AZALANSTAT DIHYDROCHLORIDE

Possibly Marketed Outside US

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C22H24ClN3O2S.2ClH
Molecular Weight	502.885
Optical Activity	UNSPECIFIED
Defined Stereocenters	2 / 2
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

Cl.Cl.NC1=CC=C(SC[C@@H]2CO[C@](CCC3=CC=C(Cl)C=C3)(CN4C=CN=C4)O2)C=C1

InChI

InChIKey=UTHWWPSFKXCLMU-HWELVIDPSA-N

InChI=1S/C22H24ClN3O2S.2ClH/c23-18-3-1-17(2-4-18)9-10-22(15-26-12-11-25-16-26)27-13-20(28-22)14-29-21-7-5-19(24)6-8-21;;/h1-8,11-12,16,20H,9-10,13-15,24H2;2*1H/t20-,22-;;/m0../s1

HIDE SMILES / InChI

Molecular Formula	ClH
Molecular Weight	36.461
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Molecular Formula	C22H24ClN3O2S
Molecular Weight	429.963
Charge	0
Count

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	2 / 2
E/Z Centers	0
Optical Activity	UNSPECIFIED

Description
Sources: https://adisinsight.springer.com/drugs/800002302 | https://www.ncbi.nlm.nih.gov/pubmed/7646560 | https://www.ncbi.nlm.nih.gov/pubmed/8161528

Azalanstat is a synthetic imidazole. It has been shown to inhibit cholesterol synthesis in HepG2 cells, human fibroblasts, hamster hepatocytes and hamster liver, by inhibiting the cytochrome P450 enzyme lanosterol 14 alpha-demethylase. In hamsters it lowered serum cholesterol in a dose-dependent manner. Azalanstat preferentially lowered low density lipoprotein (LDL) cholesterol and apo B relative to high density lipoprotein (HDL) cholesterol and apo A-1. Azalanstat inhibited hepatic microsomal hydroxymethylglutaryl-CoA (HMG-CoA) reductase activity in hamsters in a dose-dependent manner and this was highly correlated with serum cholesterol lowering. In vitro studies with HepG2 cells indicated that this modulation of reductase activity was indirect, occurring at a post-transcriptional step. Azalanstat has been in preclinical phase for the treatment of hyperlipidaemia but this research has been discontinued.

Approval Year

PubMed

Title	Date	PubMed
Selective inhibition of mammalian lanosterol 14 alpha-demethylase: a possible strategy for cholesterol lowering.	1993 Jul 23	8340925
Selective inhibition of mammalian lanosterol 14 alpha-demethylase by RS-21607 in vitro and in vivo.	1994 Apr 19	8161528
Role of meiosis-activating sterols in rat oocyte maturation: effects of specific inhibitors and changes in the expression of lanosterol 14alpha-demethylase during the preovulatory period.	2001 Jan	11133687
Roles of gonadotropins and meiosis-activating sterols in meiotic resumption of cultured follicle-enclosed mouse oocytes.	2004 Apr 15	15130520
Synthesis and evaluation of azalanstat analogues as heme oxygenase inhibitors.	2005 Mar 1	15713406
The source of endogenous carbon monoxide formation in human placental chorionic villi.	2005 Oct 3	16309566
Lanosterol 14alpha-demethylase expression in the mouse ovary and its participation in cumulus-enclosed oocyte spontaneous meiotic maturation in vitro.	2006 Sep 15	16650467
3',5'-cyclic adenosine monophosphate response element binding protein up-regulated cytochrome P450 lanosterol 14alpha-demethylase expression involved in follicle-stimulating hormone-induced mouse oocyte maturation.	2008 Jul	18467523
Inhibition of heme oxygenase activity in newborn mice by azalanstat.	2008 Oct	18841169
Synthesis and evaluation of imidazole-dioxolane compounds as selective heme oxygenase inhibitors: effect of substituents at the 4-position of the dioxolane ring.	2009 Mar 15	19268600
Structural characterization of human heme oxygenase-1 in complex with azole-based inhibitors.	2010 Mar	19917515

Sample Use Guides

In Vivo Use Guide

30 mg/kg once daily for 7 days

Route of Administration: Oral

Substance Class	Chemical Created by `admin` on `Fri Dec 15 15:32:39 GMT 2023` Edited by `admin` on `Fri Dec 15 15:32:39 GMT 2023`
Record UNII	X30J960B4D
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

AZALANSTAT DIHYDROCHLORIDE

Official Name

English

RS-21607-197

Code

English

AZALANSTAT DIHYDROCHLORIDE [USAN]

Common Name

English

1-(((2S,4S)-4-(((P-AMINOPHENYL)THIO)METHYL)-2-(P-CHLOROPHENETHYL)-1,3-DIOXOLAN-2-YL)METHYL)IMIDAZOLE DIHYDROCHLORIDE

Common Name

English

BENZENAMINE, 4-(((2-(2-(4-CHLOROPHENYL)ETHYL)-2-(1H-IMIDAZOL-1-YLMETHYL)-1,3-DIOXOLAN-4-YL)METHYL)THIO)-, DIHYDROCHLORIDE, (2S-CIS)-

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C29703