2-[(2R)-2-methylpyrrolidin-2-yl]-1H-1,3-benzodiazole-7-carboxamide

• ChemBase ID: 4883
• Molecular Formular: C13H16N4O
• Molecular Mass: 244.29234
• Monoisotopic Mass: 244.13241115
• SMILES: c12c(cccc1nc([C@]1(CCCN1)C)[nH]2)C(=O)N
• Canonical SMILES: NC(=O)c1cccc2c1[nH]c(n2)[C@@]1(C)CCCN1
• InChI: InChI=1S/C13H16N4O/c1-13(6-3-7-15-13)12-16-9-5-2-4-8(11(14)18)10(9)17-12/h2,4-5,15H,3,6-7H2,1H3,(H2,14,18)(H,16,17)/t13-/m1/s1
• InChIKey: JNAHVYVRKWKWKQ-CYBMUJFWSA-N

NAMES AND DATABASE IDS

Names

• IUPAC name: 2-[(2R)-2-methylpyrrolidin-2-yl]-1H-1,3-benzodiazole-7-carboxamide; 2-[(2R)-2-methylpyrrolidin-2-yl]-1H-1,3-benzodiazole-4-carboxamide
• IUPAC Traditional name: 2-[(2R)-2-methylpyrrolidin-2-yl]-3H-1,3-benzodiazole-4-carboxamide; 2-[(2R)-2-methylpyrrolidin-2-yl]-1H-1,3-benzodiazole-4-carboxamide
• Synonyms: (2R)-2-(7-carbamoyl-1H-benzimidazol-2-yl)-2-methylpyrrolidinium; Veliparib; ABT-888; 2-[(2R)-2-Methyl-2-pyrrolidinyl]-1H-benzimidazole-7-carboxamide; A 861695; ABT 888

Database IDs

• CAS Number: 912444-00-9
• PubChem SID: 160968315; 99443703
• PubChem CID: 11960529

CALCULATED PROPERTIES

JChem

• Acid pKa: 9.209064
• H Acceptors: 3
• H Donor: 3
• LogD (pH = 5.5): -2.3482244
• LogD (pH = 7.4): -1.1125933
• Log P: 0.18238126
• Molar Refractivity: 68.6215 cm^3
• Polarizability: 27.486767 Å^3
• Polar Surface Area: 83.8 Å^2
• Rotatable Bonds: 2
• Lipinski's Rule of Five: true

ALOGPS 2.1

• Log P: 1.1
• LOG S: -2.95
• Solubility (Water): 2.75e-01 g/l

PROPERTIES

Physical Property

• Solubility: DMSO; Methanol
• Apperance: White Solid
• Melting Point: 194-196°C

Safety Information

• Storage Condition: -20°C

Pharmacology Properties

• Target: PARP

Product Information

• Salt Data: Free Base

DETAILS

DrugBank - DB07232

Drug information: experimental

Selleck Chemicals - S1004

Research Area

• Description: Cancer

Protocol

• Protocol: Kinase Assay ^[1]
• In vitro PARP assays: PARP assays are conducted in a buffer containing 50 mM Tris (pH 8.0), 1 mM DTT, 1.5 μM [^3H]NAD^+ (1.6 μCi/mmol), 200 nM biotinylated histone H1, 200 nM slDNA, and 1 nM PARP-1 or 4 nM PARP-2 enzyme. Reactions are terminated with 1.5 mM benzamide, transferred to streptavidin Flash plates, and counted using a TopCount microplate scintillation counter.
• Protocol: Animal Study ^[1]
• Animal Models: NCI-H460, H460, B16F10 and 9L xenografts in C57BL/6 mice
• Formulation: Formulated in solution containing 0.9% NaCl adjusted to pH 4.0
• Doses: ~25 mg/kg
• Administration: Orally administered

References

• References: [1] Donawho CK, et al, Clin Cancer Res, 2007, 13 (9), 2728-2737.
• References: [2] Penning TD, et al, J Med Chem, 2009, 52(2), 514-523.
• References: [3] Albert JM, et al, Clin Cancer Res, 2007, 13(10), 3033-3042.
• References: [4] Kinders RJ, et al, Clin Cancer Res, 2008, 14(21), 6877-6885.
• References: [5] Kinders RJ, et al, Clin Cancer Res, 2008, 14(21), 6877-6885.
• References: [6] Horton TM, et al. 2007 ASCO Annual Meeting, Abstract 9528.
• References: [7] Liu X, et al. Mol Cancer Res, 2009, 7(10), 1686-1692.
• References: [8] Palma JP, et al. Clin Cancer Res, 2009, 15(23), 7277-7290.
• References: [9] Horton TM, et al. ASCO Annual Meeting, 2007, Abs 9528.
• References: [10] Clark CC, et al. Mol Cancer Ther, 2012 Jul 9.

Toronto Research Chemicals - A112580

ABT-888 is a potent, orally bioavailable PARP-1/-2 inhibitor shown to potentiate DNA damaging agents. The ability to potentiate temozolomide (TMZ) and develop a biological marker for PARP inhibition was evaluated in vivo.

REFERENCES

• Kinders RJ, et al, Clin Cancer Res, 2008, 14(21), 6877-6885.
• Clark CC, et al. Mol Cancer Ther, 2012 Jul 9.
• Donawho CK, et al, Clin Cancer Res, 2007, 13 (9), 2728-2737.
• Penning TD, et al, J Med Chem, 2009, 52(2), 514-523.
• Albert JM, et al, Clin Cancer Res, 2007, 13(10), 3033-3042.
• Kinders RJ, et al, Clin Cancer Res, 2008, 14(21), 6877-6885.
• Horton TM, et al. 2007 ASCO Annual Meeting, Abstract 9528.
• Liu X, et al. Mol Cancer Res, 2009, 7(10), 1686-1692.
• Palma JP, et al. Clin Cancer Res, 2009, 15(23), 7277-7290.
• Horton TM, et al. ASCO Annual Meeting, 2007, Abs 9528.
• Virag, L., et al.: Pharmacol. Rev., 54, 375 (2002)
• Tentori, L., et al.: Clin. Cancer Res., 9, 5370 (2002)
• Kim, M., et al.: Cell, 119, 803 (2002)
• Tentori, L., et al.: Pharmacol. Res., 52, 25 (2002)