Pharmaceutically active amines

Claim 1

An aromatic amine of the formula (I) ##STR39## where: (I) R 1 or R 2 and R 3 taken together are --O--CH 2 --O-- and the other of R 1 or R 2 is --H; R 22 is --H, --Cl or C 1 -C 3 alkyl; R 23 is --H, --Cl or C 1 -C 3 alkyl; or (II) R 1 and R 2 are the same or different and are --H, C 1 -C 4 alkyl, --F, --Cl and --Br, and R 3 is --H, --OH, C 1 -C 3 alkoxy, --O--SO 2 --CH 3 , --O--CO--(C 1 -C 4 alkyl) and --O-prodrug where prodrug is --PO 2 --O - , --CO--CH 2 --CO--NH--CH 2 --SO 2 --O - , --CO--(CH 2 ) n21 --R 51 where n 21 is 1-7 and R 51 is --COO - , --NR 51-1 R 51-2 where R 51-1 and R 51-2 are the same or different and are --H or C 1 -C 3 alkyl, --N + R 51-1 R 51-2 R 51-3 halide - where R 51-1 R 51-2 R 51-3 are the same or different and are --H or C 1 -C 3 alkyl, and where halide is --Cl or --Br, --CO--CH═CH--CO--O - , --CO--N*--CH═CH--N═CH* where the atoms marked with an asterisk (*) are bonded to each other resulting in the formation of a ring, --CO--C*═C[(CH 2 ) n22 --NH 2 ]--CH═CH--CH═CH* where n 22 is 1 or 2 and where the atoms marked with an asterisk (*) are bonded to each other resulting in the formation of a ring, --CO--C*═CH--CH═C(--NR 52 )--CH═CH* where R 52 is --H or C 1 -C 3 alkyl and where the atoms marked with an asterisk (*) are bonded to each other resulting in the formation of a ring, --CO--(CH 2 ) n21 --CO--O--[C 6 H 12 O 6 sugars], --CO--O--CH(CH 2 --O--CO--R 53 ) 2 where the R 53 's are the same or different and are C 1 -C 18 , --CO--(CH 2 ) 6 --CO--N(CH 3 )--CH 2 --CH 2 --SO 3 - cation + where cation + is sodium, potassium or trialkylammonium where alkyl is C 1 -C 3 , --CH 2 --O--CO--(CH 2 ) n21 --NR 51-1 R 51-2 where n 21 , R 51-1 and R 51-2 are as defined above, --CO--NH--C 6 H 4 --R 55 where R 55 is --H or C 1 -C 3 alkyl, --NO 2 , --NR 51-1 R 51-2 where R 51-1 and R 51-2 are as defined above and R 22 is --H, --OH, --Cl, C 1 -C 3 alkyl, --OCH 3 or --OC 2 H 5 ; R 23 is --H, --OH, --Cl, C 1 -C 3 alkyl, --OCH 3 or --OC 2 H 5 ; with the proviso that only two of R 3 , R 22 and R 23 can have a variable substituent containing an oxygen atom attached to the benzene ring; where X 1 is --O--, --CH 2 --, --C(CH 3 )(CH 3 )--, --C(H)(R 24 )-- where R 24 is C 1 -C 3 alkyl or phenyl optionally substituted with 1 or 2 --OH, --CH 3 or --OCH 3 , --C(OH)(R 13 ) where R 13 is --H or C 1 -C 3 alkyl, or phenyl optionally substituted with 1 or 2 --OH, --CH 3 or --OCH 3 , --S--, --Si--, --CO--, --NH--CO-- and --NR 4 -- where R 4 is --H or C 1 -C 4 alkyl; n 1 is 0-10; R 8 and R 9 are the same or different and are --H or C 1 -C 3 alkyl; n 13 is 0 or 1; n 14 is 2-5; M is (I') --NR A R B where: R A and R B are taken together with the attached nitrogen atom to form a heterocyclic ring selected from the group consisting of (1) 2-(carboxy)-1-pyrrolidinyl optionally as the C 1 -C 3 alkyl ester or as a pharmaceutically acceptable salt, (F-27) (2) 2-(carboxy)-1-piperidinyl optionally as the C 1 -C 3 alkyl ester or as a pharmaceutically acceptable salt, (F-28) (3) 2-(carboxy)-1-hexamethyleneimino optionally as the C 1 -C 3 alkyl ester or as a pharmaceutically acceptable salt, (F-29) (4) 2-(carboxy)-1-heptamethyleneimino optionally as the C 1 -C 3 alkyl ester or as a pharmaceutically acceptable salt, (F-30) (5) 1-piperazinyl optionally substituted in the 4-position with R M-12 --CO--(CH 2 ) j -- where where j is 0 through 3, R M-12 is -aryl, where aryl is phenyl optionally substituted with 1 -F or --CF 3 or with 1 or 2 -F, --Cl, --Br, C 1 -C 3 alkoxy, --COOH, --NH 2 , C 1 -C 3 alkylamino, di(C 1 -C 3 )alkylamino, where the alkyl groups are the same or different, 1-pyrrolidinyl-, 1-piperidinyl, 1-hexamethylenimino-, 1-heptamethyleneimino-, C 2 -C 4 acylamino and --NH--CHO; or R M-12 is -heteroaryl, where heteroaryl is: (a) pyridin-2- (F-1), 3- (F-2) or 4-yl (F-3) or the N-oxide thereof optionally substituted by 1 or 2 R M-2 , being the same or different, where R M-2 is (i) --F, (ii) --Cl, (iii) --Br, (iv) C 1 -C 5 alkyl, (v) --CH 2 --CH═CH 2 , (vi) -aryl, where aryl is as defined above, (vii) --NR M-3 R M-3 where the R M-3 s are the same or different and are --H, C 1 -C 3 alkyl or --CH 2 --CH═CH 2 , (viiiα) *CH 2 --(CH 2 ) q --CH 2 --N*-- where the atoms marked with an asterisk (*) are bonded to each other resulting in the formation of a ring, where q is 1 through 5, (viiiβ) *CH 2 --(CH 2 ) c --G--(CH 2 ) d --CH 2 --N*-- where the atoms marked with an asterisk (*) are bonded to each other resulting in the formation of a ring (F-4), where G is --O--, --S--, --SO--, --SO 2 -- or --NR M-4 --, where R M-4 is --H, C 1 -C 3 alkyl, or aryl as defined above, where c and d are the same or different and are 0 through 2 with the proviso that the total number of ring carbon atoms is 4, 5 or 6, (ix) 3-pyrrolin-1-yl, (F-5) (x) pyrrol-1-yl optionally substituted with C 1 -C 3 alkyl, (F-6) (xi) piperidin-1-yl optionally substituted with 1 or 2 C 1 -C 3 alkyl, (F-7) (xii) 1,2,3,6-tetrahydropyridin-1-yl, (F-8) (xiii) 1-hexamethyleneimino containing a 3-or 4- double bond or 3- and 5-double bonds, (xiv) 1,4-dihydro-1-pyridinyl substituted in the 4 position by two C 1 -C 3 alkyl being the same or different, (F-10) (xv) --OH, (xvi) C 1 -C 3 alkoxy, (xvii) --NR M-7 --(CH 2 ) e --Q where Q is 2-pyridinyl where R M-7 is --H or C 1 -C 3 alkyl and e is 0 through 3, (xviii) pyridin-2-, 3- or 4-yl, (xix) --CF 3 , (xx) --CCl 3 , (xxi) --S--CH 3 , (b) 1,3,5-triazin-2-yl or the N-oxide thereof optionally substituted at the 4- and/or 6-position with R M-2 is as defined above, (F-11) (c) pyrimidin-4-yl or the N-oxide thereof optionally substituted at the 2- and/or 6-, and 5- and/or 6-position with R M-2 is as defined above, (F-12) (d) pyrimidin-2-yl optionally substituted at 4- and/or 6-position with 1 or 2 R M-2 as is defined above, (F-13) (e) pyrazin-2-yl optionally substituted with 1 or 2 R M-2 as is defined above, (F-14) (f) imidazol-2-yl optionally substituted in the 1 position with C 1 -C 3 alkyl or -aryl, where aryl is as defined above, and further optionally substituted with 1 or 2 R M-2 as defined above, (F-15) (g) 1,3,4-triazol-2-yl optionally substituted in the 1 position with C 1 -C 3 alkyl or -aryl, where aryl is as defined above, and further optionally substituted with R M-2 as defined above, (F-16) (h) imidazol-4- or 5-yl optionally substituted in the 1 position with C 1 -C 3 alkyl or -aryl, where aryl is as defined above, and further optionally substituted with 1 or 2 R M-2 as defined above, (F-17) (i) benzo[b]thien-2-yl, (F-18) (j) indol-2-yl, (F-19) (k) benzo[b]thiazol-2-yl, (F-20) (l) benzimidazol-2-yl, (F-21) (m) 4-[2-[4-[2,6-bis(1-pyrrolidinyl)-4-pyrimidinyl]-1-piperazinyl]ethyl], (F-22) (n) 1,2,4-triazin-3-yl optionally substituted at the 5- and/or 6-position with R M-2 as is defined above, (F-23) or R M-12 is 2-furanyl, or R M-12 is --NR M13 heteroaryl, where R M-13 is --H or C 1 -C 3 alkyl, and heteroaryl is as defined above, (F-31) (6) 1-piperazinyl substituted in the 4-position with heteroaryl-(CH 2 ) j --, where heteroaryl and j are as defined above, (F-32) (7) 1-piperazinyl substituted in the 4-position with aryl--(CH 2 ) j --, where aryl and j are as defined above, (F-33) (8) 4-hydroxy-1-piperidinyl substituted in the 4-position with aryl where aryl is as defined above, (F-34) (9) 1-piperazinyl substituted in the 4-position with heteroaryl-NR M-13 --CO--(CH 2 ) i --, where i is 1 thru 4 and where heteroaryl and R M-13 are as defined above; (F-35) (10) 1-piperazinyl substituted in the 4-position with --(CH 2 ) j --C*═C(2-pyridinyl)--N═N--C(2-pyridinyl)═C*H, where * and j are as defined above, (F-36) (11) 1-piperazinyl substituted in the 4-position with --(CH 2 ) i --[4-[2,6-bis(1-pyrrolidinyl)-4-pyrimidinyl]-1-piperazine] (F-37) or M is (II') --C*═C(2-pyridinyl)--N═N--C(2-pyridinyl)═C*H where * is as defined above and pharmaceutically acceptable salts thereof, and hydrates and solvates thereof.