Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Having -c- – wherein x is chalcogen – bonded directly to...
Reexamination Certificate
2003-06-13
2004-02-10
Ramsuer, Robert W. (Department: 1626)
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Having -c-, wherein x is chalcogen, bonded directly to...
C548S366100, C548S371100
Reexamination Certificate
active
06689805
ABSTRACT:
BACKGROUND OF THE INVENTION
1. Field of the Invention
The present invention relates to a pyrazole-3-one derivative or a n-toxic salt thereof, a method for preparing the same, and a pharmaceutical composition containing the same as an active ingredient.
2. Description of the Related Art
Most nonsteroidal antiinflammatory agents are responsible for locking enzyme, cyclooxygenase (COX) or prostaglandin G/H synthase, o reduce inflammation, pain, or fever. In addition, they inhibit uterus contraction caused by hormones and also inhibit growth of several cancers. Cyclooxygenase-1 (COX-1) was first discovered in bovine. The COX-1 is constitutively expressed in a variety of cell types. Unlike the COX-1, cyclooxygenase-2 (COX-2) is a recently discovered isoform of cyclooxygenase that can be easily induced by mitogen, endotoxin, hormone, growth factor, or cytokine.
Prostaglandin is a potent mediator for various pathological and physiological processes. The COX-1 plays important physiological roles such as in the release of endogenous prostaglandin, the maintenance of the shape and the function of stomach, and the blood circulation in the kidney. On the other hand, the COX-2 is induced by an inflammatory factor, hormone, a growth factor, or cytokine. Therefore, the COX-2 is involved in pathological processes of prostaglandin, unlike the constitutive COX-1. In this regard, selective inhibitors of the COX-2 produce fewer and less side effects in terms of action mechanism in comparison with conventional nonsteroidal antiinflammatory agents. In addition, they reduce inflammation, pain, and fever and inhibit uterus contraction caused by hormones and growth of several cancers. In particular, they are effective in decreasing side effects such as stomach toxicity and kidney toxicity. Still furthermore, they inhibit the synthesis of contractile prostanoid, thereby leading to suppression of the contraction of smooth muscles. Therefore, they help in preventing premature birth, menstrual irregularity, asthma, and eosinophilic disease.
Recently, it was reported that nonsteroidal antiinflammatory agents are effective in treating large intestine cancer [
European Journal of Cancer,
Vol 37, p2302, 2001], prostate cancer [
Urology,
Vol 58, p127, 2001], and dementia [
Exp. Opin. Invest. Drugs,
Vol 9, p671, 2000].
In addition, it is anticipated that selective inhibitors of the COX-2 would be effective in treating osteoporosis and glaucoma. Utility of selective inhibitors of the COX-2 is well described in publications [John Vane, “Towards a Better Aspirin” in
Nature,
Vol.367, pp215-216, 1994; Bruno Battistini, Regina Botting and Y. S. Bakhle, “COX-1 and COX-2: Toward the Development of More Selective NSAIDs” in
Drug News and Perspectives,
Vol.7, pp501-512, 1994; David B. Reitz and Karen Seibert, “Selective Cyclooxygenase Inhibitors” in
Annual Reports in Medicinal Chemistry,
James A. Bristol, Editor, Vol. 30, pp179-188, 1995].
Various selective COX-2 inhibitors having different structures are known. Among them, a selective COX-2 inhibitor having a diaryl heterocyclic structure, i.e. a tricyclic structure has been widely studied as a potent candidate. The diaryl heterocyclic structure has a central ring and a sulfonamide or methylsulfone group attached to one of the aryl rings. An initial substance having such diaryl heterocyclic structure is Dup697
[Bioorganic
&
Medicinal Chemistry Letters,
Vol 5, p2123, 1995]. Since then, SC-58635 having a pyrazol ring (
Journal of Medicinal Chemistry,
Vol 40, p1347, 1997) and MK-966 having a furanone ring (WO 95/00501) were discovered as derivatives of the Dup697.
