(2R,3R)-2,3-dihydroxybutanedioic acid 4-(4-{3-[(3R)-3-(dimethylamino)pyrrolidin-1-yl]propoxy}phenyl)benzonitrile hydrate

• ChemBase ID: 154235
• Molecular Formular: C26H35N3O8
• Molecular Mass: 517.5714
• Monoisotopic Mass: 517.2424151
• SMILES: CN(C)[C@@H]1CCN(C1)CCCOc1ccc(cc1)c1ccc(cc1)C#N.[C@@H]([C@H](C(=O)O)O)(C(=O)O)O.O
• Canonical SMILES: OC(=O)[C@@H]([C@H](C(=O)O)O)O.N#Cc1ccc(cc1)c1ccc(cc1)OCCCN1CC[C@H](C1)N(C)C.O
• InChI: 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
• InChIKey: BWZMVOINNVPOGW-LZXZYUBDSA-N

NAMES AND DATABASE IDS

Names

• IUPAC name: (2R,3R)-2,3-dihydroxybutanedioic acid 4-(4-{3-[(3R)-3-(dimethylamino)pyrrolidin-1-yl]propoxy}phenyl)benzonitrile hydrate
• IUPAC Traditional name: 4-(4-{3-[(3R)-3-(dimethylamino)pyrrolidin-1-yl]propoxy}phenyl)benzonitrile L(+)-tartaric acid hydrate
• Synonyms: 4′-[3-[3(R)-Dimethylamino-1-pyrrolidinyl]propoxy]-[1,1-biphenyl]-4′-carbonitrile L-tartrate hydrate; A-331440 L-tartrate hydrate

Database IDs

• CAS Number: 392338-13-5(freebase)
• PubChem SID: 162248374
• PubChem CID: 71311819

CALCULATED PROPERTIES

• H Acceptors: 4
• H Donor: 0
• LogD (pH = 5.5): -0.31751436
• LogD (pH = 7.4): 1.0834454
• Log P: 3.3643467
• Molar Refractivity: 106.8492 cm^3
• Polarizability: 42.76552 Å^3
• Polar Surface Area: 39.5 Å^2
• Rotatable Bonds: 10
• Lipinski's Rule of Five: false

PROPERTIES

Physical Property

• Solubility: DMSO: ≥10 mg/mL; ethanol: insoluble; H2O: insoluble; methanol: insoluble
• Apperance: white to off-white solid

Safety Information

• German water hazard class: 3
• Personal Protective Equipment: Eyeshields, Gloves, type N95 (US), type P1 (EN143) respirator filter

Product Information

• Purity: ≥98% (HPLC)
• Empirical Formula (Hill Notation): C22H27N3O · xC4H6O6 · yH2O

DETAILS

Sigma Aldrich - A3104

Legal Information
Subject to U.S. Patent numbers 6,515,013 and 6,620,839. Sold under license from Abbott Laboratories
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 (Ki<=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.