626238-80-0Relevant academic research and scientific papers
2-Cyclohexylcarbonylbenzimidazoles as potent, orally available and brain-penetrable opioid receptor-like 1 (ORL1) antagonists
Kobayashi, Kensuke,Uchiyama, Minaho,Takahashi, Hirobumi,Kawamoto, Hiroshi,Ito, Satoru,Yoshizumi, Takashi,Nakashima, Hiroshi,Kato, Tetsuya,Shimizu, Atsushi,Yamamoto, Izumi,Asai, Masanori,Miyazoe, Hiroshi,Ohno, Akio,Hirayama, Mioko,Ozaki, Satoshi,Tani, Takeshi,Ishii, Yasuyuki,Tanaka, Takeshi,Mochidome, Takanobu,Tadano, Kiyoshi,Fukuroda, Takahiro,Ohta, Hisashi,Okamoto, Osamu
scheme or table, p. 3096 - 3099 (2010/03/31)
The synthesis and biological evaluation of new potent opioid receptor-like 1 (ORL1) antagonists are presented. Conversion of the thioether linkage of the prototype [It is reported prior to this communication as a consecutive series.: Kobayashi, K.; Kato, T.; Yamamoto, I.; Shimizu, A.; Mizutani, S.; Asai, M.; Kawamoto, H.; Ito, S.; Yoshizumi, T.; Hirayama, M.; Ozaki, S.; Ohta, H.; Okamoto, O. Bioorg. Med. Chem. Lett., in press] to the carbonyl linker effectively reduces susceptibility to P-glycoprotein (P-gp) efflux. This finding led to the identification of 2-cyclohexylcarbonylbenzimizole analogue 7c, which exhibited potent ORL1 activity, excellent selectivity over other receptors and ion channels, and poor susceptibility to P-gp. Compound 7c also showed satisfactory pharmacokinetic profiles and brain penetrability in laboratory animals. Furthermore, 7c showed good in vivo antagonism. Hence, 7c was selected as a clinical candidate for a brain-penetrable ORL1 antagonist.
Identification of novel benzimidazole series of potent and selective ORL1 antagonists
Okamoto, Osamu,Kobayashi, Kensuke,Kawamoto, Hiroshi,Ito, Satoru,Satoh, Atsushi,Kato, Tetsuya,Yamamoto, Izumi,Mizutani, Sayaka,Hashimoto, Masaya,Shimizu, Atsushi,Sakoh, Hiroki,Nagatomi, Yasushi,Iwasawa, Yoshikazu,Takahashi, Hiroyuki,Ishii, Yasuyuki,Ozaki, Satoshi,Ohta, Hisashi
scheme or table, p. 3278 - 3281 (2009/04/05)
Structure-activity studies on benzimidazole lead 1 obtained from library screening led to the discovery of potent and selective ORL1 antagonist 28, 5-chloro-2-[(1-ethyl-1-methylpropyl)thio]-6-[4-(2-hydroxyethyl)piperazin-1-yl]-1H-benzimidazole, which is s
Benzimidazole derivatives
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Page 47, (2010/11/30)
This invention provides compounds which are represented by a general formula [I] [in which X stands for hydrogen or halogen; B stands for halogen, cyano or optionally fluorine-substituted lower alkyl; D stands for a 3-10 membered aliphatic nitrogen-containing heterocyclic group; R3, R4 and R5 may be same or different, and each stands for hydrogen, lower alkyl optionally having substituent group(s) and the like; and a is 0 or 1]. These compounds exhibit high affinity to nociceptin receptors and whereby inhibit actions of nociceptin, and are useful as an analgesic, antiobestic, agent for ameliorating brain function, treating agents for Alzheimer's disease and dementia, and therapeutic agents for schizophrenia, neurodegenerative diseases, depression, diabetes insipidus, polyuria, hypotension and the like.
