Design, Synthesis and Biological Evaluation of 5-Oxo-1,4,5,6,7,8 Hexahydroquinoline Derivatives as Selective Cyclooxygenase-2 Inhibitors

نویسندگان

  • Afshin Zarghi Department of Medicinal Chemistry, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran
  • Bahram Daraie Department of Toxicology, School of Medicine, Tarbiat Modarres University of Medical Sciences, Tehran, Iran
  • Iman Sabakhi The Scientific Thecnological Centre of Organic and Pharmaceutical Chemistry NASRAAL. Mnjoyan Institute of Fine Organic Chemistry, Yerevan, Armenia
  • Vigen Topuzyan The Scientific Thecnological Centre of Organic and Pharmaceutical Chemistry NASRAAL. Mnjoyan Institute of Fine Organic Chemistry, Yerevan, Armenia
  • Zahra Hajimahdi Department of Pharmaceutical Chemistry, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran
چکیده مقاله:

A group of regioisomeric 5-oxo-1,4,5,6,7,8 hexahydroquinoline derivatives possessing a COX-2 SO2Me pharmacophore at the para position of the C-2 or C-4 phenyl ring, in conjunction with a C-4 or C-2 phenyl (4-H) or substituted-phenyl ring (4-F,4-Cl,4-Br,4-OMe,4-Me, 4-NO2), were designed for evaluation as selective cyclooxygenase-2 (COX-2) inhibitors. These target 5-oxo-1,4,5,6,7,8 hexahydroquinolines were synthesized via a Hansch condensation reaction. In vitro COX-1/COX-2 isozyme inhibition structure-activity studies identified 7,8-dihydro-7,7-dimethyl-2-(4-methoxyphenyl)-4-(4-(methylsulfonyl)phenyl)quinolin-5(1H,4H,6H)-one (9c) as a potent COX-2 inhibitor (IC50 = 0.17 microM) with a high COX-2 selectivity index (S.I. = 97.6) comparable to the reference drug celecoxib (COX-2 IC50 = 0.05 microM; COX-2 S.I= 405). A molecular modeling study where 9c was docked in active site of COX-2 showed that the p-SO2Me substituent on the C-2 phenyl ring is inserted into the secondary COX-2 binding site. The structure activity data acquired indicate that the position of the COX-2 SO2Me pharmacophore and type of substituent are important for COX-2 inhibitory activity.

برای دانلود باید عضویت طلایی داشته باشید

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

design, synthesis and biological evaluation of 5-oxo-1,4,5,6,7,8 hexahydroquinoline derivatives as selective cyclooxygenase-2 inhibitors

a group of regioisomeric 5-oxo-1,4,5,6,7,8 hexahydroquinoline derivatives possessing a cox-2 so2me pharmacophore at the para position of the c-2 or c-4 phenyl ring, in conjunction with a c-4 or c-2 phenyl (4-h) or substituted-phenyl ring (4-f,4-cl,4-br,4-ome,4-me, 4-no2), were designed for evaluation as selective cyclooxygenase-2 (cox-2) inhibitors. these target 5-oxo-1,4,5,6,7,8 hexahydroquino...

متن کامل

Design, Synthesis and Biological Evaluation of 5-Oxo-1,4,5,6,7,8 Hexahydroquinoline Derivatives as Selective Cyclooxygenase-2 Inhibitors

A group of regioisomeric 5-oxo-1,4,5,6,7,8 hexahydroquinoline derivatives possessing a COX-2 SO2Me pharmacophore at the para position of the C-2 or C-4 phenyl ring, in conjunction with a C-4 or C-2 phenyl (4-H) or substituted-phenyl ring (4-F,4-Cl,4-Br,4-OMe,4-Me, 4-NO2), were designed for evaluation as selective cyclooxygenase-2 (COX-2) inhibitors. These target 5-oxo-1,4,5,6,7,8 hexahydroquino...

متن کامل

Design, Synthesis and Biological Evaluation of new 1,4-Dihydropyridine (DHP) Derivatives as Selective Cyclooxygenase-2 Inhibitors

As a continuous research for discovery of new COX-2 inhibitors, chemical synthesis, in vitro biological activity and molecular docking study of anew group of 1,4-dihydropyridine (DHP) derivatives were presented. Novel synthesized compounds possessing a COX-2 SO2Me pharmacophore at the para position of C-4 phenyl ring, different hydrophobic groups (R1) at C-2 position and alkoxycarbonyl groups (...

متن کامل

Design, Synthesis and Biological Evaluation of new 1,4-Dihydropyridine (DHP) Derivatives as Selective Cyclooxygenase-2 Inhibitors

As a continuous research for discovery of new COX-2 inhibitors, chemical synthesis, in vitro biological activity and molecular docking study of anew group of 1,4-dihydropyridine (DHP) derivatives were presented. Novel synthesized compounds possessing a COX-2 SO2Me pharmacophore at the para position of C-4 phenyl ring, different hydrophobic groups (R1) at C-2 position and alkoxycarbonyl groups (...

متن کامل

Novel Group of Imidazole Derivatives as Atypical Selective Cyclooxygenase-2 Inhibitors: Design, Synthesis and Biological Evaluation

In this study, a new series of 5-substituted 1-benzyl-2-(methylsulfonyl)-1-H-imidazolewith atypical structure-activity relationship was designed, synthesized, and biologicalevaluated as selective cyclooxygenase-2 inhibitors. Docking studies revealed that althoughthe pharmacophoric substitute of the compound 5b, methylsulfonyl group, has been directlyattached to the central ring, it is in the sa...

متن کامل

منابع من

با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

ذخیره در منابع من قبلا به منابع من ذحیره شده

{@ msg_add @}


عنوان ژورنال

دوره 13  شماره Supplement

صفحات  61- 69

تاریخ انتشار 2014-02-01

با دنبال کردن یک ژورنال هنگامی که شماره جدید این ژورنال منتشر می شود به شما از طریق ایمیل اطلاع داده می شود.

میزبانی شده توسط پلتفرم ابری doprax.com

copyright © 2015-2023