compound 39 [PMID: 31742400]   Click here for help

GtoPdb Ligand ID: 10585

Immunopharmacology Ligand
Compound class: Synthetic organic
Comment: Compound 39 is a dual antagonist of the CC-chemokine receptors CCR2 and CCR5 [3]. It is one of the most potent lead molecules that were reported in this 2019 Journal of Medicinal Chemistry paper. Experiments measuring antagonism of CCL3-induced [35S]GTPγS binding indicates that 39 binds to an allosteric site of both target receptors, which is likely to be located on the intracellular face of the receptiors. The compound is described as an insurmountable antagonist.
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2D Structure
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Physico-chemical Properties
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Hydrogen bond acceptors 3
Hydrogen bond donors 2
Rotatable bonds 3
Topological polar surface area 89.07
Molecular weight 351.07
XLogP 3.79
No. Lipinski's rules broken 0
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Canonical SMILES Nc1nn2c(n1)[nH]c(c(c2=O)Cc1cccc(c1Cl)Cl)C(C)C
Isomeric SMILES Nc1nn2c(n1)[nH]c(c(c2=O)Cc1cccc(c1Cl)Cl)C(C)C
InChI InChI=1S/C15H15Cl2N5O/c1-7(2)12-9(6-8-4-3-5-10(16)11(8)17)13(23)22-15(19-12)20-14(18)21-22/h3-5,7H,6H2,1-2H3,(H3,18,19,20,21)
1. Fantuzzi L, Tagliamonte M, Gauzzi MC, Lopalco L. (2019)
Dual CCR5/CCR2 targeting: opportunities for the cure of complex disorders.
Cell Mol Life Sci, 76 (24): 4869-4886. [PMID:31377844]
2. Friedman SL, Ratziu V, Harrison SA, Abdelmalek MF, Aithal GP, Caballeria J, Francque S, Farrell G, Kowdley KV, Craxi A et al.. (2018)
A randomized, placebo-controlled trial of cenicriviroc for treatment of nonalcoholic steatohepatitis with fibrosis.
Hepatology, 67 (5): 1754-1767. [PMID:28833331]
3. Ortiz Zacarías NV, van Veldhoven JPD, den Hollander LS, Dogan B, Openy J, Hsiao YY, Lenselink EB, Heitman LH, IJzerman AP. (2019)
Synthesis and Pharmacological Evaluation of Triazolopyrimidinone Derivatives as Noncompetitive, Intracellular Antagonists for CC Chemokine Receptors 2 and 5.
J Med Chem, 62 (24): 11035-11053. [PMID:31742400]
4. Zhao Q. (2010)
Dual targeting of CCR2 and CCR5: therapeutic potential for immunologic and cardiovascular diseases.
J Leukoc Biol, 88 (1): 41-55. [PMID:20360402]