85102-93-8Relevant articles and documents
Design, synthesis and biological activities of 2,3-dihydroquinazolin-4(1H)-one derivatives as TRPM2 inhibitors
Zhang, Han,Liu, Huan,Luo, Xiao,Wang, Yuxi,Liu, Yuan,Jin, Hongwei,Liu, Zhenming,Yang, Wei,Yu, Peilin,Zhang, Liangren,Zhang, Lihe
, p. 235 - 252 (2018/05/09)
Transient receptor potential melastatin 2 (TRPM2), a Ca2+-permeable cationic channel, plays critical roles in insulin release, cytokine production, body temperature regulation and cell death as a reactive oxygen species (ROS) and temperature sensor. However, few TRPM2 inhibitors have been reported, especially TRP-subtype selective inhibitors, which hampers the investigation and validation of TRPM2 as a drug target. To discover novel TRPM2 inhibitors, 3D similarity-based virtual screening method was employed, by which 2,3-dihydroquinazolin-4(1H)-one derivative H1 was identified as a TRPM2 inhibitor. A series of novel 2,3-dihydroquinazolin-4(1H)-one derivatives were subsequently synthesized and characterized. Their inhibitory activities against the TRPM2 channel were evaluated by calcium imaging and electrophysiology approaches. Some of the compounds exhibited significant inhibitory activity, especially D9 which showed an IC50 of 3.7 μM against TRPM2 and did not affect the TRPM8 channel. The summarized structure-activity relationship (SAR) provides valuable insights for further development of specific TRPM2 targeted inhibitors.
Heteroarylalkyl-8-azabicyclo[3.2.1]octane compounds as mu opioid receptor antagonists
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Page/Page column 15, (2009/04/24)
The invention provides heteroarylene substituted 8-azabicyclo[3.2.1]octane compounds of formula (I): wherein R1, R2, A, and m are defined in the specification, or a pharmaceutically-acceptable salt thereof, that are antagonists at th
Regioselective alkylation of 2-alkyl-5,6,7,8-tetrahydro-3H- cycloheptimidazol-4-ones and 2-alkyl-3H-cycloheptimidazol-4-ones
Sonegawa, Motoharu,Yokota, Masayuki,Tomiyama, Hiroshi,Tomiyama, Tsuyoshi
, p. 706 - 710 (2007/10/03)
Regioselective alkylation of 2-alkyl-5,6,7,8-tetrahydro-3H- cycloheptimidazol-4-one (1) and 2-alkyl-3H-cycloheptimidazol-4-one (2) was investigated. 3-[2′-(1-tert-Butyl-1H-tetrazol-5-yl)biphenyl-4-ylmethyl]-2- propyl-5,6,7,8-tetrahydro-1H-cycloheptimidazol-4-one (6) was preferentially obtained under the conditions by using NaH in DMF or THF. On the other hand, 3-[2′-(1-tert-butyl-1H-tetrazol-5-yl)biphenyl-4-ylmethyl]-2-propyl-5,6,7, 8-tetrahydro-3H-cycloheptimidazol-4-one (5), the synthetic intermediate compound of Pratosartan, was obtained selectively in the presence of n-Bu4NBr in toluene by using aqueous sodium hydroxide as a base. In this reaction, it was found that the concentration of the alkaline solution influences its regioselectivity. This selectivity was observed even for aldehyde and ester derivatives.