Amino substituted piperidine Derivatives, Pharmaceutical compositions and the use of these derivatives for the preparation of drugs as inhibitors of gamma secretase, and for the treatment of Alzheimer's disease

摘要

Amino substituted piperidine Derivatives, comprising a compound of the formula (1) or pharmaceutically acceptable salts or solvates thereof, wherein: aR1 and ar2 are independently selected from aryl and heteroaryl; and it's a Link.Or represents a Group (- C (R3) 1 - 3 - 2); each R1 is independently selected from alkyl (C1: 6); aryl; aryl substituted with one or more substituents CF3, independently selected from Halogen, alkyl, alkoxy (C1 - 6) (C1 - 6), ocf3, NH2 or heteroaryl heteroaryl substituted; NC; One or more substituents independently selected from Halogen, alkyl (C1 - CF3, 6),Alkoxy (C1 - 6), ocf3, NH2 or CN; Halogen; - Cf3; - ocf3; CN; NO2 -; - NH2, - C (o) nhalquilo (C1 - 6) - C (o) n (alkyl (C1 - 6) 2, where the alkyl group (C1 - 6) is equal to or different from the other, - C (o) n (alkyl (C1 - 6) 2Where the alkyl group (C1 - 6) is equal to or different from the others and the alkyl groups (C1 - 6) taken together with nitrogen which are United to form a Ring; - NHC (or alkyl (C1) - 6 - (NHC), or oalquilo (C1) - 6) - NHC (O) nhalquilo (C1 - 6)- nhso2alquilo (C1 - 6); Oh; OC (or alkyl (C1) - 6 - (C1); oalquilo - 6); oarilo; or - oaralquilo (C1 - 6); each R2 is independently selected from alkyl (C1: 6); Halogen; - Cf3 - ocf3;; CN; No2 -; - NH2, - C (o) oalquilo (C1 - 6 - C (o); (6) nhalquilo C1 - (alkyl) - N (C1 - 2 - 6) where each Substituent alkyd ILO (C1 - 6) is equal to or different from the other; n - (alkyl (C1 - 6) 2Where each Substituent alkyl (C1 - 6) is equal to or different from the other and alkyl substituents (C1 - 6)Along with the nitrogen Atom to which they are United to form a Ring; - NHC (or alkyl (C1) - 6 - (NHC); or oalquilo (C1) - 6 - (NHC); or nhalquilo (C1) - 6 - (C1); nhso2alquilo - 6); - OC (- Oh; or alkyl (C1) - 6 - (C1); oalquilo - 6); oarilo OAR; alkyl; aryl (C1 - 6); aryl substituted with one or more substituents inde Among them: CF3, halogen, alkyl, alkoxy (C1 - 6) (C1 - 6), ocf3,NH2 or heteroaryl heteroaryl substituted; CN; with one or more substituents CF3, independently selected from Halogen, alkyl, alkoxy (C1 - 6) (C1 - 6) ocf3, NH2 or CN, - C (o) n (alkyl (C1 - 6) 2 where each alkyl group is independently selected; C (o) n (alkyl (C1 2 - 6) where each group) PO is independently selected where the alkyl and alkyl groups,Taken together with the nitrogen Atom.Form a ring heterocicloalquilo; or a selected Group among the remains of formulas (2) to (6); each R3 is independently selected from H and alkyl (c1-3); each is independently selected from alkyl R4: (c1-3); Oh; or - oalquilo (c1-3); R5 is selected among Hydrogen; Alkyl (C1 - 6); aryl heteroaryl; rent; - (c1-3) - oalquilo (c1-3); - Rent (C1 - (6) - s or - C1 2alquilo (0)3); - Rent (C1 - 8) - S (o) 0 - 2nhalquilo (c1-3); (o) - C (C1 - 6 alkyl (or aryl); (c) - C (o) aralquilo (c1-3) - C (o) - heteroaryl; C (o) heteroaralquilo (c1-3) - C (o) oalquilo (C1 - 6) - C (o) nhalquilo (C1 - 6) - C (o) n (alkyl (C1 - 6) 2, where each alkyl group C1 - 6 is equal or different from others; - C (o) n (alkyl ( C1 - 6) 2Where the alkyl group C1 - 6 is equal or different from the others and where the alkyl groups C1 - 6, taken together with the nitrogen which are United,Form a ring heterocicloalquilo; - C (o) Rent (c1-3) - nhalquilo (c1-3) - C (o) Rent (c1-3) n - (alkyl (c1-3); 2 where each alkyl group is selected independently; - so2alquilo (C1 - 6); - so2nhalquilo (C1 - 6); so2n (alkyl (C1 - 6); 2 where each alkyl group C1 - 6 is the same or different L Other so2n; - (alkyl (C1 - 6) 2Where the alkyl group C1 - 6 is equal or different from the others and where the alkyl groups C1 - 6, taken together with the nitrogen which are United to form a ring heterocicloalquilo or a group of the formula (7), (8), (9) or (10); R6 - H (C1 - 6) or alkyl; X is selected between CH2, or, S, so, SO2 or N - R7; R7 is selected from alkyl, cycloalkyl (C1 - 6) (C3 - 6)Rent (c1-3) - cycloalkyl (C3 - 6); aralquilo aryl, heteroaryl (c1-3), heteroaralquilo (c1-3) alkyl, - C (o) (C1 - 6), C (aryl) -, - C (o) aralquilo (c1-3), - C (or C - (heteroaryl); or (3) heteroaralquilo C1 -, - C (o) oalquilo (C1 -, - C (6) or (6) nhalquilo C1 -, - C (o) n (alkyl (C1 - 6) 2, where each group C1 - 6 is the same L or different to others; - C (o) n (alkyl (C1 - 6) 2Where the alkyl group C1 - 6 is equal or different from the others and where the alkyl groups C1 - 6, taken together with the nitrogen which are United to form a ring heterocicloalquilo; - C (o) Rent (c1-3) - nhalquilo (c1-3), rent (- C (o) C1 - (alkyl) - n 3 (c1-3)) 2Where the c1-3 alkyl groups are equal or different; or - Rent (c1-3) - o-alkyl (c1-3); n and P are independently selected from 0 to 3 to form a Ring of 4 to 7 members; R is 0 to 3; Q represents 0 to 3 and t is 0 to 3.It also describes Pharmaceutical compositions and the use of such compounds for preparing Medicines for inhibiting the gamma secretase and for the treatment of Alzheimer's disease.