LEVCROMAKALIM

Investigational

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C16H18N2O3
Molecular Weight	286.3257
Optical Activity	UNSPECIFIED
Defined Stereocenters	2 / 2
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CC1(C)OC2=CC=C(C=C2[C@H]([C@@H]1O)N3CCCC3=O)C#N

InChI

InChIKey=TVZCRIROJQEVOT-CABCVRRESA-N

InChI=1S/C16H18N2O3/c1-16(2)15(20)14(18-7-3-4-13(18)19)11-8-10(9-17)5-6-12(11)21-16/h5-6,8,14-15,20H,3-4,7H2,1-2H3/t14-,15+/m1/s1

HIDE SMILES / InChI

Molecular Formula	C16H18N2O3
Molecular Weight	286.3257
Charge	0
Count

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

Description
Sources: https://business.highbeam.com/436989/article-1G1-92793234/levcromakalim-glaxosmithkline-discontinued-japan | https://www.ncbi.nlm.nih.gov/pubmed/23374501https://www.ncbi.nlm.nih.gov/pubmed/9055194 | https://www.ncbi.nlm.nih.gov/pubmed/1703602

Cromakalim is an ATP-sensitive potassium (KATP) channel opener, which was studied for the treatment of gastric ulcer, hypertension and preventing a cardiomyopathy. But the development of this drug was discontinued due to heart lesions found in monkey chronic toxicity studies.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Sulfonylurea receptor 2 9 Target ID: CHEMBL3244 Sources: https://www.ncbi.nlm.nih.gov/pubmed/9746521 \| https://www.ncbi.nlm.nih.gov/pubmed/16226739 \| https://www.ncbi.nlm.nih.gov/pubmed/8401925 \| https://www.ncbi.nlm.nih.gov/pubmed/9401776	Opener 34		7.12 null [pKi]
ATP-sensitive potassium (KATP) channel 4 Target ID: ATP-sensitive potassium (KATP) channel Sources: https://www.ncbi.nlm.nih.gov/pubmed/7898103	Opener 34

Conditions

Condition	Modality	Highest Phase	Product
Hypertension 575 Sources: http://adisinsight.springer.com/drugs/800000036 https://www.ncbi.nlm.nih.gov/pubmed/7575747	Primary	Preclinical	Unknown Approved Use Unknown
Asthma 244 Sources: http://adisinsight.springer.com/drugs/800000036 https://www.ncbi.nlm.nih.gov/pubmed/8493625	Primary	Preclinical	Unknown Approved Use Unknown
Gastric ulcer 74 Sources: https://www.ncbi.nlm.nih.gov/pubmed/9055194	Primary	Withdrawn	Unknown Approved Use Unknown
Cardiomyopathy 21 Sources: https://www.ncbi.nlm.nih.gov/pubmed/8950075	Preventing	Withdrawn	Unknown Approved Use Unknown
Hypertension 575 Sources: https://www.ncbi.nlm.nih.gov/pubmed/1703602	Primary	Withdrawn	Unknown Approved Use Unknown

