.

Pharmaceutical Business Intelligence

  • Anticipate P&T budget requirements
  • Evaluate market entry opportunities
  • Find generic sources and suppliers
  • Predict branded drug patent expiration

► Plans and Pricing

Upgrade to enjoy subscriber-only features like email alerts and data export. See the Plans and Pricing

DrugPatentWatch Database Preview

Details for Patent: 6,469,040

« Back to Dashboard

Details for Patent: 6,469,040

Title: Method of using cyclooxygenase-2 inhibitors in the treatment and prevention of neoplasia
Abstract:This invention relates to the use of cyclooxygenase-2 inhibitors or derivatives thereof in preventing and treating neoplasia. In particular, the invention describes the method of preventing and treating epithelial cell neoplasia in a subject, said method comprising treating the subject with a therapeutically-effective amount of a compound of Formula I. ##STR1## wherein A, R.sup.2 and R.sup.3 are as described in the specification.
Inventor(s): Seibert; Karen (St. Louis, MO), Masferrer; Jaime (Ballwin, MO), Gordon; Gary B (Highland Park, IL)
Assignee: G.D. Searle & Co. (Chicago, IL)
Filing Date:May 21, 2001
Application Number:09/862,128
Claims:1. A method of treating a neoplasia in a subject in need of such treatment, said method comprising treating the subject with a therapeutically-effective amount of a compound of Formula II ##STR4##

or a pharmaceutically acceptable salt thereof wherein R.sup.1 is methyl or amino; R.sup.4 is (i) C.sub.1 -C.sub.6 haloalkyl, (ii) phenyl optionally substituted with one or more members independently selected from the group consisting of C.sub.1 -C.sub.6 alkyl, C.sub.1 -C.sub.6 alkoxy, nitro, cyano, halogen, hydroxy, amino, C.sub.1 -C.sub.6 alkyl amino, and di-C.sub.1 -C.sub.6 alkylamino groups, or (iii) thienyl optionally substituted with one or more members independently selected from the group consisting of C.sub.1 -C.sub.6 alkyl, C.sub.1 -C.sub.6 alkoxy, nitro, cyano, halogen, hydroxy, amino, C.sub.1 -C.sub.6 alkylamino, and di(C.sub.1 -C.sub.6)alkylamino groups; and R.sup.6 is phenyl optionally substituted at a substitutable position with one or more radicals selected from the group consisting of halo, C.sub.1 -C.sub.6 alkylthio, C.sub.1 -C.sub.6 alkylsulfonyl, cyano, nitro, C.sub.1 -C.sub.6 haloalkyl, C.sub.1 -C.sub.6 alkyl, hydroxyl, C.sub.1 -C.sub.6 alkenyl, C.sub.1 -C.sub.6 hydroxyalkyl, carboxyl, C.sub.1 -C.sub.6 cycloalkyl, C.sub.1 -C.sub.6 alkylamino, C.sub.1 -C.sub.6 dialkylamino, C.sub.1 -C.sub.6 alkoxycarbonyl, aminocarbonyl, C.sub.1 -C.sub.6 alkoxy, C.sub.1 -C.sub.6 haloalkoxy, sulfamyl, five or six membered heterocyclic radicals, and amino.

2. The method of claim 1 wherein the neoplasia is selected from the group consisting of colorectal cancer, gastrointestinal cancer, liver cancer, bladder cancer, cervical cancer, prostate cancer, lung cancer, breast cancer and skin cancer.

