This invention provides a progesterone receptor antagonist of formula 1 having the structure wherein T is O, S, or absent; R 1 , and R 2 are each, independently, hydrogen, alkyl, substituted alkyl; or R 1 and R 2 are taken together form a ring and together contain —CH 2 (CH 2 ) n CH 2 —, —CH 2 CH 2 CMe 2 CH 2 CH 2 —, —O(CH 2 ) p CH 2 —, —O(CH 2 ) q O—, —CH 2 CH 2 OCH 2 CH 2 —, or —CH 2 CH 2 NR 7 CH 2 CH 2 —; n=1–5; p=1–4; q=1–4; R 3 is hydrogen, OH, NH 2 , alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, or COR A ; R A is hydrogen, alkyl, substituted alkyl, alkoxy, substituted alkoxy, aminoalkyl, or substituted aminoalkyl; R 4 is hydrogen, halogen, CN, NH 2 , alkyl, substituted alkyl, alkoxy, substituted alkoxy, aminoalkyl, or substituted aminoalkyl; R 5 is hydrogen, alkyl, or substituted alkyl; R 6 is hydrogen, alkyl, substituted alkyl, or COR B ; R B is hydrogen, alkyl, substituted alkyl, alkoxy, substituted alkoxy, aminoalkyl, or substituted aminoalkyl; R 7 is hydrogen or alkyl, or a pharmaceutically acceptable salt thereof.
1. A compound having the structure of formula 1:
wherein:
T is S;
R 1 and R 2 are each, independently, hydrogen, alkyl, or substituted alkyl; or
R 1 and R 2 are taken together to form a ring selected from the group consisting of —CH 2 (CH 2 ) n CH 2 —, —CH 2 CH 2 C(CH 3 ) 2 CH 2 CH 2 —, —O(CH 2 ) p CH 2 —, —O(CH 2 ) q O—, —CH 2 CH 2 OCH 2 CH 2 —, and —CH 2 CH 2 NR 7 CH 2 CH 2 —;
n=1–5;
p=1–4;
q=1–4;
R 3 is hydrogen, OH, NH 2 , alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, or COR A ;
R A is hydrogen, alkyl, substituted alkyl, alkoxy, substituted alkoxy, aminoalkyl, or substituted aminoalkyl;
R 4 is hydrogen, halogen, CN, NH 2 , alkyl, substituted alkyl, alkoxy, substituted alkoxy, aminoalkyl, or substituted aminoalkyl;
R 5 is hydrogen, alkyl, or substituted alkyl;
R 6 is hydrogen, alkyl, substituted alkyl, or COR B ;
R B is hydrogen, alkyl, substituted alkyl, alkoxy, substituted alkoxy, aminoalkyl, or substituted aminoalkyl;
R 7 is hydrogen or alkyl;
or a pharmaceutically acceptable salt thereof.
2. The compound according to claim 1 , wherein:
R 1 and R 2 are taken together to form the ring —CH 2 (CH 2 ) n CH 2 —;
R 3 is hydrogen;
R 4 is hydrogen or halogen;
R 5 is hydrogen or alkyl;
R 6 is hydrogen or alkyl.
3. A method of providing contraception in a mammal in need thereof, which comprises administering an effective amount of a compound having the structure of formula 1:
wherein:
T is O or S;
R 1 and R 2 are each, independently, hydrogen, alkyl, or substituted alkyl; or
R 1 and R 2 are taken together to form a selected from the group consisting of —CH 2 (CH 2 ) n CH 2 —, —CH 2 CH 2 C(CH 3 ) 2 CH 2 CH 2 —, —O(CH 2 ) p CH 2 —, —O(CH 2 ) q O—, —CH 2 CH 2 OCH 2 CH 2 —, and —CH 2 CH 2 NR 7 CH 2 CH 2 —;
n=1–5;
p=1–4;
q=1–4;
R 3 is hydrogen, OH, NH 2 , alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, or COR A ;
R A is hydrogen, alkyl, substituted alkyl, alkoxy, substituted alkoxy, aminoalkyl, or substituted aminoalkyl;
R 4 is hydrogen, halogen, CN, NH 2 , alkyl, substituted alkyl, alkoxy, substituted alkoxy, aminoalkyl, or substituted aminoalkyl;
R 5 is hydrogen, alkyl, or substituted alkyl;
R 6 is hydrogen, alkyl, substituted alkyl, or COR B ;
R B is hydrogen, alkyl, substituted alkyl, alkoxy, substituted alkoxy, aminoalkyl, or substituted aminoalkyl;
R 7 is hydrogen or alkyl;
or a pharmaceutically acceptable salt thereof, to said mammal.
4. A pharmaceutical composition, which comprises a compound having the structure of formula 1:
wherein:
T is S;
R 1 and R 2 are each, independently, hydrogen, alkyl, or substituted alkyl; or
R 1 and R 2 are taken together to form a ring selected from the group consisting of —CH 2 (CH 2 ) n CH 2 —, —CH 2 CH 2 C(CH 3 ) 2 CH 2 CH 2 —, —O(CH 2 ) p CH 2 —, —O(CH 2 ) q O—, —CH 2 CH 2 OCH 2 CH 2 —, and —CH 2 CH 2 NR 7 CH 2 CH 2 —;
n=1–5;
p=1–4;
q=1–4;
R 3 is hydrogen, OH, NH 2 , alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, or COR A ;
R A is hydrogen, alkyl, substituted alkyl, alkoxy, substituted alkoxy, aminoalkyl, or substituted aminoalkyl;
R 4 is hydrogen, halogen, CN, NH 2 , alkyl, substituted alkyl, alkoxy, substituted alkoxy, aminoalkyl, or substituted aminoalkyl;
R 5 is hydrogen, alkyl, or substituted alkyl;
R 6 is hydrogen, alkyl, substituted alkyl, or COR B ;
R B is hydrogen, alkyl, substituted alkyl, alkoxy, substituted alkoxy, aminoalkyl, or substituted aminoalkyl;
R 7 is hydrogen or alkyl;
or a pharmaceutically acceptable salt thereof and a pharmaceutical carrier.