Claims for Patent: 8,673,919

Summary for Patent: 8,673,919

Title:	Dihydropyridin sulfonamides and dihydropyridin sulfamides as MEK inhibitors
Abstract:	This invention concerns N-(ortho phenylamino dihydropyridyl)sulfonamides and N-(ortho phenylamino dihydropyridyl), N\'-alkyl sulfamides which are inhibitors of MEK and are useful in the treatment of cancer and other hyperproliferative diseases.
Inventor(s):	Vernier; Jean-Michel (San Diego, CA), Kim; Hong Woo (San Diego, CA), Hitchcock; Marion (Berlin, DE), Yan; Shunqi (Irvine, CA)
Assignee:	Ardea Biosciences, Inc. (San Diego, CA)
Application Number:	13/259,239
Patent Claims:	1. A compound of formula I, or a pharmaceutically acceptable salt, thereof: ##STR00101## wherein B is H, C.sub.1-C.sub.6 alkyl or C.sub.2-C.sub.6 alkenyl; wherein said C.sub.1-C.sub.6 alkyl is optionally substituted with one or two groups independently selected from the group consisting of hydroxy, alkoxy, oxy, amine and substituted amine; A and A' are each independently H, C.sub.1-C.sub.6 alkyl, or C.sub.2-C.sub.6 alkenyl; wherein each C.sub.1-C.sub.6 alkyl is optionally substituted with one or two groups independently selected from the group consisting of hydroxy, alkoxy, oxy, amine and substituted amine; or A and A' together with the carbon atom to which they are attached, form a cyclopropyl, cyclobutyl, or cyclopentyl group, wherein each cyclopropyl, cyclobutyl, or cyclopentyl group is optionally substituted with one or two groups independently selected from the group consisting of methyl, hydroxy, and halogen; X and Y are each independently halogen, methyl, SCH.sub.3 or trifluoromethyl; R.sub.1 is H, C.sub.1-C.sub.6 alkyl, C.sub.3-C.sub.6 cycloalkyl, C.sub.2-C.sub.6 alkenyl, C.sub.5-C.sub.6 cycloalkenyl or C.sub.2-C.sub.6 alkynyl; wherein each alkyl, cycloalkyl, alkenyl, cycloalkenyl or alkynyl group is optionally substituted with 1-3 substituents independently selected from the group consisting of halogen, hydroxy, C.sub.1-C.sub.4 alky, C.sub.1-C.sub.4 alkoxy, cyano, cyanomethyl, nitro, azido, trifluoromethyl difluoromethoxy and phenyl, and one or two ring carbon atoms of said C.sub.3-C.sub.6 cycloalkyl group are optionally replaced with, independently, O, N, or S; or R.sub.1 is a 5 or 6-atom heterocyclic group, which group is saturated, unsaturated, or aromatic, containing 1-5 heteroatoms independently selected from the group consisting of O, N, and S, which heterocyclic group is optionally substituted with 1-3 substituents independently selected from the group consisting of halogen, hydroxy, C.sub.1-C.sub.4 alky, C.sub.1-C.sub.4 alkoxy, cyano, cyanomethyl, nitro, azido, trifluoromethyl difluoromethoxy and phenyl; and R.sub.2 is H, halogen, hydroxy, azido, cyano, cyanomethy, C.sub.1-C.sub.6 alkyl, C.sub.3-C.sub.6 cycloalkyl, C.sub.2-C.sub.6 alkenyl, C.sub.5-C.sub.6 cycloalkenyl or C.sub.2-C.sub.6 alkynyl, wherein each alkyl, cycloalkyl, alkenyl cycloalkenyl or alkynyl group is optionally substituted with 1-3 substituents independently selected from the group consisting of halogen, hydroxy, C.sub.1-C.sub.4 alkoxy, cyano, cyanomethyl, nitro, azido, trifluoromethyl and phenyl. 2. The compound of claim 1, where X and Y are both halogen. 3. The compound of claim 1, where X is F and Y is Br or I. 4. The compound of claim 1, where one or both of X and Y are methyl, SCH.sub.3 or trifluoromethyl. 5. The compound of claim 1, where A and A' together with the carbon atom to which they are attached, form a cyclopropyl, cyclobutyl, or cyclopentyl group, wherein each cyclopropyl, cyclobutyl, or cyclopentyl group is optionally substituted with one or two groups independently selected from the group consisting of methyl, hydroxy, and halogen. 