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

33 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",

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

language = "English",

volume = "5",

pages = "867--872",

journal = "Bioorganic and Medicinal Chemistry Letters",

issn = "0960-894X",

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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 - http://www.scopus.com/inward/record.url?scp=0028952998&partnerID=8YFLogxK

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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