73671-86-0Relevant articles and documents
Azasteroids as Inhibitors of Rat Prostatic 5α-Reductase
Rasmusson, Gary H.,Reynolds, Glenn F.,Utne, Torleif,Jobson, Ronald B.,Primka, Raymond L.,et al.
, p. 1690 - 1701 (2007/10/02)
A series of A-ring heterocyclic steroids has been prepared and tested for inhibition of rat prostatic steroid 5α-reductase in vitro.Strinkingly high inhibitory activity was found with a group of 17β-substituted 4-methyl-4-aza-5α-androstan-3-ones.These compounds were prepared from 3-keto-Δ4-precursors by oxidative (O3 or NaIO4-KMnO4) A-ring cleavage followed, in turn, by ring closure with an amine and hydrogenation over platinum catalyst.Other A-ring azasteroids were made by Beckmann rearrangement of oximes of 2-oxo-A-nor-, 3-oxo- and 4-oxo-5α-androstanes.An A-nor-2-oxo-3-azasteroid was prepared by oxidative decarbonylation of a precursor 2,3-dioxo-4-azasteroid with m-chloroperbenzoic acid.A-ring modifications of the 4-azasteroids included Δ1-unsaturation, 2- and 4-substituents, and 3-carbonyl replacements.Side chains at the 17-position were varied with an emphasis on carboxylate derivatives (salts, esters, and amides).
Preparation of 4-aza-17-substituted-5α-androstan-3-ones useful as 5α-reductase inhibitors
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, (2008/06/13)
A method of preparing a compound of the formula: STR1 where Formula (I) may also have the structure of partial Formula (III); wherein, STR2 R' is hydrogen or methyl; R" is hydrogen or β-methyl; R'" is β-methyl or hydroxy; Z is (1) oxo; (2) β-hydrogen and α-hydroxy; or α-hydrogen or α-hydroxyl and (3) (Y)n Q where n=0 or 1, Y is a straight or branched hydrocarbon chain of 1 to 12 carbon atoms and Q is STR3 where R8 is, STR4 where the dashed bond replaces the 17α hydrogen; (6) cyano; or (7) tetrazolyl; and pharmaceutically acceptable salts of the above compounds; CHARACTERIZED IN THAT (I.) a compound of the formula: STR5 , where A has the meanings above except --CH=CH--, is (1) treated with an oxidizing agent at reduced temperatures to form the corresponding 5-oxo-3,5-seco-androstan-3-oic acid compound; (2) treating the product of step (1) with an amine of formula: R1 NH2 to form the corresponding 4-aza-5-androsten-3-one compound substituted in the 4-position with R1 ; and (3) treating the product of step (2) with hydrogen under catalytic conditions to form the compound of Formula I and I & II wherein B is STR6 (II.) and where it is desired to prepare compounds of Formula I wherein B is STR7 additionally carrying out the following steps on the products prepared by the procedures in (I.) above: (1) alkylating the lactim carbonyl by treating it with trialkyloxonium tetrafluoroborate to form the corresponding alkyl iminium ether, i.e., the compound of Formula I where B is as above and R4 =OR5 ; (2) treating the product of step (1) with an amine of formula HNR6 R7 followed by treatment with a mineral acid to form the compound of Formula I where B is as above and R4 =NR6 R7 ; (III.) and where it is desired to prepare compounds of Formula I wherein A is --CH=CH--, additionally carrying out the following steps on the products prepared by the procedures in (I.) above: (1) treating the 1,2 saturated compound with lithium diisopropyl amide to form the corresponding enolate; (2) treating the enolate of step (1) in situ with diphenyldisulfide to form the corresponding α-phenylthio compound; (3) oxidizing the product of step (2) to form the corresponding sulfoxide compound; and (4) heating the product of step (3) to form the compound of Formula I wherein A is --CH=CH--.
