Patent ID: 6544970
Filing Date: 2003-04-08
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; b) a second phase of from 1 to 7 daily dosage units of an antiprogestin of the formula: â€ƒwherein: R1 and R2 are selected independently from the group consisting of H, alkyl, substituted alkyl, OH, O(alkyl), O(substituted alkyl), O(acetyl), 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€”CH2CH2C(CH3)2CH2CH2â€”, â€”O(CH2)mCH2â€”, â€”O(CH2)pOâ€”, â€”CH2CH2OCH2CH2â€”, â€”CH2CH2N(H)CH2CH2â€”, or â€”CH2CH2N(alkyl)CH2CH2â€”; or R1 and R2 comprise a double bond to CMe2, C(cycloalkyl), O, or C(cycloether); n is an integer from 0 to 5; m is an integer from 1 to 4; p is an integer from 1 to 4; R3 is selected from the group consisting of H, OH, NH2, C1 to C6 alkyl, substituted C1 to C6 alkyl, C3 to C6 alkenyl, alkynyl, substituted alkynyl, and CORA; RA is selected from the group consisting of H, C1 to C3 alkyl, substituted C1 to C3 alkyl, C1 to C3 alkoxy, substituted C1 to C3 alkoxy, C1 to C3 aminoalkyl, and substituted C1 to C3 aminoalkyl; R4 is selected from the group consisting of 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, and substituted C1 to C6 aminoalkyl; R5 is selected from the group consisting of (i), (ii), (iii), (iv) and (v): (i) a substituted benzene ring with the substituents X, Y and Z as shown below: â€ƒwherein: 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 heterocyclic 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 C3 alkyl, and C1 to C3 thioalkyl; (ii) a five membered heterocyclic ring having in its backbone 1, 2, or 3 heteroatoms selected from the group consisting of O, S, SO, and SO2 and having one or two independent substituents selected from the group consisting of H, halogen, CN, NO2, C1 to C3 alkyl, C1 to C3 alkoxy, C1 to C3 aminoalkyl, CORD, and NRECORD; (iii) a five membered heterocyclic ring having in its backbone 1 NR6 heteroatom and having one or two independent substituents selected from the group consisting of H, halogen, NO2, C1 to C3 alkyl, C1 to C3 alkoxy, C1 to C3 aminoalkyl, CORD, and NRECORD; and (iv) a six membered heterocyclic ring having in its backbone 1, 2, or 3 heteroatoms selected from the group consisting of O, S, SO, SO2 and NR6 and having one or two independent substituents selected from the group consisting of H, halogen, CN, NO2, C1 to C3 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 R6 is H or C1 to C3 alkyl; and v) 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; or a pharmaceutically acceptable salt thereof, at a daily dose of from about 2 to 50 mg; and c) optionally, an orally and pharmaceutically acceptable placebo for each remaining day of the 28 consecutive days.