39624-97-0Relevant articles and documents
Heterocyclic compounds, their production and use
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, (2008/06/13)
Heterocyclic compounds represented by the general formula (I) wherein R stands for an optionally substituted aromatic heterocyclic group; X stands for oxygen atom, an optionally oxidated sulfur atom, —C(═O)— or —CH(OH)—; Y stands for CH or N; m denotes an integer of 0 to 10: n denotes an integer of 1 to 5: cyclic group ?stands for an optionally substituted aromatic azole group; and ring A is optionally further substituted, or salts thereof. The compound (I) possesses action of inhibiting tyrosine kinase and useful as antitumor agents.
Discovery of ritonavir, a potent inhibitor of HIV protease with high oral bioavailability and clinical efficacy
Kempf, Dale J.,Sham, Hing L.,Marsh, Kennan C.,Flentge, Charles A.,Betebenner, David,Green, Brian E.,McDonald, Edith,Vasavanonda, Sudthida,Saldivar, Ayda,Wideburg, Norman E.,Kati, Warren M.,Ruiz, Lisa,Zhao, Chen,Fino, Lynnmarie,Patterson, Jean,Molla, Akhteruzzaman,Plattner, Jacob J.,Norbeck, Daniel W.
, p. 602 - 617 (2007/10/03)
The structure-activity studies leading to the potent and clinically efficacious HIV protease inhibitor ritonavir are described. Beginning with the moderately potent and orally bioavailable inhibitor A-80987, systematic investigation of peripheral (P3 and P2') heterocyclic groups designed to decrease the rate of hepatic metabolism provided analogues with improved pharmacokinetic properties after oral dosing in rats. Replacement of pyridyl groups with thiazoles provided increased chemical stability toward oxidation while maintaining sufficient aqueous solubility for oral absorption. Optimization of hydrophobic interactions with the HIV protease active site produced ritonavir, with excellent in vitro potency (EC50 = 0.02 μM) and high and sustained plasma concentrations after oral administration in four species. Details of the discovery and preclinical development of ritonavir are described.
RETROVIRAL PROTEASE INHIBITING PIPERAZINE COMPOUNDS
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, (2008/06/13)
Retroviral protease inhibiting compounds of the formula: STR1 are disclosed.
RETROVIRAL PROTEASE INHIBITING COMPOUNDS
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, (2008/06/13)
A retroviral protease inhibiting compound of the formula: STR1 is disclosed wherein R 1, R 2, R 5, R 6, Y m and Y' n are herein defined.