Claims for Patent: 8,691,852

Summary for Patent: 8,691,852

Title:	Amino nicotinic and isonicotinic acid derivatives as DHODH inhibitors
Abstract:	The present disclosure relates to compounds of formula (I): ##STR00001## or a pharmaceutically acceptable salt or N-oxide thereof. The present disclosure also relates to pharmaceutical compositions comprising the compounds of formula (I), and to their methods of use in therapy.
Inventor(s):	Castro Palomino Laria; Julio Cesar (Barcelona, ES), Erra Sola; Montserrat (Barcelona, ES), Lozoya Toribio; Maria Estrella (Barcelona, ES), Navarro Romero; Eloisa (Barcelona, ES)
Assignee:	Amirall, S.A. (Barcelona, ES)
Application Number:	13/567,437
Patent Claims:	1. A compound of formula (I) ##STR00072## wherein the G.sup.1 groups represent a CR.sup.c group; G.sup.2 is a CR.sup.d group; R.sup.1 is chosen from hydrogen atoms, halogen atoms, C.sub.1-4 alkyl groups, and C.sub.3-8 cycloalkyl groups; R.sup.2 is chosen from hydrogen atoms, halogen atoms, and C.sub.1-4 alkyl groups; R.sup.a is chosen from hydrogen atoms, halogen atoms, and C.sub.1-4 alkyl groups; R.sup.b is chosen from hydrogen atoms and halogen atoms; and R.sup.c is chosen from hydrogen atoms and C.sub.1-4 alkyl groups; R.sup.d is chosen from hydrogen atoms, (OCF.sub.3), and (OCHF.sub.2); G.sup.3 is a nitrogen atom; G.sup.4 is a CH group; and M is a hydrogen atom or an pharmaceutically acceptable cation; or a pharmaceutically acceptable salt or N-oxide thereof. 2. The compound according to claim 1, wherein R.sup.1 is chosen from hydrogen atoms, bromine atoms, chlorine atoms, methyl, and cyclopropyl groups. 3. The compound according to claim 1, wherein each R.sup.c is independently chosen from hydrogen atoms, and methyl groups. 4. The compound according to claim 1, wherein R.sup.d is chosen from hydrogen atoms. 5. The compound according to claim 1, wherein R.sup.a is chosen from hydrogen atoms, fluorine atoms, chlorine atoms, and methyl groups. 6. The compound according to claim 5, wherein R.sup.b is chosen from hydrogen atoms and fluorine atoms. 7. The compound according to claim 1, wherein R.sup.2 is chosen from hydrogen atoms, methyl groups, and halogen atoms. 8. The compound according to claim 7, wherein R.sup.2 is chosen from hydrogen atoms, methyl groups, and chlorine atoms. 9. The compound according to claim 1, wherein R.sup.a is a fluorine atom, R.sup.b is chosen from hydrogen atoms and fluorine atoms, and R.sup.1 is chosen from hydrogen atoms, bromine atoms, chlorine atoms, methyl groups, and cyclopropyl groups. 10. The compound according to claim 9, wherein G.sup.2 is chosen from C C(OCF.sub.3) and C(OCHF.sub.2). 11. The compound according to claim 9, wherein R.sup.c is a hydrogen atom, R.sup.d is chosen from C(OCF.sub.3) and C(OCHF.sub.2), and R.sup.2 is a hydrogen atom. 12. The compound according to claim 11, wherein R.sup.b is a fluorine atom. 13. The compound according to claim 1, chosen from: 2-(2-Methyl-3'-(trifluoromethoxy)biphenyl-4-ylamino)nicotinic acid, 2-(3-Chloro-3'-(trifluoromethoxy)biphenyl-4-ylamino)nicotinic acid, 2-(3-Methyl-3'-(trifluoromethoxy)biphenyl-4-ylamino)nicotinic acid, 2-(3'-(Difluoromethoxy)-3-fluorobiphenyl-4-ylamino)nicotinic acid, 2-(5-Fluoro-2-methyl-3'-(trifluoromethoxy)biphenyl-4-ylamino)nicotinic acid, 2-(2'-chloro-3,5-difluorobiphenyl-4-ylamino)nicotinic acid, 2-(3,5-difluoro-2-methylbiphenyl-4-ylamino)nicotinic acid, 