DAZMEGREL

Details

Stereochemistry	ACHIRAL
Molecular Formula	C16H17N3O2
Molecular Weight	283.3251
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CC1=C(CN2C=CN=C2)C3=C(C=CC=C3)N1CCC(O)=O

InChI

InChIKey=DEQLGSOHGTZKFB-UHFFFAOYSA-N

InChI=1S/C16H17N3O2/c1-12-14(10-18-9-7-17-11-18)13-4-2-3-5-15(13)19(12)8-6-16(20)21/h2-5,7,9,11H,6,8,10H2,1H3,(H,20,21)

HIDE SMILES / InChI

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/3520468 | http://adisinsight.springer.com/drugs/800000419 | https://www.ncbi.nlm.nih.gov/pubmed/2622975

Dazmegrel [UK 38485] is a thromboxane synthetase inhibitor which was undergoing development in the treatment of thrombosis, ischaemic heart disease, arrhythmias and asthma. Pfizer were conducting phase II studies in Denmark and the UK, phase I studies in Germany and Italy, and preclinical studies in France. Later this research was discontinued.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Thromboxane-A synthase 21 Target ID: CHEMBL1835 Sources: https://www.ncbi.nlm.nih.gov/pubmed/9341919 \| https://www.ncbi.nlm.nih.gov/pubmed/3081722	Inhibitor 8297		28.0 nM [IC50]

Conditions

Condition	Modality	Highest Phase	Product
Cardiac arrhythmia 19 Sources: https://www.ncbi.nlm.nih.gov/pubmed/3520978	Primary	Phase I 428	Unknown Approved Use Unknown
Asthma 241 Sources: https://www.ncbi.nlm.nih.gov/pubmed/8370428 http://adisinsight.springer.com/drugs/800000419	Primary	Phase I 428	Unknown Approved Use Unknown
Thrombosis 22 Sources: http://adisinsight.springer.com/drugs/800000419	Primary	Phase I 428	Unknown Approved Use Unknown

C_max

Value	Dose	Co-administered	Analyte	Population
3 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/3513767	200 mg 2 times / day multiple, oral dose: 200 mg route of administration: Oral experiment type: MULTIPLE co-administered:		DAZMEGREL plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED

T_1/2

Value	Dose	Co-administered	Analyte	Population
0.88 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/3513767	200 mg 2 times / day multiple, oral dose: 200 mg route of administration: Oral experiment type: MULTIPLE co-administered:		DAZMEGREL plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED

Doses

Dose	Population	Adverse events
200 mg 3 times / day multiple, oral Highest studied dose Dose: 200 mg, 3 times / day Route: oral Route: multiple Dose: 200 mg, 3 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/3513767 Page: p.764	healthy, ADULT n = 9 Health Status: healthy Age Group: ADULT Sex: M Food Status: FASTED Population Size: 9 Sources: https://pubmed.ncbi.nlm.nih.gov/3513767 Page: p.764	Sources: https://pubmed.ncbi.nlm.nih.gov/3513767 Page: p.764

Sourcing

Vendor/Aggregator	ID	URL
Alfa Chemistry	ACM76894774	http://www.alfa-chemistry.com/search.aspx?q=ACM76894774
ChemBridge	5107120	http://www.hit2lead.com/screening-compounds/5107120
Compound Cloud	53555
Debye Scientific	DA-03506	https://www.debyesci.com/index.php?id=product&ext[cno]=DA-03506
IBScreen	Bio-0598
MolPort	MolPort-002-320-893	https://www.molport.com/shop/molecule-link/MolPort-002-320-893
MuseChem	I006014	https://www.musechem.com/product/I006014.html
Vitas-M Laboratory	STK094650	http://www.vitasmlab.biz/search/STK094650
eMolecules	2745060	https://orderbb.emolecules.com/search/#?query=2745060
mcule	MCULE-1200400346	https://mcule.com/MCULE-1200400346/

PubMed

Title	Date	PubMed
Increased glomerular thromboxane synthesis as a possible cause of proteinuria in experimental nephrosis.	1985 Jan	4038407
Thromboxane A2 and development of genetic hypertension in the Lyon rat strain.	1990 Dec	2147173
The effects of thromboxane synthase inhibition on reperfusion injury and endothelin-1,2 levels in allograft kidney transplantation in rats.	1999 Apr	10369085
Endothelium-dependent noradrenergic hyperresponsiveness induced by thapsigargin in human saphenous veins: role of thromboxane and calcium.	2004 Jan 26	14744614

Patents

Sample Use Guides

In Vivo Use Guide

After dazmegrel 50-200 mg p.o. peak plasma levels of 0.7-3 mu/ml were reached within 1 hr. Elimination was of first order with a half life of 0.88 +/- 0.17 hr. Platelet count and bleeding time were unchanged by all regimes of dazmegrel used (100 and 200 mg b.i.d.; 50, 100 and 200 mg t.i.d.). Serum thromboxane (TXB2) was more than 95% suppressed one hour after all doses studied, but 200 mg t.i.d. were needed suppress circadian serum TXB2 profiles more than 90% at all times.

Route of Administration: Oral

In Vitro Use Guide

Pretreatment of lung strips for 60 min with the thromboxane synthetase inhibitor, dazmegrel (10 uM),relaxed the spontaneous tone of the tissues, abolished the LTD4 (200 nM)-stimulated release of TXB2 and significantly enhanced (~two fold) the elaboration of 6-keto-PGF1alpha.

Name

Type

Language

DAZMEGREL

Official Name

English

UK-38,485

Code

English

UK-38485

Code

English

DAZMEGREL [USAN]

Common Name

English

3-(Imidazol-1-ylmethyl)-2-methylindole-1-propionic acid

Systematic Name

English

dazmegrel [INN]

Common Name

English

DAZMEGREL [MART.]

Common Name

English

1H-INDOLE-1-PROPANOIC ACID, 3-(1H-IMIDAZOL-1-YLMETHYL)-2-METHYL-

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C471