6. The compound of claim 5, where R.sub.1 is H, C.sub.1-C.sub.6 alkyl, or C.sub.3-C.sub.6 cycloalkyl. 7. The compound of claim 6, where R.sub.2 is H, halogen, or C.sub.1-C.sub.3 alkyl. 8. The compound of claim 1, where R.sub.1 is furyl, imidazolyl, imidazolinyl, imidazolidinyl, dihydrofuryl, tetrahydrofuryl, pyrrolyl, pyrrolidinyl, pyrrolinyl, morpholyl, piperidinyl, pyridyl, or thienyl. 9. The compound of claim 5, where R.sub.1 is furyl, imidazolyl, imidazolinyl, imidazolidinyl, dihydrofuryl, tetrahydrofuryl, pyrrolyl, pyrrolidinyl, pyrrolinyl, morpholyl, piperidinyl, pyridyl, or thienyl. 10. The compound of claim 1, where R.sub.1 is C.sub.2-C.sub.6 alkenyl or C.sub.2-C.sub.6 alkynyl, optionally substituted with 1-3 substituents independently selected from the group consisting of halogen, hydroxy, C.sub.1-C.sub.4 alky, C.sub.1-C.sub.4 alkoxy, cyano, cyanomethyl, nitro, azido, trifluoromethyl difluoromethoxy and phenyl. 11. The compound of claim 5, where R.sub.1 is C.sub.2-C.sub.6 alkenyl or C.sub.2-C.sub.6 alkynyl, optionally substituted with 1-3 substituents independently selected from the group consisting of halogen, hydroxy, C.sub.1-C.sub.4 alky, C.sub.1-C.sub.4 alkoxy, cyano, cyanomethyl, nitro, azido, trifluoromethyl difluoromethoxy and phenyl. 12. The compound of claim 1, where B is C.sub.1-C.sub.6 alkyl, unsubstituted or substituted with one or two hydroxy groups. 13. The compound of claim 5, where B is C.sub.1-C.sub.6 alkyl, unsubstituted or substituted with one or two hydroxy groups. 14. A compound, which is one of the following compounds ##STR00102## ##STR00103## ##STR00104## ##STR00105## ##STR00106## or a pharmaceutically acceptable salt, thereof. 15. A pharmaceutical composition comprising a compound of formula (I), or a salt thereof, according to claim 1, and a pharmaceutically acceptable diluent or carrier. 16. A pharmaceutical combination comprising: one or more compounds of formula (I), or a salt thereof, according to claim 1; and one or more agents selected from the group consisting of: a taxane, Docetaxel, Paclitaxel, Taxol; an epothilone, Ixabepilone, Patupilone, Sagopilone; Mitoxantrone; Predinisolone; Dexamethasone; Estramustin; Vinblastin; Vincristin; Doxorubicin; Adriamycin; Idarubicin; Daunorubicin; Bleomycin; Etoposide; Cyclophosphamide; Ifosfamide; Procarbazine; Melphalan; 5-Fluorouracil; Capecitabine; Fludarabine; Cytarabine; Ara-C; 2-Chloro-2'-deoxyadenosine; Thioguanine; an anti-androgen, Flutamide, Cyproterone acetate, Bicalutamide; Bortezomib; a platinum derivative, Cisplatin, Carboplatin; Chlorambucil; Methotrexate; and Rituximab. 17. The compound of claim 1, or a pharmaceutically acceptable salt thereof. 18. The compound of claim 14, or a pharmaceutically acceptable salt thereof. 19. A pharmaceutical composition comprising a compound according to claim 14 and a pharmaceutically acceptable carrier. 20. The compound of claim 14, which is one of the following compounds ##STR00107## ##STR00108## ##STR00109## 21. The compound of claim 14, which is one of the following compounds ##STR00110## ##STR00111## ##STR00112## ##STR00113## 22. The compound of claim 14, which is one of the following compounds ##STR00114## ##STR00115## ##STR00116## ##STR00117##

Details for Patent 8,673,919

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Genentech, Inc.	RITUXAN	rituximab	Injection	103705	11/26/1997		2029-03-27
Idec Pharmaceuticals Corp.	RITUXAN	rituximab	Injection	103737	02/19/2002		2029-03-27
Genentech, Inc.	RITUXAN HYCELA	rituximab and hyaluronidase human	Injection	761064	06/22/2017		2029-03-27