| US 7,456,196 B2 | ||
| Bicyclic-substituted amines as histamine-3 receptor ligands | ||
| Robert J. Altenbach, Chicago, Ill. (US); Marlon D. Cowart, Round Lake Beach, Ill. (US); and Huaqing Liu, Buffalo Grove, Ill. (US) | ||
| Assigned to Abbott Laboratories, Abbott Park, Ill. (US) | ||
| Filed on May 05, 2006, as Appl. No. 11/418,699. | ||
| Application 11/418699 is a division of application No. 10/689735, filed on Oct. 22, 2003, granted, now 7,153,889. | ||
| Claims priority of provisional application 60/425376, filed on Nov. 12, 2002. | ||
| Prior Publication US 2006/0194798 A1, Aug. 31, 2006 | ||
| Int. Cl. A61K 31/4709 (2006.01); C07D 401/12 (2006.01); C07D 401/14 (2006.01) | ||
| U.S. Cl. 514—311 [546/153; 546/157; 546/162; 546/176; 546/177; 514/312; 514/313; 514/314; 514/228.2; 514/235.2; 514/253.06; 544/62; 544/128; 544/363] | 27 Claims |
1. A compound of the formula:
 Y, and Y′ are each independently selected from the group consisting of CH, CF, and N, provided that one of Y or Y′ is N and
the other is CH or CF;
X, X′, Z, and Z′ are each C;
one of R1 and R2 is selected from the group consisting of halogen, and L2R6;
the other of R1 and R2 is selected from the group consisting of hydrogen, alkyl, alkoxy, aryl, cycloalkyl, halogen, and thioalkoxy;
R3 is selected from the group consisting of hydrogen, alkyl, alkoxy, halogen, cyano, and thioalkoxy;
R3a is selected from the group consisting of hydrogen, methyl, alkoxy, halogen, and cyano;
R3b is selected from the group consisting of hydrogen, alkyl, alkoxy, halogen, hydroxy, cyano, and thioalkoxy;
R4 and R5 taken together with the nitrogen atom to which each is attached form a non-aromatic ring of the formula:
 R6 is selected from the group consisting of heteroaryl, heterocycle, and cycloalkyl;
R7, R8, R9, and R10 at each occurrence are each independently selected from the group consisting of hydrogen, hydroxyalkyl, fluoroalkyl, and alkyl;
or one of the pair R7 and R8 or the pair R9 and R10 is taken together with the carbon atom to which each is attached to form a C3-C6 ring, wherein 0, 1, or 2 heteroatoms selected from O, N, or S replace a carbon atom in the ring;
R11, R12, R13, and R14 are each independently selected from the group consisting of hydrogen, hydroxy, hydroxyalkyl, alkyl, and fluoro;
Q is selected from the group consisting of a bond, O, S, and NR15;
L is —[C(R16)(R17)]n— or —[C(R16)(R17)]pO—;
L2 is selected from the group consisting of a bond, —O—, —C(═O)—, —S—, —[C(R18)(R19)]q—, —O—[C(R18)(R19)]q—, —NH— and —N(alkyl)-;
R15 is selected from the group consisting of hydrogen, alkyl, acyl, amido, and formyl;
R16 and R17 at each occurrence are independently selected from the group consisting of hydrogen, alkyl, alkoxy, and fluoro;
R18 and R19 at each occurrence are each independently selected from the group consisting of hydrogen, hydroxy, alkyl, alkoxy, and fluoro;
Rx and Ry at each occurrence are independently selected from the group consisting of hydrogen, hydroxy, alkyl, alkoxy, alkylamino, dialkylamino,
and fluoro, or one of Rx or Ry represents a covalent bond when taken together with Rx or Ry on an adjacent carbon atom such that a double bond is represented between the adjacent carbon atoms;
m is an integer from 1 to 5;
n is an integer from 1 to 6;
q is an integer from 2 to 6;
q is integer from 1 to 4.
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