Synergistic combinations of vr-1 antagonists and cox-2 inhibitors

A synergistic combination according to any preceding claim, wherein the vanilloid receptor VR-1 antagonist is selected from a compound according to Formula (I):

• wherein
• R1 and R2 together are —NH—C(SR6)═N—C(O)—, —NR7—C(R8)═N—C(O)—, —N═C(SR9)—NR10—C(O)—, —NR11—X—NR12C(O)—, —NH—X—NH—, —NH—X—N═C(R13)—, —NH—X—NH—CH2—, —N═Z—NH—, —N═Z—NH—CH2—, —N═Z—NH—C(O)— and —N═Z—N═C(R14)—, wherein X is C(O), C(S) or C(O)—C(O);
• Z is N or CR15, R6 is C1-C4alkyl;
• R7 and R8 are each independently hydrogen, C1-C4alkyl, C3-C8cycloalkyl or form together with the adjacent atoms a 5 or 6 membered heterocyclic ring;
• R9 and R10 together are C1-C4alkylene;
• R11 is hydrogen;
• C1-C4alkyl;
• C1-C4alkyl substituted by C(O)OC1-C4alkyl;
• or phenyl substituted by C1-C4alkyl;
• R12 is hydrogen, NH2;
• C1-C4alkyl;
• or phenyl substituted by C1-C4alkyl;
• R13 is hydrogen, halogen, NH2 or C1-C4alkoxy;
• R14 is hydrogen, hydroxy, halogen, NH2, C1-C4alkyl or C1-C4alkoxy;
• and
• R15 is hydrogen, halogen, C1-C4alkyl, C1-C4alkoxy or SCH2C(O)OC(CH3)3;
• R3 is hydrogen;
• OH;
• CN;
• C1-C6alkyl;
• phenyl;
• or C(O)OC1-C4alkyl;
• R4 is hydrogen;
• halogen;
• NH2;
• CN;
• C1-C6alkyl;
• C1-C6alkyl substituted by OH;
• phenyl;
• phenyl substituted by OH, halogen, C1-C6alkyl, C1-C6haloalkyl or C1-C6alkoxy;
• benzyl;
• benzoyl substituted by OH;
• or C(O)OC1-C6alkyl;
• 5 or 6 membered aromatic or aliphatic heterocyclic ring;
• R5 is hydrogen;
• OH;
• NH2;
• halogen;
• C1-C6alkyl;
• C1-C6alkyl substituted by halobenzyl;
• C3-C6cycloalkyl;
• phenyl;
• pyridinyl;
• NHC1-C4alkyl;
• or N═CHN(C1-C4alkyl)2;
• with the proviso that compounds of formula I are not pyrido[3,2-d]pyrimidine-2,4(1H,3H)-dione and 6-chloro-2-methyl-4-oxo-pyrido[3,2-d]pyrimidine;
• in free base or acid addition salt form;
• and
• a compound according to formula (II):
• wherein
• R1 is C1-C6alkyl, (C1-C6alkyl)C1-C6alkyl, di-(C1-C6alkyl)C1-C6alkyl, C3-C6cycloalkyl, (C1-C6alkyl)amino or di-(C1-C6alkyl)amino;
• each R2, independently, is halogen, C1-C6alkyl, halogen-substituted C1-C6alkyl, hydroxyC1-C6alkyl, cyano or a group —C(═O)—R2a, where R2a is C1-C6alkyl;
• R3 is hydrogen, halogen, C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, hydroxy, hydroxy-substituted C1-C6alkyl, C1-C6alkoxy, C3-C6cycloalkyl, cyano, —C(═O)H, phenyl, (C3-C6cycloalkyl)C1-C6alkoxy, (C1-C6alkoxycarbonylamino)C1-C6alkoxy or (C1-C6alkylcarbonylamino)C1-C6alkoxy;
• R4 is hydroxy, esterified hydroxy, etherified hydroxy, amino, (C1-C6alkyl)amino, a group
• or a group,
• where R4a is C1-C6alkyl or halogen-substituted C1-C6alkyl, or a group
• where R4b is benzyl or phenylethyl;
• R5 is hydrogen or hydroxy;
• and
• m is 1 or 2,
• in free form or in salt form.