- XANTHINE DERIVATIVES AND USES THEREOF AS INHIBITORS OF BROMODOMAINS OF BET PROTEINS
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The present invention relates to a compound having the following formula (I): (I) wherein: - R is a (C1-C6)alkyl group;- R'' is preferably H;- Ar is a (C5-C12)arylene radical;- X1 is -C(=O)- or -SO2-; and- R' is chosen from the group consisting of possibly substituted (C1-C6)alkyl, heteroaryl, (C5-C12)aryl, and (hetero)cycloalkyl groups, or a pharmaceutically acceptable salt and/or tautomeric form thereof, or its racemates, diastereomers or enantiomers.
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- Phenyl Benzenesulfonylhydrazides Exhibit Selective Indoleamine 2,3-Dioxygenase Inhibition with Potent in Vivo Pharmacodynamic Activity and Antitumor Efficacy
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Tryptophan metabolism has been recognized as an important mechanism in immune tolerance. Indoleamine 2,3-dioxygenase plays a key role in local tryptophan metabolism via the kynurenine pathway and has emerged as a therapeutic target for cancer immunotherapy. Our prior study identified phenyl benzenesulfonyl hydrazide 2 as a potent in vitro (though not in vivo) inhibitor of indoleamine 2,3-dioxygenase. Further lead optimization to improve in vitro potencies and pharmacokinetic profiles resulted in N′-(4-bromophenyl)-2-oxo-2,3-dihydro-1H-indole-5-sulfonyl hydrazide 40, which demonstrated 59% oral bioavailability and 73% of tumor growth delay without apparent body weight loss in the murine CT26 syngeneic model, after oral administration of 400 mg/kg. Accordingly, 40, is proposed as a potential drug lead worthy of advanced preclinical evaluation.
- Lin, Shu-Yu,Yeh, Teng-Kuang,Kuo, Ching-Chuan,Song, Jen-Shin,Cheng, Ming-Fu,Liao, Fang-Yu,Chao, Min-Wu,Huang, Han-Li,Chen, Yi-Lin,Yang, Chun-Yu,Wu, Mine-Hsine,Hsieh, Chia-Ling,Hsiao, Wenchi,Peng, Yi-Hui,Wu, Jian-Sung,Lin, Li-Mei,Sun, Manwu,Chao, Yu-Sheng,Shih, Chuan,Wu, Su-Ying,Pan, Shiow-Lin,Hung, Ming-Shiu,Ueng, Shau-Hua
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p. 419 - 430
(2016/01/28)
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- Synthesis of 7-sulfamoyl-substituted 2-oxo-2,3,4,5-tetrahydro-1H-benzo[b] azepines
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Sulfochlorination of 2-oxo-2,3,4,5-tetrahydro-1H-benzo[b]azepine led to regioselective formation of the corresponding 7-chlorosulfonyl derivative. Starting from this reagent, a large number of substituted 2-oxo-7-sulfamoyl-2,3, 4,5-tetrahydro-1H-benzo[b]a
- Dorogov, Mikhail V.,Ivanovsky, Sergey A.,Khakhina, Maria Y.,Kravchenko, Dmitry V.,Tkachenko, Sergey E.,Ivachtchenko, Alexandre V.
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p. 3525 - 3535
(2007/10/03)
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