155432-10-3Relevant academic research and scientific papers
Benzothiazole derivatives and their uses
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Paragraph 0163; 0165; 0166; 0187; 0188, (2022/01/05)
The present invention relates to benzothiazole derivatives and their uses, specifically to compounds shown in formula I or stereoisomers thereof and pharmaceutically acceptable salts, solvates or prodrugs thereof, methods of preparation thereof, and pharmaceutical compositions containing the compounds, wherein the substituentsR1,R2,R8 , X, Y, Z, Q have the meaning given in the instruction manual. The present invention further relates to the application of compounds of formula I in the preparation of drugs for the treatment and / or prevention of sEH-mediated diseases, in particular in the preparation of drugs for the treatment of inflammatory diseases, cardiovascular and cerebrovascular diseases, diabetes mellitus, diabetic complications, diabetes-related diseases, fibrotic diseases, neurological and psychiatric diseases, pain, ulcerative diseases and the like.
Ligand-based optimization to identify novel 2-aminobenzo[d]thiazole derivatives as potent sEH inhibitors with anti-inflammatory effects
Han, Yufei,Huang, Desheng,Xu, Sicong,Li, Lingling,Tian, Ye,Li, Shuo,Chen, Cong,Li, Yingxiu,Sun, Yanping,Hou, Yunlei,Sun, Yongjun,Qin, Mingze,Gong, Ping,Gao, Zibin,Zhao, Yanfang
, (2020/12/07)
Inhibition of the soluble epoxide hydrolase (sEH) is a promising new therapeutic approach in the treatment of inflammation. Driven by the in-house database product lead 1, a hybridization strategy was utilized for the design of a series of novel benzo [d]thiazol derivatives. To our delight, D016, a byproduct of compound 9, was obtained with an extraordinarily low IC50 value of 0.1 nM but poor physical and chemical properties. After removal of a non-essential urea moiety or replacement of the urea group by an amide group, compounds 15a, 17p, and 18d were identified as promising sEH inhibitors, and their molecular binding modes to sEH were constructed. Furthermore, compounds 15a and 18d exhibited more effective in vivo anti-inflammatory effect than t-AUCB in carrageenan-induced mouse paw edema. Compound 15a also showed moderate metabolic stability with a half-time of 34.7 min. Although 18d was unstable in rat liver microsomes, it might be a “prodrug”. In conclusion, this study could provide valuable insights into discovery of new sEH inhibitors, and compounds 15a and 18d were worthy of further development as potential drug candidates to treat inflammation.
Azobenzene-Semicarbazone Enables Optical Control of Insect Sodium Channels and Behavior
Chen, Ruijia,Fu, Wen,Li, Zhong,Qiao, Zhi,Shao, Xusheng,Xu, Zhiping,Zhang, Yongchao
, p. 15554 - 15561 (2021/12/27)
Photopharmacology uses molecular photoswitches to establish control over the action of bioactive molecules. The application of photopharmacology in the research of invertebrate sodium channels has not been investigated. Here we report several photochromic ligands of metaflumizone. One ligand, termed ABM04, underwent reversible trans-cis isomerization under ultraviolet or blue light irradiation. cis-ABM04 had excellent larvicidal activity against mosquito larvae with an LC50 value of 4.39 μM and showed insecticidal activity against Mythimna separata with an LC50 value of 7.19 μM. However, trans-ABM04 was not found to have biological activity. ABM04 (10 μM) can induce depolarization of dorsal unpaired median neurons and enable the real-time photoregulation of mosquito larval behavior. The precise regulation of invertebrate sodium channels is realized for the first time, which provides a new strategy for the basic and accurate research of invertebrate sodium channels.
CYCLOPROPANECARBOXAMIDO-SUBSTITUTE AROMATIC COMPOUNDS AS ANTI-TUMOR AGENTS
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Paragraph 0416; 0417, (2015/07/22)
Provided are cyclopropanecarboxamido-substituted aromatic compounds that inhibit protein kinases and their use in anti-tumor area. In particular, tyrosine-kinase inhibitors and Raf-kinase inhibitors as anti-tumor agents, their preparation, pharmaceutical composition, and their use in the treatment of cancer are also provided.
