Get our Free Patent Expiration Newsletter

Serving leading biopharmaceutical companies globally:

Johnson and Johnson
McKesson
Moodys
Medtronic
Dow
Colorcon

Last Updated: October 19, 2019

DrugPatentWatch Database Preview

Claims for Patent: 8,748,626

See Plans and Pricing

« Back to Dashboard

Summary for Patent: 8,748,626
Title:Oxazole and thiazole compounds as KSP inhibitors
Abstract: Disclosed are new substituted oxazole and thiazole compounds of Formula (I) and pharmaceutically acceptable salts, esters or prodrugs thereof, compositions of the derivatives together with pharmaceutically acceptable carriers, and uses thereof: ##STR00001##
Inventor(s): Barsanti; Paul A. (Pleasant Hill, CA), Ding; Yu (Union City, CA), Han; Wooseok (San Ramon, CA)
Assignee: Novartis AG (Basel, CH)
Application Number:13/640,561
Patent Claims:1. A compound of Formula (I) or a pharmaceutically acceptable salt thereof: ##STR00090## wherein: R.sup.1 is selected from the group consisting of alkyl, branched alkyl, and substituted alkyl; R.sup.2 is selected from the group consisting of hydrogen, alkyl, and substituted alkyl; R.sup.3 is selected from the group consisting of -L.sub.1-A.sup.1, wherein L.sup.1 is selected from the group consisting of --C(O)--, --C(S)--, --S(O)--, and --S(O).sub.2-- and A.sup.1 is selected from the group consisting of alkyl, substituted alkyl, alkoxy, substituted alkoxy, aryl, substituted aryl, heteroaryl, substituted heteroaryl, cycloalkyl, substituted cycloalkyl, heterocycloalkyl, substituted heterocycloalkyl, and NR.sup.8R.sup.9; R.sup.4 is selected from the group consisting of hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, and substituted alkynyl, and optionally substituted pyrrolidinyl; X is O or S; R.sup.6 is selected from the group consisting of cycloalkyl, heterocycloalkyl, aryl, and heteroaryl, all of which may be optionally substituted with --(R.sup.10).sub.m where R.sup.10 is as defined herein, m is 1, 2, 3, or 4, and each R.sup.10 may be the same or different when m is 2, 3, or 4; R.sup.7 is -L.sup.2-A.sup.2 wherein L.sup.2 is C.sub.1-C.sub.5 alkylene and A.sup.2 is selected from the group consisting of aryl, substituted aryl, heteroaryl, substituted heteroaryl, cycloalkyl, substituted cycloalkyl, heterocycloalkyl, and substituted heterocycloalkyl; R.sup.8 is selected from the group consisting of hydrogen and alkyl; R.sup.9 is selected from the group consisting of hydrogen, hydroxy, alkyl, substituted alkyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, cycloalkyl, substituted cycloalkyl, heterocycloalkyl, and substituted heterocycloalkyl; or R.sup.8 and R.sup.9 together with the nitrogen atom pendent thereto join to form a heterocycloalkyl or substituted heterocycloalkyl; R.sup.10 is selected from the group consisting of cyano, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, --CF.sub.3, alkoxy, substituted alkoxy, halo, and hydroxy; and R.sup.11 is selected from the group consisting of hydrogen, alkyl, substituted alkyl, --SO.sub.2alkyl, and --SO.sub.2substituted alkyl.

2. A compound of claim 1, wherein R.sup.1 is alkyl.

3. A compound of claim 1, wherein R.sup.2 is C.sub.1-4 alkyl or H.

4. A compound of claim 3, wherein R.sup.2 is H.

5. A compound of claim 4, wherein R.sup.1 is i-propyl, or t-butyl.

6. A compound of claim 5, wherein R.sup.3 is selected from -L.sup.1-A.sup.1, wherein L.sup.1 is selected from the group consisting of --C(O)--, --C(S)--, --S(O)--, and --S(O).sub.2-- and A.sup.1 is selected from the group consisting of alkyl, and substituted alkyl.

7. A compound of claim 6, wherein R.sup.3 is selected from -L.sup.1-A.sup.1, wherein L.sup.1 is --C(O)--, and A.sup.1 is substituted alkyl.

