Patent ID: 6352997
Filing Date: 2002-03-05
Classification: A61K

Abstract:
A method of improving the response to in vitro fertilization which comprises the administration to a subject in need thereof of an effective amount of a compound of structural formula I: 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; R1 is selected from the group consisting of hydrogen and C1-10 alkyl; R2 is selected from the group consisting of hydrogen and C1-10 alkyl; one of R3 and R4 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) methyl; (e) OH; (f) â€”C(O)NRbRc, where Rb and Rc are independently H, C1-6alkyl, aryl, or arylC1-6alkyl; wherein the alkyl moiety is unsubstituted or substituted with 1 to 3 of: halo; C1-4alkoxy; or trifluoromethyl; and the aryl moiety is unsubstituted or substituted with 1 to 3 of: halo; C1-4alkyl; C1-4alkoxy; or trifluoromethyl; (g) C1-10alkyl-Xâ€”; (h) C2-10alkenyl-Xâ€”; â€ƒwherein the C1-10 alkyl in (g) and C2-10 alkenyl in (h) can be unsubstituted or substituted with one to three of: i) halo; hydroxy; cyano; nitro; mono-, di- or trihalomethyl; oxo; hydroxysulfonyl; carboxy; ii) hydroxyC1-6alkyl; C1-6alkyloxy; C1-6 alkylthio; C1-6alkylsulfonyl; C1-6 alkyloxycarbonyl; in which the C1-6 alkyl moiety is unsubstituted or substituted with 1 to 3 of: halo; C1-4 alkoxy; or trifluoromethyl; iii) arylthio; aryl; aryloxy; arylsulfonyl; aryloxycarbonyl; in which the aryl moiety is unsubstituted or substituted with 1 to 3 of: halo; C1-4 alkyl; C1-4 alkoxy; or trifluoromethyl; iv) â€”C(O)NRbRc; â€”N(Rb)â€”C(O)â€”Rc; â€”NRbRc; where Rb and Rc are defined above; (i) aryl-Xâ€”; (j) heteroaryl-Xâ€”, 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 (i) and heteroaryl in (j) is unsubstituted or substituted with one to three of: v) halo; hydroxy; cyano; nitro; mono-, di- or trihalomethyl; mono-, di- or trihalomethoxy; C2-6 alkenyl; C3-6 cycloalkyl; formyl; hydrosulfonyl; carboxy; ureido; vi) C1-6 alkyl; hydroxy C1-6 alkyl; C1-6 alkyloxy; C1-6 alkyloxy C1-6alkyl; C1-6 alkylcarbonyl; C1-6 alkylsulfonyl; C1-6 alkylthio; C1-6 alkylsulfinyl; C1-6 alkylsulfonamido; C1-6 alkylarylsulfonamido; C1-6 alkyloxy-carbonyl; C1-6 alkyloxycarbonyl C1-6alkyl; RbRcNâ€”C(O)â€”C1-6alkyl; C1-6 alkanoylamino C1-6 alkyl; aroylamino C1-6 alkyl; wherein the C1-6 alkyl moiety is unsubstituted or substituted with 1 to 3 of: halo; C1-4alkoxy; or trifluoromethyl; vii) aryl; aryloxy; arylcarbonyl; arylthio; arylsulfonyl; arylsulfinyl; arylsulfonamido; aryloxycarbonyl; wherein the aryl moiety is unsubstituted or substituted with 1 to 3 of: halo; C1-4alkyl; C1-4alkoxy; or trifluoromethyl; viii) â€”C(O)NRbRc; â€”Oâ€”C(O)â€”NRbRc; â€”N(Rb)â€”C(O)â€”Rc; â€”NRbRc; Rbâ€”C(O)â€”N(Rc)â€”; where Rb and Rc are defined in (f) above; and â€”N(Rb)â€”C(O)â€”ORg, wherein Rg is C1-6alkyl or aryl, in which the alkyl moiety is unsubstituted or substituted with 1 to 3 of: halo; C1-4alkoxy; or trifluoromethyl, and the aryl moiety is unsubstituted or substituted with 1 to 3 of: halo; C1-4alkyl; C1-4 alkoxy, or trifluoromethyl; â€”N(Rb)â€”C(O)NRcRd, wherein Rd is selected from H, C1-6 alkyl, and aryl; in which said C1-6alkyl and aryl is unsubstituted or substituted as described above in (f) for Rb and Rc; 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 can be aromatic, unsaturated, or saturated, wherein the heterocyclic ring can be fused with a benzo ring, and wherein said heterocyclic ring is unsubstituted or substituted with 1 to 3 substituents, as defined above for v), vi), vii) and viii), excluding ix) a heterocyclic group; and (k) R3 and R4 taken together can be carbonyl oxygen; (l) R3 and R4 taken together can be &boxH;CHâ€”Rg, wherein Rg is defined in viii); and wherein: X is selected from the group consisting of: â€”Oâ€”; â€”S(O)nâ€”; â€”C(O)â€”; â€”CH(Re)â€”; â€”C(O)â€”Oâ€”*; â€”C(O)â€”N(Re)â€”*; â€”N(Re)â€”C(O)â€”Oâ€”*; â€”Oâ€”C(O)â€”N(Re)â€”*; â€”N(Re)C(O)â€”N(Re)â€”; â€”Oâ€”CH(Re)â€”*; â€”N(Re)â€”; wherein Re is H, C1-3 alkyl, aryl, aryl-C1-3 alkyl, or unsubstituted or substituted heteroaryl, as defined above in (j); wherein the asterisk (*) denotes the bond which is attached to the 16-position in Structure I; and n is zero, 1 or 2, or a pharmaceutically acceptable salt thereof.