Synthesis of thio-heterocyclic analogues from Baylis-Hillman bromides as potent cyclooxygenase-2 inhibitors

Amlipur Santhoshi; Budde Mahendar; Saidulu Mattapally; Partha Sarathi Sadhu; Sanjay Kumar Banerjee; Vaidya Jayathirtha Rao

doi:10.1016/j.bmcl.2014.02.073

Synthesis of thio-heterocyclic analogues from Baylis-Hillman bromides as potent cyclooxygenase-2 inhibitors

Amlipur Santhoshi, Budde Mahendar, Saidulu Mattapally, Partha Sarathi Sadhu, Sanjay Kumar Banerjee, Vaidya Jayathirtha Rao

Research output: Contribution to journal › Article › peer-review

12 Scopus citations

Abstract

A series of thio-substituted pyrimidine, benzoxazole, benzothiazole and triazole analogues were synthesized from Baylis-Hillman bromides in a clean and efficient way. The synthesized twenty new compounds were subjected to in vitro COX-1 and COX-2 inhibitory activity. Majority of compounds found to be highly selective COX-2 inhibitor. Seven compounds (16e, 16f, 16k, 16l, 16m, 16r and 16s) displayed anti-inflammatory activity at micromolar concentrations with IC₅₀ values for COX-2 inhibition ranging from 2.93 to 5.34 μM compared to reference drug whose IC₅₀ is 2.66 μM. All these seven compounds had very little COX-1 inhibition property and thus are suitable candidates for anti-inflammatory drugs with less gastrointestinal side effect.

Original language	English (US)
Pages (from-to)	1952-1957
Number of pages	6
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	24
Issue number	8
DOIs	https://doi.org/10.1016/j.bmcl.2014.02.073
State	Published - Apr 15 2014
Externally published	Yes

Bibliographical note

Funding Information:
The authors thank the Director, CSIR-Indian Institute of Chemical Technology, for encouragement. A.S. and P.S.S. acknowledge CSIR-New Delhi, B.M. acknowledge UGC-New Delhi and S.M. acknowledge ICMR-New Delhi for research fellowship. Origin-CSC-0108 and SMiLE–CSC112 projects are acknowledged for funding. S.K.B. is thankful to DBT for providing Ramalingaswami Fellowship.

Keywords

Anti-inflammatory
Baylis-Hillman bromide
Cyclooxygenase
Thiobenzothiazole
Thiobenzotriazole
Thiobenzoxazole
Thiopyrimidine

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title = "Synthesis of thio-heterocyclic analogues from Baylis-Hillman bromides as potent cyclooxygenase-2 inhibitors",

abstract = "A series of thio-substituted pyrimidine, benzoxazole, benzothiazole and triazole analogues were synthesized from Baylis-Hillman bromides in a clean and efficient way. The synthesized twenty new compounds were subjected to in vitro COX-1 and COX-2 inhibitory activity. Majority of compounds found to be highly selective COX-2 inhibitor. Seven compounds (16e, 16f, 16k, 16l, 16m, 16r and 16s) displayed anti-inflammatory activity at micromolar concentrations with IC50 values for COX-2 inhibition ranging from 2.93 to 5.34 μM compared to reference drug whose IC50 is 2.66 μM. All these seven compounds had very little COX-1 inhibition property and thus are suitable candidates for anti-inflammatory drugs with less gastrointestinal side effect.",

keywords = "Anti-inflammatory, Baylis-Hillman bromide, Cyclooxygenase, Thiobenzothiazole, Thiobenzotriazole, Thiobenzoxazole, Thiopyrimidine",

author = "Amlipur Santhoshi and Budde Mahendar and Saidulu Mattapally and Sadhu, {Partha Sarathi} and Banerjee, {Sanjay Kumar} and {Jayathirtha Rao}, Vaidya",

note = "Funding Information: The authors thank the Director, CSIR-Indian Institute of Chemical Technology, for encouragement. A.S. and P.S.S. acknowledge CSIR-New Delhi, B.M. acknowledge UGC-New Delhi and S.M. acknowledge ICMR-New Delhi for research fellowship. Origin-CSC-0108 and SMiLE–CSC112 projects are acknowledged for funding. S.K.B. is thankful to DBT for providing Ramalingaswami Fellowship. ",

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AU - Banerjee, Sanjay Kumar

AU - Jayathirtha Rao, Vaidya

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N2 - A series of thio-substituted pyrimidine, benzoxazole, benzothiazole and triazole analogues were synthesized from Baylis-Hillman bromides in a clean and efficient way. The synthesized twenty new compounds were subjected to in vitro COX-1 and COX-2 inhibitory activity. Majority of compounds found to be highly selective COX-2 inhibitor. Seven compounds (16e, 16f, 16k, 16l, 16m, 16r and 16s) displayed anti-inflammatory activity at micromolar concentrations with IC50 values for COX-2 inhibition ranging from 2.93 to 5.34 μM compared to reference drug whose IC50 is 2.66 μM. All these seven compounds had very little COX-1 inhibition property and thus are suitable candidates for anti-inflammatory drugs with less gastrointestinal side effect.

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Synthesis of thio-heterocyclic analogues from Baylis-Hillman bromides as potent cyclooxygenase-2 inhibitors

Abstract

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Keywords

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