pavinetant   Click here for help

GtoPdb Ligand ID: 5775

Synonyms: AZD-2624 | AZD4901 | MLE4901
Compound class: Synthetic organic
Comment: Pavinetant (AZD2624) is an orally active antagonist of neurokinin receptor 3 (TACR3) developed initially by AstraZeneca as a potential therapeutic for schizophrenia. This compound was included in AstaZeneca's Open Innovation Pharmacology Toolbox (but has since been removed). Later renamed to AZD4901 it was acquired by Millendo Therapeutics who gave it a new research code of MLE4901 for their development programs for polycystic ovary syndrome and menopausal hot flushes. A successful Phase 2 study for the latter indication was reported in April 2017 [5]. A total of eight analogues are disclosed in the AstraZeneca composition of matter filing [6],
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2D Structure
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Physico-chemical Properties
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Hydrogen bond acceptors 6
Hydrogen bond donors 2
Rotatable bonds 8
Topological polar surface area 96.54
Molecular weight 459.16
XLogP 5.82
No. Lipinski's rules broken 1
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Canonical SMILES CCC(c1ccccc1)NC(=O)c1c(NS(=O)(=O)C)c(nc2c1cccc2)c1ccccc1
Isomeric SMILES CC[C@@H](c1ccccc1)NC(=O)c1c(NS(=O)(=O)C)c(nc2c1cccc2)c1ccccc1
InChI InChI=1S/C26H25N3O3S/c1-3-21(18-12-6-4-7-13-18)28-26(30)23-20-16-10-11-17-22(20)27-24(19-14-8-5-9-15-19)25(23)29-33(2,31)32/h4-17,21,29H,3H2,1-2H3,(H,28,30)/t21-/m0/s1
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Summary of Clinical Use Click here for help
As AZD2624 the compound failed in a schizophrenia proof-of-principle study [3] (see NCT00686998). A trial of AZD4901 for polycystic ovary syndrome (PCOS) was reported in 2016 [2] (see NCT01872078). As MLE4901 this compound has completed Phase 2 clinical trial for management of menopausal hot flushes [5]. MLE4901 was found to be safe and effective in this trial (see NCT02668185). A Phase 2 study for the treatment of PCOS (NCT02865915) was terminated because the risk/benefit profile did not warrant continued development.
Clinical Trials
Clinical Trial ID Title Type Source Comment References
NCT02668185 Neuropeptide Treatment for Hot Flushes During the Menopause Phase 2 Interventional Imperial College London 4-5
NCT00686998 Phase IIA Study in Patients With Schizophrenia Phase 2 Interventional AstraZeneca
NCT01872078 A Study of AZD4901 in Females With Polycystic Ovary Syndrome Phase 2 Interventional AstraZeneca
NCT02865915 MLE4901 vs. Placebo for the Treatment of PCOS Phase 2 Interventional Millendo Therapeutics, Inc.