GB1530153A - Substituted acetic acids - Google Patents

Abstract

1530153 Substituted acetic acids SANDOZ Ltd 23 Oct 1975 [29 Oct 1974] 43680/75 Heading C2C The invention comprises compounds of the formula wherein R 1 is hydrogen or alkyl or 1 or 2 carbon atoms; R 2 is hydrogen or halogen of atomic number from 9 to 35; (a) (i) each of R 3 and R 4 is hydrogen, or (ii) R 3 and R 4 together are oxygen, and (i) R 5 is hydrogen or alkyl of 1 to 4 carbon atoms, or (ii) R 5 and R 7 are attached to the same carbon atom, and form an alkylene chain of 3 to 6 carbon atoms, or (b) when A as defined hereinafter is -(CH 2 ) 2 - R 3 is hydrogen and R 4 and R 5 together form a bond; R 6 is hydrogen or alkyl of 1 to 4 carbon atoms; and A is -(CH 2 ) n -, wherein n is 0, 1 or 2 depending on the following: n may be 0 provided that R 3 and R 4 together are oxygen: n may be 1 provided that (i) at least one of R 5 , R 6 and R 7 is alkyl of 1 to 4 carbon atoms; (ii) R 5 and R 7 together form an alkylene chain of 3 to 6 carbon atoms; or (iii) R 2 is halogen, R 3 and R 4 are oxygen, and R 5 , R 6 and R 7 are all hydrogen ; n may be 2 provided that (i) R 3 and R 4 together are oxygen; (ii) R 4 and R 5 together form a bond, or (iii) R 2 is halogen; (iv) at least one of the substituents R 1 , R 5 , R 6 and R 7 is alkyl of 1 to 4 carbon atoms; or (v) R 5 and R 7 together form an alkylene chain of 3 to 6 carbon atoms, or provided that R 5 and R 7 are both hydrogen, R 6 and A may alternatively be together with the carbon atom to which they are bound a 1,2-cyclo-alkylene group of formula wherein m is 3 or provided that R 3 and R 4 together are oxygen alternatively 4; and R 7 is attached to any carbon atom of ring B except that marked * in the formula and is hydrogen or provided that R 6 is hydrogen may alternatively be alkyl of 1 to 4 carbon atoms, and acid addition salts thereof. The compounds may be prepared as follows (a) for a compound of Formula Ia wherein R 1 and R 2 are as defined above, R<SP>1</SP> 5 is hydrogen, alkyl of 1 to 4 carbon atoms, or, when R<SP>1</SP> 5 and R<SP>1</SP> 7 are bound to the same carbon atom R<SP>1</SP> 5 together with R<SP>1</SP> 7 may alternatively form an alkylene chain of 3 to 6 carbon atoms, R<SP>1</SP> 6 is hydrogen or alkyl or 1 to 4 carbon atoms, and A<SP>1</SP> is wherein n<SP>1</SP> is 0, 1 or 2 with the proviso that n is other than 1 when R 2 , R<SP>1</SP> 5 , R<SP>1</SP> 6 and R<SP>1</SP> 7 are all hydrogen, or provided that R<SP>1</SP> 5 and R<SP>1</SP> 7 are both hydrogen, R<SP>1</SP> 6 and A may alternatively be together with the carbon atom to which they are bound a 1,2-cycloalkylene group of Formula XIV wherein m is 3 or 4, and R<SP>1</SP> 7 is hydrogen or provided that R<SP>1</SP> 6 is hydrogen, may alternatively be alkyl of 1 to 4 carbon atoms, by cyclization of a compound of Formula II, wherein R 1 , R 2 , R<SP>1</SP> 5 , R<SP>1</SP> 6 , R<SP>1</SP> 7 and A<SP>1</SP> are as defined above, or a reactive acid derivative thereof, or (b) for a compound of Formula Ib, wherein R 1 and R 2 are as defined above, each of R<SP>1</SP> 3 and R<SP>1</SP> 4 is hydrogen, R<SP>11</SP> 5 is hydrogen or alkyl of 1 to 4 carbon atoms, or, when R<SP>11</SP> 5 and R<SP>11</SP> 7 are bound to the same carbon atom, R<SP>11</SP> 5 and R<SP>11</SP> 7 together form an alkylene chain of 3 to 6 carbon atoms, R<SP>11</SP> 6 is hydrogen or alkyl of 1 to 4 carbon atoms, and wherein n<SP>11</SP> may be 1 provided that one of the substituents R<SP>11</SP> 5 , R<SP>11</SP> 6 and R<SP>11</SP> 7 is alkyl of 1 to 4 carbon atoms, or R<SP>11</SP> 5 together with R<SP>11</SP> 7 form an alkylene chain of 3 to 6 carbon atoms; or n<SP>11</SP> may be 2 provided that (i) R 2 is halogen; (ii) at least one of the substituents R 1 , R<SP>11</SP> 5 , R<SP>11</SP> 6 and R<SP>11</SP> 7 is alkyl of 1 to 4 carbon atoms; or (iii) R<SP>11</SP> 5 together with R<SP>11</SP> 7 form an alkylene chain of 3 to 6 carbon atoms, or provided that R<SP>11</SP> 5 and R<SP>11</SP> 7 are both hydrogen, R<SP>11</SP> 6 and A<SP>11</SP> together with the carbon atom to which they are bound form a 1,2-cyclopentylene group of formula and R<SP>11</SP> 7 is hydrogen or when R<SP>11</SP> 6 is hydrogen alternatively alkyl of 1 to 4 carbon atoms, by reduction of a compound of Formula III, wherein R 1 , R 2 , R<SP>11</SP> 6 , R<SP>11</SP> 7 and A<SP>11</SP> are as defined above, (the significance of A<SP>11</SP> where necessary depending on R<SP>11</SP> 5 depending instead on R<SP>111</SP> 5 ), R<SP>11</SP> 3 and R<SP>11</SP> 4 together are oxygen, and R<SP>111</SP> 5 is hydrogen or alkyl of 1 to 4 carbon atoms, or, when R<SP>111</SP> 5 and R<SP>11</SP> 7 are bound to the same carbon atom, R<SP>111</SP> 5 and R<SP>11</SP> 7 form an alkylene chain of 3 to 6 carbon atoms or R<SP>11</SP> 4 and R<SP>111</SP> 5 together form a bond and R<SP>11</SP> 3 is hydrogen, and R 8 is hydrogen, or, when R<SP>11</SP> 4 and R<SP>11</SP> 3 together are oxygen, a radical capable of being split off hydrolytically, and, in case R 8 is a radical capable of being split off hydrolytically concomitant removal of this radical, or (c) for a compound of Formula Ic, wherein R 1 , R 2 and R<SP>1</SP> 3 are so defined above, and R<SP>111</SP> 7 is hydrogen or alkyl of 1 to 4 carbon atoms by splitting off water, and in case R 9 is a radical capable of being split off acidolytically, concomitant removal of this radical from a compound of Formula IV wherein R 1 , R 2 , R<SP>1</SP> 3 and R<SP>111</SP> 7 are as defined above, and R 9 is hydrogen or a radical capable of being removed acidolytically. The compounds may be used as analgesic, antiphlogistic or antiarthritic agents.