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Details

Stereochemistry ACHIRAL
Molecular Formula C22H21ClN6O2
Molecular Weight 436.8949
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of EXP-3174

SMILES

CCCCc1nc(c(C(=O)O)n1Cc2ccc(cc2)-c3ccccc3-c4n[nH]nn4)Cl

InChI

InChIKey=ZEUXAIYYDDCIRX-UHFFFAOYSA-N
InChI=1S/C22H21ClN6O2/c1-2-3-8-18-24-20(23)19(22(30)31)29(18)13-14-9-11-15(12-10-14)16-6-4-5-7-17(16)21-25-27-28-26-21/h4-7,9-12H,2-3,8,13H2,1H3,(H,30,31)(H,25,26,27,28)

HIDE SMILES / InChI

Molecular Formula C22H21ClN6O2
Molecular Weight 436.8949
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

E-3174 is an active carboxylic acid metabolite of losartan and is an antagonist of the angiotensin II receptor, type 1 (AT1). Losartan was the first orally active AT1 receptor antagonist available on the market, and it is the antagonist with which the greatest clinical experience has been accumulated. EXP3174 is 10 to 20 times more potent than losartan and has a longer duration of action than losartan. However, the oral bioavailability of EXP 3174 is very low. Thus, the drug on the market is losartan, but most of the losartan’s antihypertensive effect is due to EXP 3174.

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
Target ID: P30556
Gene ID: 185.0
Gene Symbol: AGTR1
Target Organism: Homo sapiens (Human)
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Unknown

Approved Use

Unknown
PubMed

PubMed

TitleDatePubMed
Angiotensin II receptors and angiotensin II receptor antagonists.
1993 Jun
Distinction between surmountable and insurmountable selective AT1 receptor antagonists by use of CHO-K1 cells expressing human angiotensin II AT1 receptors.
1999 Feb
Comparative study of TA-606, a novel angiotensin II receptor antagonist, with losartan in terms of species difference and orthostatic hypotension.
1999 Sep
EXP3174, the AII antagonist human metabolite of losartan, but not losartan nor the angiotensin-converting enzyme inhibitor captopril, prevents the development of lethal ischemic ventricular arrhythmias in a canine model of recent myocardial infarction.
1999 Sep
Inhibitory effects of angiotensin II receptor antagonists and leukotriene receptor antagonists on the transport of human organic anion transporter 4.
2006 Nov
Patents

Sample Use Guides

in dogs: EXP3174 (0.1 mg/kg + 0.01 mg/kg/min) or vehicle were infused in anesthetized dogs with recent (8.1 +/- 0.4 days) anterior myocardial infarction.
Route of Administration: Intravenous
The response to angiotensin II, measured as the mean force development in response to increasing concentrations of angiotensin II, was recorded in the absence and presence of candesartan, 0.003-10 nmol/l, irbesartan, 1-100 nmol/l, losartan, 1-100 nmol/l, and EXP-3174, 0.01-10 nmol/l, for a period of 90 min. In contrast, irbesartan, losartan, and EXP-3174 all caused a parallel shift of the concentration-response curve. It appeared unlikely that losartan exerted any significant inhibitory effect at therapeutic plasma levels, and the main AT 1 - blocking effect observed after oral losartan is probably exerted by EXP-3174. It was concluded that AT 1 -receptor blockers differ in their ability to inhibit angiotensin II-mediated vascular contraction and that the antagonistic characteristics are similar in vessel preparations of different origins and with different degrees of AT 1 -receptor reserve.
Substance Class Chemical
Created
by admin
on Fri Jun 25 22:54:45 UTC 2021
Edited
by admin
on Fri Jun 25 22:54:45 UTC 2021
Record UNII
GD76OCH73X
Record Status Validated (UNII)
Record Version
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Name Type Language
EXP-3174
Common Name English
1H-IMIDAZOLE-5-CARBOXYLIC ACID, 2-BUTYL-4-CHLORO-1-((2'-(2H-TETRAZOL-5-YL)(1,1'-BIPHENYL)-4-YL)METHYL)-
Systematic Name English
EXP3174
Code English
E-3174
Code English
LOSARTAN CARBOXYLIC ACID
Common Name English
ALLISARTAN [WHO-DD]
Common Name English
Code System Code Type Description
PUBCHEM
108185
Created by admin on Fri Jun 25 22:54:45 UTC 2021 , Edited by admin on Fri Jun 25 22:54:45 UTC 2021
PRIMARY
EPA CompTox
124750-92-1
Created by admin on Fri Jun 25 22:54:45 UTC 2021 , Edited by admin on Fri Jun 25 22:54:45 UTC 2021
PRIMARY
CAS
124750-92-1
Created by admin on Fri Jun 25 22:54:45 UTC 2021 , Edited by admin on Fri Jun 25 22:54:45 UTC 2021
PRIMARY
FDA UNII
GD76OCH73X
Created by admin on Fri Jun 25 22:54:45 UTC 2021 , Edited by admin on Fri Jun 25 22:54:45 UTC 2021
PRIMARY
Related Record Type Details
BINDER->LIGAND
Related Record Type Details
PARENT -> METABOLITE ACTIVE