5-cyclopropyl-2-(3,5-difluoro-3'-(trifluoromethoxy)biphenyl-4-ylamino)nic- otinic acid, 2-(2'-chloro-3,5-difluorobiphenyl-4-ylamino)-5-cyclopropylnicotinic acid, 2-(2'-chloro-3,5-difluoro-2-methylbiphenyl-4-ylamino)nicotinic acid, 5-chloro-2-(3,5-difluorobiphenyl-4-ylamino)nicotinic acid, 5-chloro-2-(2'-chloro-3,5-difluorobiphenyl-4-ylamino)nicotinic acid, 2-(3,5-difluoro-2'-methylbiphenyl-4-ylamino)nicotinic acid, 2-(3-Fluoro-3'(trifluoromethoxy)biphenyl-4-ylamino)nicotinic acid, 2-(3,5-Difluoro-3'(trifluoromethoxy)biphenyl-4-ylamino)nicotinic acid, 5-Bromo-2-(3-fluoro-3'-(trifluoromethoxy)biphenyl-4-ylamino)nicotinic acid, 2-(3-Fluoro-3'-(trifluoromethoxy)biphenyl-4-ylamino)-5-methylnicoti- nic acid; or a pharmaceutically acceptable salt or a N-oxide thereof. 14. A method of treating a pathological condition or disease, comprising administering to a mammal in need thereof, an effective amount of a compound according to claim 1, wherein the pathological condition or disease is chosen from rheumatoid arthritis, psoriatic arthritis, and multiple sclerosis. 15. A method of treating a pathological condition or disease, comprising administering to a mammal in need thereof an effective amount of a compound according to claim 1, wherein the pathological condition or disease is chosen from ankylosing spondilytis, Wegener's granulomatosis, systemic lupus erythematosus, psoriasis and sarcoidosis. 16. A pharmaceutical composition comprising a compound according to claim 1 and a pharmaceutically acceptable diluent or carrier. 17. A composition comprising (i) a compound according to claim 1; and (ii) another compound chosen from: a) Anti-TNF-alpha monoclonal antibodies; b) TNF-alpha Antagonists; c) Calcineurin (PP-28) Inhibitors/INS Expression Inhibitors; d) IL-1 Receptor Antagonists; e) Anti-CD20 monoclonal antibodies; f) p38 Inhibitors; g) NF-kappa8 (NFK8) Activation Inhibitors; and h) Dihydrofolate Reductase (DHFR) Inhibitors. 18. The composition according to claim 17, wherein: a) the Anti-INF-alpha monoclonal antibody is chosen from Infliximab, Certolizumab pegol, Golimumab, Adalimumab and AME-527; b) the INF-alpha Antagonist is chosen from Etanercept, Lenercept, Onercept and Pegsunercept; c) the Calcineurin (PP-28) Inhibitor INS Expression Inhibitor is chosen from cyclosporine A, Tacrolimus and ISA-247; d) the IL-1 Receptor Antagonist is chosen from Anakinra and AMG-719; the Anti-CD20 monoclonal antibody is chosen from Rituximab, Ofatumumab, Ocrelizumab and TRU-015; f) the p38 Inhibitor is chosen from AMG-548, ARRY-797, Chlormethiazole edisylate, Doramapimod, PS-540446, 38-203580, S8-242235, S8-235699, S8-281832, S8-681323, 38-856553, KC-706, LE0-1606, LE0-15520, SC-80036, SD-06, RWJ-67657, R0-3201195, RO-4402257, AVE-9940, SCI0-323, SCI0-469, TA-5493, and VX-745 and VX-702; g) the NF-kappaB (NFKB) Activation Inhibitor is chosen from Sulfasalazine and Iguratimod; and the Dihydrofolate Reductase (DHFR) Inhibitor is chosen from Methrotexate, Aminopterin and CH-1504.

Details for Patent 8,691,852

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Genentech, Inc.	RITUXAN	rituximab	Injection	103705	11/26/1997		2026-12-22
Idec Pharmaceuticals Corp.	RITUXAN	rituximab	Injection	103737	02/19/2002		2026-12-22
Janssen Biotech, Inc.	REMICADE	infliximab	For Injection	103772	08/24/1998		2026-12-22
Immunex Corporation	ENBREL	etanercept	For Injection	103795	11/02/1998		2026-12-22