30129-53-4Relevant articles and documents
NOVEL CONDENSED HETEROCYCLIC COMPOUND
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Paragraph 0245, (2017/05/12)
PROBLEM TO BE SOLVED: To provide a compound having PDE2A selective inhibitory action, and a pharmaceutical composition comprising the same. SOLUTION: The present invention provides a compound represented by formula (I) or their pharmaceutically acceptable salt, or their solvate, and a pharmaceutical composition comprising them [m is an integer of 1 to 5; Y1 is N or C; Y2 is C-R2a or N-R2b; ring B is a benzene ring or the like; Z is CR5aR5b or O; R1 is a C1-6 alkyl group or the like; R2a is a halogen atom, a C1-6 alkyl group or the like; R2b is a C1-6 alkyl group or the like; R3a and R3b each independently represent H, a C1-6 alkyl group or the like; R4 independently represent a hydroxy group, a halogen atom or the like; R5a and R5b in Z each independently represent H, a C1-6 alkyl group and the like]. SELECTED DRAWING: None COPYRIGHT: (C)2017,JPOandINPIT
Discovery and preliminary structure–activity relationship of 1H-indazoles with promising indoleamine-2,3-dioxygenase 1 (IDO1) inhibition properties
Qian, Shan,He, Tao,Wang, Wei,He, Yanying,Zhang, Man,Yang, Lingling,Li, Guobo,Wang, Zhouyu
, p. 6194 - 6205 (2016/12/06)
Indoleamine 2,3-dioxygenase 1 (IDO1)-mediated kynurenine pathway of tryptophan degradation is identified as an important immune effector pathway in the tumor cells to escape a potentially effective immune response. IDO1 is an attractive target for anticancer therapy and the discovery of IDO1 inhibitors has been intensely ongoing in both academic research laboratories and pharmaceutical organizations. Our study discovered that 1H-indazole was a novel key pharmacophore with potent IDO1 inhibitory activity. A series of new 1H-indazole derivatives were synthesized and determined the enzyme inhibitory activities, and the compound 2g exhibited the highest activity with an IC50value of 5.3 μM. The structure–activity relationships (SARs) analysis of the 1H-indazole derivatives as novel IDO1 inhibitors indicated that the 1H-indazole scaffold is necessary for IDO1 inhibition, and the substituent groups at the both 4-position and 6-position largely affect inhibitory activity. The docking model exhibited that the effective interactions of 1H-indazoles with ferrous ion of heme and key residues of hydrophobic Pocket A and B ensured the IDO1 inhibitory activities. The study suggested that the 1H-indazole was a novel interesting scaffold for IDO inhibition for further development.
Substituted annellated pyrimidines and use thereof
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Paragraph 1660; 1661; 1662; 1663, (2014/02/15)
The present application relates to novel substituted annellated pyrimidines, methods for production thereof, use thereof alone or in combinations for treating and/or preventing diseases and use thereof for the production of medicinal products for treating
Bioisosteric transformations and permutations in the triazolopyrimidine scaffold to identify the minimum pharmacophore required for inhibitory activity against plasmodium falciparum dihydroorotate dehydrogenase
Marwaha, Alka,White, John,El-mazouni, Farah,Creason, Sharon A,Kokkonda, Sreekanth,Buckner, Frederick S.,Charman, Susan A.,Phillips, Margaret A.,Rathod, Pradipsinh K.
, p. 7425 - 7436 (2012/11/07)
Plasmodium falciparum causes approximately 1 million deaths annually. However, increasing resistance imposes a continuous threat to existing drug therapies. We previously reported a number of potent and selective triazolopyrimidine-based inhibitors of P.
Structure-based design of a novel series of potent, selective inhibitors of the class i phosphatidylinositol 3-kinases
Smith, Adrian L.,D'Angelo, Noel D.,Bo, Yunxin Y.,Booker, Shon K.,Cee, Victor J.,Herberich, Brad,Hong, Fang-Tsao,Jackson, Claire L. M.,Lanman, Brian A.,Liu, Longbin,Nishimura, Nobuko,Pettus, Liping H.,Reed, Anthony B.,Tadesse, Seifu,Tamayo, Nuria A.,Wurz, Ryan P.,Yang, Kevin,Andrews, Kristin L.,Whittington, Douglas A.,McCarter, John D.,Miguel, Tisha San,Zalameda, Leeanne,Jiang, Jian,Subramanian, Raju,Mullady, Erin L.,Caenepeel, Sean,Freeman, Daniel J.,Wang, Ling,Zhang, Nancy,Wu, Tian,Hughes, Paul E.,Norman, Mark H.
experimental part, p. 5188 - 5219 (2012/08/28)
A highly selective series of inhibitors of the class I phosphatidylinositol 3-kinases (PI3Ks) has been designed and synthesized. Starting from the dual PI3K/mTOR inhibitor 5, a structure-based approach was used to improve potency and selectivity, resulting in the identification of 54 as a potent inhibitor of the class I PI3Ks with excellent selectivity over mTOR, related phosphatidylinositol kinases, and a broad panel of protein kinases. Compound 54 demonstrated a robust PD-PK relationship inhibiting the PI3K/Akt pathway in vivo in a mouse model, and it potently inhibited tumor growth in a U-87 MG xenograft model with an activated PI3K/Akt pathway.
KINASE MODULATORS AND METHODS OF USE
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Page/Page column 100, (2010/02/15)
The present invention relates to compounds of the Formula I and II wherein R, R21, R25-R33, m, n, X21-X23, and Q1 are defined herein. The compounds modulate protein kinase enzymatic activity to modulate cellular activities such as proliferation, differentiation, programmed cell death, migration and chemoinvasion. Compounds of the invention inhibit, regulate and/or modulate kinases, particularly p70S6 and/or Akt kinases. Methods of using and preparing the compounds, and pharmaceutical compositions thereof, to treat kinase-dependent diseases and conditions are also an aspect of the invention.
