14192-45-1Relevant articles and documents
USE OF A DHODH INHIBITOR IN COMBINATION WITH AN INHIBITOR OF PYRIMIDINE SALVAGE
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Paragraph 00206, (2017/07/31)
Compounds and methods are provided for the treatment of pathogenic virus infections or cancer. The formulations combine an inhibitor of de novo pyrimidine synthesis, and an inhibitor of a pyrimidine salvage pathway enzyme.
A novel CAN-SiO2-mediated one-pot oxidation of 1-keto-1,2,3,4-tetrahydrocarbazoles to carbazoloquinones: Efficient syntheses of murrayaquinone A and koeniginequinone A
Chakraborty, Suchandra,Chattopadhyay, Gautam,Saha, Chandan
scheme or table, p. 331 - 338 (2011/06/19)
One-pot oxidations of substituted 1-keto-1,2,3,4-tetrahydrocarbazoles (1) to carbazole-1,4-quinones (2) are efficiently carried out by CAN-SiO 2-mediated reaction. This generalized protocol was successfully extended to the synthesis of two naturally occurring carbazoloquinones: murrayaquinone A (2b) and koeniginequinone A (2g). A plausible mechanism for this novel reaction involves formation of a 9-hydroxy-2,3,4,9-tetrahydro-1H- carbazole-1-one followed by rearrangement to 1-hydroxycarbazole derivatives, which are further oxidized by cerium (IV) to carbazoloquinones.
Conformationally restrained carbazolone-containing α,γ-diketo acids as inhibitors of HIV integrase
Li, Xingnan,Vince, Robert
, p. 2942 - 2955 (2007/10/03)
Since α,γ-diketo acid (DKA) compounds were identified as potent and selective inhibitors for HIV integrase, numerous structural modification studies have been carried out to search for a clinical candidate as a supplement for the highly active antiretroviral therapy regimen. Due to the lack of structural information on inhibitor-integrase interactions, a comprehensive structure-activity relationship study is necessary. Most of the reported modification studies on the key α,γ-diketo acid pharmacophore focused on substituting the carboxylate moiety with its bioisosteres or other electron-pair bearing heterocycles. We were interested in studying the conformation and geometry of the central diketo moiety. A series of carbazolone-containing α,γ-diketo acids were designed and synthesized by applying conformational restraint onto the open-chain form of the diketo acid. These compounds showed anti-integrase activity in the low micromolar range, and integrase assay results indicated that the geometry of the diketo acid moiety is crucial to potency. Carbazol-1-one containing DKA analogs (7-8) showed a 2- to 3-fold increase in activity compared with those of carbazol-4-one containing DKA analogs (5 and 6). Alkylation of carbazol-4-one DKA nitrogen (6a-c) led to a loss of activity, suggesting this nitrogen atom may directly interact with the active site of integrase. The halogens (7b-d) and para-fluorobenzyl substituents (8a-d) on carbazol-1-one ring had little effect on potency.
