Patent ID: 6503939
Filing Date: 2003-01-07
Classification: A61K,A61P

Abstract:
A method of contraception which comprises administering to a female of child bearing age over a period of 28 consecutive days:a) a first phase of from 18 to 21 daily dosage units of a progestational agent equal in progestational activity to about 35 to about 150 &mgr;g levonorgestrel, and ethinyl estradiol at a daily dose range of from about 10 to about 35 &mgr;g; and b) a second phase of from 1 to 7 daily dosage units of an antiprogestin at a daily dose of from about 2 to 50 mg; wherein said antiprogestin is of the formula: â€ƒwherein: R1 and R2 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, alkylheteroaryl, 1-propynyl, and 3-propynyl; or R1 and R2 are joined to form a ring comprising â€”CH2(CH2)nCH2â€”; â€”CH2CH2CMe2CH2CH2â€”; â€”O(CH2)mCH2â€”; O(CH2)pOâ€”; â€”CH2CH2OCH2CH2â€”; â€”CH2CH2N(alkyl)CH2CH2â€”; or â€”CH2CH2NHCH2CH2â€”; 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 R1 and R2 together comprise a double bond to &boxH;C(CH3)2, &boxH;C(C3-C6 cycloalkyl), &boxH;O, or &boxH;C(cycloether), wherein said cycloether is selected from the group consisting of tetrahydrofuranyl and hexahydropyranyl; R3 is H, OH, NH2, C1 to C6 alkyl, substituted C1 to C6 alkyl, C3 to C6 alkenyl, alkynyl, substituted alkynyl, or CORA; RA is H, C1 to C3 alkyl, substituted C1 to C3 alkyl, C1 to C3 alkoxy, substituted C1 to C3 alkoxy, C1 to C3 aminoalkyl, or substituted C1 to C3 aminoalkyl; R4 is H, halogen, CN, NH2, C1 to C6 alkyl, substituted C1 to C6 alkyl, C1 to C6 alkoxy, substituted C1 to C6 alkoxy, C1 to C6 aminoalkyl, or substituted C1 to C6 aminoalkyl; R5 is selected from the group consisting of (i), (ii), and (iii): (i) a substituted benzene ring of the formula: X is selected from the group consisting of halogen, OH, CN, C1 to C3 alkyl, substituted C1 to C3 alkyl, C1 to C3 alkoxy, substituted C1 to C3 alkoxy, C1 to C3 thioalkyl, substituted C1 to C3 thioalkyl, S(O)alkyl, S(O)2alkyl, C1 to C3 aminoalkyl, substituted C1 to C3 aminoalkyl, NO2, C1 to C3 perfluoroalkyl, 5 or 6 membered heteroryclic ring containing in its backbone 1 to 3 heteroatoms, CORB, OCORB, and NRCCORB; RB is H, C1 to C3 alkyl, substituted C1 to C3 alkyl, aryl, substituted aryl, C1 to C3 alkoxy, substituted C1 to C3 alkoxy, C1 to C3 aminoalkyl, or substituted C1 to C3 aminoalkyl; RC is H, C1 to C3 alkyl, or substituted C1 to C3 alkyl: Y and Z are independently selected from the group consisting of H, halogen, CN, NO2, C1 to C3 alkoxy, C1 to C4 alkyl, and C1 to C3 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, SO2 and NR6â€² and containing one or two independent substituents selected from the group consisting of H, halogen, CN, NO2, C1 to C4 alkyl, C1 to C3 alkoxy, C1 to C3 aminoalkyl, CORD, and NRECORD; RD is H, C1 to C3 alkyl, substituted C1 to C3 alkyl, aryl, substituted aryl, C1 to C3 alkoxy, substituted C1 to C3 alkoxy, C1 to C3 aminoalkyl, or substituted C1 to C3 aminoalkyl; RE is H, C1 to C3 alkyl, or substituted C1 to C3 alkyl; R6â€² is H, C1 to C3 alkyl or C1 to C4 CO2 alkyl; R6 and R7 are independently selected from the group consisting of H, methyl, ethyl, propyl, butyl, iso-propyl, isobutyl, cyclohexyl aryl, substituted aryl, heteroaryl, and substituted heteroaryl; 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, NO2, lower alkoxy, and CF3; c) optionally, an orally and pharmaceutically acceptable placebo for each remaining day of the 28 consecutive days.