Patent ID: 6329416
Filing Date: 2001-12-11
Classification: A61K,A61P

Abstract:
A method of contraception which omprises administering to a female of child bearing age for 28 consecutive days:a) a first phase of from 14 to 24 daily dosage units of a progestational agent equal in progestational activity to about 35 to about 100 .mu.g levonorgestrel;b) a second phase of from 1 to 11 daily dosage units, at a daily dosage of from about 2 to 50 mg, of an antiprogestin compound of Formula I: ##STR24##wherein:R.sub.1 and R.sub.2 are independently selected from the group consisting of H, alkyl, substituted alkyl, OH; O(alkyl), O(substituted alkyl), OAc, aryl, substituted aryl, heteroaryl, substituted heteroaryl, alkylaryl, alkysheteroaryl, 1-propynyl, and 3 -propynyl;or R.sub.1 and R.sub.2 are joined to form a ring comprising --CH.sub.2 (CH.sub.2).sub.n CH.sub.2 --; --CH.sub.2 CH.sub.2 CMe.sub.2 CH.sub.2 CH.sub.2 --; --O(CH.sub.2).sub.m CH.sub.2 --; O(CH.sub.2).sub.p O--; --CH.sub.2 CH.sub.2 OCH.sub.2 CH.sub.2 --; --CH.sub.2 CH.sub.2 N(alkyl)CH.sub.2 CH.sub.2 --, or --CH.sub.2 CH.sub.2 NHCH.sub.2 CH.sub.2 --;n is an integer from 0 to 5;m is an integer from 1 to 4;p is an integer from 1 to 4;or R.sub.1 and R.sub.2 together comprise a double bond to .dbd.C(CH.sub.3).sub.2 ; .dbd.C(C.sub.3 -C.sub.6 cycloalkyl), .dbd.O, or .dbd.C(cycloether), wherein said cycloether is selected from the group consisting of tetrahydrofuranyl and hexahydropyranyl;R.sub.3 is H, OH, NH.sub.2, C.sub.1 to C.sub.6 alkyl, substituted C.sub.1 to C.sub.6 alkyl, C.sub.3 to C.sub.6 alkenyl, alkynyl, substituted alkynyl, or COR.sup.A ;R.sub.A is H, C.sub.1 to C.sub.3 alkyl, substituted C.sub.1 to C.sub.3 alkyl, C.sub.1 to C.sub.3 alkoxy, substituted C.sub.1 to C.sub.3 alkoxy, C.sub.1 to C.sub.3 aminoalkyl, or substituted C.sub.1 to C.sub.3 aminoalkyl;R.sub.4 is H, halogen, CN, NH2, C.sub.1 to C.sub.6 alkyl, substituted C.sub.1 to C.sub.6 alkyl, C.sub.1 to C.sub.6 alkoxy, substituted C.sub.1 to C.sub.6 alkoxy, C.sub.1 to C.sub.6 aminoalkyl, or substituted C.sub.1 to C.sub.6 aminoalkyl;R.sub.5 is selected from the group consisting of (i), (ii), and (iii):(i) a substituted benzene ring of the formula: ##STR25##X is selected from the group consisting of halogen, OH, CN, C.sub.1 to C.sub.3 alkyl, substituted C.sub.1 to C.sub.3 alkyl, C.sub.1 to C.sub.3 alkoxy, substituted C.sub.1 to C.sub.3 alkoxy, C.sub.1 to C.sub.3 thioalkyl, substituted C.sub.1 to C.sub.3 thioalkyl, S(O)alkyl, S(O).sub.2 alkyl, C.sub.1 to C.sub.3 aminoalkyl, substituted C.sub.1 to C.sub.3 aminoalkyl, NO.sub.2, C.sub.1 to C.sub.3 perfluoroalkyl, 5 or 6 membered heterocyclic ring containing 1 to 3 heteroatoms, COR.sup.B, OCOR.sup.B, and NR.sup.C COR.sup.B ;R.sup.B is H, C.sub.1 to C.sub.3 alkyl, substituted C.sub.1 to C.sub.3 alkyl, aryl, substituted aryl, C.sub.1 to C.sub.3 alkoxy, substituted C.sub.1 to C.sub.3 alkoxy, C.sub.1 to C.sub.3 aminoalkyl, or substituted C.sub.1 to C.sub.3 aminoalkyl;R.sup.C is H, C.sub.1 to C.sub.3 alkyl, or substituted C.sub.1 to C.sub.3 alkyl:Y and Z are independently selected from the group consisting of H, halogen, CN, NO.sub.2, C.sub.1 to C.sub.3 alkoxy, C.sub.1 to C.sub.4 alkyl, and C.sub.1 to C.sub.3 thioalkyl;(ii) a five or six membered ring having it its backbone 1, 2, or 3 heteroatoms selected from the group consisting of O, S, SO, SO.sub.2 and NR.sub.6, and containing one or two independent substituents selected from the group consisting of H, halogen, CN, NO.sub.2 and C.sub.1 to C.sub.4 alkyl, C.sub.1 to C.sub.3 alkoxy, C.sub.1 to C.sub.3 aminoalkyl, COR.sup.D, and NR.sup.E COR.sup.D ;R.sup.D is H, C.sub.1 to C.sub.3 alkyl, substituted C.sub.1 to C.sub.3 alkyl, aryl, substituted aryl, C.sub.1 to C.sub.3 alkoxy, substituted C.sub.1 to C.sub.3 alkoxy, C.sub.1 to C.sub.3 aminoalkyl, or substituted C.sub.1 to C.sub.3 aminoalkyl;R.sup.E is H, C.sub.1 to C.sub.3 alkyl, or substituted C.sub.1 to C.sub.3 alkyl;R.sub.6, is H, C.sub.1 to C.sub.3 alkyl, or C.sub.1 to C.sub.4 CO.sub.2 alkyl; and(iii) an indol-4-yl, indol-7-yl or benzo-2-thiophene moiety, the moiety being optionally substituted by from 1 to 3 substituents selected from the group consisting of halogen, lower alkyl, CN, NO.sub.2, lower alkoxy, and CF.sub.3 ;wherein R.sub.6 and R.sub.7 are independently selected from the group consisting of H, methyl, ethyl, propyl, butyl, iso-propyl, iso-butyl, cyclohexyl, aryl, substituted aryl, heteroaryl, or substituted heteroaryl; or pharmaceutically acceptable salt thereof; andc) optionally, a third phase of daily dosage units of an orally and pharmaceutically acceptable placebo for the remaining days of the 28 consecutive days in which no antiprogestin, progestin or estrogen is administered; wherein the total daily dosage units of the first, second and third phases equals 28.