Prenalterol

Prenalterol
Clinical data
Trade names	Hyprenan
Other names	CGP-7760B; CGP-7760/B; H-133/22; IHP
Routes of; administration	Oral, IV
ATC code	C01CA13 (WHO) ;
Legal status
Legal status	In general: ℞ (Prescription only);
Identifiers
	IUPAC name 4-{[(2S)-2-hydroxy-3-(isopropylamino)propyl]oxy}phenol;
CAS Number	57526-81-5 ;
PubChem CID	42396;
IUPHAR/BPS	537;
ChemSpider	38665 ;
UNII	M4G34404CX;
ChEMBL	ChEMBL1160714 ;
CompTox Dashboard (EPA)	DTXSID8023507 ;
ECHA InfoCard	100.055.246
Chemical and physical data
Formula	C12H19NO3
Molar mass	225.288 g·mol−1
3D model (JSmol)	Interactive image;
	SMILES O(c1ccc(O)cc1)C[C@@H](O)CNC(C)C;
	InChI InChI=1S/C12H19NO3/c1-9(2)13-7-11(15)8-16-12-5-3-10(14)4-6-12/h3-6,9,11,13-15H,7-8H2,1-2H3/t11-/m0/s1 ; Key:ADUKCCWBEDSMEB-NSHDSACASA-N ;
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Prenalterol, sold under the brand name Hyprenan, is a sympathomimetic agent and cardiac stimulant which acts as a β₁-adrenergic receptor partial agonist and is used in the treatment of heart failure.^[1]^[2]^[3]^[4]^[5] It has selectivity for the β₁-adrenergic receptor.^[1]^[2]^[3]^[4] Its partial agonist activity or intrinsic sympathomimetic activity is about 60%.^[6] It is said to have much greater impact on myocardial contractility than on heart rate.^[4] The drug has been marketed in Denmark, Norway, and Sweden.^[2]

Chemistry

Synthesis

Stereospecific

Prenalterol exhibits adrenergic agonist activity in spite of an interposed oxymethylene group. The stereospecific synthesis devised for this molecule relies on the fact that the side chain is very similar in oxidation state to that of a sugar.^[7]^[8]

Condensation of monobenzone (2) with the epoxide derived from α-D-glucofuranose^[9] affords the glycosylated derivative (3). Hydrolytic removal of the acetonide protecting groups^[10] followed by cleavage of the sugar with periodate gives aldehyde (4). This is reduced to the glycol by means of NaBH₄ and the terminal alcohol is converted to the mesylate (5). Displacement of the leaving group with isopropylamine followed by hydrogenolytic removal of the O-benzyl ether affords the β₁-adrenergic selective adrenergic agonist prenalterol (6).

Racemic

Several preparations of the racemic mixture have been reported.^[11]^[12]^[13]^[14]^[15]

References

^ ^a ^b Elks J (2014). The Dictionary of Drugs: Chemical Data: Chemical Data, Structures and Bibliographies. Springer US. p. 1014. ISBN 978-1-4757-2085-3. Retrieved 2024-08-29.
^ ^a ^b ^c Schweizerischer Apotheker-Verein (2000). Index Nominum 2000: International Drug Directory. Index nominum. Medpharm Scientific Publishers. p. 873. ISBN 978-3-88763-075-1. Retrieved 29 August 2024.
^ ^a ^b Morton IK, Hall JM (2012). Concise Dictionary of Pharmacological Agents: Properties and Synonyms. Springer Netherlands. p. 231. ISBN 978-94-011-4439-1. Retrieved 2024-08-29.
^ ^a ^b ^c Kendall MJ, Goodfellow RM, Westerling S (June 1982). "Prenalterol--a new cardioselective inotropic agent". J Clin Hosp Pharm. 7 (2): 107–118. doi:10.1111/j.1365-2710.1982.tb01010.x. PMID 7050180.
^ Hadfield SE, Slee SJ, Snow HM (1989). "The cardiovascular pharmacology of xamoterol, cicloprolol, prenalterol and pindolol in the anaesthetised dog". British Journal of Clinical Pharmacology. 28 (Suppl 1): 78S–81S. doi:10.1111/j.1365-2125.1989.tb03580.x. PMC 1379883. PMID 2572262.
^ Wirtzfeld A, Klein G, Bibra HV, Sauer E (January 1985). "Prenalterol: a partial beta 1-adrenoceptor agonist or a beta-blocker with intrinsic activity?". Int J Clin Pharmacol Ther Toxicol. 23 (1): 20–27. PMID 2859252.
^ DE 2503968, Jaeggi KA, Schröter H, Ostermayer F, "Optisch aktive Derivate des 1-Phenoxy-2-hydroxy-3-aminopropan und Verfahren zu ihrer Herstellung [Optically active derivatives of 1-phenoxy-2-hydroxy-3-aminopropane and the process for their production]", published 1975-08-14, assigned to Ciba-Geigy AG Chem. Abstr. 84, 5322 (1976).
^ corresp to U.S. patent 3,978,041 and U.S. patent 4,049,797 (1975, 1976, 1977, all to Ciba-Geigy)
^ "Α-D-Glucofuranose | C6H12O6". ChemSpider.
^ Liu Z, Hu BH, Messersmith PB (May 2010). "Acetonide Protection of Dopamine for the Synthesis of Highly Pure N-docosahexaenoyldopamine". Tetrahedron Letters. 51 (18): 2403–2405. doi:10.1016/j.tetlet.2010.02.089. PMC 2882309. PMID 20543896.
^ NL 6409883 H. Köppe et al.
^ U.S. patent 3,637,852 (1965, 1972 both to Boehringer Ingelheim)
^ NL 301580 A. F. Crowther, L. H. Smith
^ U.S. patent 3,501,769 (1965, 1970 both to ICI)
^ Crowther AF, Gilman DJ, McLoughlin BJ, Smith LH, Turner RW, Wood TM (July 1969). "Beta-Adrenergic blocking agents. V. 1-Amino-3-(substituted phenoxy)-2-propanols". Journal of Medicinal Chemistry. 12 (4): 638–642. doi:10.1021/jm00304a018. PMID 5793156.