SULMAZOLE

Details

Stereochemistry	RACEMIC
Molecular Formula	C14H13N3O2S
Molecular Weight	287.337
Optical Activity	( + / - )
Defined Stereocenters	0 / 1
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

COC1=C(C=CC(=C1)[S+](C)[O-])C2=NC3=C(N2)C=CC=N3

InChI

InChIKey=XMFCOYRWYYXZMY-UHFFFAOYSA-N

InChI=1S/C14H13N3O2S/c1-19-12-8-9(20(2)18)5-6-10(12)13-16-11-4-3-7-15-14(11)17-13/h3-8H,1-2H3,(H,15,16,17)

HIDE SMILES / InChI

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/6330195 | https://www.ncbi.nlm.nih.gov/pubmed/3004210 | https://www.ncbi.nlm.nih.gov/pubmed/2418353 | https://www.ncbi.nlm.nih.gov/pubmed/6084757

Sulrnazole (the former AR-L 115 BS) is a benzimidazole derivative with positive inotropic, positive chronotropic and vasodilator effects. Sulrnazole also has been shown to improve cardiac index and reduce pulmonary capillary wedge pressure without significant change in heart rate or arterial pressure. Intravenous administration caused a 217 per cent increase in cardiac output with a 25 per cent decrease in pulmonary wedge pressure. Short-term oral administration resulted in a 317 per cent increase in cardiac index and a 317 per cent increase in ejection fraction. Side effects have included visual blurring and transient colour blindness. Sulmazol has been demonstrated to improve regional wall motion in patients with ischemic heart disease and to abolish pacing-induced ischemia. Sulrnazole is an A1 adenosine receptor antagonist. It is also a phosphodiesterase inhibitor.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Adenosine A1 receptor 50 Target ID: CHEMBL226 Sources: https://www.ncbi.nlm.nih.gov/pubmed/1725275 \| https://www.ncbi.nlm.nih.gov/pubmed/2392160	Antagonist 2778
Phosphodiesterase 3 60 Target ID: CHEMBL2094125 Sources: https://www.ncbi.nlm.nih.gov/pubmed/6084757 \| https://www.ncbi.nlm.nih.gov/pubmed/2472514 \| https://www.ncbi.nlm.nih.gov/pubmed/8388468	Inhibitor 8297		49.0 µM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Heart failure 103 Sources: http://adisinsight.springer.com/drugs/800002407 https://www.ncbi.nlm.nih.gov/pubmed/2418353	Primary		Phase I 428	Unknown Approved Use Unknown

Doses

Dose	Population	Adverse events
450 mg 4 times / day multiple, oral Dose: 450 mg, 4 times / day Route: oral Route: multiple Dose: 450 mg, 4 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/6395955	unhealthy n = 2 Health Status: unhealthy Condition: heart attack Sex: M+F Food Status: UNKNOWN Population Size: 2 Sources: https://pubmed.ncbi.nlm.nih.gov/6395955	Disc. AE: Nausea and vomiting... AEs leading to discontinuation/dose reduction: Nausea and vomiting (2 patients) Sources: https://pubmed.ncbi.nlm.nih.gov/6395955

AEs

AE	Significance	Dose	Population
Nausea and vomiting	2 patients Disc. AE	450 mg 4 times / day multiple, oral Dose: 450 mg, 4 times / day Route: oral Route: multiple Dose: 450 mg, 4 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/6395955	unhealthy n = 2 Health Status: unhealthy Condition: heart attack Sex: M+F Food Status: UNKNOWN Population Size: 2 Sources: https://pubmed.ncbi.nlm.nih.gov/6395955

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
activator 80 inhibitor 1587	inhibitor 1767	inhibitor 1852

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP1A2 1524 P-gp 1461 CYP2C19 1478 CYP19A1 60 OATP1B1 788 OATP1B3 706

Drug as perpetrator

Target	Modality	Activity
CYP19A1 60	inhibitor 3277 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/743139#sid=144204236	no
CYP2C19 1553	inhibitor 3277 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/899#sid=11112839	no
CYP2C9 1819	inhibitor 3277 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/884#sid=26750016	no
CYP2D6 1891	inhibitor 3277 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/891#sid=11112839	no
CYP3A4 1925	activator 214 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/885#sid=11112839	no
CYP3A4 1925	inhibitor 3277 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/884#sid=26750016	no
P-gp 1650	inhibitor 3277 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/377#sid=10321921	no
CYP1A2 1692	inhibitor 3277	yes [IC50 0.251 uM]
OATP1B1 803	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/23571415/	yes [Inhibition 10 uM]
OATP1B3 715	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/23571415/	yes [Inhibition 10 uM]

Sourcing

Vendor/Aggregator	ID	URL
001 Chemical	DY569457	https://www.001chemical.com/chem/73384-60-8
3B Scientific (Wuhan) Corp	3B2-4524	http://www.3bsc.com/index/pro_info.php?id=79464
Ambinter	Amb10843172	http://www.ambinter.com/reference/10843172
Aurora Fine Chemicals LLC	A17.877.833	http://online.aurorafinechemicals.com/info?ID=A17.877.833
BOC Sciences	73384-60-8	https://www.bocsci.com/2-2-methoxy-4-methylsulfinyl-phenyl-1h-imidazo-4-5-b-cas-73384-60-8-item-31576.html
DC Chemicals	DC32220	http://www.dcchemicals.com//product_show-Sulmazole.html
Debye Scientific	DA-03205	http://www.debyesci.com/cas_73384-60-8.html
Finetech	FT-0748740	http://www.finetechnology-ind.com/prod/detail/pub/73384-60-8.html
Molcore	MC569457	https://www.molcore.com/product/73384-60-8
MuseChem	I009628	https://www.musechem.com/product/I009628.html
Smolecule	S544216	http://www.smolecule.com/products/s544216
THE BioTek	bt-285919	https://www.thebiotek.com/product/inhibitors/bt-285919
eNovation Chemicals	D676971	https://www.enovationchem.com/ProductDetails.asp?ProductID=D676971

