N-methyl tetrahydroquinoline M1 receptor positive allosteric modulators

摘要

The present invention is directed to N-methyl tetrahydroquinoline compounds of formula (I) which are M1 receptor positive allosteric modulators and that are useful in the treatment of diseases in which the M1 receptor is involved, such as Alzheimer's disease, schizophrenia, pain or sleep disorders. The invention is also directed to pharmaceutical compositions comprising the compounds, and to the use of the compounds and compositions in the treatment of diseases mediated by the M1 receptor.;

主权项

1. A compound of formula (I):and pharmaceutically acceptable salts thereof, wherein
--- represents a bond which can be absent or present, Y is selected from the group consisting of
(1) a C5-10 heterocycle group, said heterocycle optionally substituted with 1 to 3 groups of R1, and(2) C6-10 aryl group, said aryl optionally substituted with 1 to 3 groups of R1, X and X1 are independently selected from —CH2 and —O—; R1 is selected from the group consisting of
(1) hydrogen,(2) C6-10aryl,(3) C5-10 heterocycle,(4) (CH2)nhalogen,(5) —CN,(6) —O—C1-6 alkyl,(7) —C1-6 alkyl,(8) —C2-6 alkenyl(9) —S(═O)n—R2,(10) —(C(O)O)mNR3AR3B,(11) —OH,(12) -oxo,(13) —C(═O)—(O)m—R4,(14) CF3,wherein said aryl, heterocycle, alkyl and alkenyl moiety is optionally substituted with one to three of
(a) halogen,(b) hydroxy,(c) —O—C1-6 alkyl,(d) —C1-6 alkyl,(e) —C(═O)—(O)m—R4,(f) —N(R3AR3B),(g) —S(═O)n—R5, or(h) C5-10heteroaryl, which is optionally substituted with 1 to 3 groups of C1-6 alkyl, R2, R4, and R5 are independently selected from the group consisting of
(1) hydrogen,(2) —C1-6 alkyl,(3) —C2-6 alkenyl, and(3) —(CH2)n-aryl,(4) —N(R1)2 wherein said R2, R4 and R5 alkyl or aryl moiety is optionally substituted with one or more
(a) halogen,(b) cyano, and(c) —O—C1-6 alkyl, wherein said alkyl is optionally substituted with one or more halogen; R3A and R3B are selected from the group consisting of
(1) hydrogen,(2) —C1-6 alkyl,(3) —C3-6 cycloalkyl,(4) —C(═O)—O—R4,(5) —S(O)2—R4,or R3A and R3B are linked together with the nitrogen to which they are both attached to form a 2-6 membered carbocyclic ring, wherein one or two of the ring carbon atoms is optionally replaced by a nitrogen, oxygen or sulfur; m is 0 or 1; and n is 0, 1 or 2.