CAS: 885278-42-2; Methyl 6-Bromo-1H-Indazole-3-Carboxylate

上下游产品

6-溴吲唑-3-羧酸 6-Bromo-1H-Indazole-3-Carboxylic Acid 660823-36-9

2-(4-溴苯基)-2-氧代乙酸置于盐酸,氯化亚砜,Sodium Nitrite体系中,化学反应 7.0H,反应生成 6-溴-1H-吲唑-3-甲酸甲酯
参考文献:Design And Synthesis Of 1H-Indazole-3-Carboxamide Derivatives As Potent And Selective Pak1 Inhibitors With Anti-Tumour Migration And Invasion Activities
标题:Design And Synthesis Of 1H-Indazole-3-Carboxamide Derivatives As Potent And Selective Pak1 Inhibitors With Anti-Tumour Migration And Invasion Activities
摘要:Aberrant Activation Of P21-Activated Kinase 1 (Pak1) Is Associated With Tumour Progression,And Pak1 Has Been Recognized As A Promising Target For Anticancer Drug Discovery. However,The Development Of Potent Pak1 Inhibitors With Satisfactory Kinase Selectivity And Favourable Physicochemical Properties Remains A Daunting Challenge. Herein,We Identified The 1H-Indazole-3-Carboxamide Derivatives As Potential Pak1 Inhibitors Using A Fragment-Based Screening Approach. The Representative Compound 301 Exhibited Excellent Enzyme Inhibition (Pak1 Ic50 = 9.8 Nm) And High Pak1 Selectivity Toward A Panel Of 29 Kinases. The Structure-Activity Relationship (Sar) Analysis Showed That Substituting Of An Appropriate Hydrophobic Ring In The Deep Back Pocket And Introducing A Hydrophilic Group In The Bulk Solvent Region Were Critical For Pak1 Inhibitory Activity And Selectivity. Additionally,The Herg Channel Activity Of 301 Demonstrated Its Low Risk Of Herg Toxicity. Furthermore,It Significantly Suppressed The Migration And Invasion Of Mda-Mb-231 Cells By Downregulating Snail Expression Without Affecting The Tumour Growth. These Results Provide A New Type Of Chemical Scaffolds Targeting Pak1 And Suggested That 1H-Indazole-3-Carboxamide Derivatives May Serve As Lead Compounds For The Development Of Potential And Selective Pak1 Inhibitors. (C) 2020 Elsevier Masson Sas. All Rights Reserved.
DOI:10.1016/j.Ejmech.2020.112517

专利信息

专利号:WO-2011050245-A1
优先权日:2009-10-23
标 题:Bicyclic heteroaryls as kinase inhibitors
发明人：FENG YANGBO; CHEN YEN TING; SESSIONS HAMPTON; MISHRA JITENDRA K; CHOWDHURY SARWAT; YIN YAN; LOGRASSO PHILIP; LUO JUN-LI; BANNISTER THOMAS; SCHROETER THOMAS
权利人:FENG YANGBO; CHEN YEN TING; SESSIONS HAMPTON; MISHRA JITENDRA K; CHOWDHURY SARWAT; YIN YAN; LOGRASSO PHILIP; LUO JUN-LI; BANNISTER THOMAS; SCHROETER THOMAS
摘要:The invention is directed to heteroaryl compounds useful as inhibitors of various kinase enzymes. In various embodiments, the invention provides a heteroaryl compound having inhibitory bioactivity with respect to a Rho kinase, an AKT kinase, a p70S6K kinase, a LIM kinase, an IKK kinase, a Flt kinase, an Aurora kinase, or a Src kinase, or any combination thereof. Compounds of the invention include bicyclic heteroaryl compounds of formula (I), which can contain a bridging nitrogen atom at a ring junction. The invention further provides methods of synthesis of compounds of the invention, pharmaceutical compositions, pharmaceutical combinations, and methods of treatment of malconditions using compounds of the invention.

专利号:US-8952042-B2
优先权日:2009-08-19
标 题 :FXR (NR1H4) binding and activity modulating compounds
发明人：KREMOSER CLAUS; ABEL ULRICH; STEENECK CHRISTOPH; KINZEL OLAF
权利人:KREMOSER CLAUS; ABEL ULRICH; STEENECK CHRISTOPH; KINZEL OLAF; PHENEX PHARMACEUTICALS AG
摘要:The present invention relates to compounds of formula (1): n nwhere R, A, Q and Z are defined herein, or an enantiomer, diastereomer, tautomer, solvate, prodrug or pharmaceutical acceptable salt thereof. These compounds bind to the NR1H4 receptor (FXR) and act as agonists of the NR1H4 receptor (FXR). The invention further relates to the use of the compounds for the preparation of a medicament for the treatment of diseases and/or conditions through binding of said nuclear receptor by said compounds, and to a process for the synthesis of said compounds.