3. A method of claim 1, wherein the neoplasia is adenomatous polyps.

4. A method of treating a subject suffering from a neoplastic disease state with a conjunctive therapy, said method comprising treating the subject with a therapeutically-effective amount of a cyclooxygenase-2 selective compound and a compound selected from the group consisting of antibiotic agents, alkylating agents, antimetabolite agents, hormonal agents, immunological agents, interferon agents, metallomatrix proteases (MMP) inhibitors, SOD, and .alpha..sub.v.beta..sub.3 inhibitors, wherein the selective COX-2 inhibitor is a compound of formula II or formula III ##STR5##

or a pharmaceutically acceptable salt thereof wherein each R.sup.1 is methyl or amino; R.sup.4 is (i) C.sub.1 -C.sub.6 haloalkyl, (ii) phenyl optionally substituted with one or more members independently selected from the group consisting of C.sub.1 -C.sub.6 alkyl, C.sub.1 -C.sub.6 alkoxy, nitro, cyano, halogen, hydroxy, amino, C.sub.1 -C.sub.6 alkyl amino, and di-C.sub.1 -C.sub.6 alkylamino groups, or (iii) thienyl optionally substituted with one or more members independently selected from the group consisting of C.sub.1 -C.sub.6 alkyl, C.sub.1 -C.sub.6 alkoxy, nitro, cyano, halogen, hydroxy, amino C.sub.1 -C.sub.6 alkylamino, and di(C.sub.1 -C.sub.6) alkylamino groups; each R.sup.6 is phenyl optionally substituted at a substitutable position with one or more radicals selected from the group consisting of halo, C.sub.1 -C.sub.6 alkythio, C.sub.1 -C.sub.6 alkylsulfonyl, cyano, nitro, C.sub.1 -C.sub.6 haloalkyl, C.sub.1 -C.sub.6 alkyl, hydroxyl, C.sub.1 -C.sub.6 alkenyl, C.sub.1 -C.sub.6 HYDROXYALKYL, carboxyl, C.sub.1 -C.sub.6 cycloalkyl, C.sub.1 -C.sub.6 alkylamino, C.sub.1 -C.sub.6 dialkylamino, C.sub.1 -C.sub.6 alkoxycarbonyl, aminocarbonyl, C.sub.1 -C.sub.6 alkoxy, C.sub.1 -C.sub.6 haloalkoxy, sulfamyl, five or six membered heterocyclic radicals, and amino; R.sup.8 hydrogen or C.sub.1 -C.sub.6 haloalkyl; and R.sup.9 is C.sub.1 -C.sub.6 alkenyl, C.sub.1 -C.sub.6 alkoxycarbonyl(C.sub.1 -C.sub.2) alkyl N-phenylacetamido, or phenyl(C.sub.1 -C.sub.6)alkyl.

5. The method of claim 4 wherein the compound is selected from compounds, and their pharmaceutically acceptable salts, of the group consisting of 5-(4-flurophenyl)-1-[4-(methysulfonyl)phenyl]-3-(trifluromethyl)pyrazole; 4-(4-flurophenyl)-5-[4-(methysulfonyl)phenyl]-1-phenyl-3-(trifluoromethyl)p yrazole; 4-(5-(4-chlorophenyl)-3-(4-methoxyphenyl)-1H-pyrazol-1-yl)benzenesulfonamid e; 4-(3,5-bis(4-methyphenyl)-1H-pyrazol-1-yl)benzenesulfonamide; 4-(5-(4-chlorophenyl)-3-phenyl-1H-pyrazol-1-yl)benzenesulfonamide; 4-(3,5-bis(4-methoxyphenyl)-1H-pyrazol-1-yl)benzenesulfonamide; 4-(5-(4-chlorophenyl)-3-(4-methlphenyl)-1H-pyrazol-1-yl)benezenesulfonamide ; 4-(5-(4-chlorophenyl)-3-(4-nitrophenyl)-1H-pyrazol-1-yl)benezenesulfonamide ; 4-(5-(4-chlorophenyl)-3-(5-chloro-2-thienyl)-1H-pyrazol-1-yl)benzensulfonam ide; 4-(4-chloro-3,5-diphenyl-1H-pyrazol-1-yl)benzenesulfonamide; 4-[4-chloro-5-(4-chlorophenyl)-3-(trifluoromethyl]-1H-pyrazol-1yl)benezensu lfonamide; 4-[3-cyano-5-(4-fluorophenyl)-1H-pyrazol-1-yl]benzenesulfonamide; 4-[4-chloro-5-phenyl-1H-pyrazol-1-yl]benzenesulfonamide; 4-[(5-(4-chlorophenyl)-3-(hydroxymethyl)-1H-pyrazol-1-yl]benzenesulfonamide ; 1-allyl-4-(4-flurophenyl)-3-(4-(methysulsonyl)phenyl)-5-(trifluoromethyl)-1 H-pyrazole; 4-[1-ethyl-4-(4-fluorophenyl)-5-(trifluoromethyl)1H-pyrazol-3yl]benzenesulf onamide; N-phenyl-[4-(4-fluorophenyl)-3-(4-(methyysulfonyl)phenyl)-5-(trifluromethyl )-1H-pyrazol-1yl]acetamide; ethyl[4-(4-fluorophenyl)-3-(4-methysulfonyl)phenyl)-5-(trifluoromethyl)-1H- pyrazol-1-yl]acetate; 4-(4-fluorophenyl)-3-[4-methysulfonyl)phenyl]-1-(2-phenylethyl)-1H-pyrazole ; 4-(4-fluorophenyl)-3-[4-methysulfonyl]phenyl)-1-(2-phenylethyl)-5-(trifluor omethyl)pyrazole; and 1-ethyl-4-(4-fluorophenyl)-3-(4-(methysulfonyl)phenyl)-5-(trifluoromethyl)- 1H-pyrazole.

