GB1436378A - Prostaglandin derivatives - Google Patents

Abstract

1436378 Prostaglandins AMERICAN HOME PRODUCTS CORP 2 Aug 1973 [21 Aug 1972] 36785/73 Heading C2C The invention comprises (i) compounds of Formula II in which R<SP>1</SP> = CH 2 NO 2 , vinyl, Ph, Bz, Me, CN, SH, SAlkyl, SPh, CH(CN)COOH, CH(COOAlkyl) 2 , CH(CN) 2 or CH(CN)CONH 2 R<SP>2</SP> = OH, OTHP or OAc and R<SP>3</SP> = H, (ii) compounds of Formula V in which R<SP>1</SP> = CN, COOH, CONH 2 , CHO, CH 2 OH, CH(OH)CH 3 or CH 2 NO 2 , R<SP>2</SP> = OH or OAc and R<SP>3</SP> = H, (iii) compounds of Formula VI in which R<SP>1</SP> = COOH, COCH 3 , CONH 2 , CH 2 OH or CH(OH)CH 3 , (iv)-(vii) compounds of Formulµ VII, VIII, IX and X in which R<SP>1</SP> = CH 2 NO 2 or CN and R<SP>2</SP> = Me or Ph (viii) compounds of Formula IV in which R<SP>1</SP> = CONH 2 , Me, COOH, Bz, CH 2 NO 2 , Ph, CN, CH(CN)COOAlk, CH(COOH) 2 , CH 2 OH, COCH 3 or CH(OH)CH 3 , R<SP>2</SP> = OH, OTHP or OAc, provided that R<SP>2</SP> = OH when R<SP>1</SP> = COOH, COCH 3 , CONH 2 , CH 2 OH or CH(OH)CH 3 , and R<SP>3</SP> = H and (ix) compounds of Formula III in which R<SP>1</SP> = SH, CH 2 NO 2 , vinyl, Ph, Me, Bz, CN, SAlkyl, SPh, CH(CN)COOH, or CH(CN)CONH 2 , R<SP>2</SP> = OH or OTHP and R<SP>3 </SP>= H; and C 1 -C 6 alkyl esters and alkali metal, ammonium and basic amine salts of the said compounds. Compounds II are prepared from compounds I by 1,4-conjugate addition to the α,#-unsaturated ketone system, e.g. by means of Grignard reagents. Compounds III are prepared by treatment of compounds II with a hydride reducing agent. Compounds VI are prepared by deketalization of compounds V. Compounds VII are prepared by oxidation of compounds V. Compounds VIII are prepared by reaction of compounds VII with a methyl or phenyl Grignard reagent. Compounds IX are prepared by deketalization of compounds VIII. Compounds X are prepared by hydrogenation of compounds IX. Compounds IV are prepared by hydrogenation of compounds II or VI. Compounds V in which R<SP>1</SP> = CN or CH 2 NO 2 are prepared from corresponding compounds II by ketalization. Compounds V in which R<SP>1</SP> = COOH, CONH 2 , CHO or COCH 3 are prepared from compounds V in which R<SP>1</SP> = CN. Compounds V in which R<SP>1</SP> = CH 2 OH or CH(OH)CH 3 are prepared by reduction of compounds V in which R<SP>1</SP> = CHO or COCH 3 . Esters and salts may be prepared from compounds containing free OH or COOH groups, and vice versa. Intermediates.-PGA 2 , methyl ester; PGA 2 , 15 - tetrahydropyran - 2 - yl ether, PGA 2 , 15 - tetrahydropyran - 2 - yl ether, methyl ester, 15 - epi - PGA 2 , 15 - tetrahydropyran - 2 - yl ether; and PGA 2 , methyl ester, acetate are prepared in examples. Pharmaceutical compositions having bronchodilating activity for oral, parenteral and oral inhalation activity, comprise a compound of Formula II, III, IV, V, VI, IX or X together with a pharmaceutical carrier.