Nolomirole (INNTooltip International Nonproprietary Name; 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

References

  1. 1 2 3 4 5 6 7 8 9 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.
  2. 1 2 3 4 5 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.
  3. 1 2 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.
  4. 1 2 3 "Nolomirole hydrochloride". AdisInsight. 9 January 2002. Retrieved 19 June 2025.
  5. ↑ 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.


source: https://en.wikipedia.org/wiki/Nolomirole