Chemistry:Nolomirole
Nolomirole (INN; developmental code name CHF-1035), also known as 5,6-diisobutyryloxy-N-methyl-2-aminotetralin, is a dual dopamine D2 and α2-adrenergic receptor agonist which was under development for the treatment of heart failure but was never marketed.[1][2][3][4] It is taken orally.[1][2]
Pharmacology
The drug acts as an agonist of the dopamine D2 receptor, with an affinity (Ki) of 120 nM for the (–)- enantiomer and 2,400 nM for the (+)- enantiomer, and as an agonist of the α2-adrenergic receptor, with an affinity (Ki) of 130 nM for the (–)- enantiomer and 1,600 nM for the (+)- enantiomer.[1][2] It is a prodrug of CHF-1024 (5,6-dihydroxy-N-methyl-2-aminotetralin), to which it is rapidly hydrolyzed by circulating esterase enzymes.[1] The elimination half-life of nolomirole is said to be 3 hours and its log P is 1.97.[3]
Chemistry
Nolomirole and its active form CHF-1024 are cyclized phenethylamines and 2-aminotetralin analogues of the catecholamine neurotransmitter dopamine and its N-methyl derivative epinine (deoxyepinephrine, N-methyldopamine).[1][2]
History
Nolomirole was first described in the scientific literature by 1992.[1][5] It was being developed by the pharmaceutical company Chiesi Farmaceutici in the 1990s and 2000s.[1][4] Nolomirole reached phase 3 clinical trials prior to the discontinuation of its development.[1][4]
See also
- Cyclized phenethylamine
- Rotigotine
- 5-OH-DPAT
- 7-OH-DPAT
- Ibopamine
- Fosopamine
- O,O′-Diacetyldopamine
- Docarpamine
- Neurotransmitter prodrug
- Carmoxirole
References
- ↑ 1.0 1.1 1.2 1.3 1.4 1.5 1.6 1.7 "Nolomirole Hydrochloride". Drugs of the Future 26 (11): 1046. 2001. doi:10.1358/dof.2001.026.11.642071. http://access.portico.org/stable?au=pjbf78xdt6c. Retrieved 19 June 2025.
- ↑ 2.0 2.1 2.2 2.3 "Novel pharmacological treatments for heart failure". Expert Opinion on Investigational Drugs 12 (11): 1791–1801. November 2003. doi:10.1517/13543784.12.11.1791. PMID 14585055.
- ↑ 3.0 3.1 Lead Optimization for Medicinal Chemists: Pharmacokinetic Properties of Functional Groups and Organic Compounds. John Wiley & Sons. 4 February 2013. ISBN 978-3-527-64565-7. https://books.google.com/books?id=YTeY9ZEfNccC&dq=nolomirole&pg=PA275. Retrieved 19 June 2025.
- ↑ 4.0 4.1 4.2 "Nolomirole hydrochloride". 9 January 2002. https://adisinsight.springer.com/drugs/800003364.
- ↑ "Application of γ-cyclodextrin to enantiomeric purity determination of a new 2-amino-tetralin derivative by 1 H-NMR spectroscopy". Chirality 4 (6): 404–405. 1992. doi:10.1002/chir.530040613. ISSN 0899-0042. https://onlinelibrary.wiley.com/doi/10.1002/chir.530040613. Retrieved 19 June 2025.
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