6. The method of claim 5 wherein the compound is selected from compounds, and their pharmaceutically acceptable salts, of the group consisting of 4-[5-(4-chlorophenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]benzenesulfonamid e; 4-[5-(4-methylphenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]benzenesulfonamid e; and 4-[5-(3-fluoro-4-methoxyphenyl)-3-(difluoromethyl)-1H-pyrazol-1-yl]benzenes ulfonamide.

7. A method of treating a neoplasia in a subject in need of such treatment, said method comprising treating the subject with a therapeutically-effective amount of a compound of the formula

##STR6##

or a pharmaceutically acceptable salt thereof wherein R.sup.1 is methyl or amino; R.sup.6 is phenyl optionally substituted at a substitutable position with one or more radicals selected from the group consisting of halo, C.sub.1 -C.sub.6 alkylthio, C.sub.1 -C.sub.6 alkylsulfonyl, cyano, nitro, C.sub.1 -C.sub.6 haloalkyl, C.sub.1 -C.sub.6 alkyl, hydroxyl, C.sub.1 -C.sub.6 alkenyl, C.sub.1 -C.sub.6 hydroxyalkyl, carboxyl, C.sub.1 -C.sub.6 cyloalalkyl, C.sub.1 -C.sub.6 alkylamico, C.sub.1 -C.sub.6 dialkylamino, C.sub.1 -C.sub.6 alkoxycarbonyl, aminocarbonyl, C.sub.1 -C.sub.6 alkoxy, C.sub.1 -C.sub.6 haloalkoxy, sulfamyl, five or six membered heterocyclic radicals, and amino; R.sup.8 is hydrogen or C.sub.1 -C.sub.6 hyloalkyl; and R.sup.9 C.sub.1 -C.sub.6 alkyl, C.sub.2 -C.sub.6 alkenyl, C.sub.1 -C.sub.6 alkoxycarbonyl (C.sub.1 -C.sub.2) alkyl, N-phenylacetamido, or phenyl (C.sub.1 -C.sub.6) alkyl.

