Muscarinic modulators
The present invention relates to modulators of muscarinic receptors. The present invention also provides compositions comprising such modulators, and methods therewith for treating muscarinic receptor mediated diseases.
1. A compound of formula III
or a pharmaceutically acceptable salt thereof, wherein
R 1 is one selected from N-(ethoxy(carbonyl))piperidine-4-yl; N-(ethoxy(carbonyl))-8-azabicyclo[3.2.1]octane-3-yl; N-(butoxy(carbonyl))-8-azabicyclo[3.2.1]octane-3-yl; N-(isopropoxy(carbonyl))-8-azabicyclo[3.2.1]octane-3-yl; N-(tert-butoxy(carbonyl))-8-azabicyclo[3.2.1]octane-3-yl; N-(cyclobutoxy(carbonyl))-8-azabicyclo[3.2.1]octane-3-yl; tetrahydro-4H-pyran-4-yl; 4-(ethyl)cyclohexane-yl; bicyclo[2.2.1]heptane-2-yl; bicyclo[3.2.1]octane-3-yl; cyclohexane-yl; (cyclopentyl)methyl; bicyclo[2.2.1]hept-2-ylmethyl; cycloheptane-yl; cyclooctane-yl; bicyclo[3.3.1]nonane-9-yl; (tetrahydro-4H-pyran-2-yl)methyl; N-(butoxy(carbonyl))-8-azabicyclo[3.2.1]octane-3-yl; N-2,2-difluoroethoxy(carbonyl))-8-azabicyclo[3.2.1]octane-3-yl; N-(2-fluoroethoxy(carbonyl))-8-azabicyclo[3.2.1]octane-3-yl; N-(but-2-ynoxy(carbonyl))-8-azabicyclo[3.2.1]octane-3-yl; N-(trifluoromethyl(carbonyl))-8-azabicyclo[3.2.1]octane-3-yl; N-(methoxy(carbonyl))-8-azabicyclo[3.2.1]octane-3-yl; N-(methoxy(ethoxy(carbonyl))-8-azabicyclo[3.2.1]octane-3-yl; N-(ethyl(carbonyl))-8-azabicyclo[3.2.1]octane-3-yl; N-(phenyl(carbonyl))-8-azabicyclo[3.2.1]octane-3-yl; N-(N,N-(dimethyl(amino(carbonyl))-8-azabicyclo[3.2.1]octane-3-yl; N-(phenyl(sulfonyl))-8-azabicyclo[3.2.1]octane-3-yl; 4-(ethoxy(imino))cyclohexane-yl; 4-(propoxy(imino))cyclohexane-yl; bicyclo[3.2.1]octane-3-yl; N-(isobutoxy(carbonyl))-8-azabicyclo[3.2.1]octane-3-yl; N-(2,2-dimethylpropyloxy(carbonyl))-8-azabicyclo[3.2.1]octane-3-yl; 4-(but-2-ynyloxyimino)cyclohexane-yl; and 4-(pent-2-ynyl(imino))cyclohexane-yl;
R 2b is —Z I R 12 , wherein Z I is a bond or an optionally substituted straight or branched C 1-5 aliphatic chain; R 12 is an aryl, a cycloaliphatic, a heteroaryl, or an aliphatic, each of which is optionally substituted with 1-3 of R Z6 ;
Each R Z6 is independently selected from halo, optionally substituted aliphatic, and alkoxy;
R 3b is —Z J R 13 , wherein Z J is —C(O)—, —S(O) 2 —, —C(O)NH—, or —C(O)O—, and R 13 is hydrogen or an optionally substituted aliphatic, or an optionally substituted aryl;
R 3C is hydrogen, or R 3C and R 3b together with the atoms to which they are attached form an optionally substituted 5-6 membered heterocycloaliphatic; and
n is 1-8;
Provided that:
only one of R 2b and R 3b is an optionally substituted aryl or an optionally substituted heteroaryl;
when Z A is a bond, and R 4 is a substituted piperidine-4-yl; then R 4 is substituted with 1-3 of halo, hydroxy, cyano, or optionally substituted aliphatic, optionally substituted cycloaliphatic, optionally substituted aryl, optionally substituted heteroaryl, or combinations thereof; and
when Z I is a bond and R 12 is a phenyl, R 12 is optionally substituted with 1-3 of halo, unsubstituted aliphatic, haloaliphatic, alkoxy, or combinations thereof.
2. The compound of claim 1 , wherein R 2b is —Z I R 12 , wherein Z I is a bond or an optionally substituted straight or branched C 1-5 aliphatic chain, and R 12 is an aryl optionally substituted with 1-5 of R Z4 .
3. The compound of claim 1 , wherein R 2b is —Z I R 12 , wherein Z I is a bond or an optionally substituted straight or branched C 1-5 aliphatic chain, and R 12 is a C 1-5 aliphatic that is optionally substituted with 1-5 of R Z4 .
4. The compound of claim 3 , wherein R 2b is —Z I R 12 , wherein Z I is a bond, and R 12 is a methyl optionally substituted with aryl or cycloaliphatic.
5. The compound of claim 1 , wherein R 2b is —Z I R 12 , wherein Z I is a bond or an optionally substituted straight or branched C 1-5 aliphatic chain, and R 12 is a cycloaliphatic that is optionally substituted with 1-3 of R Z4 .
6. The compound of claim 1 , wherein R 2b is —Z I R 12 , wherein Z I is a bond or an optionally substituted straight or branched C 1-5 aliphatic chain, and R 12 is a heteroaryl optionally substituted with 1-3 of R Z4 .
7. The compound of claim 1 , wherein R 2b is one selected from 4-fluorophenyl; phenyl; 2-fluorophenyl; phenylmethyl; 3-fluorophenyl; 4-methylphenyl; 3-methylphenyl; 3,4 -dimethylphenyl; 3-methoxyphenyl; 4-methoxyphenyl; 4-(tert-butyl)phenyl; 3-chlorophenyl; 3 -methoxycarbonyl; 4-chlorophenyl; cyclohexane-yl; 2,4-difluorophenyl; isopropyl; cyclopentane -yl; cyclobutane-yl; propyl; 2-chloro-4-methyl-pyrimidine-6-yl; and isobutyl.
8. The compound of claim 1 , wherein R 3b is —Z J R 13 , Z J is —C(O)—, and R 13 is an optionally substituted aliphatic, or an optionally substituted aryl.
9. The compound of claim 1 , wherein R 3b is —Z J R 13 , Z J is —S(O) 2 —, and R 13 is an aliphatic or an aryl, each of which is optionally substituted.
10. The compound of claim 9 , wherein R 3b is one selected from (propyl(amino))carbonyl; methylcarbonyl; (methoxy)carbonyl; (isopropyl)carbonyl; (ethyl)carbonyl; methyl; ethyl; (methyl)sulfonyl; propyl; and 4-(trifluoro(methyl(phenyl)))sulfonyl.
11. A compound selected from:
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12. A pharmaceutical composition comprising a compound as described in claim 1 and a pharmaceutically acceptable carrier.
13. A pharmaceutical composition comprising a compound as described in claim 11 and a pharmaceutically acceptable carrier.