{{short description|Chemical compound}} {{Drugbox | verifiedrevid = 448141571 | IUPAC_name = (''RS'')-4-[3-(tert-butylamino)-2-hydroxypropoxy]-2-methylisoquinolin-1-one | image = Tilisolol.svg | image_class = skin-invert-image | chirality = Racemic mixture | drug_name = <!--Clinical data--> | tradename = | Drugs.com = {{drugs.com|international|tilisolol}} | pregnancy_AU = <!-- A / B1 / B2 / B3 / C / D / X --> | pregnancy_US = <!-- A / B / C / D / X --> | pregnancy_category = | legal_AU = <!-- S2, S3, S4, S5, S6, S7, S8, S9 or Unscheduled--> | legal_CA = <!-- Schedule I, II, III, IV, V, VI, VII, VIII --> | legal_UK = <!-- GSL, P, POM, CD, or Class A, B, C --> | legal_US = <!-- OTC / Rx-only / Schedule I, II, III, IV, V --> | legal_status = Rx-only | routes_of_administration = Oral
<!--Pharmacokinetic data--> | bioavailability = | protein_bound = | metabolism = | elimination_half-life = | excretion =
<!--Identifiers--> | CAS_number_Ref = {{cascite|correct|??}} | CAS_number = 85136-71-6 | CAS_supplemental = <br/>{{CAS|62774-96-3}} (hydrochloride) | ATC_prefix = none | ATC_suffix = | ATC_supplemental = | PubChem = 5474 | DrugBank_Ref = {{drugbankcite|correct|drugbank}} | DrugBank = | UNII_Ref = {{fdacite|correct|FDA}} | UNII = QUF41MF56G | KEGG_Ref = {{keggcite|correct|kegg}} | KEGG = D08598 | ChemSpiderID = 5275
<!--Chemical data--> | C=17 | H=24 | N=2 | O=3 | smiles = CC(C)(C)NCC(COC1=CN(C(=O)C2=CC=CC=C21)C)O | StdInChI = 1S/C17H24N2O3/c1-17(2,3)18-9-12(20)11-22-15-10-19(4)16(21)14-8-6-5-7-13(14)15/h5-8,10,12,18,20H,9,11H2,1-4H3 | StdInChIKey = TWVUMMQUXMYOOH-UHFFFAOYSA-N }}
'''Tilisolol''' (INN, trade name '''Selecal''') is a beta blocker.<ref name="pmid2906248">{{cite journal | vauthors = Imaizumi T, Takeshita A, Nakamura N, Hirooka Y, Suzuki S, Yoshida M, Nakamura M | title = Vasodilating effect of the new beta-blocker tilisolol hydrochloride in humans | journal = Arzneimittel-Forschung | volume = 38 | issue = 9 | pages = 1342–4 | date = September 1988 | pmid = 2906248 | doi = | url = }}</ref>
==Synthesis== [[File:Tilisolol synthesis.svg|center|500px|thumb|class=skin-invert-image|[https://pharmaceutical-substances.thieme.com/ps/search-results?docUri=KD-20-0089 Thieme] [https://www.chemdrug.com/article/8/3284/16419653.html ChemDrug] Synthesis:<ref>Serradell, MN; Blancafort, P.; Thorpe, PJ; Castaer, J.; N-696. Drugs Fut 1982, 7, 12, 889.</ref> Patent:<ref>Hideo Saitama Jp Fukushima, Yoshikuni Kawagoe Saitama Jp Suzuki, DE2631080 (1985 to Nisshin Flour Milling Co., Ltd., Tokio / Tokyo, Jp).</ref> Precursor:<ref>Lombardino, J. G. (October 1970). "Synthesis of 4‐hydroxy‐2‐methylisocarbostyril‐3‐carboxanilides". Journal of Heterocyclic Chemistry. 7 (5): 1057–1060. doi:10.1002/jhet.5570070509.</ref> Sino:<ref>Li Leilei, et al. CN102115459 (2011 to Dihon Pharmaceutical Group Co Ltd).</ref> HPLC:<ref>Yonezawa K, Sato K, Kobayashi A. High-performance liquid chromatography of a new beta-blocker, 4-[3-(tert.-butylamino)-2-hydroxypropoxy]-N-methylisocarbostyril hydrochloride, in plasma using fluorometric detection. J Chromatogr. 1985 Apr 12;339(1):219-22. doi: 10.1016/s0378-4347(00)84648-4. PMID: 2862154.</ref>]]
The methanolysis of Phthalic anhydride [85-44-9] (1) gives Methyl hydrogen phthalate [4376-18-5] (2). Schotten-Baumann amidation with Methyl sarcosinate [5473-12-1] (3) gives Methyl 2-[(2-methoxy-2-oxoethyl)-methylcarbamoyl]benzoate, PC11644670 (4). Intramolecular lactamization with sodium methoxide afforded Methyl 4-hydroxy-2-methyl-1-oxoisoquinoline-3-carboxylate, PC54684295 (5). In lye saponification followed by decarboxylation occurred to give 4-hydroxy-2-methylisoquinolin-1(2H)-one [30236-50-1] (6). Treatment with Epichlorhydrin [106-89-8] (7) in the presence of base led to 2-Methyl-4-[(oxiran-2-yl)methoxy]isoquinolin-1(2H)-one [62775-08-0] (8). Opening of the oxirane ring with tert-Butylamine [75-64-9] (9) completed the synthesis of Tilisolol (10).
== References == {{Reflist}}
{{Beta blockers}}
Category:Beta blockers Category:Lactams Category:Isoquinolines Category:Phenol ethers Category:Secondary alcohols Category:Secondary amines Category:Tert-butyl compounds
{{antihypertensive-stub}}