CH-4051

Ligand id: 9844

Name: CH-4051

Structure and Physico-chemical Properties

2D Structure
Calculated Physico-chemical Properties
Hydrogen bond acceptors 10
Hydrogen bond donors 5
Rotatable bonds 10
Topological polar surface area 181.52
Molecular weight 449.17
XLogP 1.13
No. Lipinski's rules broken 0

Molecular properties generated using the CDK

Classification
Compound class Synthetic organic
IUPAC Name
(2S)-2-[[4-[2-(2,4-diaminoquinazolin-6-yl)ethyl]benzoyl]amino]-4-methylidenepentanedioic acid
Synonyms
Formula (10) [WO2012078708A1]
Comments
CH-4051 is an orally available methotrexate (MTX) analogue that is designed to resist metabolic degradation [4-5]. This strategy was employed to improve the safety and tolerability profile compared to MTX, since a significant proportion of the toxicity profile of MTX can be attributed to its polyglutamylated and hydroxylated metabolites. Like MTX, CH-4051 has anti-inflammatory, autoimmune and anti-tumour properties and is a potent inhibitor of dihydrofolate reductase, an enzyme required for cell proliferation. The racemic mixture of CH-4051, known as CH-1405 (represented by the non-chiral structure in PubChem CID 9846537) [3], completed Phase 2 development for rheumatoid arthritis, and exhibited comparable efficacy to MTX [1-2]. Structurally, CH-4051 is the more active L-4'-methylene-glutamic acid containing diastereomer (or S-enantiomer) of CH-1405 [5].
Database Links
GtoPdb PubChem SID 363894138
PubChem CID 11532464
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