PubMed

Title	Date	PubMed
Shear stress increases expression of a KATP channel in rat and bovine pulmonary vascular endothelial cells.	2003-10	12826604
The role of K+ channels in vasorelaxation induced by hypoxia and the modulator effects of lidocaine in the rat carotid artery.	2003-08	12873913
Effect of acute hypoxia on ATP-sensitive potassium currents in substantia gelatinosa neurons of juvenile rats.	2003-08	12811563
Antiulcer activity of levcromakalim and nicorandil in albino rats: a comparative study.	2003-07-15	12856831
Differential role of PTK and ERK MAPK in superoxide impairment of K(ATP) and K(Ca) channel cerebrovasodilation.	2003-07	12793995
Differential antivasoconstrictor effects of levcromakalim and rilmakalim on the isolated human mammary artery and saphenous vein.	2003-06	12832838
Defibrillatory action of glibenclamide is independent from ATP-sensitive K+ channels and free radicals.	2003-06	12775970
Mitochondrial K ATP channel activation is important in the antiarrhythmic and cardioprotective effects of non-hypotensive doses of nicorandil and cromakalim during ischemia/reperfusion: a study in an intact anesthetized rabbit model.	2003-06	12741997
Role of cyclooxygenase-1 and -2, phospholipase C, and protein kinase C in prostaglandin-mediated gastroprotection.	2003-06	12626649
Increased superoxide dismutase and Na+, K+-ATPase activities in aortic strips from potassium-adapted rats: implication for altered vascular reactivity.	2003-05	12781841
Dualistic actions of cromakalim and new potent 2H-1,4-benzoxazine derivatives on the native skeletal muscle K ATP channel.	2003-05	12770930
Effect of hypoxia on vasodilator responses to S-nitroso-N-acetylpenicillamine and levcromakalim in guinea pig basilar artery.	2003-05	12669187
Potassium channel activators based on the benzopyran substructure: synthesis and activity of the C-8 substituent.	2003-04-17	12659752
Coronary myogenic constriction antagonizes EDHF-mediated dilation: role of KCa channels.	2003-04	12642510
Dual effect of agmatine in the bisected rat vas deferens.	2003-03	12724044
Differential effects of ascorbate on endothelium-derived hyperpolarizing factor (EDHF)-mediated vasodilatation in the bovine ciliary vascular bed and coronary artery.	2003-03	12684274
[Analyses of Ca-related ion channel currents and their involvement in Ca mobilization in smooth muscle and endothelial cells].	2003-03	12673948
Mexiletine differentially modulates vasorelaxation mediated by adenosine triphosphate-sensitive K+ channels in aortas from normotensive and hypertensive rats.	2003-03	12598241
Contractile responses of the human umbilical artery to KCl and serotonin in Ca-free medium and the effects of levcromakalim.	2003-02-07	12527030
Apamin inhibits NO-induced relaxation of the spontaneous contractile activity of the myometrium from non-pregnant women.	2003-02-05	12646073
[Effect of levcromakalim and cromakalim on ATP-sensitive K+ channel of pulmonary arterial smooth muscle cells in pulmonary hypertensive rats].	2003-02	12783661
Differential effects of sulphonylureas on the vasodilatory response evoked by K(ATP) channel openers.	2003-02	12588631
In vivo evaluation of the potency and bladder-vascular selectivity of the ATP-sensitive potassium channel openers (-)-cromakalim, ZD6169 and WAY-133537 in rats.	2003-02	12581020
Inhibition of cromakalim-activated K+ current by ethanol in follicle-enclosed Xenopus oocytes.	2003-01	12616345
Inhibitory effects of etomidate and ketamine on adenosine triphosphate-sensitive potassium channel relaxation in canine pulmonary artery.	2003-01	12502986
Effects of ATP-sensitive K+ channel openers and tolterodine on involuntary bladder contractions in a pig model of partial bladder outlet obstruction.	2003	12579633
Alterations in KATP and KCa channel function in cerebral arteries of insulin-resistant rats.	2002-12	12388242
Ketamine stereoselectively affects vasorelaxation mediated by ATP-sensitive K(+) channels in the rat aorta.	2002-10	12357154
Fluorescence-based functional assay for sarcolemmal ATP-sensitive potassium channel activation in cultured neonatal rat ventricular myocytes.	2002-08-08	12164259
Molecular modeling and QSAR studies on K(ATP) channel openers of the benzopyran type.	2002-08	12413029
Effects of chronic treatment with cromakalim and glibenclamide in alloxan-induced diabetic rats.	2002-08	12220947
Synthesis and vasorelaxant activity of new 1,4-benzoxazine derivatives potassium channel openers.	2002-08	12057655
Protein tyrosine kinase and mitogen-activated protein kinase activation contribute to K(ATP) and K(ca) channel impairment after brain injury.	2002-07-12	12101050
Involvement of K+ channels in adenosine A2A and A2B receptor-mediated hyperpolarization of porcine coronary artery endothelial cells.	2002-07	12072576
Potassium channels and human corporeal smooth muscle cell tone: diabetes and relaxation of human corpus cavernosum smooth muscle by adenosine triphosphate sensitive potassium channel openers.	2002-07	12050569
Modified ionic models of cardiac tissue for efficient large scale computations.	2002-06-07	12108777
The novel diazoxide analog 3-isopropylamino-7-methoxy-4H-1,2,4-benzothiadiazine 1,1-dioxide is a selective Kir6.2/SUR1 channel opener.	2002-06	12031979
Active relaxation of human gallbladder muscle is mediated by ATP-sensitive potassium channels.	2002	12239463
Involvement of ATP-sensitive potassium channels in a model of a delayed vascular hyporeactivity induced by lipopolysaccharide in rats.	1999-07	10455295
Glibenclamide-sensitive hypotension produced by helodermin assessed in the rat.	1998-12	9881641
Role of potassium channels in halothane-epinephrine arrhythmias.	1998-06	9730012
K+ channel openers delay intestinal transit and have antidiarrheal activity.	1995-12-12	8749038
Cellular localization of the inhibitory action of relaxin against uterine spasm.	1995-12	8680739
Effect of four potassium channel agonists on bupivacaine-induced toxicity in mice.	1995	7643714
Effects of potassium channel modulation during global ischaemia in isolated rat heart with and without cardioplegia.	1992-11	1291083
Effects of NG-nitro-L-arginine methyl ester on vasodilator responses to adrenaline or BRL 38227 in conscious rats.	1991-11	1797333
Effects of cromakalim and pinacidil on large epicardial and small coronary arteries in conscious dogs.	1990-11	2173761
Preclinical pharmacology of Ro 31-6930, a new potassium channel opener.	1990-02	1689412
Effects of pinacidil and cromakalim (BRL 34915) on bladder function in rats with detrusor instability.	1989-10	2795743
The relaxant action of BRL 34915 in rat uterus.	1987-08	2444298

