Patent ID: 6204273
Filing Date: 2001-03-20
Classification: A61P,C07J

Abstract:
A method for treating the conditions of androgenic alopecia, female hirsutism, benign prostatic hyperplasia, and prostatitis comprising the step of administering to a mammal in need of such treatment a therapeutically effective amount of a compound of structural formula I: ##STR18##or a pharmaceutically acceptable salt or ester thereof wherein:the C1--C2 carbon-carbon bond may be a single bond, or a double bond as indicated by the dashed line;R.sup.1 is selected from the group consisting of hydrogen and C.sub.1-10 alkyl;R.sup.2 is selected from the group consisting of hydrogen and C.sub.1-10 alkyl;one of R.sup.3 and R.sup.4 is selected from the group consisting of hydrogen and methyl, and the other is selected from the group consisting of:(a) amino;(b) cyano;(c) fluoro;(d) OH;(e) --C(O)NR.sub.b R.sub.c, where R.sub.b and R.sub.c are independently H, C.sub.1-6 alkyl, aryl, or arylC.sub.1-6 alkyl; wherein the alkyl moiety is unsubstituted or substituted with 1-3 substituents selected from: halo; C.sub.1-4 alkoxy; and trifluoromethyl; and the aryl moiety can be substituted with 1-3 substituents selected from: halo; C.sub.1-4 alkyl; C.sub.1-4 alkoxy; and trifluoromethyl;(f) C.sub.1-10 alkyl-X--, with the proviso that X is not --CH(R.sub.e)--;(g) C.sub.2-10 alkenyl-X--, with the proviso that X is not --CH(R.sub.e)--;wherein the C.sub.1-10 alkyl in (f) and C.sub.2-10 alkenyl in (g) is unsubstituted or substituted with one to three of:i) halo; hydroxy; cyano; nitro; mono-, di- or trihalomethyl; oxo; hydroxysulfonyl; carboxy;ii) hydroxyC.sub.1-6 alkyl; C.sub.1-6 alkyloxy; C.sub.1-6 alkylthio; C.sub.1-6 alkylsulfonyl; C.sub.1-6 alkyloxycarbonyl; in which the C.sub.1-6 alkyl moiety is unsubstituted or substituted with 1-3 substituents selected from: halo; C.sub.1-4 alkoxy; and trifluoromethyl;iii) arylthio; aryl; aryloxy; arylsulfonyl; aryloxycarbonyl; in which the aryl moiety is unsubstituted or substituted with 1-3 substituents selected from: halo; C.sub.1-4 alkyl; C.sub.1-4 alkoxy; and trifluoromethyl;iv) --C(O)NR.sub.b R.sub.c ; --N(R.sub.b)--C(O)--R.sub.c ; --NR.sub.b R.sub.c ; where R.sub.b and R.sub.c are defined above;(h) aryl-X--;(i) heteroaryl-X--, wherein heteroaryl is a 5, 6 or 7 membered heteroaromatic ring containing at least one member selected from the group consisting of: one ring oxygen atom, one ring sulfur atom, 1-4 ring nitrogen atoms, or combinations thereof; in which the heteroaromatic ring can also be fused with one benzo or heteroaromatic ring;wherein the aryl in (h) and heteroaryl in (i) is unsubstituted or substituted with one to three of;v) halo; hydroxy; cyano; nitro; mono-, di- or trihalomethyl; mono-, di- or trihalomethoxy; C.sub.2-6 alkenyl; C.sub.3-6 cycloalkyl; formyl; hydrosulfonyl; carboxy; ureido;vi) C.sub.1-6 alkyl; hydroxy C.sub.1-6 alkyl; C.sub.1-6 alkyloxy; C.sub.1-6 alkyloxy C.sub.1-6 alkyl; C.sub.1-6 alkylcarbonyl; C.sub.1-6 alkylsulfonyl; C.sub.1-6 alkylthio; C.sub.1-6 alkylsulfinyl; C.sub.1-6 alkylsulfonamido; C.sub.1-6 alkylarylsulfonamido; C.sub.1-6 alkyloxy-carbonyl; C.sub.1-6 alkyloxycarbonyl C.sub.1-6 alkyl; R.sub.b R.sub.c N--C(O)--C.sub.1-6 alkyl; C.sub.1-6 alkanoylamino C.sub.1-6 alkyl; aroylamino C.sub.1-6 alkyl; wherein the C.sub.1-6 alkyl moiety is unsubstituted or substituted with 1-3 substituents selected from: halo; C.sub.1-4 alkoxy; and trifluoromethyl;vii) aryl; aryloxy; arylcarbonyl; arylthio; arylsulfonyl; arylsulfinyl; arylsulfonamido; aryloxycarbonyl; wherein the aryl moiety is unsubstituted or substituted with 1-3 substituents selected from: halo; C.sub.1-4 alkyl; C.sub.1-4 alkoxy; and trifluoromethyl;viii) --C(O)NR.sub.b R.sub.c ; --O--C(O)--NR.sub.b R.sub.c ; --N(R.sub.b)--C(O)--R.sub.c ; --NR.sub.b R.sub.c ; R.sub.b --C(O)--N(R.sub.c)--; where R.sub.b and R.sub.c are defined in (e) above; and --N(R.sub.b)--C(O)--OR.sub.g, wherein R.sub.g is C.sub.1-6 alkyl or aryl, in which the alkyl moiety is unsubstituted or substituted with 1-3 substituents selected from: halo; C.sub.1-4 alkoxy, and trifluoromethyl, and the aryl moiety is unsubstituted or substituted with 1-3 substituents selected from: halo; C.sub.1-4 alkyl; C.sub.1-4 alkoxy, and trifluoromethyl; --N(R.sub.b)--C(O)NR.sub.c R.sub.d, wherein R.sub.d is selected from H, C.sub.1-6 alkyl, and aryl; in which said C.sub.1-6 alkyl and aryl is unsubstituted or substituted as described above in (e) for R.sub.b and R.sub.c ;ix) a heterocyclic group, which is a 5, 6 or 7 membered ring, containing at least one member selected from the group consisting of: one ring oxygen atom, one ring sulfur atom, 1-4 ring nitrogen atoms, or combinations thereof; in which the heterocyclic ring is aromatic, unsaturated, or saturated, wherein the heterocyclic ring is optionally fused with a benzo ring, andwherein said heterocyclic ring is unsubstituted or substituted with one to three substituents, as defined above for v), vi), vii) and viii), excluding ix) a heterocyclic group; and(j) R.sup.3 and R.sup.4 taken together are carbonyl oxygen;(k) R.sup.3 and R.sup.4 taken together are .dbd.CH--R.sub.g, wherein R.sub.g is defined in viii); and wherein:X is selected from the group consisting of:--O--; --S(O).sub.n --; --C(O)--; --CH(R.sub.e)--; --C(O)--O--*; --C(O)--N(R.sub.e)--*;--N(R.sub.e)--C(O)--O--*; --O--C(O)--N(R.sub.e)--*; --N(R.sub.e)C(O)--N(R.sub.e)--;--O--CH(R.sub.e)--*; --N(R.sub.e)--; wherein R.sub.e is H, C.sub.1-3 alkyl, aryl, aryl-C.sub.1-3 alkyl, or unsubstituted or substituted heteroaryl, as defined above in (i);wherein the asterisk (*) denotes the bond which is attached to the 16-position in structural formula I; and n is zero, 1 or 2;or a therapeutically effective amount of a compound of structural formula I in combination with an inhibitor of 5.alpha.-reductase 2.