Patent ID: 6444668
Filing Date: 2002-09-03
Classification: A61K,Y10S

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 I: â€ƒwherein: R1 and R2 are independent substituents selected from the group consisting of H, C1 to C6 alkyl, substituted C1 to C6 alkyl, C2 to C6 alkenyl, substituted C2 to C6 alkenyl, C2 to C6 alkynyl, substituted C2 to C6 alkynyl, C3 to C8 cycloalkyl, substituted C3 to C8 cycloalkyl, aryl, substituted aryl, heterocyclic, substituted heterocyclic, CORA, and NRBCORA; or R1 and R2 are fused to form: i) a 3 to 8 membered saturated spirocyclic carbon-based ring; ii) a 3 to 8 membered spirocyclic carbon-based ring having one or more carbon-carbon double bonds; or iii) a 3 to 8 membered heterocyclic ring containing one to three heteroatoms selected from the group consisting of O, S and N; the spirocyclic rings of i), ii), and iii) being optionally substituted by from 1 to 4 groups selected from the group consisting of fluorine, C1 to C6 alkyl, C1 to C6 alkoxy, C1 to C6 thioalkyl, CF3, OH, CN, NH2, NH(C1 to C6 alkyl), and N(C1 to C6 alkyl)2; RA 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; RB is H, C1 to C3 alkyl, or substituted C1 to C3 alkyl; R3 is H, OH, NH2, C1 to C6 alkyl, substituted C1 to C6 alkyl, C3 to C6 alkenyl, substituted C3 to C6 alkenyl, alkynyl, substituted alkynyl, or CORC; RC 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; R4 is H halogen, CN, NO2, C1 to C6 alkyl, substituted C1 to C6 alkyl, alkynyl, substituted alkynyl, C1 to C6 alkoxy, substituted C1 to C6 alkoxy, amino, C1 to C6 aminoalkyl, or substituted C1 to C6 aminoalkyl; R5 is selected from the group consisting of iv), v), vi), and vii): iv) a substituted benzene ring containing the substituents X, Y and Z as shown below: â€ƒwherein: X is selected from the group consisting of R halogen, CN, C1 to C3 alkyl, substituted C1 to C3 alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, C1 to C3 alkoxy, substituted C1 to C3 alkoxy, C1 to C3 thioalkoxy, substituted C1 to C3 thioalkoxy, amino, 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, CORD, OCORD, 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; Y and Z are independent substituents selected from the group consisting of H, halogen, CN, NO2, amino, aminoalkyl, C1 to C3 alkoxy, C1 to C3 alkyl, and C1 to C3 thioalkoxy, wherein not all of X, Y and Z are H; or v) a five membered ring having in its backbone 1, 2, or 3 heteroatoms selected from the group consisting of O, S, SO, and SO2 and containing one or two independent substituents selected from the group consisting of H halogen, CN, NO2, amino, C1 to C3 alkyl, C1 to C3 alkoxy, C1 to C3 aminoalkyl, CORF, and NRECORF; vi) a five membered ring having in its backbone 1, 2, or 3 NR6 heteroatoms and containing one or two independent substituents selected from the group consisting of H, halogen, NO2, amino, C1 to C3 alkyl, C1 to C3 alkoxy, C1 to C3 aminoalkyl, CORF, and NRGCORF; and vii) a six membered ring having in its backbone 1, 2, or 3 heteroatoms selected from the group consisting of O, S, SO, SO2 and NR6 and containing one or two independent substituents selected from the group consisting of H, halogen, CN, NO2, amino, C1 to C3 alkyl, C1 to C3 alkoxy, C1 to C3 aminoalkyl, CORF, and NRGCORF; RF 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; RG is H, C1 to C3 alkyl, or substituted C1 to C3 alkyl; R6 is H or C1 to C3 alkyl; or 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.