35700-40-4Relevant articles and documents
Discovery and structure-activity relationship of novel 2,3- dihydrobenzofuran-7-carboxamide and 2,3-dihydrobenzofuran-3(2 h)-one-7-carboxamide derivatives as poly(ADP-ribose)polymerase-1 Inhibitors
Patel, Maulik R.,Bhatt, Aaditya,Steffen, Jamin D.,Chergui, Adel,Murai, Junko,Pommier, Yves,Pascal, John M.,Trombetta, Louis D.,Fronczek, Frank R.,Talele, Tanaji T.
, p. 5579 - 5601 (2014/08/05)
Novel substituted 2,3-dihydrobenzofuran-7-carboxamide (DHBF-7-carboxamide) and 2,3-dihydrobenzofuran-3(2H)-one-7-carboxamide (DHBF-3-one-7-carboxamide) derivatives were synthesized and evaluated as inhibitors of poly(ADP-ribose) polymerase-1 (PARP-1). A structure-based design strategy resulted in lead compound 3 (DHBF-7-carboxamide; IC50 = 9.45 μM). To facilitate synthetically feasible derivatives, an alternative core was designed, DHBF-3-one-7-carboxamide (36, IC50 = 16.2 μM). The electrophilic 2-position of this scaffold was accessible for extended modifications. Substituted benzylidene derivatives at the 2-position were found to be the most potent, with 3′,4′-dihydroxybenzylidene 58 (IC50 = 0.531 μM) showing a 30-fold improvement in potency. Various heterocycles attached at the 4′-hydroxyl/4′-amino of the benzylidene moiety resulted in significant improvement in inhibition of PARP-1 activity (e.g., compounds 66-68, 70, 72, and 73; IC50 values from 0.718 to 0.079 μM). Compound 66 showed selective cytotoxicity in BRCA2-deficient DT40 cells. Crystal structures of three inhibitors (compounds (-)-13c, 59, and 65) bound to a multidomain PARP-1 structure were obtained, providing insights into further development of these inhibitors.
Quaternary ammonium compounds as tachykinin antagonists
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, (2008/06/13)
The present invention provides a compound of formula (I) wherein R is phenyl, C3-C7cycloalkyl or heteroaryl, each of which being optionally benzo- or C3-C7cycloalkyl-fused and optionally substituted, including in the benzo- or C3-C7cycloalkyl-fused portion, by from 1 to 3 substituents each independently selected from C1-C4alkyl, fluoro(C1-C4)alkyl, C1-C4alkoxy, fluoro(C1-C4)alkoxy, phenoxy, C2-C4alkanoyl, halo, C1-C4alkoxycarbonyl, C3-C7cycloalkyl, —S(O)m(C1-C4alkyl), cyano, —NR2R3, —S(O)mNR2R3, —NR4(C1-C4alkanoyl) and —CONR2R3, or R is 2,3-dihydrobenzo[b]furanyl or chromanyl; R1is H or C1-C6alkyl; W is a direct link, methylene or ethylene; X is unbranched C2-C4alkylene; Y is phenyl, naphthyl, benzyl, pyridyl, thienyl or C3-C7cycloalkyl, each of which being optionally substituted by from 1 to 3 substituents each independently selected from C1-C4alkyl, fluoro(C1-C4)alkyl, C1-C4alkoxy, fluoro(C1-C4)alkoxy, halo and cyano; Ar is phenyl, naphthyl, benzyl, thienyl, benzo[b]thienyl or indolyl, each of which being optionally substituted by from 1 to 3 substituents each independently selected from C1-C4alkyl, fluoro(C1-C4)alkyl, C1-C4alkoxy, fluoro(C1-C4)alkoxy, halo and cyano, or Ar is 1,3-benzodioxolan-4 or 5-yl or 1,4-benzodioxan-5 or 6-yl; ZAis a pharmaceutically acceptable anion; with the proviso that when W is a direct link and R is optionally fused and optionally substituted heteroaryl, said heteroaryl is linked by a ring carbon atom to the carbonyl group. The compounds are tachykinin antagonists.
Inhibitors of farnesyl-protein transferase
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, (2008/06/13)
The present invention is directed to compounds which inhibit farnesyl-protein transferase (FTase) and the farnesylation of the oncogene protein Ras. The invention is further directed to chemotherapeutic compositions containing the compounds of this invention and methods for inhibiting farnesyl-protein transferase and the farnesylation of the oncogene protein Ras. The compounds of formula A are representative of the compounds of the present invention: STR1