8. The method of claim 7 wherein the compound is selected from compounds, and their pharmaceutically acceptable salts, of the group consisting of 5-(4-fluorophenyl)-1-4-(methylsulfonyl)phenyl)-3-(trifluoromethyl)pyrazole; 4-(4-fluorophenyl)-5-4-(methylsulfonyl)phenyl)-1-phenyl-3-(trifluoromethyl) pyrazole; 4-(5-(4-chlorophenyl)-3-(4-methoxyphenyl)-1H-pyrazol-1-yl)benzenesulfonamid e; 4-(3,5-bis(4-methylphenyl)-1H-pyrazol-1-yl)benzenesulfonamide; 4-(5-(4-chlorophenyl)-3-phenyl-1H-pyrazol-1-yl)benzenesulfonamide; 4-(3,5-bis(4-methoxyphenyl)-1H-pyrazol-1-yl)benzenesulfonamide; 4-(5-(4-chlorophenyl)-3-(4-methylphenyl)-1H-pyrazol-1-pyrazol)benzenesulfon amide; 4-(5-(4-chlorophenyl)-3-(4-nitrophenyl)-1H-pyrazol-1yl)benzenesulfonamide; 4-(5-(4-chlorophenyl)-3-(5-chloro-2-thienyl)-1H-pyrazol-1-yl)benzenesulfona mide; 4-(4-chloro-3,5-diphenyl-1H-pyrazol-1-yl)benzenesulfonamide; 4-[4-chloro-5-(4-chlorophenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]benzenes ulfonamide; 4-[3-cyano-5-(4-fluorophenyl)-1H-pyrazol-1-yl]benzenesulfonamide; 4-[4-chloro-5-phenyl-1H-pyrazol-1-yl]benzenesulfonamide; and 4-[(5-(4-chlorophenyl)-3-(hydroxymethyl)-1H-pyrazol-1-yl]benzenesulfonamide .

9. The method of claim 7 wherein the compound is selected from compounds, and their pharmaceutically acceptable salts, of the group consisting of 1-allyl-4-(4-fluorophenyl)-3-[4-(methysulfonyl)phenyl]-5-(trifluoromethyl)- 1H-pyrazole; 4-[1-ethyl-4-(4-fluorophenyl)-5-(trifluoromethyl)-1H-pyrazol-3-yl]benzenesu lfonamide; N-phenyl-4-(4-fluorophenyl)-3-[4-(methylsulfonyl)phenyl-5-(trifluromethyl)- 1H-pyrazol-1-yl]acetamide; ethyl4-(4-fluorophenyl)-3-[4-(methylsulfonyl)phenyl-5-(trifluoromethyl)-1H- pyrazol-1-yl]acetate; 4-(4-fluorophenyl)-3-4-[(methylsulfonyl)phenyl]-1-(2-phenylethyl)-1H-pyrazo le; 4-(4-fluorophenyl)-3-[4-(methylsulfonyl)phenyl]-1-(2-phenylethyl)-5-(triflu oromethyl)pyrazole; and 1-ethyl-4-(4-fluorophenyl)-3-[4-(methylsulfonyl)phenyl]-5-(trifluoromethyl) -1H-pyrazole.

10. A method of treating familial adenomatous polyps in a subject in need of such treatment, said method comprising administering to the subject a therepeutically-effective amount of a compound which is 4-5-(4-methylphenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl)benzenesulfonamid e.

11. A method of treating familial adenomatous polyps in a subject in need of such treatment, said method comprising admistering to the subject a pharmaceutical composition comprising 4-5-(4-methylphenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl)benzenesulfonamid e together with a pharmaceutically acceptable carrier.

12. A method according to claim 11, wherein the carrier comprises lactose, magnesium stearate, and gelatin.
« Back to Dashboard

For more information try a trial or see the database preview and plans and pricing

How are People Using DrugPatentWatch?

Drugs may be covered by multiple patents or regulatory protections. All trademarks and applicant names are the property of their respective owners or licensors. Although great care is taken in the proper and correct provision of this service, thinkBiotech LLC does not accept any responsibility for possible consequences of errors or omissions in the provided data. The data presented herein is for information purposes only. There is no warranty that the data contained herein is error free. thinkBiotech performs no independent verifification of facts as provided by public sources nor are attempts made to provide legal or investing advice. Any reliance on data provided herein is done solely at the discretion of the user. Users of this service are advised to seek professional advice and independent confirmation before considering acting on any of the provided information. thinkBiotech LLC reserves the right to amend, extend or withdraw any part or all of the offered service without notice.

`abc