1206799-15-6 (Merestinib)
Chemical Formula: C30H22F2N6O3
Exact Mass: 552.17215
N-(3-fluoro-4-((1-methyl-6-(1H-pyrazol-4-yl)-1H-indazol-5-yl)oxy)phenyl)-1-(4-fluorophenyl)-6-methyl-2-oxo-1,2-dihydropyridine-3-carboxamide
- OriginatorEli Lilly
- ClassAmides; Antineoplastics; Dihydropyridines; Pyrazoles; Small molecules
- Mechanism of ActionMKNK1 protein inhibitors; MKNK2 protein inhibitors; Proto oncogene protein c met inhibitors; ROS1-protein-inhibitors
- 29 Jun 2015Immunocore in collaboration with Eli Lilly plans a phase Ib/II trial for Uveal Melanoma (Metastatic disease, Combination therapy)
- 18 Jun 2015Eli Lilly completes a phase I bioavailability trial in healthy volunteers in USA (NCT02370485)
- 01 Feb 2015Eli Lilly initiates enrolment in a phase I bioavailability trial in healthy volunteers in USA (NCT02370485)
| Company | Eli Lilly and Co. |
| Description | C-Met inhibitor |
| Molecular Target | c-Met receptor tyrosine kinase (c-MET) (MET) (HGFR) (c-Met proto-oncogene) |
| Mechanism of Action | c-Met receptor tyrosine kinase inhibitor |
| Therapeutic Modality | Small molecule |
| Latest Stage of Development | Phase II |
| Standard Indication | Cancer (unspecified) |
| Indication Details | Treat advanced cancer |
LY2801653 was identified and developed as a novel, potent, and orally active small molecule inhibitor of human c-Met. It demonstrated dose dependent inhibition of c-Met phosphorylation in xenograft tumors with a long lasting PD effect. LY2801653 displayed potent anti-tumor efficacy in a number of non small cell lung, renal, pancreatic, and breast tumor models. Examination of c-Met expression in these tumors by immunohistochemistry (IHC) revealed a good correlation between response and c-Met expression in the tumor tissue. LY2801653 treatment led to increase in functional vessel areas, and decrease in tumor hypoxia. Enhanced anti-tumor efficacy was achieved when Erlotinib was combined with LY2801653. . (source: http://cancerres.aacrjournals.org/cgi/content/meeting_abstract/70/8_MeetingAbstracts/3611).
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References |
1: Yan SB, Peek VL, Ajamie R, Buchanan SG, Graff JR, Heidler SA, Hui YH, Huss KL, Konicek BW, Manro JR, Shih C, Stewart JA, Stewart TR, Stout SL, Uhlik MT, Um SL, Wang Y, Wu W, Yan L, Yang WJ, Zhong B, Walgren RA. LY2801653 is an orally bioavailable multi-kinase inhibitor with potent activity against MET, MST1R, and other oncoproteins, and displays anti-tumor activities in mouse xenograft models. Invest New Drugs. 2012 Dec 29. [Epub ahead of print] PubMed PMID: 23275061.
An NH4Cl-catalyzed ethoxy ethyl deprotection was developed for the synthesis of merestinib, a MET inhibitor. Alternative reactor technologies using temperatures above the solvent boiling point are combined with this mild catalyst to promote the deprotection reaction. The reaction is optimized for flow and has been used to synthesize over 100 kg of the target compound. The generality of the reaction conditions is also demonstrated with other compounds and protecting groups.
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Filed under: Uncategorized
