CoMFA and CoMSIA studies on 6,7-disubstituted-4-phenoxyquinoline derivatives as c-Met kinase inhibitors and anticancer agents

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• 作者：Palak Parikh ; Manjunath Ghate ; Vivek K. Vyas
• 关键词：c ; Met kinase inhibitors ; CoMFA ; CoMSIA ; 3D QSAR ; Tripos
• 刊名：Medicinal Chemistry Research
• 出版年：2015
• 出版时间：December 2015
• 年：2015
• 卷：24
• 期：12
• 页码：4078-4092
• 全文大小：2,319 KB
• 参考文献：Asses Y, Leroux V, Tairi-Kellou S, Dono R, Maina F, Maigret B (2009) Analysis of c-Met kinase domain complexes: a new specific catalytic site receptor model for defining binding modes of ATP-competitive ligands. Chem Biol Drug Des 74:560鈥?70CrossRef PubMed
  Caballero J, Quiliano M, Alzate-Morales JH, Zimic M, Deharo E (2011) Docking and quantitative structure鈥揳ctivity relationship studies for 3-fluoro-4-(pyrrolo[2,1-f][1,2,4]triazin-4-yloxy)aniline,3-fluoro-4-(1H-pyrrolo[2,3-b]pyridin-4-yloxy)aniline, and 4-(4-amino-2-fluorophenoxy)-2-pyridinylamine derivatives as c-Met kinase inhibitors. J Comput Aided Mol Des 25(4):349鈥?69CrossRef PubMed
  Chen CY (2008) Discovery of novel inhibitors for c-Met by virtual screening and pharmacophore analysis. J Chin Inst Chem Eng, 39:617鈥?24CrossRef
  Christensen JG, Schreck R, Burrows J, Kuruganti R, Chan E, Le P, Chen J, Wang X, Ruslim L, Blake R, Lipson KE, Ramphal J, Do S, Cui JJ, Cherrington JM, Mendel DB (2003) A selective small molecule inhibitor of c-Met kinase inhibits c-Met-dependent phenotypes in vitro and exhibits cytoreductive antitumor activity in vivo. Cancer Res 63:7345鈥?355PubMed
  Clark M, Cramer RD, Opdenbosch NV (1989) Validation of the general purpose Tripos 5.2 force field. J Comput Chem 10:982鈥?012CrossRef
  Cramer RD III, Bunce JD, Patterson DE (1988a) Crossvalidation, bootstrapping, and partial least squares compared with multiple regression in conventional QSAR studies. Quant Struct Act Relat 7:18鈥?5CrossRef
  Cramer RD, Patterson DE, Bunce JD (1988b) Comparative molecular field analysis (CoMFA). 1. Effect of shape on binding of steroids to carrier proteins. J Am Chem Soc 110:5959鈥?967CrossRef PubMed
  Cui JJ (2014) Targeting receptor tyrosine kinase MET in cancer: small molecule inhibitors and clinical progress. J Med Chem 57(11):4427鈥?453CrossRef PubMed
  Cui JJ, McTigue M, Nambu M, Tran-Dub茅 M, Pairish M, Shen H, Jia L, Cheng H, Hoffman J, Le P, Jalaie M, Goetz GH, Ryan K, Grodsky N, Deng Y, Parker M, Timofeevski S, Murray BW, Yamazaki S, Aguirre S, Li Q, Zou H, Christensen J (2012) Discovery of a novel class of exquisitely selective mesenchymal鈥揺pithelial transition factor (c-MET) protein kinase inhibitors and identification of the clinical candidate 2-(4-(1-(Quinolin-6-ylmethyl)-1H-[1,2,3]triazolo[4,5-b]pyrazin-6-yl)-1H-pyrazol-1-l)ethanol (PF-04217903) for the treatment of cancer. J Med Chem 55:8091鈥?109CrossRef PubMed
  Eder JP, Woude GFV, Boerner SA, LoRusso PM (2009) Novel therapeutic inhibitors of the c-MET signaling pathway in cancer. Clin Cancer Res 15:2207鈥?214CrossRef PubMed
  Gasteiger J, Marsili M (1980) Iterative partial equalization of orbital electronegativity鈥攁 rapid access to atomic charges. Tetrahedron 36:3219鈥?228CrossRef
  Gavernet L, Palestro PH, Bruno-Blanch L (2012) Docking applied to the study of inhibitors of c-Met kinase. ISRN Phys Chem (Article ID 391897):1鈥?
  Gherardi E, Birchmeier W, Birchmeier C, Woude GV (2012) Targeting MET in cancer: rationale and progress. Nat Rev 12:89鈥?03CrossRef
  He CX, Ai J, Xing WQ, Chen Y, Zang HT, Huang M, Hu YH, Ding J, Gene MY (2014) Yhhu3813 is a novel selective inhibitor of c-Met kinase that inhibits c-Met-dependent neoplastic phenotypes of human cancer cells. Acta Pharmacol Sin 35:89鈥?7PubMedCentral CrossRef PubMed
  Huang D, Zhu X, Tang C, Mei Y, Chen W, Yang B, Han J, Qian H, Huang W (2012) 3D QSAR pharmacophore modeling for c-Met kinase inhibitors. Med Chem 8:1117鈥?125PubMed
  Klebe G, Abraham U, Mietzner T (1994) Molecular similarity indices in a comparative analysis (CoMSIA) of drug molecules to correlate and predict their biological activity. J Med Chem 37:4130鈥?146CrossRef PubMed
  Lee JY, Lee K, Kim HR, Chae CH (2013) 3D-QSAR studies on chemical features of 3-(benzo[d]oxazol-2-yl)pyridine-2-amines in the external region of c-Met active site. Bull Korean Chem Soc 34(12):3553鈥?558CrossRef
