Patent NZ-306625-A (NZ)
Title: Tetrahydro-pyridine compounds, their preparation, and pharmaceuticals thereof; useful as neuraminidase inhibitors
Inventor: BISCHOFBERGER NORBERT W
IPC: A61K31/13
Filed: 1996-02-26
Abstract: A composition comprising a compound of formula (I) or (II): wherein: A1 is -C(J1)=, or -N=; A2 is-C(J1)2-, -N(J1)-, -N(O)(J1)-, -N(O)=, -S-, -S(O)-, -S(O)2- or -O-; E1 is -(CR1R1)m1W1; G1 is N3, CN, -OH, -OR6a -NO2, or -(CR1R1)m1W2; T1 is -NR1W3, a heterocycle, or is taken together with U1 or G1 to form a group of formula (III) U1 is H or -X1W6; J1 and J1a are independently R1, Br, Cl, F, I, CN, N02 or N3; J2 and J2a are independently H or R1; R1 is independently H or alkyl, R2 is independently R3 or R4 wherein each R4 is independently substituted with 0 to 3 R3 groups; 3 is independently F, Cl, Br, I, -CN, N3, -NO2, -OR6a, -OR1, -N(R1)2, -N(R1)(R6b), -N(R6b)2, -SR1, -SR6a, -S(O)R1, -S(0)2R1, -S(O)OR1, -S(O)OR6a, -S(O)2OR1, -S(O)2OR6a, -C(O)OR1, -C(O)R6c, -C(O)OR6a, -OC(O)R1, -N(R1)(C(O)R1), -N(R6b)(C(O)R1), -N(R1)(C(O)OR1), -N(R6b)(C(O)OR1), -C(O)N(R1)2, -C(O)N(R6b)(R1), -C(O)N(R6b)2, -C(NR1)(N(R1)2), -C(N(R6b))(N(R1)2), -C(N(R1))(N(R1)(R6b)), -C(N(R6b))(N(R1)(R6b)), -C(N(R1))(N(R6b)2), -C(N(R6b))(N(R6b)2), -N(R1)C(N(R1))(N(R1)2), -N(R1)C(N(R1))(N(R1)(R6b)), -N(R1)C(N(R6b))(N(R1)2), -N(R6b)C(N(R1))(N(R1)2), -N(R6b)C(N(R6b))(N(R1)2), -N(R6b)C(N(R1))(N(R1)(R6b)), -N(R1)C(N(6b))(N(R1)(R6b)), -N(R1)C(N(R1))(N(R6b)2), -N(R6b)C(N(R6b))(N(R1)(R6b)), -N(R6b)C(N(Rl ))(N(R6b)2) -N(R1)C(N(R6b))(N(R6b)2), -N(R6b)C(N(R6b))(N(R6b)2), =0, =S, =N(R1) or =N(R6b); R4 is independently alkyl, alkenyl, or alkynyl; R5 is independently R4 wherein each R4 is substituted with 0-3 R3 groups; R5a is independently alkylene, alkenylene, or alkynylene all of which may be substituted with 0-3 R3 groups; R6a is independently H or an ether- or ester-forming group; R6b is independently H, a protecting group for amino or the residue of a carboxyl-containing compound; R6c is independently H or the residue of an amino-containing compound; W1 is a group comprising an acidic hydrogen, a protected acidic group, or an R6c amide of the group comprising an acidic hydrogen; W2 is a group comprising a basic heteroatom or a protected basic heteroatom, or an R6b amide of the basic heteroatom; W3 is W4 or W5; W4 is R5 or -C(O)R5, -C(O)W5, -SO2R5, or -SO2W5; W5 is carbocycle or heterocycle wherein W5 is independently substituted with 0 to 3 R2 groups; W6 is -R5, -W5, -R5aW5, -C(O)OR6a, -C(O)R6c, -C(O)N(R6b)2, -C(NR6b)(N(R6b)2), -C(NR6b)(N(H)(R6b)), -C(N(H)(N(R6b)2), -C(S)N(R6b)2, -C(O)R2, -(CH2)m1C((CH2)m3R5aW5)3, -(CH2)m1C((CH2)m3R3)((CH2)m3R5aW5)2, where m3 is 1-3; X1 is a bond, -0-, -N(H)-, -N(W6)-, -N(OH)-, -N(0W6)-, -N(NH2)-, -N(N(H)(W6))-, -N(N(W6)2)-, -N(H)N(W6)-, -S-, -SO-, or -SO2-; and m1 is independently 0 to 2; provided, however, that compounds are excluded wherein: a)A1 is -CH= or -N= and A2 is -CH2-; b)E1 is COOH, P(O)(OH)2, SOOH, SO3H, or tetrazol; c)G1 is CN, N(H)R20, N3, SR20, OR20, guanidino, -N(H)CN, -N(R20)(OR20), -N(R20)(H), -N(R20)(®O), -N(R20)(N(R20)2), pyrimidinyl-, or pyrimidinylmethyl-; d)T1 is -NHR2O, where R20 is H; acyl group; linear or cyclic alkyl group or haloalkyl thereof; allyl group; unsubstituted aryl; aryl group substituted by halogen, OH, N02, NH2 or COOH group; e)J1 is H and J1a is H, F Cl, Br or CN; f)J2 is H and J2a is H, CN or N3; g)U1 is CH2YR20a, CHYR20aCH2YR20a or CHYR20aCHYR20aCH2YR20a; where R20a is H or acyl having 1 to 4 carbon atoms; Y is O, S, H or NH; 0 to 2 YR20a are H, and successive Y moieties in a U1 group are the same or different, and when Y is H then R20a is a covalent bond, and when G1 is N3 then U1 is not -CH2OCH2Ph, and the pharmaceutically acceptable salts and solvates thereof; and the salts, solvates, resolved enantiomers and purified diastereomers thereof. There are also compounds as named in Table 6 of the specification and processes for the preparation of these compounds and for the preparation of the pharmaceutical compositions described above.  These compounds and compositions are useful as neuraminidase inhibitors.