Benzopyrido piperidine, piperidylidene and piperazine compounds, compositions, methods of manufacture and methods of use

Claim 1

A compound represented by the structural formula or a pharmaceutically acceptable salt or solvate thereof, wherein: one of a, b, c and d represents nitrogen or -NR 11 -, where R 11 is -O-, -CH 3 or -(CH 2 )pC0 2 H where p is 1 to 3, and the remaining a, b, c and d groups are CH which may be substituted with R 1 and/or R 2 ; R 1 and R 2 may be the same or different and each independently represents halo, -CF 3 , -OR 10 , -C(O)R 10 , -S-(O) e R 12 where e is 0, 1 or 2, -N(R 10 ) 2 , -N0 2 , SH, CN, OC(O)R 10 , -CO 2 R 10 , -OCO 2 R 12 , -NR 10 C(O)R 10 , alkyl, alkenyl or alkynyl, which alkyl or alkenyl groups may be substituted with halo, -OR 10 or -CO 2 R 10 , or R 1 and R 2 may together form a benzene ring fused to the pyridine ring; R 10 represents H, alkyl or aryl; R 12 represents alkyl or aryl; R 3 and R 4 may be the same or different and each independently represents H or any of the substituents of R' and R 2 , or R 3 and R 4 may be taken together to represent a saturated or unsaturated C S -C 7 ring fused to the benzene ring; R 5 , R 6 , R 7 and R 8 each independently represents H, -CF 3 , -CO 2 R 10 , -C(O)R 10 , alkyl or aryl, which alkyl or aryl may be substituted with -OR 10 , -SR 10 , -N(R 10 ) 2 , -N0 2 , -C(O)R 10 , -OC(O)R 10 , -OCO 2 R 12 , -CO 2 R 10 and -OPO 3 (R 10 ) 2 , or one of R 5 , R 6 , R 7 and R 8 may be taken in combination with R as defined below to represent -(CH 2 ) r -where r is 1 to 4, said combination being optionally substituted with lower alkyl, lower alkoxy, -CF 3 or aryl, or R 5 may be combined with R 6 to represent =O or =S, and/or R 7 may be combined with R 8 to represent = 0 or = S; T represents carbon or nitrogen, with the dotted line attached to T representing an optional double bond when T is carbon; m and n are integers 0, 1, 2, or 3, such that the sum of m plus n equals 0 to 3 with the proviso that: when m plus n equals 1, X represents -O-, -S(O) e - where e is 0, 1 or 2. -NR 10 -, -C(0)NR'°-, NR 10 C(O)-, -C-(S)NR'°-, -NR 10 C(S)-, -C0 2 - or -OC(O)-,- when m plus n equals 2, X represents -O-, -S(O) e - where e is 0, 1 or 2, or -NR 10 -; when m plus n equals 0, X can be any substituent for m plus n equalling 1 and X can also be a direct bond, cyclopropylene, or propenylene; when m plus n equals 3, X equals a direct bond; each R a may be the same or different, and each independently represents H, lower alkyl or phenyl; Z represents =O, = S or =NR 13 where R 13 represents R 10 or CN, such that (a) when Z is 0, R may be taken in combination with R 5 , R 6 , R 7 or R 8 as defined above, or R represents H, alkyl, aryl, -SR 12 , -N(R 10 ) 2 , cycloalkyl, alkenyl, alkynyl or -D wherein -D represents heterocycloalkyl, wherein R 3 and R 4 are as previously defined and W is 0, S or NR 10 and where Y is N or NR 11 , said cycloalkyl, alkyl, alkenyl and alkynyl being optionally substituted with from 1-3 groups selected from halo, -CON(R 10 ) 2 , aryl, -CO 2 R 10 , -OR 14 , -SR 14 , -N(R 10 ) 2 , -N(R 10 )CO 2 R 10 , -COR 14 , -N0 2 or -D, wherein R' 4 represents R 10 , -(CH 2 ) r OR 10 or -(CH 2 ) q CO 2 R 10 and wherein r is 1 to 4 and q is 0 to 4, said alkenyl and alkynyl R groups not containing -OH, -SH or -N(R 10 ) 2 on a carbon in a double or triple bond respectively; (b) when Z represents S, R represents in addition to those R groups above, aryloxy or alkoxy; and (c) when Z represents NR 13 , R represents H, alkyl, aryl, -N(R 10 ) 2 , cycloalkyl, alkenyl or alkynyl.

Claim 17

A method of manufacturing a pharmaceutical composition comprising admixing a compound of formula I with a pharmaceutically acceptable carrier.

Claim 18

A method of manufacturing a pharmaceutical composition comprising admixing a compound of formula I with a pharmaceutically acceptable carrier.

Claim 19

A method of manufacturing a compound of formula I comprising: A. reacting a compound of formula II with a compound of formula III where L represents a suitable leaving group; B. reacting a compound of formula V with a suitable compound of formula III C. Cyclizing a compound of XLV to a compound of formula I; D. Reacting a compound of formula XXX with a compound of formula XXXII or XXIX to produce a compound of formula I if R C is Z(C)R

Claim 20

A method of manufacturing a compound of formula I comprising: A. reacting a compound of formula II with a compound of formula III where L represents a suitable leaving group; B. reacting a compound of formula V with a suitable compound of formula III C. Cyclizing a compound of XLV to a compound of formula I; D. Reacting a compound of formula XXX with a compound of formula XXXII or XXIX to produce a compound of formula I if R C is Z(C)R