PubMed

Title	Date	PubMed
A new non-glycoside, non-adrenergic cardiotonic agent AR-L 115 BS. Hemodynamic proof of its efficacy after both i.v. and oral administration.	1981	7195241
Effects of AR-L 115 BS on hemodynamics and contractility of the heart in cardiac patients.	1981	7195239
Ergometric and hemodynamic studies on a new cardiotonic agent AR-L 115 BS.	1981	7195238
Study of the acute effect of AR-L 115 BS, a new positive-inotropic agent in patients with exercise-induced heart failure.	1981	7195237
The acute effect of a new positive inotropic agent (AR-L 115 BS) on cardiac hemodynamics and contractility in patients with severe chronic congestive heart failure.	1981	7195235
Influence on hemodynamic parameters after parenteral administration of AR-L 115 BS in patients with acute myocardial infarction.	1981	7195234
The hemodynamic effect of AR-L 115 BS, a new positive-inotropic agent, in patients with left ventricular failure.	1981	7195233
Hemodynamic effects of single-dose administration of AR-L 115 BS in patients with coronary artery disease.	1981	7195232
A double blind crossover tolerance study of AR-L 115 BS in health volunteers.	1981	7195231
[Human pharmacokinetics of AR-L 115 BS (author's transl)].	1981	7195229
[AR-L 115 BS, comparison of human metabolite pattern and biotransformation with other species].	1981	7195228
[Animal studies on the tolerability of AR-L 115 BS (author's transl)].	1981	7195227
[Pharmacokinetics of AR-L 115 BS in rhesus monkeys (author's transl)].	1981	7195226
The absorption, metabolism and excretion of (14C)-AR-L 115 BS in the baboon.	1981	7195225
[Comparison of blood levels, excretion and metabolite pattern in rats non-pretreated and pretreated with subacute doses of AR-L 115 BS].	1981	7195223
[Pharmacokinetics of AR-L 115 BS in the rat (author's transl)].	1981	7195222
Effects of AR-L 115 BS on arterial and venous muscle tone in vitro.	1981	7195220
[Calcium transport in sarcoplasmic reticulum in the presence of AR-L 115 BS].	1981	7195219
Activating effects of AR-L 115 BS on the Ca2+ sensitive force, stiffness and unloaded shortening velocity (Vmax) in isolated contractile structures from mammalian heart muscle.	1981	7195218
Experiments with AR-L 115 BS on skinned cardiac fibers.	1981	7195217
Interaction of AR-L 115 BS with isoprenaline on hemodynamic parameters in the isolated guinea pig heart.	1981	7195216
Analysis of the positive-inotropic activity of the benzimidazole derivative AR-L 115 BS in isolated guinea pig atria.	1981	7195212
Effects of AR-L 115 BS on hemodynamics, myocardial oxygen consumption and cardiac pumping efficiency.	1981	7195210
Action of AR-L 115 BS on myocardial oxygen consumption, cardiac performance and vascular resistance and capacitance.	1981	7195209
Effects of AR-L 115 BS, a new cardiotonic compound, on cardiac contractility, heart rate and blood pressure in anaesthetized and conscious animals.	1981	7195208
Comparative cardiovascular effects of three benzimidazole derivatives, AR-L 57 BS, AR-L 100 BS, and AR-L 115 BS.	1981	7195207
Application of the theory of sets to drug design. Development of a new cardiotonic drug AR-L 115 BS.	1981	7195206
[Mechanism of action of AR-L 115 BS compared to caffeine].	1981	6453594
[The effect of the benzimidazole derivative AR-L 115 BS on the activities of myocardial adenylate cyclase and phosphodiesterase preparations (author's transl)].	1982	6277343
The response of the calcium dependent myocardial contractility to the new cardiotonic agent sulmazole.	1984	6543125
Effects of the new cardiotonic agent sulmazole on the slow inward current of sheep cardiac Purkinje fibres.	1984	6099128
Pharmacology of LY175326: a potent cardiotonic agent with vasodilator activities.	1985 May	3999023
Supply-to-demand ratio for oxygen determines formation of adenosine by the heart.	1986 Feb	3004232
Sulmazole effects on mechanical performance of hypoxic and reoxygenated isolated mammalian myocardium.	1986 Nov	3814219

Patents

Sample Use Guides

In Vivo Use Guide

0.7 mg/kg, i.v. administration

Route of Administration: Intravenous

In Vitro Use Guide

Under normoxic conditions, sulmazole displayed a positive inotropic action with acceleration of relaxation of isolated mammalian myocardium at small concentrations ( 6.4 umol/L). Increasing doses led to a negative inotropic effect with slackened relaxation and loss of its load sensitivity (up to 390 umol/L for sulmazole).

Name

Type

Language

SULMAZOLE

Official Name

English

2-(2-METHOXY-4-(METHYLSULFINYL)PHENYL)-3H-IMIDAZO(4,5-B)PYRIDINE

Systematic Name

English

3H-IMIDAZO(4,5-B)PYRIDINE, 2-(2-METHOXY-4-(METHYLSULFINYL)PHENYL)-

Systematic Name

English

AR-L-115

Code

English

AR-L-115BS

Code

English

VARDAX

Brand Name

English

SULMAZOLE [MI]

Common Name

English

NSC-757867

Code

English

SULMAZOLE [MART.]

Common Name

English

sulmazole [INN]

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C78322