Patent ID: 6319912
Filing Date: 2001-11-20
Classification: A61K,A61P

Abstract:
A method of contraception which comprises 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 1: ##STR23##whereinR.sub.1 and R.sub.2 are each, independently, selected from the group consisting of hydrogen, alkyl, substituted alkyl, hydroxy, alkoxy, substituted alkoxy, aryl, substituted aryl, heteroaryl, substituted heteroaryl, arylalkyl, heteroarylalkyl, and alkynyl; orR.sub.1 and R.sub.2 are taken together form a ring and together contain --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.p CH.sub.2 --, --O(CH.sub.2).sub.q O--, --CH.sub.2 CH.sub.2 OCH.sub.2 CH.sub.2 --, --CH.sub.2 CH.sub.2 NR.sub.7 CH.sub.2 CH.sub.2 --; orR.sub.1 and R.sub.2 are a double bond, said double bond having two methyl groups bonded to the terminal end, having a cycloalkyl group bonded to the terminal end, having an oxygen bonded to the terminal end, or having a cycloether bonded to the terminal end;R.sub.7 is hydrogen or an alkyl having 1-6 carbon atoms;n=1-5;p=1-4;q=1-4;R.sub.3 is hydrogen, hydroxyl, NH.sub.2, alkyl, substituted alkyl, alkenyl, alkynyl, substituted alkynyl or COR.sup.A ;R.sup.A is hydrogen, alkyl, substituted alkyl, alkoxy, substituted alkoxy, aminoalkyl, or substituted aminoalkyl;R.sub.4 is hydrogen, halogen, --CN, alkyl, substituted alkyl, alkoxy, or substituted alkoxy;R.sub.5 is selected from the group consisting of (i) and (ii):(i) a substituted phenyl ring having the structure, ##STR24##X is halogen, OH, --CN, alkyl, substituted alkyl, alkoxy, substituted alkoxy, thioalkyl, substituted thioalkyl, S(O)alkyl, S(O).sub.2 alkyl, aminoalkyl, substituted aminoalkyl, --NO.sub.2, perfluoroalkyl, 5 or 6 membered heterocyclic ring containing in its backbone 1 to 3 heteroatoms, thioalkoxy, --COR.sup.B, --OCOR.sup.B, or --NR.sup.C COR.sup.B ;R.sup.B is hydrogen, alkyl, substituted alkyl, aryl, substituted aryl, alkoxy, substituted alkoxy, aminoalkyl, or substituted aminoalkyl;R.sup.C is hydrogen, alkyl, or substituted alkyl;Y and Z are each, independently, hydrogen, halogen, --CN, --NO.sub.2, alkoxy, alkyl, or thioalkyl; and(ii) a five or six membered heteroaryl ring containing in its backbone 1, 2, or 3 heteroatoms selected from the group consisting of O, S, SO, SO.sub.2 and NR.sup.6 with said ring carbons being optionally substituted with one or two substituents independently selected from the group consisting of hydrogen, halogen, CN, NO.sub.2, alkyl, alkoxy, aminoalkyl, COR.sup.D, and NR.sup.E COR.sup.D ;R.sup.D is hydrogen, alkyl, substituted alkyl, aryl, substituted aryl, alkoxy, substituted alkoxy, aminoalkyl, or substituted aminoalkyl;R.sup.E is hydrogen, alkyl, or substituted alkyl;R.sup.6 is hydrogen, alkyl, alkoxycarbonyl, or is absent when the nitrogen of NR.sup.6 is bonded to a ring double bond;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.