Amines and amides derivatives as ligands for the Neuropeptide Y y5 receptor useful in the treatment of Obesity and other disorders, their use for the production of Drugs and Pharmaceutical compositions containing same

摘要

Derived from amines and amides of formula (a) which are ligands for the Neuropeptide Y y5 receptor wherein R1 is selected independently from the group consisting of hydrogen, Hydroxy alkyl, Halo, C1 - 8; alkyl alkoxy substituted C1 - 8; 8 C1 -, alkoxy substituted C1 - 8Trifluoroalquilo; Alquiltio - 8 Alquiltio C1 and C1 - C3 - substituted cycloalkyl 8; 6; 8 cicloalcoxi C3 -, Nitro, amino, alquilamino C1 - 6, - 8 cicloalquilamino dialquilamino C1, C4 - 8; cyano; carboxy; alcoxicarbonilo C1 - 5; alquilcarboniloxi C1 - 5 Formilo;; carbamoilo; phenyl and phenyl Replaced; n is 1 - 2B1 B2 is Hydrogen; Hydrogen; methylene OR B1 and B2 can be United and formed a Ring of five or six elements; M is 0 to 3; R2 is selected independently from the group consisting of hydrogen, alkyl, Hydroxy, C1 - 6 - 6; alquenilo of C2, C3 cycloalkyl Halo; - 7; phenyl substituted; Naft ILO,Naphthyl substituted heteroaryl heteroaryl; phenoxy; phenoxy; and heterocicloalquilo; l is selected from the group consisting of 8 alquenileno alquileno C1; C2 - 10; alquinileno C2 - C3 - 10; cicloalquileno 7; cicloalquilc3 - 7alquilenoc1 - 4; alquilenoc1 - 4arilo; alquilenoc4 - 7a - Amine of formula (1); ( N - methylene) piperidin-4-yl formula (2); ILO (N - methylene) - 4 - piperacin formula (3); ILO (N - methylene) PIrrolidin - 3 - ilo formula (4); P - (N - methylene) 4 acetyl piperidin-4-yl ILO formula (5); and (N - methylene) piperidin 44 - biilo formula (6); and or methylene carbonyl; Z is selected from the group consisting of: aryl formula (7); n - sulfonamido formula (8); n - (aryl) sulfonamido formula (9); arilamido formula (10 arilureido formula (11);); arilacetamido formula (12); (ariloxi carbonylamino) for Mule (13); 2,3 dihydro - 2 - oxo - 1H benzimidazole - 1 - ilo formula (14); and 1 - aryl - 23 - dihydro - 4 - oxo - 5.5 - imidazole dilaurate formula (15); R3 is selected independently from the group consisting of C1 - alkyl substituted alkyl of C1 - 6; 8; naftililo cycloalkyl substituted cycloalkyl;,;Naftililo substituted heteroaryl heteroaryl substituted;; and; R4 is selected independently from the group consisting of hydrogen, alkyl alkoxy C1 C1 - 8 - 8 - 8; alkoxy substituted C1; Hydroxy; Halogen; cyano, Nitro,Amino and alquilamino C1 and C1 dialquilamino - 8 - 8; R5 is independently selected from the group consisting of hydrogen, alkyl of C1 - 8; alquilcarbonilo C1 - 8; aroilo, carbamoilo, amidino,Alquilamino carbonyl C1 - 8; (arilamino) carbonyl and alquilcarbonilo C1 - 8 aryl; R6 independently selected from the group consisting of hydrogen and alkyl of C1 - 8; p is 1 - 3; Q is 1 - 3; and diasteromeros enantiomers, and pharmaceutically acceptable salts of them, provided that: when L is alquileno C1 - C2 - alquenileno 6, 10, 10 cicloalquileno alquinileno C2, C3 - 7Alquileno C1 - C3 - 7 4 cicloalquil, alquileno C1 - 4 - aryl or aminoalquileno; then z is n or N - phenyl - (sulfonamido aryl sulfonamido); when l is (N - methylene) - 4 - piperacin ILO; then z is phenyl or naphthyl; when l is (n methylene) - pyrrolidin-3-yl o (N - methylene) piperidin-4-yl il; then z is Sulfonamido N -, N - (aryl) sulfonamido; 2,3 dihydro - 2 - oxo - 1H - becimidazol - 1 - benzamido, ILO;Fenilureido, phenylacetamido or (phenoxy) carbonylamino; when l is (N - acetyl methylene) - 4 - (piperidin-4-yl ILO; then z is phenyl or naphthyl and and carbonyl; when l is (N - methylene) piperidin 4,4 - dilaurate, then z Is 2,3 dihydro - 1 - aryl - 4 - oxo - 5.5 - dilaurate and imidazole and carbonyl; and when B1 and B2 are amb Os methyleneThen form a Ring of six elements and when l is selected from the group consisting of 10 alquenileno alquileno C1; C2 - 10; 10 alquinileno C2 or C1 - 4 alquileno; aryl; then z can not be sulfonamido N -, N - (phenyl or sulfonamido aryl). These derivatives are ligands for the Neuropeptide Y y5 receptor (npy5-r).Amines and amides of formula (a) are useful in the treatment of disorders and diseases associated with NPY y5 receptor subtype. In addition, it is given to know the use of these derivatives for the preparation of medicaments for the treatment of these Disorders and diseases, and Pharmaceutical compositions containing Said Derivatives.