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
1. AstraZeneca. 
Accessed on 11/09/2014. Modified on 11/09/2014.,
2. George JT, Kakkar R, Marshall J, Scott ML, Finkelman RD, Ho TW, Veldhuis J, Skorupskaite K, Anderson RA, McIntosh S et al.. (2016)
Neurokinin B Receptor Antagonism in Women With Polycystic Ovary Syndrome: A Randomized, Placebo-Controlled Trial.
J Clin Endocrinol Metab, 101 (11): 4313-4321. [PMID:27459523]
3. Litman RE, Smith MA, Desai DG, Simpson T, Sweitzer D, Kanes SJ. (2014)
The selective neurokinin 3 antagonist AZD2624 does not improve symptoms or cognition in schizophrenia: a proof-of-principle study.
J Clin Psychopharmacol, 34 (2): 199-204. [PMID:24525659]
4. Prague JK, Roberts RE, Comninos AN, Clarke S, Jayasena CN, Mohideen P, Lin VH, Stern TP, Panay N, Hunter MS et al.. (2018)
Neurokinin 3 receptor antagonism rapidly improves vasomotor symptoms with sustained duration of action.
Menopause, 25 (8): 862-869. [PMID:29533369]
5. Prague JK, Roberts RE, Comninos AN, Clarke S, Jayasena CN, Nash Z, Doyle C, Papadopoulou DA, Bloom SR, Mohideen P et al.. (2017)
Neurokinin 3 receptor antagonism as a novel treatment for menopausal hot flushes: a phase 2, randomised, double-blind, placebo-controlled trial.
Lancet, 389 (10081): 1809-1820. [PMID:28385352]
6. Simpson T et al.. (2007)
Alkylsulphonamide quinolines.
Patent number: WO2007069977. Assignee: AstraZeneca. Priority date: 12/12/2005. Publication date: 11/12/2006.