GtoPdb Ligand ID: 9844

Synonyms: Formula (10) [WO2012078708A1]
Compound class: Synthetic organic
Comment: 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].
2D Structure
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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 -0.01
No. Lipinski's rules broken 0
Canonical SMILES OC(=O)C(NC(=O)c1ccc(cc1)CCc1ccc2c(c1)c(N)nc(n2)N)CC(=C)C(=O)O
Isomeric SMILES OC(=O)[C@@H](NC(=O)c1ccc(cc1)CCc1ccc2c(c1)c(N)nc(n2)N)CC(=C)C(=O)O
InChI InChI=1S/C23H23N5O5/c1-12(21(30)31)10-18(22(32)33)26-20(29)15-7-4-13(5-8-15)2-3-14-6-9-17-16(11-14)19(24)28-23(25)27-17/h4-9,11,18H,1-3,10H2,(H,26,29)(H,30,31)(H,32,33)(H4,24,25,27,28)/t18-/m0/s1
Compound class Synthetic organic
(2S)-2-[[4-[2-(2,4-diaminoquinazolin-6-yl)ethyl]benzoyl]amino]-4-methylidenepentanedioic acid
Formula (10) [WO2012078708A1]
Database Links
GtoPdb PubChem SID 363894138
PubChem CID 11532464
Search Google for chemical match using the InChIKey NAWXUBYGYWOOIX-SFHVURJKSA-N
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