8. A compound of claim 7, wherein R.sup.4 is selected from the group consisting of hydrogen, alkyl, and substituted alkyl.

9. A compound of claim 8, wherein R.sup.4 is substituted alkyl or --CH.sub.2-fluoropyrrolidinyl.

10. A compound of claim 9, wherein R.sup.3 is selected from -L.sup.1-A.sup.1, wherein L.sup.1 is --C(O)--, and A.sup.1 is --CH(CH.sub.3)OH.

11. A compound of claim 10, wherein R.sup.4 is --(CH.sub.2).sub.2--CH(CH.sub.2F)NH.sub.2, or --CH.sub.2-3-fluoropyrrolidinyl.

12. A compound of claim 11, wherein R.sup.6 is selected from the group consisting of aryl, and heteroaryl, all of which are optionally substituted with --(R.sup.10).sub.m where m is 1, 2, 3, or 4, and each R.sup.10 may be the same or different when m is 2, 3, or 4; and R.sup.7 is -L.sup.2-A.sup.2 wherein L.sup.2 is C.sub.1-C.sub.2 alkylene and A.sup.2 is selected from the group consisting of aryl, and heteroaryl.

13. A compound of claim 12, wherein R.sup.6 represents aryl substituted with two R.sup.10 groups.

14. A compound of claim 12, wherein R.sup.6 represents phenyl substituted with two fluorine atoms.

15. A compound of claim 13, wherein R.sup.7 represents --CH.sub.2-aryl.

16. A compound of claim 14 wherein R.sup.7 represents --CH.sub.2-phenyl.

17. A compound selected from ##STR00091## ##STR00092##

18. A pharmaceutical composition comprising a therapeutically effective amount of a compound of claim 1 and a pharmaceutically acceptable carrier.

19. The composition of claim 18 further comprising at least one additional agent for the treatment of cancer.

20. The composition of claim 19, wherein the additional agent for the treatment of cancer is selected from the group consisting of irinotecan, topotecan, gemcitabine, imatinib, 5-fluorouracil, leucovorin, carboplatin, cisplatin, docetaxel, paclitaxel, tezacitabine, cyclophosphamide, vinca alkaloids, anthracyclines, rituximab, and trastuzumab.

21. A method of treating a colon cancer or breast cancer mediated, at least in part, by kinesin spindle protein (KSP) in a mammalian patient in need of such treatment comprising administering to the mammalian patient a therapeutically effective amount of a compound of claim 1.

22. A method for inhibiting KSP in a mammalian patient, wherein said method comprises administering to the patient an effective KSP-inhibiting amount of a compound of claim 1.

23. A compound of claim 1 selected from: ##STR00093##

24. A method of treating a colon cancer or breast cancer mediated, at least in part, by KSP in a mammalian patient in need of such treatment, comprising administering to the mammalian patient a therapeutically effective amount of the pharmaceutical composition of claim 18.

Summary for Patent:   Start Trial

PCT Information
PCT FiledApril 13, 2011PCT Application Number:PCT/EP2011/055855
PCT Publication Date:October 20, 2011PCT Publication Number:WO2011/128388

Details for Patent 8,748,626

Applicant Tradename Biologic Ingredient Dosage Form BLA Number Approval Date Patent No. Assignee Estimated Patent Expiration Status Orphan Source
Genentech RITUXAN rituximab VIAL 103705 001 1997-11-26   Start Trial Novartis AG (Basel, CH) 2036-04-30 RX search
Genentech HERCEPTIN trastuzumab VIAL; INTRAVENOUS 103792 001 1998-09-25   Start Trial Novartis AG (Basel, CH) 2036-04-30 RX Orphan search
>Applicant >Tradename >Biologic Ingredient >Dosage Form >BLA >Number >Approval Date >Patent No. >Assignee >Estimated Patent Expiration >Status >Orphan >Source

Make Better Decisions: Try a trial or see plans & pricing

Serving leading biopharmaceutical companies globally:

Harvard Business School
Medtronic
Baxter
Express Scripts
McKinsey
Colorcon

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.