  Liu L, Norman MH, Lee M, Xi N, Siegmund A, Boezio AA, Booker S, Choquette D, D鈥橝ngelo ND, Germain J, Yang K, Yang Y, Zhang Y, Bellon SF, Whittington DA, Harmange JC, Dominguez C, Kim TS, Dussault I (2012) Structure-based design of novel class II c-Met inhibitors: 2. SAR and kinase selectivity profiles of the pyrazolone series. J Med Chem 55:1868鈥?897CrossRef PubMed
  Ma PC, Tretiakova MS, Nallasura V, Jagadeeswaran R, Husain AN, Salgia R (2007) Downstream signalling and specific inhibition of c-Met/HGF pathway in small cell lung cancer: implications for tumour invasion. Br J Cancer 97:368鈥?77PubMedCentral CrossRef PubMed
  Maroun CR, Rowlands T (2014) The Met receptor tyrosine kinase: a key player in oncogenesis and drug resistance. Pharmacol Ther 142:316鈥?38CrossRef PubMed
  Menis J, Levra MG, Novello S (2013) c-Met inhibition in lung cancer. Transl Lung Cancer Res 3:23鈥?9
  Nisa L, Aebersold DM, Giger R, Zimmer Y, Medov谩 M (2014) Biological, diagnostic and therapeutic relevance of the MET receptor signaling in head and neck cancer. Pharmacol Ther 143:337鈥?49CrossRef PubMed
  Nishii H, Chiba T, Morikami K, Fukami TA, Sakamoto H, Ko K, Koyano H (2010) Discovery of 6-benzyloxyquinolines as c-Met selective kinase inhibitors. Bioorganic Med Chem Lett 20:1405鈥?409CrossRef
  Qi B, Mi B, Zhai X, Xu Z, Zhang X, Tian Z, Gong P (2013) Discovery and optimization of novel 4-phenoxy-6,7-disubstituted quinolines possessing semicarbazones as c-Met kinase inhibitors. Bioorganic Med Chem 21:5246鈥?260CrossRef
  Schiering N, Knapp K, Marconi M, Flocco MM, Cui J, Perego R, Rusconi L, Cristiani C (2003) Crystal structure of the tyrosine kinase domain of the hepatocyte growth factor receptor c-Met and its complex with the microbial alkaloid K-252a. Proc Natl Acad Sci USA 100:12654鈥?2659PubMedCentral CrossRef PubMed
  Tai W, Lu T, Yuan H, Wang F, Liu H, Lu S, Leng Y, Zhang W, Jiang Y, Chen Y (2012) Pharmacophore modeling and virtual screening studies to identify new c-Met inhibitors. J Mol Model 18:3087鈥?100CrossRef PubMed
  Tang Q, Zhang G, Dua X, Zhu W, Li R, Lin H, Li P, Cheng M, Gong P, Zhao Y (2014) Discovery of novel 6,7-disubstituted-4-phenoxyquinoline derivatives bearing 5-(aminomethylene)pyrimidine-2,4,6-trione moiety as c-Met kinase inhibitors. Bioorganic Med Chem 22:1236鈥?249CrossRef
  Tian Y, Shen Y, Zhang X, Ye L, Li Z, Liu Z, Zhang J, Wu S (2014) Design some new type-i c-Met inhibitors based on molecular docking and topomer CoMFA research. Mol Inf 33:536鈥?43CrossRef
  Vyas VK, Bhatt HG, Patel PK, Jalu J, Chintha C, Gupta N, Ghate M (2013) CoMFA and CoMSIA studies on C-aryl glucoside SGLT2 inhibitors as potential antidiabetic agents. SAR QSAR Environ Res 24:519鈥?51CrossRef PubMed
  Vyas VK, Patel A, Gupta N, Ghate M (2014) Design of novel anaplastic lymphoma kinase (ALK) inhibitors based on predictive 3D QSAR models using different alignment strategies. Med Chem Res 23:603鈥?17CrossRef
  Xie QQ, Zhong L, Pan YL, Wang XY, Zhou JP, Di-wu L, Huang Q, Wang YL, Yang LL, Xie HZ, Yang SY (2011) Combined SVM-based and docking-based virtual screening for retrieving novel inhibitors of c-Met. Eur J Med Chem 46:3675鈥?680CrossRef PubMed
  Yakes FM, Chen J, Tan J, Yamaguchi K, Shi Y, Yu P, Qian F, Chu F, Bentzien F, Cancilla B, Orf J, You A, Laird AD, Engst S, Lee L, Lesch J, Chou YC, Joly AH (2011) Cabozantinib (XL184), a novel MET and VEGFR2 inhibitor, simultaneously suppresses metastasis, angiogenesis, and tumor growth. Mol Cancer Ther 10:2298鈥?308CrossRef PubMed
  You WK, McDonald DM (2008) The hepatocyte growth factor/c-Met signaling pathway as a therapeutic target to inhibit angiogenesis. BMB Rep 41:833鈥?39PubMedCentral CrossRef PubMed
  Yuan H, Tai W, Hu S, Liu H, Zhang Y, Yao S, Ran T, Lu S, Ke Z, Xiong X, Xu J, Chen Y, Lu T (2013) Fragment-based strategy for structural optimization in combination with 3D-QSAR. J Comput Aided Mol Des 27:897鈥?15CrossRef PubMed
  Yuan H, Zhuang J, Hu S, Li H, Xu J, Hu Y, Xiong X, Chen Y, Lu T (2014) Molecular modeling of exquisitely selective c-Met inhibitors through 3D-QSAR and molecular dynamics simulations. J Chem Inf Model 54(9):2544鈥?554CrossRef PubMed
  
