Selective cyclooxygenase inhibitors: Novel 4-spiro 1,2-diarylcyclopentenes are potent and orally active cox-2 inhibitors

David B. Reitz; Horng Chih Huang; James J. Li; Danny J. Garland; Robert E. Manning; Gary D. Anderson; Susan A. Gregory; Carol M. Koboldt; William E. Perkins; Karen Seibert; Peter C. Isakson

doi:10.1016/0960-894X(95)00131-C

Selective cyclooxygenase inhibitors: Novel 4-spiro 1,2-diarylcyclopentenes are potent and orally active cox-2 inhibitors

David B. Reitz
, Horng Chih Huang
, James J. Li
, Danny J. Garland
, Robert E. Manning
, Gary D. Anderson
, Susan A. Gregory
, Carol M. Koboldt
, William E. Perkins
, Karen Seibert
, Peter C. Isakson

Department of Anesthesiology

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

34 Scopus citations

Abstract

Novel 4,5-diarylspiro[2.4]hept-5-enes, 6,7-diarylspiro[3.4]oct-6-enes, and 2,3-diarylspiro[4.4]non-2-enes have been synthesized and shown to be very potent inducible cyclooxygenase (COX-2) inhibitors with inhibition (IC₅₀) in the low nanomolar range and enzyme selectivity ratios as high as four orders of magnitude. The methyl sulfone spiro[2.4]hept-5-ene 1 (SC-58451) was found to be orally active (ED₅₀ = 0.3 mpk) in the rat adjuvant-induced arthritis model with no gastric lesions observed at 200 mpk.

Original language	English
Pages (from-to)	867-872
Number of pages	6
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	5
Issue number	8
DOIs	https://doi.org/10.1016/0960-894X(95)00131-C
State	Published - Apr 20 1995

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Reitz, D. B., Huang, H. C., Li, J. J., Garland, D. J., Manning, R. E., Anderson, G. D., Gregory, S. A., Koboldt, C. M., Perkins, W. E., Seibert, K., & Isakson, P. C. (1995). Selective cyclooxygenase inhibitors: Novel 4-spiro 1,2-diarylcyclopentenes are potent and orally active cox-2 inhibitors. Bioorganic and Medicinal Chemistry Letters, 5(8), 867-872. https://doi.org/10.1016/0960-894X(95)00131-C

@article{8e33d0249f5e45649e83e8f7b7a3d770,

title = "Selective cyclooxygenase inhibitors: Novel 4-spiro 1,2-diarylcyclopentenes are potent and orally active cox-2 inhibitors",

abstract = "Novel 4,5-diarylspiro[2.4]hept-5-enes, 6,7-diarylspiro[3.4]oct-6-enes, and 2,3-diarylspiro[4.4]non-2-enes have been synthesized and shown to be very potent inducible cyclooxygenase (COX-2) inhibitors with inhibition (IC50) in the low nanomolar range and enzyme selectivity ratios as high as four orders of magnitude. The methyl sulfone spiro[2.4]hept-5-ene 1 (SC-58451) was found to be orally active (ED50 = 0.3 mpk) in the rat adjuvant-induced arthritis model with no gastric lesions observed at 200 mpk.",

author = "Reitz, \{David B.\} and Huang, \{Horng Chih\} and Li, \{James J.\} and Garland, \{Danny J.\} and Manning, \{Robert E.\} and Anderson, \{Gary D.\} and Gregory, \{Susan A.\} and Koboldt, \{Carol M.\} and Perkins, \{William E.\} and Karen Seibert and Isakson, \{Peter C.\}",

year = "1995",

month = apr,

day = "20",

doi = "10.1016/0960-894X(95)00131-C",

language = "English",

volume = "5",

pages = "867--872",

journal = "Bioorganic and Medicinal Chemistry Letters",

issn = "0960-894X",

number = "8",

}

Reitz, DB, Huang, HC, Li, JJ, Garland, DJ, Manning, RE, Anderson, GD, Gregory, SA, Koboldt, CM, Perkins, WE, Seibert, K & Isakson, PC 1995, 'Selective cyclooxygenase inhibitors: Novel 4-spiro 1,2-diarylcyclopentenes are potent and orally active cox-2 inhibitors', Bioorganic and Medicinal Chemistry Letters, vol. 5, no. 8, pp. 867-872. https://doi.org/10.1016/0960-894X(95)00131-C

TY - JOUR

T1 - Selective cyclooxygenase inhibitors

T2 - Novel 4-spiro 1,2-diarylcyclopentenes are potent and orally active cox-2 inhibitors

AU - Reitz, David B.

AU - Huang, Horng Chih

AU - Li, James J.

AU - Garland, Danny J.

AU - Manning, Robert E.

AU - Anderson, Gary D.

AU - Gregory, Susan A.

AU - Koboldt, Carol M.

AU - Perkins, William E.

AU - Seibert, Karen

AU - Isakson, Peter C.

PY - 1995/4/20

Y1 - 1995/4/20

N2 - Novel 4,5-diarylspiro[2.4]hept-5-enes, 6,7-diarylspiro[3.4]oct-6-enes, and 2,3-diarylspiro[4.4]non-2-enes have been synthesized and shown to be very potent inducible cyclooxygenase (COX-2) inhibitors with inhibition (IC50) in the low nanomolar range and enzyme selectivity ratios as high as four orders of magnitude. The methyl sulfone spiro[2.4]hept-5-ene 1 (SC-58451) was found to be orally active (ED50 = 0.3 mpk) in the rat adjuvant-induced arthritis model with no gastric lesions observed at 200 mpk.

AB - Novel 4,5-diarylspiro[2.4]hept-5-enes, 6,7-diarylspiro[3.4]oct-6-enes, and 2,3-diarylspiro[4.4]non-2-enes have been synthesized and shown to be very potent inducible cyclooxygenase (COX-2) inhibitors with inhibition (IC50) in the low nanomolar range and enzyme selectivity ratios as high as four orders of magnitude. The methyl sulfone spiro[2.4]hept-5-ene 1 (SC-58451) was found to be orally active (ED50 = 0.3 mpk) in the rat adjuvant-induced arthritis model with no gastric lesions observed at 200 mpk.

UR - https://www.scopus.com/pages/publications/0028952998

U2 - 10.1016/0960-894X(95)00131-C

DO - 10.1016/0960-894X(95)00131-C

M3 - Article

AN - SCOPUS:0028952998

SN - 0960-894X

VL - 5

SP - 867

EP - 872

JO - Bioorganic and Medicinal Chemistry Letters

JF - Bioorganic and Medicinal Chemistry Letters

IS - 8

ER -

Selective cyclooxygenase inhibitors: Novel 4-spiro 1,2-diarylcyclopentenes are potent and orally active cox-2 inhibitors

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