42959-38-6Relevant academic research and scientific papers
METHODS OF TREATING AGITATION
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Page/Page column 34, (2019/06/23)
The present disclosure relates generally to the treatment of agitation associated with neurodegenerative disorders.
Computer-aided discovery of aminopyridines as novel JAK2 inhibitors
Zhao, Chao,Yang, Su Hui,Khadka, Daulat Bikram,Jin, Yifeng,Lee, Kyung-Tae,Cho, Won-Jea
, p. 985 - 995 (2015/03/04)
The Janus kinase 2 (JAK2)-mediated signaling pathway plays an important role in controlling cell survival, proliferation, and differentiation. In recent years, genetic, biological, and physiological evidence has established JAK2 inhibitors as effective chemotherapeutic agents for the treatment of many different cancers. For this reason, we sought to identify novel small molecule inhibitors of JAK2. Using Surflex-Dock software, we tested 3010 compounds with known chemical structures in silico for their ability to interact with the JAK2 ATP-binding pocket. We selected the 10 highest-scoring compounds and tested their abilities to inhibit JAK2 activity in vitro. Compound 1a (ethyl 1-(5-((3-methoxyphenyl)carbamoyl)-3-nitropyridin-2-yl)piperidine-4-carboxylate) was identified. Optimization of 1a using docking studies led to the discovery of compounds 1b and 1d, potent JAK2 inhibitors. Furthermore, as V-shaped kinase inhibitors can curve around the protein backbone and access deep into the pocket, we developed a new series of compounds with a non-linear sulfonamide bond. Nine compounds were prepared and evaluated for JAK2 inhibitory effects. Compounds 7e (IC50 = 6.9 μM) and 7h (IC50 = 12.2 μM) showed better JAK2 inhibition, validating our design approach. This study successfully applied virtual screening for hit discovery, and a docking study for hit optimization. In addition, a novel approach to drug discovery, combining structure- and shape-based drug design, facilitated the design of more potent JAK2 inhibitors. The methods provide a guide for future development of inhibitors targeting JAK2 and other kinases.
THE NITROPYRIDINYL ETHYLENEIMINE COMPOUND, THE PHARMACEUTICAL COMPOSITION CONTAINING IT, THE PREPARATION METHOD AND USE THEREOF
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Page/Page column 10, (2011/10/10)
The present invention discloses a nitropyridinyl ethyleneimine compound as shown in the formula I and a preparation method of the same, as well as use of the compound in manufacture of a prodrug and in manufacture of a drug for treating a tumor.
Dipyridodiazepinone derivatives; synthesis and anti HIV-1 activity
Khunnawutmanotham, Nisachon,Chimnoi, Nitirat,Techasakul, Supanna,Thitithanyanont, Arunee,Saparpakorn, Patchreenart,Hannongbua, Supa,Choowongkomon, Kiattawee,Pungpo, Pornpan
supporting information; experimental part, (2010/04/22)
Ten dipyridodiazepinone derivatives were synthesized and evaluated for their anti HIV-1 reverse transcriptase activity against wildtype and mutant type enzymes, K103N and Y181C. Two of them were found to be promising inhibitors for HIV-1 RT.
NOVEL ANXIOLYTIC COMPOUNDS
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Page/Page column 42-43, (2008/12/05)
The present invention relates to chemical compounds of general formula (I) which may possess useful therapeutic activity in a range of central nervous system disorders, and in particular, anxiety disorders.
CONFORMATIONALLY RESTRICTED AROMATIC INHIBITORS OF MICROSOMAL TRIGLYCERIDE TRANSFER PROTEIN AND METHOD
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Page 244, (2010/02/06)
Novel compounds are provided which are inhibitors of MTP and thus are useful for lowering serum lipids and treating atherosclerosis and related diseases, and have the structure (I) or (IA) or (IB) including pharmaceutically acceptable salts thereof or prodrug esters thereof, wherein q is 0,1 or 2; R is H, alkyl, aryl or halogen; A is (1) a bond; (2) -O-; or (3) (i); B is: (ii) or (iii) or (iv) or (v) (wherein (a = 2, 3 or 4)) or (vi) or (vii) or (viii); and wherein L, L, R, R, R, R, R, R, R, R, R, X, (ix), (x) and (xi) are as defined herein.
Hepatitis C viral IRES inhibition by phenazine and phenazine-like molecules
Wang, Wuyi,Preville, Patrice,Morin, Nicolas,Mounir, Samir,Cai, Weizhong,Siddiqui, M. Arshad
, p. 1151 - 1154 (2007/10/03)
An in vitro assay based on the expression of Fluci reporter gene under the translational control of HCV IRES was used to evaluate and screen compound libraries. A structure-activity relationship study on a phenazine hit was conducted. Our data suggest that an intact phenazine or phenazine-like core with two distal polar substitutions is crucial for potency. (C) 2000 Elsevier Science Ltd. All rights reserved.
8-arylalkyl- and 8-arylheteroalkyl-5,11-dihydro-6H-dipyrido?3,2-B:2',3'-e!?1!diazepines and their use in the treatment of HIV-1 infection
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, (2008/06/13)
Disclosed are novel 8-arylalkyl-5,11-dihydro-6H-dipyrido?3,2-b:2',3'-e!?1,4!diazepines. These are useful in the treatment of HIV-1 infection.
8-Arylalkyl- and 8-arylheteroalkyl-5, 11-dihydro-6H-dipyrido-[3,2-b:2', 3'-e][1,4]diazepines and their use in the prevention or treatment of HIV infection
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, (2008/06/13)
The invention relates to novel 8-arylalkyl-5,11-dihydro-6H-dipyrido[3,2-b:2',3'-e][1,4]diazepines of general formula 1 which are useful in the prevention or treatment of HIV infection.
Pyrido[2,3-b][1,5]benzoxazepin (and thiazepin)-5(6H)-ones and thiones and their use on the treatment of HIV infection
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, (2008/06/13)
Disclosed are pyrido[2,3-b][1,5]benzoxazepin (and thiazepin)-5(6H)-ones and -thiones. These are useful in the prevention or treatment of AIDS.