Patents

Sample Use Guides

In Vivo Use Guide

Eight patients with moderately severe asthma were given 0.125, 0.25, and 0.5 mg of Levcromakalim (BRL 38227)

Route of Administration: Oral

In Vitro Use Guide

Levcromakalim (0.1 uM) hyperpolarized the smooth muscle and decreased membrane resistance in the rat tail artery

Substance Class	Chemical Created by `admin` on `Mon Mar 31 18:00:41 GMT 2025` Edited by `admin` on `Mon Mar 31 18:00:41 GMT 2025`
Record UNII	RW7PN4BLDJ
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

LEVCROMAKALIM

Official Name

English

LEVCROMAKALIM [MI]

Preferred Name

English

(-)-CROMAKALIM

Common Name

English

Levcromakalim [WHO-DD]

Common Name

English

2H-1-BENZOPYRAN-6-CARBONITRILE, 3,4-DIHYDRO-3-HYDROXY-2,2-DIMETHYL-4-(2-OXO-1-PYRROLIDINYL)-, (3S,TRANS)-

Common Name

English

levcromakalim [INN]

Common Name

English

LEVCROMAKALIM [USAN]

Common Name

English

BRL-38227

Code

English

LEVCROMAKALIM [JAN]

Common Name

English

2H-1-BENZOPYRAN-6-CARBONITRILE, 3,4-DIHYDRO-3-HYDROXY-2,2-DIMETHYL-4-(2-OXO-1-PYRROLIDINYL)-, (3S,4R)-

Systematic Name

English

(3S,4R)-3-Hydroxy-2,2-dimethyl-4-(2-oxo-1-pyrrolidinyl)-6-chromancarbonitrile

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C270