A3104

A-331440 L-tartrate hydrate

≥98% (HPLC), solid

• Synonym(s): 4′-[3-[3(R)-Dimethylamino-1-pyrrolidinyl]propoxy]-[1,1-biphenyl]-4′-carbonitrile L-tartrate hydrate
• Empirical Formula (Hill Notation): C₂₂H₂₇N₃O · xC₄H₆O₆ · yH₂O
• CAS Number: 392338-13-5
• Molecular Weight: 349.47 (anhydrous free base basis)
• UNSPSC Code: 12352202
• PubChem Substance ID: 329770814
• NACRES: NA.77

Properties

• Assay: ≥98% (HPLC)
• form: solid
• color: white to off-white
• solubility: DMSO: ≥10 mg/mL; H₂O: insoluble; ethanol: insoluble; methanol: insoluble
• originator: Abbott
• SMILES string: [H]O[H].O[C@H]([C@@H](O)C(O)=O)C(O)=O.CN(C)[C@@H]1CCN(CCCOc2ccc(cc2)-c3ccc(cc3)C#N)C1
• InChI: 1S/C22H27N3O.C4H6O6.H2O/c1-24(2)21-12-14-25(17-21)13-3-15-26-22-10-8-20(9-11-22)19-6-4-18(16-23)5-7-19;5-1(3(7)8)2(6)4(9)10;/h4-11,21H,3,12-15,17H2,1-2H3;1-2,5-6H,(H,7,8)(H,9,10);1H2/t21-;1-,2-;/m11./s1
• InChI key: BWZMVOINNVPOGW-LZXZYUBDSA-N

Description

Biochem/physiol Actions

Histamine affects homeostatic mechanisms, including food and water consumption, by acting on central nervous system (CNS) receptors. Presynaptic histamine H₃ receptors regulate release of histamine and other neurotransmitters, and histamine H₃ receptor antagonists enhance neurotransmitter release. A-331440 [4′-[3-(3(R)-(dimethylamino)-pyrrolidin-1-yl)-propoxy]-biphenyl-4-carbonitrile] is a histamine H₃ receptor antagonist which binds potently and selectively to both human and rat histamine H₃ receptors (K_i<=25 nM). Mice were stabilized on a high-fat diet (45 kcal % lard) prior to 28-day oral b.i.d. dosing for measurement of obesity-related parameters. A-331440 administered at 0.5 mg/kg had no significant effect on weight, whereas 5 mg/kg decreased weight comparably to dexfenfluramine (10 mg/kg). A-331440 administered at 15 mg/kg reduced weight to a level comparable to mice on the low-fat diet. The two higher doses reduced body fat and the highest dose also normalized an insulin tolerance test. These data show that the histamine H₃ receptor antagonist, A-331440, has potential as an antiobesity agent.

Features and Benefits

This compound is featured on the Histamine Receptors page of the Handbook of Receptor Classification and Signal Transduction. To browse other handbook pages, click here.

This compound was developed by Abbott. To browse the list of other pharma-developed compounds and Approved Drugs/Drug Candidates, click here.

Legal Information

Subject to U.S. Patent numbers 6,515,013 and 6,620,839. Sold under license from Abbott Laboratories

Safety Information

• Storage Class Code: 11 - Combustible Solids
• WGK: WGK 3
• Flash Point(F): Not applicable
• Flash Point(C): Not applicable
• Personal Protective Equipment: dust mask type N95 (US), Eyeshields, Gloves