nolomirole
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{{Infobox drug
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| image = Nolomirole.svg
| width = 250px
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| routes_of_administration = Oral
| class = Dopamine D2 receptor agonist; α2-Adrenergic receptor agonist
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| CAS_number = 90060-42-7
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| PubChem = 216238
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| ChemSpiderID = 187439
| UNII = 6EMF80C55F
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| ChEMBL = 2105142
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| synonyms = 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
| IUPAC_name = [6-(methylamino)-1-(2-methylpropanoyloxy)-5,6,7,8-tetrahydronaphthalen-2-yl] 2-methylpropanoate
| C=19 | H=27 | N=1 | O=4
| SMILES = CC(C)C(=O)OC1=C(C2=C(CC(CC2)NC)C=C1)OC(=O)C(C)C
| StdInChI = 1S/C19H27NO4/c1-11(2)18(21)23-16-9-6-13-10-14(20-5)7-8-15(13)17(16)24-19(22)12(3)4/h6,9,11-12,14,20H,7-8,10H2,1-5H3
| StdInChIKey = OMMYLOLVPCCZQZ-UHFFFAOYSA-N
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Nolomirole ({{Abbrlink|INN|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.{{cite journal | vauthors = Leeson PA, Bayes M, Castaner J, Mealy NE | title = Nolomirole Hydrochloride | journal = Drugs of the Future | volume = 26 | issue = 11 | pages = 1046 | date = 2001 | doi = 10.1358/dof.2001.026.11.642071 | url = http://access.portico.org/stable?au=pjbf78xdt6c | access-date = 19 June 2025 }}{{cite journal | vauthors = Tang WH, Francis GS | title = Novel pharmacological treatments for heart failure | journal = Expert Opinion on Investigational Drugs | volume = 12 | issue = 11 | pages = 1791–1801 | date = November 2003 | pmid = 14585055 | doi = 10.1517/13543784.12.11.1791 }}{{cite book | vauthors = Dörwald FZ | title = Lead Optimization for Medicinal Chemists: Pharmacokinetic Properties of Functional Groups and Organic Compounds | date = 4 February 2013 | publisher = John Wiley & Sons | isbn = 978-3-527-64565-7 | url = https://books.google.com/books?id=YTeY9ZEfNccC&dq=nolomirole&pg=PA275 | access-date = 19 June 2025 }}{{cite web | title = Nolomirole hydrochloride | date = 9 January 2002 | website = AdisInsight | url = https://adisinsight.springer.com/drugs/800003364 | access-date = 19 June 2025 }} It is taken orally.
Pharmacology
The drug acts as an agonist of the dopamine D2 receptor, with an affinity (Ki) of 120{{nbsp}}nM for the (–)- enantiomer and 2,400{{nbsp}}nM for the (+)- enantiomer, and as an agonist of the α2-adrenergic receptor, with an affinity (Ki) of 130{{nbsp}}nM for the (–)- enantiomer and 1,600{{nbsp}}nM for the (+)- enantiomer. It is a prodrug of CHF-1024 (5,6-dihydroxy-N-methyl-2-aminotetralin), to which it is rapidly hydrolyzed by circulating esterase enzymes. The elimination half-life of nolomirole is said to be 3{{nbsp}}hours and its log P is 1.97.
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).
History
Nolomirole was first described in the scientific literature by 1992.{{cite journal | vauthors = Fronza G, Bovis G, Ventura P, Redenti E | title = Application of γ-cyclodextrin to enantiomeric purity determination of a new 2-amino-tetralin derivative by 1 H-NMR spectroscopy | journal = Chirality | volume = 4 | issue = 6 | pages = 404–405 | date = 1992 | doi = 10.1002/chir.530040613 | issn = 0899-0042 | url = https://onlinelibrary.wiley.com/doi/10.1002/chir.530040613 | access-date = 19 June 2025 }} It was being developed by the pharmaceutical company Chiesi in the 1990s and 2000s. Nolomirole reached phase 3 clinical trials prior to the discontinuation of its development.
See also
References
{{Reflist}}
{{Dopamine receptor modulators}}
{{Adrenergic receptor modulators}}
{{Phenethylamines}}