Synthesis and pharmacological evaluation of novel N-aryl-3,4-dihydro- 1′H-spiro[chromene-2,4′-piperidine]-1′-carboxamides as TRPM8 antagonists
Chaudhari, Sachin S.,Kadam, Ashok B.,Khairatkar-Joshi, Neelima,Mukhopadhyay, Indranil,Karnik, Pallavi V.,Raghuram, Anupindi,Rao, Shobha S.,Vaiyapuri, Thamil Selvan,Wale, Dinesh P.,Bhosale, Vikram M.,Gudi, Girish S.,Sangana, Ramchandra R.,Thomas, Abraham
, p. 6542 - 6553 (2013/10/22)
A novel series of N-aryl-3,4-dihydro-1′H-spiro[chromene-2,4′- piperidine]-1′-carboxamides was identified as transient receptor potential melastatin 8 (TRPM8) channel blockers through analogue-based rational design, synthesis and screening. Details of the synthesis, effect of aryl groups and their substituents on in-vitro potency were studied. The effects of selected functional groups on the 4-position of the chromene ring were also studied, which showed interesting results. The 4-hydroxy derivatives showed excellent potency and selectivity. Optical resolution and screening of alcohols revealed that (R)-(-)-isomers were in general more potent than the corresponding (S)-(+)-isomers. The isomer (R)-(-)-10e (IC50: 8.9 nM) showed a good pharmacokinetic profile upon oral dosing at 10 mg/kg in Sprague-Dawley (SD) rats. The compound (R)-(-)-10e also showed excellent efficacy in relevant rodent models of neuropathic pain.
Optically active antifungal azoles. VIII synthesis and antifungal activity of 1-[(1R,2R)-2-(2,4-difluoro- and 2-fluorophenyl)-2-hydroxy-1- methyl-3-(1H-1,2,4-triazol-1-yl)propyl]-3-(4-substituted phenyl)2(1H,3H)- imidazolones and 2-imidazolidinones
Kitazaki, Tomoyuki,Tasaka, Akihiro,Tamura, Norikazu,Matsushita, Yoshihiro,Hosono, Hiroshi,Hayashi, Ryogo,Okonogi, Kenji,Itoh, Katsumi
, p. 351 - 359 (2007/10/03)
New optically active antifungal azoles, 1-[(1R,2R)-2-(2,4-difluoro- and 2-fluorophenyl)-2-hydroxy-1-methyl-3-(1H-1,2,4-triazol-1-yl)propyl]-3-(4- substituted phenyl)-2(1H,3H)-imidazolones (1, 2) and 2-imidazolidinones (3, 4), were prepared in a stereocontrolled manner from (1S)-1-[(2R)-2-(2,4- difluoro- and 2-fluorophenyl)-2-oxi-ranyl]ethanols (15, 16). Compounds 1 - 4 showed potent antifungal activity against Candida albicans in vitro and in vivo, as well as a broad antifungal spectrum for various fungi in vitro. Furthermore, the imidazolidinones, 3b - e and 4d, e, were found to exert extremely strong growth-inhibitory activity against Aspergillus fumigatus.
Optically active antifungal azoles. VI. Synthesis and antifungal activity of N-[(1R,2R)-2-(2,4-difluorophenyl)-2-hydroxy-1-methyl-3-(1H-1,2,4-triazol-1-yl) propyl]-N′-(4-substituted phenyl)-3(2H,4H)-1,2,4-triazolones and 5(1H,4H)-tetrazolones
Kitazaki, Tomoyuki,Tamura, Norikazu,Tasaka, Akihiro,Matsushita, Yoshihiro,Hayashi, Ryogo,Okonogi, Kenji,Itoh, Katsumi
, p. 314 - 327 (2007/10/03)
A new series of optically active antifungal azoles, N-[(1R,2R)-2-(2,4-difluorophenyl)-2-hydroxy-1-methyl-3-(1H-1,2,4-triazol-1-yl) propyl]-N′-(4-substituted phenyl)-3(2H,4H)-1,2,4-triazolones (1,2) and 5(1H,4H)-tetrazolones (3), were prepared from the triflate derivative of (1S)-1-[(2R)-2-(2,4-difluorophenyl)-2-oxiranyl]ethanol (13) by an SN2 displacement reaction with the union of an azolone (17-19) and subsequent ring-opening reaction with 1H-1,2,4-triazole. The optically active oxiranylethanol 13 was synthesized from methyl (R)-lactate in a stereocontrolled manner. The azolones 1-3 prepared showed potent antifungal activities in vitro and in vivo.
