.

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

Claims for Patent: 6,534,524

« Back to Dashboard

Claims for Patent: 6,534,524

Title: Indazole compounds and pharmaceutical compositions for inhibiting protein kinases, and methods for their use
Abstract:Indazole compounds that modulate and/or inhibit the activity of certain protein kinases are described. These compounds and pharmaceutical compositions containing them are capable of mediating tyrosine kinase signal transduction and thereby modulate and/or inhibit unwanted cell proliferation. The invention is also directed to the therapeutic or prophylactic use of pharmaceutical compositions containing such compounds, and to methods of treating cancer and other disease states associated with unwanted angiogenesis and/or cellular proliferation, such as diabetic retinopathy, neovascular glaucoma, rheumatoid arthritis, and psoriasis, by administering effective amounts of such compounds.
Inventor(s): Kania; Robert Steven (San Diego, CA), Bender; Steven Lee (Oceanside, CA), Borchardt; Allen J. (San Diego, CA), Cripps; Stephan James (San Diego, CA), Hua; Ye (La Jolla, CA), Johnson; Michael David (San Diego, CA), Johnson, Jr.; Theodore Otto (San Diego, CA), Luu; Hiep The (San Diego, CA), Palmer; Cynthia Louise (San Diego, CA), Reich; Siegfried Heinz (Solana Beach, CA), Tempczyk-Russell; Anna Marie (Ramona, CA), Teng; Min (San Diego, CA), Thomas; Christine (West Borough, MA), Varney; Michael David (Solana Beach, CA), Wallace; Michael Brennan (San Diego, CA), Collins; Michael Raymond (San Diego, CA)
Assignee: Agouron Pharmaceuticals, Inc. (La Jolla, CA)
Application Number:09/983,783
Patent Claims: 1. A compound of the Formula I: ##STR1261##

wherein: R.sup.1 is an unsubstituted aryl or substituted or unsubstituted heteroaryl, or a group of the formula CH.dbd.CH--R.sup.3 or CH.dbd.N--R.sup.3 where R.sup.3 is a substituted or unsubstituted alkyl, alkenyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; and R.sup.2 is a substituted or unsubstituted aryl, heteroaryl, or Y--X, where Y is O, S, C.dbd.CH.sub.2, C.dbd.O, S.dbd.O, SO.sub.2, alkylidene, or N--(C.sub.1 -C.sub.8 alkyl), and X is substituted or unsubstituted Ar, heteroaryl, NH--(alkyl), NH--(cycloalkyl), NH--(heterocycloalkyl), NH(aryl), NH(heteroaryl), NH--(alkoxyl), or NH--(dialkylamide), where Ar is aryl;

or a pharmaceutically acceptable prodrug, pharmaceutically active metabolite, or pharmaceutically acceptable salt thereof.

2. A compound according to claim 1, wherein: R.sup.1 is a group of the formula CH.dbd.CHR--R.sup.3, where R.sup.3 is an unsubstituted heteroaryl; and R.sup.2 is Y--X, where Y is S, and X is a substituted Ar;

or a pharmaceutically acceptable prodrug, pharmaceutically active metabolite, or pharmaceutically acceptable salt thereof.

3. A compound of the Formula I(a): ##STR1262##

wherein: R.sup.1 is a substituted or unsubstituted aryl or heteroaryl, or a group of the formula CH.dbd.CH--R.sup.3 or CH.dbd.N--R.sup.3, where R.sup.3 is a substituted or unsubstituted alkyl, alkenyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; and R.sup.1 is a substituted or unsubstituted aryl or Y--Ar, where Y is O, S, C.dbd.CH.sub.2 C.dbd.O, S.dbd.O, SO.sub.2, CH.sub.2, CHCH.sub.3, NH, or N--(C.sub.1 -C.sub.8 alkyl), and Ar is a substituted or unsubstituted aryl;

or a pharmaceutically acceptable prodrug, pharmaceutically active metabolite, or pharmaceutically acceptable salt thereof.

4. A compound of the Formula II: ##STR1263##

wherein: R.sup.1 is a substituted or unsubstituted aryl or heteroaryl, or a group of the formula CH.dbd.CH--R.sup.3 or CH.dbd.N--R.sup.3, where R.sup.3 is a substituted or unsubstituted alkyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; R.sup.4 and R.sup.7 are each independently hydrogen, OH, halo, C.sub.1 -C.sub.8 alkyl, C.sub.1 -C.sub.8 alkoxy, C.sub.1 -C.sub.8 alkenyl, aryloxy, thioaryl, CH.sub.2 --OH, CH.sub.2 --O--(C.sub.1 -C.sub.8 alkyl), CH.sub.2 --O-aryl, CH.sub.2 --S--(C.sub.1 -C.sub.8 alkyl), or CH.sub.2 --S-aryl; and R.sup.5 and R.sup.6 are each independently hydrogen, OH, halo, Z-alkyl, Z-aryl, or Z--CH.sub.2 CH.dbd.CH.sub.2, where Z is O, S, NH, or CH.sub.2 and the alkyl and aryl moiety of Z-alkyl and Z-aryl are each optionally substituted;

or a pharmaceutically acceptable prodrug, pharmaceutically active metabolite, or pharmaceutically acceptable salt thereof.

