Patent ID: 6462032
Filing Date: 2002-10-08
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 &mgr;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: â€ƒwherein: R1 and R2 are selected independently from the group consisting of H, alkyl, substituted alkyl, OH, O(alkyl), O(substituted alkyl), (Oacetyl), 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€”CH2CH2OCH2â€”, 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 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 or 2 or 3 NR6 heteroatoms 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 with 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; 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 with 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; and c) 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.