The present invention makes available methods and reagents for inhibiting aberrant growth states resulting from hedgehog gain-of-function, ptc loss-of-function or smoothened gain-of-function comprising contacting the cell with a hedgehog antagonist, such as a small molecule, in a sufficient amount to aberrant growth state, e.g., to agonize a normal ptc pathway or antagonize smoothened or hedgehog activity.

Mediators of hedgehog signaling pathways, compositions and uses related thereto

Composes de formule (I) caracterises en ce que .bullet. X represente oxygene ou soufre, .bullet. Y represente oxygene,-NH ou -N(C1-C6)alkyle, .bullet. Ra represente hydrogene, halogene, (C1-C3)alkyle, hydroxy, ou (C1-C3)alkoxy, .bullet. Rb represente hydrogene, halogene, ou (C1-C3)alkyle, .bullet. A represente phenyle, pyridyle, (C5-C6)cycloalkyle ou (C5-C6)cycloalkenyle, .bullet. R1 et R2 representent chacun un groupement choisi parmi hydrogene, halogene, cyano, nitro, halogenoalkyle, halogenoalkoxy, alkyle, alkenyle, alkynyle, -OR4, -NR4R5, -S(O)nR4, -C(O)R4, -C02R4, -OC(O)R4, -C(O)NR4R5, -NR5-C(O)R4, -NR5-S02R4, -T-CN, -T-OR4, -T-OCF3, -T-NR4R5, -TS(O)nR4, -TC(O)R4, -T-C02R4, -TOC(O)R4, -TC(O)NR4R5, -T-NR4-C(O)R5, -T-NR4-S02R5, -R6, et -T-R6 dans lesquels n, T, R4, R5 et R6 sont tels que definis dans la description, .bullet. R3 represente un groupement -R7 ou -U-R11, dans lesquels R7 represente hydrogene, alkyle, aryle, cycloalkyle ou heterocycle, U represente une chaine alkylene lineaire ou ramifiee, et R11, est tel que defini dans la description, leurs isomeres optiques ou leurs sels d'addition a un acide ou a une base pharmaceutiquement acceptable, et leur utilisation en tant qu'inhibiteur de metalloproteinase et plus specifiquement de la metalloproteinase -12.

Novel thiophene derivatives, preparation method thereof and pharmaceutical compositions containing same

A compound of the formula: Ar.sub.1 --B--Ar.sub.2 wherein Ar 1 is unsubstituted or substituted phenyl, thienyl, furanyl, or pyrrolyl, in which each substituent of the substituted phenyl, substituted thienyl, substituted furanyl, and substituted pyrrolyl, independently, is aldehyde, acyl, ester, carboxyl, amido, nitrile, nitro, cyano, acetal, ketal, oxoalkyl, aminoalkyl, hydroxyalkyl, haloalkyl, iminoalkyl, acid halide, aminoalkylaminoalkyl, aminoalkylaminoalkylamino, hydroxyalkylaminoalkyl, or hydroxyalkylaminoalkylaminoalkyl; B is, --CH═CH--, or --C C--, in which R is H, alkyl, hydroxyl, alkoxy, ester, aldehyde, hydroxyalkyl, aminoalkyl, carboxyl, --CH(OR 1 ) 2 , or NR 2 R 3 , where each R 1 , independently, is H, alkyl, or acyl; and each of R 2 and R 3 , independently, is H, alkyl, hydroxyalkyl, or aminoalkyl; and Ar 2 is substituted phenyl, substituted thienyl, substituted furanyl, or substituted pyrrolyl, in which each substituent of the substituted phenyl, substituted thienyl, substituted furanyl, and substituted pyrrolyl, independently, is amido, nitrile, nitro, cyano, acetal, ketal, oxoalkyl, aminoalkyl, haloalkyl, iminoalkyl, acid halide, aminoalkylaminoalkyl, aminoalkylaminoalkylamino, hydroxyalkylaminoalkyl, or hydroxyalkylaminoalkylaminoalkyl; or a salt thereof. Also disclosed is a composition which contains a pharmaceutical acceptable carrier and an effective amount of a compound of the above formula.

Yuh-Lin Yang

Papers

Polyaryl antitumor agents