3-{5-bromo-4-methyl-2-[(2S)-morpholin-2-ylmethoxy]phenyl}-1-(5-methylpyrazin-2-yl)urea

• ChemBase ID: 73156
• Molecular Formular: C18H22BrN5O3
• Molecular Mass: 436.30298
• Monoisotopic Mass: 435.09060159
• SMILES: c1c(c(cc(c1OC[C@@H]1CNCCO1)NC(=O)Nc1cnc(cn1)C)Br)C
• Canonical SMILES: O=C(Nc1cc(Br)c(cc1OC[C@@H]1CNCCO1)C)Nc1cnc(cn1)C
• InChI: InChI=1S/C18H22BrN5O3/c1-11-5-16(27-10-13-8-20-3-4-26-13)15(6-14(11)19)23-18(25)24-17-9-21-12(2)7-22-17/h5-7,9,13,20H,3-4,8,10H2,1-2H3,(H2,22,23,24,25)/t13-/m0/s1
• InChIKey: SYYBDNPGDKKJDU-ZDUSSCGKSA-N

NAMES AND DATABASE IDS

Names

• IUPAC name: 3-{5-bromo-4-methyl-2-[(2S)-morpholin-2-ylmethoxy]phenyl}-1-(5-methylpyrazin-2-yl)urea
• IUPAC Traditional name: 3-{5-bromo-4-methyl-2-[(2S)-morpholin-2-ylmethoxy]phenyl}-1-(5-methylpyrazin-2-yl)urea
• Synonyms: IC-83; LY 2603618; LY2603618

Database IDs

• CAS Number: 911222-45-2
• PubChem SID: 162038076
• PubChem CID: 11955855

CALCULATED PROPERTIES

• Acid pKa: 10.467224
• H Acceptors: 6
• H Donor: 3
• LogD (pH = 5.5): -0.57649153
• LogD (pH = 7.4): 1.1525708
• Log P: 2.010504
• Molar Refractivity: 107.2403 cm^3
• Polarizability: 40.06984 Å^3
• Polar Surface Area: 97.4 Å^2
• Rotatable Bonds: 5
• Lipinski's Rule of Five: true

PROPERTIES

Safety Information

• Storage Condition: -20°C

Pharmacology Properties

• Target: CHK

Product Information

• Salt Data: Free Base

DETAILS

Selleck Chemicals - S2626

Biological Activity

• Description: LY2603618 (IC-83) is a selective Chk1 inhibitor with potential anti-tumor activity.
• Targets: Chk1
• In Vitro: Chk1 is an ATP-dependent serine-threonine kinase and a key component in the DNA replication-monitoring checkpoint system activated by double-stranded breaks (DSBs). Chk1 contributes to all currently defined cell cycle checkpoints, including G1/S, intra-S-phase, G2/M, and the mitotic spindle checkpoint. By inhibiting the activity of chk1, LY2603618 prevents the repair of DNA caused by DNA-damaging agents, thus potentiating the antitumor efficacies of various chemotherapeutic agents. However, preclinical data involving LY2603618 has not been published until now. ^[1] Inhibition of Chk1 is predicted to enhance the effects of antimetabolites, such as gemcitabine. ^[2] LY2603618 treatment impairs DNA synthesis, increases DNA damage (via mitotic defects), induces apoptosis, and has synergistic activity with pemetrexed, especially in p53 mutant tumor cells. ^[3]
• In Vivo: In xenograft models, LY2603618 delays tumor growth when given in combination with pemetrexed. ^[3]
• Clinical Trials: A Phase I study of to assess the effect of LY2603618 on the metabolic pathway of Desipramine is ongoing.

References

• References: [1] Dai Y, et al. Clin Cancer Res, 2010, 16(2), 376-383.
• References: [2] Emiliano Calvo1, et al. Mol Cancer Ther, 2011, A94.
• References: [3] Govindan R. J Thorac Oncol, 2011, 6(11 Suppl 4), S1757.

REFERENCES

• Dai Y, et al. Clin Cancer Res, 2010, 16(2), 376-383.
• Emiliano Calvo1, et al. Mol Cancer Ther, 2011, A94.
• Govindan R. J Thorac Oncol, 2011, 6(11 Suppl 4), S1757.