Tilisolol

Tilisolol
Clinical data
AHFS/Drugs.com	International Drug Names
Routes of; administration	Oral
ATC code	none;
Legal status
Legal status	In general: ℞ (Prescription only);
Identifiers
	IUPAC name (RS)-4-[3-(tert-butylamino)-2-hydroxypropoxy]-2-methylisoquinolin-1-one;
CAS Number	85136-71-6 ; 62774-96-3 (hydrochloride);
PubChem CID	5474;
ChemSpider	5275;
UNII	QUF41MF56G;
KEGG	D08598 ;
CompTox Dashboard (EPA)	DTXSID0043846 ;
Chemical and physical data
Formula	C17H24N2O3
Molar mass	304.390 g·mol−1
3D model (JSmol)	Interactive image;
Chirality	Racemic mixture
	SMILES CC(C)(C)NCC(COC1=CN(C(=O)C2=CC=CC=C21)C)O;
	InChI InChI=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; Key:TWVUMMQUXMYOOH-UHFFFAOYSA-N;
	(verify)

Tilisolol (INN, trade name Selecal) is a beta blocker.^[1]

Synthesis

Thieme ChemDrug Synthesis:^[2] Patent:^[3] Precursor:^[4] Sino:^[5] HPLC:^[6]

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

^ Imaizumi T, Takeshita A, Nakamura N, Hirooka Y, Suzuki S, Yoshida M, Nakamura M (September 1988). "Vasodilating effect of the new beta-blocker tilisolol hydrochloride in humans". Arzneimittel-Forschung. 38 (9): 1342–4. PMID 2906248.
^ Serradell, MN; Blancafort, P.; Thorpe, PJ; Castaer, J.; N-696. Drugs Fut 1982, 7, 12, 889.
^ Hideo Saitama Jp Fukushima, Yoshikuni Kawagoe Saitama Jp Suzuki, DE2631080 (1985 to Nisshin Flour Milling Co., Ltd., Tokio / Tokyo, Jp).
^ 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.
^ Li Leilei, et al. CN102115459 (2011 to Dihon Pharmaceutical Group Co Ltd).
^ 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.

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[pmid2906248-1] Imaizumi T, Takeshita A, Nakamura N, Hirooka Y, Suzuki S, Yoshida M, Nakamura M (September 1988). "Vasodilating effect of the new beta-blocker tilisolol hydrochloride in humans". Arzneimittel-Forschung. 38 (9): 1342–4. PMID 2906248.

[2] Serradell, MN; Blancafort, P.; Thorpe, PJ; Castaer, J.; N-696. Drugs Fut 1982, 7, 12, 889.

[3] Hideo Saitama Jp Fukushima, Yoshikuni Kawagoe Saitama Jp Suzuki, DE2631080 (1985 to Nisshin Flour Milling Co., Ltd., Tokio / Tokyo, Jp).

[4] 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.

[5] Li Leilei, et al. CN102115459 (2011 to Dihon Pharmaceutical Group Co Ltd).

[6] 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.

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Clinical data

AHFS/Drugs.com	International Drug Names
Routes of administration	Oral
ATC code	none
Legal status
Legal status	In general: ℞ (Prescription only)
Identifiers
IUPAC name (RS)-4-[3-(tert-butylamino)-2-hydroxypropoxy]-2-methylisoquinolin-1-one
CAS Number	85136-71-6^Y 62774-96-3 (hydrochloride)
PubChem CID	5474
ChemSpider	5275
UNII	QUF41MF56G
KEGG	D08598^Y
CompTox Dashboard (EPA)	DTXSID0043846
Chemical and physical data
Formula	C₁₇H₂₄N₂O₃
Molar mass	304.390 g·mol⁻¹
3D model (JSmol)	Interactive image
Chirality	Racemic mixture
SMILES CC(C)(C)NCC(COC1=CN(C(=O)C2=CC=CC=C21)C)O
InChI InChI=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 Key:TWVUMMQUXMYOOH-UHFFFAOYSA-N
(verify)