One selective COX-2 inhibitor, Celecoxib of formula 14 is disclosed in U.S. Pat. No. 5,466,823. The Celecoxib is a substituted pyrazolyl benzenesulfonamide derivative.
Another selective COX-2 inhibitor, Rofecoxib of formula 15 is disclosed in WO 95/00501. The Rofecoxib has a diaryl heterocyclic structure with a central furanone ring.
Valdecoxib of formula 16 as another selective COX-2 inhibitor is disclosed in U.S. Pat. No. 5,633,272. The Valdecoxib has a phenylsulfonamide moiety with a central isoxazole ring.
The selective COX-2 inhibitors of formulas 14 to 16 are effective inflammatory therapeutic agents with fewer and less side effects in comparison with conventional nonsteroidal antiinflammatory agents.
SUMMARY OF THE INVENTION
An aspect of the present invention provides a pyrazole-3-one derivative of formula 1 or a non-toxic salt thereof.
Another aspect of the present invention provides a method for preparing a pyrazole-3-one derivative or a non-toxic salt thereof.
Another aspect of the present invention provides a pharmaceutical composition comprising a pyrazole-3-one derivative or a non-toxic salt thereof as an active ingredient for the treatment of fever, pain, and inflammation.
Yet another aspect of the present invention provides a pharmaceutical composition comprising a pyrazole-3-one derivative or a non-toxic salt thereof as an active ingredient for the treatment of cancers and dementia.
REFERENCES:
patent: 5466823 (1995-11-01), Talley et al.
patent: 5633272 (1997-05-01), Talley et al.
patent: 95/00501 (1995-01-01), None
“Current Perspective Recent advances in the management of colorectal cancer”; Authors: E.V. Cutsem, M. Dicato, J. Wils; European Journal of Cancer 37; Elsevier Science Ltd.; 2001; pp. 2302-2309.
Monthly Focus: Central & Peripheral Nervous Systems; “Anti-inflammatory drugs: a hope for Alzheimer's disease?”; Authors: Michael Hull, Klaus Lieb & Bernd L. Fiebich; Asley Publications Ltd.; 2000; pp. 671-683.
News and Views; “Towards a better aspirin”; Author: John Vane; Nature, vol. 367; Jan. 20, 1994; pp. 215-216.
Meeting Report; “COX-1 and COX-2: Toward the Development of More Selective NSAIDs”; Authors: Bruno Battistini, Regina Botting and Y.S. Bakhle; DN & P 7 (8); Oct. 1994; pp. 501-512.
Chapter 19; “Selective Cycloozygenase Inhibitors”; Authors: David B. Reitz and Karen Seibert; Annual Reports in Medicinal Chemistry-30; Academic Press, Inc.; 1995; pp. 179-188.
Pergamon; “Synthesis and Biological Evaluation of 2, 3-Diarylthiophenes as Selective COX-2 and COX-1 Inhibitors”; Authors: Yves Leblanc, Jacques Yves Gauthier, Diane Ethier, Jocelyne Guay, Joseph Mancini, Denis Riendeau, Philip Tagari, Philip Vichers, Elizabeth Wong and Petpiboon Prasit; Bioorganic & Medicinal Chemistry Letters, vol. 5, No. 18; Elsevier Science Ltd.; 1995; pp. 2123-2128.
“Synthesis and Biological Evaluation of the 1, 5-Diarylpyrazole Class of Cycloozygenase-2 Inhibitors: Indentification of 4-[5-(4-Methylphenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl] benzenesulfonamide (SC-58635, Celeoxib)”; Authors: Thomas D.Penning, et al.; Journal of Medicinal Chemistry vol. 40, No. 9; American Chemical Society; 1997; pp. 1347-1365.
Chae Myeong Yun
Cho Il Hwan
Jung Sung Hak
Kim Dal Hyun
Kim Jong Hoon
Cantor & Colburn LLP
CJ Corp.
Ramsuer Robert W.
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