Design and synthesis of N-phenylacetyl (sulfonyl) 4,5-dihydropyrazole derivatives as potential antitumor agents

Bioorganic and Medicinal Chemistry Letters

Volumn 21, Issue 10, 2011, Pages 2916-2920

  Liu, Xin Hua ^a,b   Ruan, Ban Feng ^a   Liu, Jing Xin ^a   Song, Bao An ^c   Jing, Ling Hong ^c   Li, Jun ^b   Yang, Yang ^a   Zhu, Hai Liang ^a   Qi, Xing Bao ^d  

^a NANJING UNIVERSITY   (China)

^b ANHUI MEDICAL UNIVERSITY   (China)

^c GUIZHOU UNIVERSITY   (China)

^d CHINA PHARMACEUTICAL UNIVERSITY   (China)

Author keywords

Antitumor agent; Dihydropyrazole; Synthesis; Telomerase inhibitors

Indexed keywords

(2 CHLOROPHENYL)[5 (2 HYDROXYPHENYL) 3 METHYL 4,5 DIHYDROPYRAZOL 1 YL]METHANONE; 1 [5 (2 HYDROXYPHENYL) 3 METHYL 4,5 DIHYDROPYRAZOL 1 YL] 2 (4 NITROPHENYL)ETHANONE; 2 (3 METHYL 1 TOSYL 4,5 DIHYDRO 1H PYRAZOL 5 YL)PHENOL; 2 [3 METHYL 1 (4 NITROPHENYLSULFONYL) 4,5 DIHYDRO 1H PYRAZOL 5 YL)PHENOL; 2 [3 METHYL 1 (PHENYLSULFONYL) 4,5 DIHYDRO 1H PYRAZOL 5 YL]PHENOL; 2 CHLORO 1 [5 (2 HYDROXYPHENYL) 3 METHYL 4,5 DIHYDROPYRAZOL 1 YL]ETHANONE; [5 (2 HYDROXY 3 METHYLPHENYL) 3 METHYL 4,5 DIHYDROPYRAZOL 1 YL](PHENYL)METHANONE; [5 (2 HYDROXYPHENYL) 3 METHYL 4,5 DIHYDROPYRAZOL 1 YL](2 TOLYL)METHANONE; [5 (2 HYDROXYPHENYL) 3 METHYL 4,5 DIHYDROPYRAZOL 1 YL](4 TOLYL)METHANONE; [5 (2 HYDROXYPHENYL) 3 METHYL 4,5 DIHYDROPYRAZOL 1 YL](PHENYL)METHANONE; ANTINEOPLASTIC AGENT; ETHIDIUM BROMIDE; FLUOROURACIL; N PHENYLACETYL(SULFONYL) 4,5 DIHYDROPYRAZOLE DERIVATIVE; PYRAZOLE DERIVATIVE; TELOMERASE; TELOMERASE INHIBITOR; UNCLASSIFIED DRUG;

ANTINEOPLASTIC ACTIVITY; ARTICLE; CANCER CELL; CRYSTAL STRUCTURE; CYTOTOXICITY; DRUG DESIGN; DRUG STRUCTURE; DRUG SYNTHESIS; ENZYME INHIBITION; HUMAN; HUMAN CELL; IC 50; LIVER CANCER; PROSTATE CANCER; STOMACH CANCER;

ANTINEOPLASTIC AGENTS; CELL LINE; CELL LINE, TUMOR; CELL PROLIFERATION; DRUG DESIGN; HUMANS; INHIBITORY CONCENTRATION 50; MODELS, MOLECULAR; MOLECULAR STRUCTURE; PYRAZOLES; TELOMERASE;

EID: 79955559793     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bmcl.2011.03.066     Document Type: Article

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19. Discovery Studio 2.1 (DS 2.1, Accelrys Software Inc., San Diego, California, USA). Crystal structure of telomerase (PDB entry 3DU6 ) was used as template. Hydrogen atoms were added to protein model. The added hydrogen atoms were minimized to have stable energy conformation and to also relax the conformation from close contacts. The active site was defined and sphere of 4 was generated around the active site pocket, with the active site pocket of BSAI model using C-DOCKER, a molecular dynamics (MD) simulated annealing-based algorithm module from DS 2.1. Random substrate conformations are generated using high-temperature MD. Candidate poses are then created using random rigid-body rotations followed by simulated annealing. The structure of protein, substrate were subjected to energy minimization using CHARMm forcefield as implemented in DS 2.1. A full potential final minimization was then used to refine the substrate poses. Based on C-DOCKER, energy docked conformation of the substrate was retrieved for postdocking analysis.