Patent CA-1246558-A (CA)
Inventor: SKUBALLA WERNER
IPC: A61K31/557
Filed: 1983-06-30
Granted: 1988-12-13
Abstract: ABSTRACT OF THE DISCLOSURE          Novel carbacyclin amides of the general formula   wherein R1 is NHR4, wherein R4 is (a) -(CH2)n-R8' (b) C2-10-alkenyl, (c) C1-10-alkyl or C2-10-alkenyl each substituted by C6-10-aryl or by C6-10-aryl substituted by 1-3 halogen atoms, a phenyl group, 1-3 C1-4 alkyl groups or a chloromethyl, fluo-romethyl, trifluoromethyl, carboxy, hydroxy or C1-4 alkoxy group; (d) C3-10-cycloalkyl (e) C3-10-cycloalkyl substituted by C1-4-alkyl, (f) C6-10-aryl, (g) C6-l0-aryl substituted by 1-3 halogen atoms, a phenyl group, 1-3 C1-4-alkyl groups or a chloromethyl, fluoromethyl, trifluoromethyl, carboxy, hydroxy or C1-4 alkoxy group;  or (h) C2-8-alkyl substituted by 1-5 hydroxy groups, or R1 is -NR4R5, wherein R4 and R5 each is C2-8-alkyl substituted by 1-5 hydroxy groups or R4 and R5 together with the N-atom form a 5- or 6- membered heterocycle containing up to 1 additional O, S, or N atom wherein an additional N-atom can be substituted by C1-4-alkyl, or R1 is -NR4R5 wherein R4 is (a) C1-10-alkyl, (b) C2-10-alkenyl, (c) C1-10-alkyl or C2-10-alkenyl each substituted by C6-10-aryl or C6-10-aryl substituted by 1-3 halogen atoms, a phenyl group, 1-3 C1-4 alkyl groups or a chloromethyl, fluoromethyl, trifluoromethyl, carboxy, hydroxy or C1-4-alkoxy group;  (d) C3-10-cycloalkyl or (e) C3-10-cycloalkyl substituted by C1-4-alkyl, and R5 is (a) C2-10-alkenyl, (b) C1-10-alkyl or C2-10-alkenyl each substituted by C6-10-aryl or by C6-10-aryl substituted by 1-3 halogen atoms, a phenyl group, 1-3 C1-4 alkyl groups or a chloromethyl, fluoromethyl, trifluoromethyl, carboxy, hydroxy or C1-4-alkoxy group;  (c) C3-10-cycloalkyl, (d) C3-10-cycloalkyl substituted by C1-4-alkyl, (e) C6-10-aryl, (f) C6-10-aryl substituted by 1-3 halogen atoms, a phenyl group, 1-3 C1-4 alkyl groups or a chloromethyl, fluoromethyl, trifluoromethyl, carboxy, hydroxy or C1-4-alkoxy group;  or (g) C2-8-alkyl substituted by 1-5 hydroxy groups, n is 1, 2, 3 or 4, R8 is -CONH2 or -N(C1-C4-alkyl)2;  R2 is OR:  R3 is (a) C1-10-alkyl, (b) C2-10 alkenyl, (c) C1-10-alkyl or C2-10-alkenyl each substituted by C6-10-aryl or by C6-10-aryl substituted by 1-3 halogen atoms, a phenyl group, 1-3 C1-4 alkyl groups or a chloromethyl, fluoromethyl, trifluoromethyl, carboxy, hydroxy or C1-4 alkoxy group;  (d) C3-10-cycloalkyl, (e) C3-10-cycloalkyl substituted by C1-4 alkyl, (f) C6-10-aryl, (g) C6-10-aryl substituted by 1-3 halogen atoms, a phenyl group, 1-3 C1-4 alkyl groups or a chloromethyl, fluoromethyl, trifluoromethyl, carboxy, hydroxy or C1-4 alkoxy group;  or (h) an aromatic heterocycle of 5 or 6 ring atoms one of which is O, N or S the remainder being carbon atoms;          X is -O- or -CH2-; A-W-D-E-R3 is   Y is H or CH3;? represents .alpha.- or .beta. -bond;       represents a single, double or triple bond, the double bond in the 13-position being in the trans-configuration;       C1-3-alkyl;  di-C1-3-alkyl;  H, H;  H, F;  or CH2(CH2)mCH2;  Z and Z' each is H or C1-5-alkyl;  m is 1, 2 or 3 and R is H, tetrahydropyranyl, tetrahydrofuranyl, .alpha.-ethoxyethyl, trimethylsilyl, dimethyl-tert-butyl-silyl, tribenzylsilyl acetyl, propionyl, butynyl and benzoyl.The novel carbacyclin amides have inter alia a hypotensive and brochodilative action and may accordingly be made up into pharmaceutical preparations with suitable carriers.