Patent ID: 6759408
Filing Date: 2004-07-06
Classification: A61K,Y10S

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 containing a progestational agent at a daily dose equal in progestational activity to from 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, each daily dosage unit containing an antiprogestin of the formula: 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 carbon-based 3 to 8 membered saturated spirocyclic ring; (ii) a carbon-based 3 to 8 membered spirocyclic ring having in its backbone one or more carbon-carbon double bonds; or (iii) a 3 to 8 membered heterocyclic ring having in its backbone 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 (iv), (v), (vi), or (vii) (iv) a substituted benzene ring having the substituents X, Y and Z: â€ƒwherein: X is selected from the group consisting of 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 having 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; (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 having 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; (vi) a five membered ring having in its backbone 1, 2, or 3 NR6 heteroatoms and having 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; or (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 having 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;at a concentration of from 2 to 50 mg and ethinyl estradiol at a concentration of from about 10 to about 35 &mgr;g; andc) optionally, a third phase of daily dosage units of an orally and pharmaceutically acceptable placebo, the total of the daily dosage units being 28.