Nolomirole
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| Other names | CHF-1035; CHF1035; 5,6-Diisobutyryloxy-N-methyl-2-aminotetralin; 5,6-Diisobutyryloxy-2-(methylamino)-1,2,3,4-tetrahydronaphthalene; 5,6,7,8-Tetrahydro-6-(methylamino)-1,2-naphthylene diisobutyrate; N-Methyl-2-aminotetralin |
| Routes of administration | Oral[1][2] |
| Drug class | Dopamine D2 receptor agonist; α2-Adrenergic receptor agonist |
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| Chemical and physical data | |
| Formula | C19H27NO4 |
| Molar mass | 333.428 g·mol−1 |
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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
- ^ a b c d e f g h i Leeson PA, Bayes M, Castaner J, Mealy NE (2001). "Nolomirole Hydrochloride". Drugs of the Future. 26 (11): 1046. doi:10.1358/dof.2001.026.11.642071. Retrieved 19 June 2025.
- ^ a b c d e Tang WH, Francis GS (November 2003). "Novel pharmacological treatments for heart failure". Expert Opinion on Investigational Drugs. 12 (11): 1791–1801. doi:10.1517/13543784.12.11.1791. PMID 14585055.
- ^ a b Dörwald FZ (4 February 2013). Lead Optimization for Medicinal Chemists: Pharmacokinetic Properties of Functional Groups and Organic Compounds. John Wiley & Sons. ISBN 978-3-527-64565-7. Retrieved 19 June 2025.
- ^ a b c "Nolomirole hydrochloride". AdisInsight. 9 January 2002. Retrieved 19 June 2025.
- ^ Fronza G, Bovis G, Ventura P, Redenti E (1992). "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. doi:10.1002/chir.530040613. ISSN 0899-0042. Retrieved 19 June 2025.