleates, succinates, tricarballylates, glutarates and glutaconates.

Claim 6

A compound as claimed in claim 1 which is methyl 2β-ethoxy-3α-hydroxy-11α-(3-methylbutylamino)-5α-androstane-17β-carboxylate, and its physiologically acceptable acid addition salts.

Claim 7

A compound as claimed in claim 1 which is methyl 2β-methoxy-3α-hydroxy-11α-(3-methylbutylamino)-5α-androstane-17β-carboxylate, and its physiologically acceptable acid addition salts.

Claim 8

A compound as claimed in claim 1 which is methyl 11α-cyclohexylamino-3α-hydroxy-2β-methoxy-5α-androstane-17β-carboxylate, and its physiologically acceptable acid addition salts.

Claim 9

A compound as claimed in claim 1 which is methyl 11α-cyclohexylamino-3α-hydroxy-5α-androstane-17β-carboxylate, and its physiologically acceptable acid addition salts.

Claim 10

Compounds as claimed in any of claims 5 to 8 in the form of their hydrochlorides.

Claim 11

Pharmaceutical compositions comprising at least one compound of formula (I) as claimed in claim 1 or a physiologically acceptable acid addition salt thereof in admixture with one or more pharmaceutical carriers or excipients.

Claim 12

A process for the manufacture of a compound of the formula (I) as claimed in claim 1 including (A) reacting a corresponding 11α-amino compound or a corresponding 11α-amino-17β-carboxylic acid with a compound of formula R 1 X wherein R 1 is as defined in claim 1 and X is a readily displaceable atom or group; (B) (where a 2β-substituted 5α-compound is desired) treating a corresponding 2α,3α-epoxide with a compound HR 2 under acidic conditions or a compound which produces the anion (R 2 ) - wherein R 2 is as defined in claims 1 other then hydrogen, and then, when the initial product possesses a deprotonated 3α-hydroxy group, treating the product obtained with a source of protons; (C) reacting a corresponding 11α-amino compound in the presence of a reducing agent with a monocarbonyl compound serving to introduce the group R 1 ; (D) (where a 2β-unsubstituted compound is desired) reducing with a suitable reducing agent a corresponding 3-oxo compound; (E) converting a corresponding N,N-disubstituted 11α-amino compound into a N-monosubstituted compound; (F) esterifying a corresponding 17β-carboxylic acid; (g) reacting a corresponding Δ 16 -compound with a suitable reducing agent; (H) transesterifying a corresponding compound having a 17β-ester group other than the desired group R 3 (as defined in claim 1) with an alcohol of formula R 3 OH (wherein R 3 is as defined in claim 1); (I) inverting a corresponding 3β-hydroxy compound; or (J) deprotecting a corresponding compound having a protected 3α-hydroxy group, followed where necessary, by the formation of acid addition salts.

Claim 13

Compounds of formula: ##STR5## (wherein R 2 is as defined in claim 1 (provided that when the compounds contain a 5β-hydrogen atom, R 2 is a hydrogen atom); R 4 is a hydrogen atom or a group R 1 as defined in claim 1; and R 5 is a hydrogen atom or a group R 3 as defined in claim 1; provided that at least one of R 4 and R 5 is a hydrogen atom and the D-homo analogues thereof having the group --CO 2 R 5 at the 17aβ-position and salts and zwitterionic forms thereof.

Claim 14

A method of treatment or prophylaxis of a human or animal subject suffering from or liable to ventricular dysrhythmias which comprises administering to said subject an effective amount of one or more compounds as claimed in claim 1.