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US 8,273,762 B2Granted
Hexahydro-pyrrolo-isoquinoline compounds
AssigneeJanssen Pharmaceutica NV
InventorsRichard Apodaca, Ann J. Barbier, Nicholas I. Carruthers, Leslie A. Gomez, John M. Keith, Timothy W. Lovenberg, Ronald L. Wolin
Life of this patent
Estimating the term…
Abstract
Certain hexahydro-pyrrolo-isoquinoline compounds are histamine H3 receptor and serotonin transporter modulators useful in the treatment of histamine H3 receptor- and serotonin-mediated diseases.
Claims17
A compound of formula (I):
- wherein
- n is 0 or 1;
- m is 0;
- R2 and R3 may be taken together with the nitrogen to which they are attached to form a 4-8 membered heterocyclic ring, said heterocyclic ring having 0 or 1 additional heteroatom members separated from the nitrogen of attachment by at least one carbon member and selected from >O, >S(O)0-2, and >NH, having 0 or 1 double bonds, having 0, 1, or 2 carbon members separated from the nitrogen of attachment by at least one carbon member which is a carbonyl, optionally benzo or pyrido fused, optionally having one carbon member that forms a bridge, and having 0-1 substituents Rff,
- Rff is selected from the group consisting of —C1-6alkyl halo, and —C1-6alkylOH;
- R5 is selected from the group consisting of —H, —C1-6alkyl, —OH, —OC1-6alkyl, —SC1-6alkyl, and halo;
- Ar1 is a heteroaryl ring selected from the group consisting of:
- d) a monocyclic aromatic hydrocarbon group having five ring atoms, having a carbon atom which is the point of attachment, having one carbon atom replaced by >O, >S, >NH, or >N(C1-4alkyl), having up to one additional carbon atom optionally replaced by —N═, optionally mono- or di-substituted with Rt
- Rt is a substituent independently selected from the group consisting of:
- —OH, —C1-6alkyl, —OC1-6alkyl, phenyl, —CN, —NO2, —N(Ru)Rv (wherein Ru and Rv are independently —H or —C1-6alkyl), —C(O)N(Ru)Rv, —N(Ru)C(O)Rv, —N(Ru)SO2C1-6alkyl, —C(O)C1-6alkyl, —S(O)0-2-C1-6alkyl, —SO2N(Ru)Rv, —SCF3, halo, —CF3, —OCF3, —OCHF2, —COOH, and —COOC1-6alkyl;
- e) a monocyclic aromatic hydrocarbon group having six ring atoms, having a carbon atom which is the point of attachment, having one or two carbon atoms replaced by —N═, optionally mono- or di-substituted with Rt;
- and enantiomers, diastereomers thereof, and pharmaceutically acceptable salts, esters and amides thereof.
9 more elements
A compound selected from the group consisting of:
- Cis-9-(3-Piperidin-1-yl-propoxy)-6-thiophen-2-yl-1,2,3,5,6,10b-hexahydro-pyrrolo[2,1-a]isoquinoline;
- Cis-9-(3-Piperidin-1-yl-propoxy)-6-thiophen-3-yl-1,2,3,5,6,10b-hexahydro-pyrrolo[2,1-a]isoquinoline;
- Trans-9-(3-piperidin-1-yl-propoxy)-6-thiophen-3-yl-1,2,3,5,6,10b-hexahydro-pyrrolo[2,1-a]isoquinoline;
- Cis-9-(3-Piperidin-1-yl-propoxy)-6-pyridin-2-yl-1,2,3,5,6,10b-hexahydro-pyrrolo[2,1-a]isoquinoline;
- Cis-9-(3-Piperidin-1-yl-propoxy)-6-pyridin-3-yl-1,2,3,5,6,10b-hexahydro-pyrrolo[2,1-a]isoquinoline;
- Cis-9-(3-Piperidin-1-yl-propoxy)-6-pyridin-4-yl-1,2,3,5,6,10b-hexahydro-pyrrolo[2,1-a]isoquinoline;
- Trans-9-(3-Piperidin-1-yl-propoxy)-6-pyridin-4-yl-1,2,3,5,6,10b-hexahydro-pyrrolo[2,1-a]isoquinoline;
- Cis-9-(3-Morpholin-4-yl-propoxy)-6-pyrazin-2-yl-1,2,3,5,6,10b-hexahydro-pyrrolo[2,1-a]isoquinoline;
- Trans-9-(3-Morpholin-4-yl-propoxy)-6-pyrazin-2-yl-1,2,3,5,6,10b-hexahydro-pyrrolo[2,1-a]isoquinoline;
- Cis-5-[9-(3-Morpholin-4-yl-propoxy)-1,2,3,5,6,10b-hexahydro-pyrrolo[2,1-a]isoquinolin-6-yl]-pyridin-2-ol;
- Trans-5-[9-(3-Morpholin-4-yl-propoxy)-1,2,3,5,6,10b-hexahydro-pyrrolo[2,1-a]isoquinolin-6-yl]-pyridin-2-ol;
- Cis-9-(3-Morpholin-4-yl-propoxy)-6-thiophen-3-yl-1,2,3,5,6,10b-hexahydro-pyrrolo[2,1-a]isoquinoline;
- Cis-9-(3-Morpholin-4-yl-propoxy)-6-thiophen-2-yl-1,2,3,5,6,10b-hexahydro-pyrrolo[2,1-a]isoquinoline;
- Cis-9-(3-Morpholin-4-yl-propoxy)-6-pyridin-3-yl-1,2,3,5,6,10b-hexahydro-pyrrolo[2,1-a]isoquinoline;
- Cis-9-(3-Morpholin-4-yl-propoxy)-6-pyridin-2-yl-1,2,3,5,6,10b-hexahydro-pyrrolo[2,1-a]isoquinoline;
- 6-(6-Chloro-pyridin-3-yl)-9-(3-morpholin-4-yl-propoxy)-1,2,3,5,6,10b-hexahydro-pyrrolo[2,1-a]isoquinoline;
- Dimethyl-{5-[9-(3-morpholin-4-yl-propoxy)-1,2,3,5,6,10b-hexahydro-pyrrolo[2,1-a]isoquinolin-6-yl]-pyridin-2-yl}-amine;
- 6-(6-Methoxy-pyridin-3-yl)-9-(3-morpholin-4-yl-propoxy)-1,2,3,5,6,10b-hexahydro-pyrrolo[2,1-a]isoquinoline;
- 6-(1H-Imidazol-2-yl)-9-(3-morpholin-4-yl-propoxy)-1,2,3,5,6,10b-hexahydro-pyrrolo[2,1-a]isoquinoline;
- 6-(1-Methyl-1H-imidazol-2-yl)-9-(3-morpholin-4-yl-propoxy)-1,2,3,5,6,10b-hexahydro-pyrrolo[2,1-a]isoquinoline;
- 6-(3H-Imidazol-4-yl)-9-(3-morpholin-4-yl-propoxy)-1,2,3,5,6,10b-hexahydro-pyrrolo[2,1-a]isoquinoline;
- and
- 6-(3-Methyl-3H-imidazol-4-yl)-9-(3-morpholin-4-yl-propoxy)-1,2,3,5,6,10b-hexahydro-pyrrolo[2,1-a]isoquinoline.
20 more elements
A pharmaceutical composition comprising a pharmaceutically acceptable carrier and at least one compound of formula (I).
Dependencies are inferred from the claim text.