- ANNELATED PYRIDAZINES FOR THE TREATMENT OF TUMORS DRIVEN BY INAPPROPRIATE HEDGEHOG SIGNALLING
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The present invention relates generally to compounds represented in Formula (I), pharmaceutical compositions comprising them and methods of treating of diseases or disorders such as cancer.
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Page/Page column 69
(2009/04/25)
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- Phthalazine compounds, compositions and methods of use
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The present invention relates generally to compounds represented in Formula I, pharmaceutical compositions comprising them and methods of treating of diseases or disorders such as cancer.
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Page/Page column 32
(2009/03/07)
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- PIPERAZINE DERIVATIVES
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The present invention relates to a crystalline form of 5-{(1S)-2-[(2R)-4-benzoyl-2-methyl-piperazin-1-yl]-1-methyl-2-oxo-ethoxy}-4-methoxy-pyridine-2-carboxylic acid methylamide, processes for the preparation thereof, compositions containing the crystalli
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Page/Page column 30
(2008/06/13)
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- Modification and structure-activity relationship of a small molecule HIV-1 inhibitor targeting the viral envelope glycoprotein gp120
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This paper describes selected modification and structure-activity relationship of the small molecule HIV-1 inhibitor, 4-benzoyl-1 -[(4-methoxy-1-H-pyrrolo[2,3-b]pyridin-3-yl)oxoacetyl]-2-(R)-methylpiperazine (BMS-378806). The results revealed: i) that both the presence and configuration (R vs. S) of the 3-methyl group on the piperazine moiety are important for the antiviral activity, with the 3-(R)-methyl derivatives showing the highest activity; ii) that the electronegativity of the C-4 substituent on the indole or azaindole ring seems to be important for the activity, with a small, electron-donating group such as a fluoro or a methoxy group showing enhanced activity, while a nitro group diminishes the activity; iii) that the N-1 position of the indole ring is not eligible for modification without losing activity; and iv) that bulky groups around the C-4 position of the indole or azaindole ring diminish the activity, probably due to steric hindrance in the binding. We found that a synthetic bivalent compound with two BMS-378806 moieties being tethered by a spacer demonstrated about 5-fold enhanced activity in an nM range against HIV-1 infection than the corresponding monomeric inhibitor. But the polyacrylamide-based polyvalent compounds did not show inhibitory activity at up to 200 nM. The Royal Society of Chemistry 2005.
- Wang, Jingsong,Le, Nhut,Heredia, Alonso,Song, Haijing,Redfield, Robert,Wang, Lai-Xi
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p. 1781 - 1786
(2007/10/03)
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- Discovery of 4-benzoyl-1-[(4-methoxy-1H-pyrrolo[2,3-b]pyridin-3-yl)oxoacetyl]-2-(R) -methylpiperazine (BMS-378806): A novel HIV-1 attachment inhibitor that interferes with CD4-gp120 interactions
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Indole derivative 1 interferes with the interaction of the HIV surface protein gp120 with the host cell receptor CD4. The 4-fluoro derivative 2 exhibited markedly enhanced potency and was bioavailable in the rat, dog, and cynomolgus monkey when administered orally as a solution formulation. However, aqueous suspensions of 2 were poorly bioavailable, indicative of dissolution-limited absorption. The 7-azaindole derivative 3, BMS-378806, exhibited improved pharmaceutical properties while retaining the HIV-1 inhibitory profile of 2.
- Wang, Tao,Zhang, Zhongxing,Wallace, Owen B.,Deshpande, Milind,Fang, Haiquan,Yang, Zheng,Zadjura, Lisa M.,Tweedie, Donald L.,Huang, Stella,Zhao, Fang,Ranadive, Sunanda,Robinson, Brett S.,Gong, Yi-Fei,Ricarrdi, Keith,Spicer, Timothy P.,Deminie, Carol,Rose, Ronald,Wang, Hwei-Gene Heidi,Blair, Wade S.,Shi, Pei-Yong,Lin, Pin-Fang,Colonno, Richard J.,Meanwell, Nicholas A.
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p. 4236 - 4239
(2007/10/03)
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