US 8,012,956 B2 · Tropane compounds

Abstract

A compound according to Formula I or II: wherein R1, R1b, R2, L1, and L2 and L2b are as defined in the specification, pharmaceutical compositions thereof, and methods of use thereof.

A compound according to Formula I:

or a pharmaceutically acceptable salt thereof, wherein:
R1 is selected from
R3 is selected from hydrogen, —CF3, —NH2, OH;
alkyl optionally substituted with 1, 2, or 3 R5;
alkoxy, dialkylaminoalkyl;
cycloalkyl optionally substituted with arylalkoxy;
aryl optionally substituted with 1, 2, or 3 groups selected from halogen, alkyl, alkoxy, dialkylaminoalkoxy, and heterocycloalkyl optionally substituted with alkyl or aryl;
alkenyl, alkynyl;
heterocycloalkyl optionally substituted with a group selected from alkyl, —C(O)O-alkyl, and arylalkyl;
arylalkyl optionally substituted with alkylheterocycloalkyl at any ring position of the aryl group;
and heteroaryl;
R4, R7, R8, and R9 are each independently selected from hydrogen, —OR16, —SR16, —N(H)R16, hydroxy, alkenyl, alkynyl, hydroxyalkynyl, halogen, hydroxyalkyl, dihydroxyalkyl, —O—C(O)—NH2, amino(imino)alkyl, —C(O)—NH2, —N(H)C(O)alkyl, alkylaminoalkyl, alkylaminoalkylamino, aminoalkylamino, arylalkylamino, heterocycloalkyl, dialkylaminoalkyl;
alkyl optionally substituted with 1-8 halogen;
dialkylamino, —N(H)alkylheterocycloalkyl, alkylsulfonylheterocycloalkylamino, cycloalkylalkylamino, cycloalkoxy, —NH2, —O-alkyl-heterocycloalkyl, dialkylaminoalkoxy, alkylsulfonylalkylamino;
and —N(H)heterocycloalkyl optionally substituted with 1, 2, or 3 groups selected from alkyl, alkoxy, and halogen;
R5 is selected from halogen, cycloalkyl, cycloalkylalkylamino;
heteroaryl optionally substituted with 1, 2, or 3 groups selected from halogen, alkyl, and alkoxy;
alkylthio;
heterocycloalkyl optionally substituted with 1, 2, or 3 groups selected from alkyl, halogen, phenyl, and oxo;
aryl optionally substituted with 1, 2, or 3 groups selected from halogen, alkyl, alkoxy, dialkylaminoalkoxy, and heterocycloalkyl optionally substituted with alkyl;
alkoxy, dialkylamino, —OH, —C(O)—NH2, —C(O)—O—CH3, —C(O)—N(H)(C1-C3)alkyl;
heteroarylamino optionally substituted with halogen;
and —OCF3;
R6 and R10 are each selected from hydrogen;
alkyl optionally substituted with 1-8 halogens;
alkylthio, alkenyl, alkynyl, hydroxyalkynyl, halogen, hydroxyalkyl, dihydroxyalkyl, amino(imino)alkyl, —C(O)—NH2, —N(H)C(O)alkyl, alkylaminoalkyl, alkylaminoalkylamino, aminoalkylamino, arylalkylamino, heterocycloalkyl, dialkylaminoalkyl;
alkylamino optionally substituted with 1-8 halogens;
dialkylamino, alkoxyalkylamino, —N(H)alkylheterocycloalkyl, cycloalkylalkylamino, alkylsulfonylheterocycloalkylamino, cycloalkylalkylamino;
cycloalkylamino optionally substituted with a group selected from —OH, alkyl, —CF3, and heterocycloalkyl;
—N(H)cycloalkyl optionally substituted with —OH or —NH2, —NH2, —N(H)-heteroaryl;
—N(H)-aryl optionally substituted with 1, 2, or 3 groups selected from alkoxy, heterocycloalkylalkoxy, and dialkylaminoalkoxy;
alkylsulfonylalkylamino and —N(H)heterocycloalkyl;
R16 is selected from hydrogen;
alkyl optionally substituted with 1-8 halogens;
cycloalkyl optionally substituted with 1 or 2 groups selected from —OH, —NH2, alkyl, heterocycloalkyl, and —CF3;
cycloalkylalkyl;
heterocycloalkyl optionally substituted with —OH or —NH2;
alkoxyalkyl;
aryl optionally substituted with 1, 2, or 3 alkoxy;
heterocycloalkylalkyl, heteroaryl, gem-dicycloalkylalkyl, and dialkylaminoalkyl;
R17, when present, is —CH2— or —CH(OH)—;
L1 is selected from —C(O)O—, —C(O)NH—, —C(O)NHSO2—, —(CH2)nC(O)NH—, —(CH2)nNHC(O)—, —(CH2)mNH—, —(CH2)nSO2NH—, —(CH2)nNHSO2—, —(CH2)mC(O)—, —(CH2)mO—, and —(CH2)mNH—(CH2)n—;
L2 is —C(O)—NH—R3, —CN, —C(O)—N(CH3)—OCH3, or —C(O)—R3;
n is 0 or 1;
m is 0, 1 or 2;
and
each p is independently 0, 1, 2, 3 or 4.

44 more elements

Tropane compounds

Life of this patent

Tropane compounds

Life of this patent

Abstract

Claims18