• 作者单位：Palak Parikh (1)
  Manjunath Ghate (1)
  Vivek K. Vyas (1)
  
  1. Department of Pharmaceutical Chemistry, Institute of Pharmacy, Nirma University, Ahmedabad, Gujarat, 382 481, India
  
• 刊物主题：Pharmacology/Toxicology; Biochemistry, general; Cell Biology;
• 出版者：Springer US
• ISSN：1554-8120

文摘

c-Met kinase is a recognized target for the development of small-molecule inhibitors for the treatment of cancer. In this study, a diverse set of 74 c-Met kinase inhibitors consisted of 6,7-disubstituted-4-phenoxyquinoline derivatives were used for CoMFA and CoMSIA (3D QSAR). 3D QSAR models were obtained using rigid body (Distill) alignment of training and test set molecules. CoMFA and CoMSIA models were found statistically significant with leave-one-out correlation coefficients (q 2) of 0.626 and 0.556, respectively, cross-validated coefficients (r _cv 2 ) of 0.532 and 0.501, respectively, and conventional coefficients (r 2) of 0.907 and 0.940, respectively. QSAR models were validated by a test set of 23 compounds giving satisfactory predicted correlation coefficients (r _pred 2 ) of 0.456 and 0.701 for CoMFA and CoMSIA models, respectively. This study will provide clues to design new compounds as c-Met kinase inhibitors. Keywords c-Met kinase inhibitors CoMFA CoMSIA 3D QSAR Tripos