Antagonists of gonadotropin releasing hormone

A compound of the formula ##STR305## wherein:

• A is a bond, C.sub.1 -C.sub.6 alkylene, substituted C.sub.1 -C.sub.6 alkylene, C.sub.2 -C.sub.6 alkenylene, substituted C.sub.2 -C.sub.6 alkenylene, C.sub.2 -C.sub.6 alkynylene, substituted C.sub.2 -C.sub.6 alkynylene, C.sub.1 -C.sub.6 alkoxy, substituted C.sub.1 -C.sub.6 alkoxy;
• B is a bond, C.sub.1 -C.sub.6 alkylene, substituted C.sub.1 -C.sub.6 alkylene;
• X is O, S, SO, SO.sub.2, NR.sub.12 or C(R.sub.13 R.sub.14);
• R.sub.1 is H, C.sub.1 -C.sub.6 alkyl, substituted C.sub.1 -C.sub.6 alkyl, C.sub.3 -C.sub.6 cycloalkyl or substituted C.sub.3 -C.sub.6 cycloalkyl;
• R.sub.2, R.sub.3 and R.sub.4 are independently H, C.sub.1 -C.sub.6 alkyl, substituted C.sub.1 -C.sub.6 alkyl, C.sub.2 -C.sub.6 alkenyl, substituted C.sub.2 -C.sub.6 alkenyl, C.sub.2 -C.sub.6 alkynyl, substituted C.sub.2 -C.sub.6 alkynyl, CN, nitro, C.sub.1 -C.sub.3 perfluoroalkyl, C.sub.1 -C.sub.3 perfluoroalkoxy, aryl, substituted aryl, C.sub.1 -C.sub.6 aralkyl, substituted C.sub.1 -C.sub.6 aralkyl, R.sub.15 O(CR.sub.13 R.sub.14).sub.p --, R.sub.16 C(O)O(CR.sub.13 R.sub.14).sub.p --, R.sub.15 OC(O)(CR.sub.13 R.sub.14).sub.p --, --(CR.sub.13 R.sub.14).sub.p S(O).sub.n R.sub.12, --(CR.sub.13 R.sub.14).sub.p C(O)NR.sub.17 R.sub.18, --(CR.sub.13 R.sub.14).sub.p NR.sub.17 C(O)R.sub.16, --(CR.sub.13 R.sub.14).sub.p N(R.sub.17 R.sub.18) or halogen;
• R.sub.2 and R.sub.3 taken together form a carbocyclic ring, saturated or unsaturated, of 3-7 carbon atoms or a heterocyclic ring containing 1-3 heteroatoms selected from N, O and S;
• R.sub.5, R.sub.6, R.sub.7 and R.sub.8, independently are H, nitro, halogen, C.sub.1 -C.sub.6 alkyl, substituted C.sub.1 -C.sub.6 alkyl, C.sub.2 -C.sub.6 alkenyl, substituted C.sub.2 -C.sub.6 alkenyl, C.sub.2 -C.sub.6 alkynyl, substituted C.sub.2 -C.sub.6 alkynyl, aryl, substituted aryl, C.sub.1 -C.sub.6 aralkyl, substituted C.sub.1 -C.sub.6 aralkyl, R.sub.15 O(CR.sub.13 R.sub.14).sub.p --, --(CR.sub.13 R.sub.14).sub.p CN, --(CR.sub.13 R.sub.14).sub.p SO.sub.n R.sub.12, --(CR.sub.13 R.sub.14).sub.p SO.sub.2 N(R.sub.17 R.sub.18), --(CR.sub.13 R.sub.14).sub.p N(R.sub.17 R.sub.18), --(CR.sub.13 R.sub.14).sub.p N(R.sub.17) C(O)R.sub.16, --(CR.sub.13 R.sub.14).sub.p N(R.sub.17)C(O)N(R.sub.17 R.sub.18), --(CR.sub.13 R.sub.14).sub.p N(R.sub.17)SO.sub.2 N (R.sub.17 R.sub.18), --(CR.sub.13 R.sub.14).sub.p N(R.sub.17)SO.sub.2 R.sub.12, --(CR.sub.13 R.sub.14).sub.p C(O)OR.sub.15, --(CR.sub.13 R.sub.14).sub.p OC(O)R.sub.16, --(CR.sub.13 R.sub.14).sub.p C(O)N(R.sub.17 R.sub.18) --(CR.sub.13 R.sub.14).sub.p OC(O)N(R.sub.17 R.sub.18), --(CR.sub.13 R.sub.14).sub.p N(R.sub.17)C(O)OR.sub.15, or ##STR306## R.sub.9a is H, C.sub.1 -C.sub.6 alkyl or substituted C.sub.1 -C.sub.6 alkyl,
