The Hospital for Sick Children

Hsc Research and Development Limited Partnership

Other

Peter M Demin

Chaim M Roifman

Olga Rounova

Tom Grunberger

Thomas Grunberger

Nigel Sharfe

Andrew Freywald

Cecil R Pace-Asciak

Octavian Laurand Cimpean

There is described compounds of Formulae I, II, III, IV and V. The compounds of Formulae I, II, III, IV and/or V are useful: in therapeutic methods and compositions for modulating cell proliferation, in diagnostic assays and as research tools.

Compounds useful for modulating abnormal cell proliferation

Novel styrylacrylonitrile compounds which are useful in treating a variety of cell proliferative disorders such as cancer are disclosed.

Compounds for modulating cell proliferation

The following compounds of formulae (I) and (III) which may be useful in treating a variety of cell proliferative disorders are disclosed: Formula (I), (II), wherein R, Rand Rare each independently selected from H, OH, Calkyl, Calkoxy, NH, NH&#x2014;Calkyl, N(Calkyl), SH, S&#x2014;Calkyl, NO, CF, OCFand halo; Ris unsubstituted Ar, or Ar substituted with 1-4 substituents, independently selected from Calkyl, Calkoxy and halo; X is selected from (CHCHO)and (CH), and n=1-4. 

There is described compounds of Formula I, and salts, solvates and hydrates thereof: wherein: R, Rand Rare each independently selected from OH, Calkyl, OCalkyl, OC(O)Calkyl, C(O)OCalkyl, NH, NH&#x2014;Calkyl, N(Calkyl)(Calkyl), C(O)NHCalkyl, C(O)N(Calkyl)(Calkyl), SH, SCalkyl, NO, CF, OCFand halogen; and Ar is an aromatic or heteroaromatic group chosen from benzene, naphthalene, quinoline, isoquinoline, indole, pyridine, pyrasine, pyrimidine, imidazole, furan and thiophene, unsubstituted or substituted with 1-4 substituents independently selected from OH, Calkyl, Calkoxy, Calkylenedioxy, NH, NH&#x2014;Calkyl, N(Calkyl)(Calkyl), SH, S&#x2014;Calkyl, NO, CF, OCFand halogen. The compounds of Formula I are useful: in therapeutic methods and compositions for modulating cell proliferation, in diagnostic assays and as research tools.

There is described compounds of Formula I, and salts, solvates and hydrates thereof: wherein: R, Rand Rare each independently selected from OH, Calkyl, OCalkyl, OC(O)Calkyl, C(O)OCalkyl, NH, NH&#x2014;Calkyl, N(Calkyl)(Calkyl), C(O)NHCalkyl, C(O)N(Calkyl)(Calkyl), SH, SCalkyl, NO, CF, OCFand halogen; and Ar is an aromatic or heteroaromatic group chosen from benzene, naphthalene, quinoline, isoquinoline, indole, pyridine, pyrasine, pyrimidine, imidazole, furan and thiophene, unsubstituted or substituted with 1&#x2013;4 substituents independently selected from OH, Calkyl, Calkoxy, Calkylenedioxy, NH, NH&#x2014;Calkyl, N(Calkyl)(C)(Calkyl), SH, S&#x2014;Calkyl, NO, CF, OCFand halogen. The compounds of Formula I are useful: in therapeutic methods and compositions for modulating cell proliferation, in diagnostic assays and as research tools.

Compounds of the general structure ##STR1## are disclosed, wherein X is O, C.sub.n, NH, or S, wherein n is 1, 2, 3 or 4; R1 is OH, CH.sub.3, CH.sub.2 OH, N.sub.3 or CH.sub.2 N.sub.3 ; R3 is H or CH.sub.3 ; R5 is Y-R2, wherein Y is a six-carbon chain optionally containing up to three double or triple bonds or a mixture of double and triple bonds up to a maximum of three; R2 is C.sub.1 -C.sub.10 alkyl OH, C.sub.1 -C.sub.10 alkyl N.sub.3 or COOR4, wherein R4 is H, a branched or unbranched C.sub.1 -C.sub.10 alkyl (including substituted alkyl radicals), cycloalkyl, preferably C.sub.5 or C.sub.6 cycloalkyl, or a five- or six-membered aryl radical (including substituted aryl radicals), i.e. R2 is COOH or an ester of R4; R6 is a seven-carbon chain optionally containing up to three double or triple bonds or a mixture of double and triple bonds up to a maximum of three; and . . . . . . indicates a single, double or triple bond. The compounds are analogs of hepoxilins and are used to modulate hepoxilin activity, for example in the control of inflammation or other processes mediated by intracellular calcium levels.

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Moscow, Russia

Peter M Demin