5. A compound, pharmaceutically acceptable prodrug, pharmaceutically active metabolite, or pharmaceutically acceptable salt according to claim 4, wherein: R.sup.1 is a substituted or unsubstituted bicyclic heteroaryl, or a group of the formula CH.dbd.CH--R.sup.3 where R.sup.3 is a substituted or unsubstituted aryl or heteroaryl; R.sup.4 and R.sup.7 are each independently hydrogen or C.sub.1 -C.sub.8 alkyl; and R.sup.5 and R.sup.6 are each independently halo, Z-alkyl, or Z--CH.sub.2 CH.dbd.CH.sub.2, where Z is O or S and alkyl is optionally substituted.

6. A compound of the Formula IV: ##STR1264##

wherein: R.sup.1 is a substituted or unsubstituted aryl or heteroaryl, or a group of the formula CH.dbd.CH--R.sup.3 or CH.dbd.N--R.sup.3, where R.sup.3 is a substituted or unsubstituted alkyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; Y is O, S, C.dbd.CH.sub.2, C.dbd.O, S.dbd.O, SO.sub.2, CH.sub.2, CHCH.sub.3, NH, or N--(C.sub.1 -C.sub.8 alkyl); R.sup.9 is a substituted or unsubstituted alkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, alkoxyl, aryloxyl, cycloalkoxyl, NH--(C.sub.1 -C.sub.8 alkyl), NH--(aryl), NH--(heteroaryl), N.dbd.CH--alkyl), NH(C.dbd.O)R.sup.11, or NH.sub.2, where R.sup.11 is independently selected from hydrogen, substituted or unsubstituted alkyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl; and R.sup.10 is independently selected from hydrogen, halogen, and lower-alkyl;

or a pharmaceutically acceptable prodrug, pharmaceutically active metabolite, or pharmaceutically acceptable salt thereof.

7. A compound, pharmaceutically acceptable prodrug, pharmaceutically active metabolite, or pharmaceutically acceptable salt according to claim 6, wherein: R.sup.1 is a group of the formula CH.dbd.CH--R.sup.3 where R.sup.3 is a substituted or unsubstituted aryl or heteroaryl; Y is S or NH; R.sup.9 is a substituted or unsubstituted alkyl, alkoxyl, or NH--(heteroaryl); and R.sup.10 is independently selected from hydrogen, halogen, and lower-alkyl.

8. A compound, pharmaceutically acceptable prodrug, pharmaceutically active metabolite, or pharmaceutically acceptable salt according to claim 7, wherein: R.sup.1 is a group of the formula CH.dbd.CH--R.sup.3, where R.sup.3 is an unsubstituted heteroaryl; Y is S; R.sup.9 is an unsubstituted alkyl; and R.sup.10 is hydrogen.

9. A compound, pharmaceutically acceptable prodrug, pharmaceutically active metabolite, or pharmaceutically acceptable salt, selected from: ##STR1265## ##STR1266##

10. A pharmaceutical composition comprising: (a) a therapeutically effective amount of a compound, pharmaceutically acceptable prodrug, pharmaceutically active metabolite, or pharmaceutically acceptable salt of claim 1; and (b) a pharmaceutically acceptable carrier, diluent, or vehicle therefor.

11. A method of treating a mammalian disease condition mediated by protein kinase activity, comprising administering to a mammal in need thereof a therapeutically effective amount of a compound, pharmaceutically acceptable prodrug, pharmaceutically active metabolite, or pharmaceutically acceptable salt as claimed in claim 1.

12. A method according to claim 11, wherein the mammalian disease condition is associated with tumor growth, cell proliferation, or angiogenesis.

13. A method of modulating the activity of a protein kinase receptor, comprising contacting the kinase receptor with an effective amount of a compound, pharmaceutically acceptable prodrug, pharmaceutically active metabolite, or pharmaceutically acceptable salt as claimed in claim 1.

14. A method according to claim 13, wherein the protein kinase receptor is a VEGF receptor.
« Back to Dashboard

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

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