• R.sub.11 is H, C.sub.1 -C.sub.6 alkyl, substituted C.sub.1 -C.sub.6 alkyl, --(CR.sub.13 R.sub.14).sub.p C(O)OR.sub.15 ;
• or
• R.sub.9 and R.sub.10 are taken together to form a saturated heterocyclic ring of 4-7 atoms containing 1-3 heteroatoms selected from O, N, and S, or;
• (R.sub.9 and R.sub.10) and (R.sub.9a and R.sub.11) can be taken together to form a heterobicyclic ring, with each ring being independently saturated or unsaturated, of 4-7 atoms containing 1-3 heteroatoms selected from O, N, and S;
• R.sub.12 is H, C.sub.1 -C.sub.6 alkyl, substituted C.sub.1 -C.sub.6 alkyl, aryl, substituted aryl, C.sub.1 -C.sub.6 aralkyl, substituted C.sub.1 -C.sub.6 aralkyl;
• R.sub.13 and R.sub.14 are independently H, C.sub.1 -C.sub.6 alkyl, substituted C.sub.1 -C.sub.6 alkyl, aryl, substituted aryl, C.sub.1 -C.sub.6 aralkyl, substituted C.sub.1 -C.sub.6 aralkyl;
• R.sub.15 is H, C.sub.1 -C.sub.6 alkyl, substituted C.sub.1 -C.sub.6 alkyl, aryl, substituted aryl, C.sub.1 -C.sub.6 aralkyl, substituted C.sub.1 -C.sub.6 aralkyl;
• R.sub.16 is H, C.sub.1 -C.sub.6 alkyl, substituted C.sub.1 -C.sub.6 alkyl, aryl, substituted aryl, C.sub.1 -C.sub.6 aralkyl, substituted C.sub.1 -C.sub.6 aralkyl;
• R.sub.17 and R.sub.18 are independently H, C.sub.1 -C.sub.6 alkyl, substituted C.sub.1 -C.sub.6 alkyl, C.sub.3 -C.sub.6 cycloalkyl, substituted C.sub.3 -C.sub.6 cycloalkyl, aryl, substituted aryl, C.sub.1 -C.sub.6 aralkyl, substituted C.sub.1 -C.sub.6 aralkyl, or taken together form a carbocyclic ring(s) of 4-7 carbon atoms each;
• R.sub.19 is H, C.sub.1 -C.sub.6 alkyl, substituted C.sub.1 -C.sub.6 alkyl or --CN;
• n is 0, 1, or 2;
• p is 0, 1, 2, 3 or 4 the alkyl, cycloalkyl, alkenyl and alkynyl substituents are selected from C.sub.1 -C.sub.6 alkyl, C.sub.3 -C.sub.7 cycloalkyl, aryl, substituted aryl, aralkyl, substituted aralkyl, hydroxy, oxo, cyano, C.sub.1 -C.sub.6 alkoxy, fluoro, C(O)OR.sub.11, aryl C.sub.1 -C.sub.3 alkoxy, substituted aryl C.sub.1 -C.sub.3 alkoxy, and the aryl substituents are as defined for R.sub.3, R.sub.4 and R.sub.5 ;
• or a pharmaceutically acceptable addition salt and/or hydrate thereof, or a geometric or optical isomer thereof.