Patent HU-0500878-A2 (HU)
Title: Amide derivatives as ccr3 receptor ligands, process for producing them, pharmaceutical compositions containing them and their use and intermediates
Inventor: PAPPNE BEHR AGNES
IPC: C07D263/54
Filed: 2005-09-22
Abstract: Amino alkyl amide derivatives and their salts, solvates and their isomers are new. Amino alkyl amide derivatives of formula Ar 1-X-N(R 1)-Y-N(R 2)-C(=O)-Z'-Ar 2 and their salts, solvates and their isomers are new. Ar 1phenyl (optionally substituted by halogen); X,Y : straight 1-4C alkylene (optionally substituted by straight or branched 1-4C alkyl); Z' : straight 2-4C alkylene or alkenylene (both optionally substituted by straight or branched 1-4C alkyl) or valence bond; R 1,R 2hydrogen atom or straight or branched 1-4C alkyl; Ar 2phenyl-, thienyl- or furyl (all optionally substituted by straight or branched 1-4C alkyl or alkoxy, hydroxyl, amino (optionally mono- or di-substituted by straight or branched 1-4C alkyl), trifluoromethyl, cyano, 1-2C alkylenedioxy or halogen atom), 5- or 6-membered heterocyclic ring (containing 1 - 3 nitrogen atoms, or 2 nitrogen atoms and 1 oxygen atom, or 1 nitrogen atom and 1 oxygen atom, or 1 nitrogen atom and 1 sulfur atom and optionally substituted by straight or branched 1-4C alkyl or alkoxy, halogen atom, nitro, cyano, carboxyl, phenyl (optionally substituted by straight or branched 1-4C alkyl, halogen atom or benzyloxy), oxo, NR 1 0R 1 1, CONR 1 0R 1 1 or SO 2NR 1 0R 1 1), the benzologs of these 5- or 6-membered heterocycle (in which the benzene ring is optionally substituted by T 1, trifluoromethyl, nitro, 1-2C alkylenedioxy or sulfonyl) or 5- or 6-membered heterocyclic ring (containing 1 - 3 nitrogen atoms, or 1 nitrogen atom and 1 oxygen atom, or 1 nitrogen atom and 1 sulfur atom and condensed with 6-membered heteroaromatic rings (containing 1 or 2 nitrogen atoms) and optionally substituted by T 1); T 1halogen atom, straight or branched 1-4C alkyl or alkoxy, cyano, carboxyl, hydroxyl, NR 1 0R 1 1, CONR 1 0R 1 1 or SO 2NR 1 0R 1 1; R 1 0,R 1 1,R 1 4hydrogen atom, straight or branched 1-4C alkyl, 3-6C cycloalkyl or benzyl; NR 1 0+R 1 1a group of formula (i); R 1 2,R 1 3hydrogen atom or straight or branched 1-4C alkyl; A : methylene group, oxygen atom, sulfur atom or NR 1 4; q : 0 - 3; r : 1 or 2; o,s : 0 or 1. Independent claims are included for the following: (1) preparation of the amino-alkyl-amide derivatives (I); and (2) a pyridine compound of formula Ar' 2-Z 1-C(=O)-W' forming a narrower group of a ketone compound of formula Ar 2-Z'-C(=O)-W' (II). Ar' 21,2,4-triazolo[1,5-a]pyridine- or triazolo[5,4-b]pyridine group (both optionally substituted by straight or branched 1-4C alkyl or alkoxy, hydroxyl, NR 1 0R 1 1, CONR 1 0R 1 1 or SO 2NR 1 0R 1 1); Z 11,3-propylene group; W' : halogen atom, hydroxyl, O(1-4C alkyl) or OCO-Z'-Ar 2. ACTIVITY : Antiasthmatic; Dermatological; Antiinflammatory; Gastrointestinal-Gen.; Antiulcer; Antiallergic; Ophthalmological; Neuroprotective; Virucide; Anti-HIV. MECHANISM OF ACTION : CC chemokine receptor 3 (CCR3) receptor antagonist. The CCR3 receptor antagonist effect of the amino-alkyl-amide derivatives (I) was examined on eotaxin binding test on human CCR3 (hCCR3) receptor expressing recombinant K562 and RBL2H3 cells and using Eotaxin labeled with radioactive iodine ( 1> 2> 3>I). The compound (I) showed IC 5 0 value of 0.5 - 500 (preferably 0.5 - 15) nM. No results for specific compounds are given.