EXP 3174

Modify Date: 2024-01-02 20:15:07

EXP 3174 structure	Common Name	EXP 3174
	CAS Number	124750-92-1	Molecular Weight	436.894
	Density	1.4±0.1 g/cm3	Boiling Point	707.8±70.0 °C at 760 mmHg
	Molecular Formula	C₂₂H₂₁ClN₆O₂	Melting Point	130-132ºC
	MSDS	N/A	Flash Point	381.8±35.7 °C

Use of EXP 3174

Losartan Carboxylic Acid (E-3174), an active carboxylic acid metabolite of Losartan, is an angiotensin II receptor type 1 (AT1) antagonist. The Ki values are 0.97, 0.57, 0.67 nM for rat AT1B/AT1A and human AT1, respectively. Losartan Carboxylic Acid blocks the angiotensin II-induced responses in vascular smoothmuscle cells (VSMC). Losartan Carboxylic Acid elevates plasma renin activities and reduces mean arterial pressure[1][2][3][4].

Name	2-butyl-5-chloro-3-[[4-[2-(2H-tetrazol-5-yl)phenyl]phenyl]methyl]imidazole-4-carboxylic acid
Synonym	More Synonyms

Description	Losartan Carboxylic Acid (E-3174), an active carboxylic acid metabolite of Losartan, is an angiotensin II receptor type 1 (AT1) antagonist. The Ki values are 0.97, 0.57, 0.67 nM for rat AT1B/AT1A and human AT1, respectively. Losartan Carboxylic Acid blocks the angiotensin II-induced responses in vascular smoothmuscle cells (VSMC). Losartan Carboxylic Acid elevates plasma renin activities and reduces mean arterial pressure[1][2][3][4].
Related Catalog	Research Areas >> Cardiovascular Disease Signaling Pathways >> GPCR/G Protein >> Angiotensin Receptor
Target	Angiotensin II receptor type 1[1]
In Vitro	The specific binding of [125I]-angiotensin II to VSMC is inhibited by Losartan Carboxylic Acid (E-3174) with an IC50 of 1.1 nM. Losartan Carboxylic Acid abolishes the angiotensin II-induced formation of inositolphosphates in VSMC. Losartan Carboxylic Acid inhibits the angiotensin II-induced elevation of intracellular cytosolic Ca2+ concentration with an IC50 of 5 nM. Losartan Carboxylic Acid is more effective than losartan in blocking the angiotensin II-induced increase in Egr-1 mRNA. Losartan Carboxylic Acid inhibits the angiotensin II-induced cell protein synthesis with an IC50 of 3 nM[1].
In Vivo	Losartan Carboxylic Acid (E-3174) (0.1 mg/kg; i.v. followed by 0.02 mg/kg/h for 5.5 h) induces a similar level of inhibition (87±4%) of the pressor responses to angiotensin I[3]. Intravenous Losartan Carboxylic Acid (0.1 mg/kg+0.01 mg/kg/min) is infused in anesthetized dogs with recent (8.1±0.4 days) anterior myocardial infarction. Electrolytic injury of the left circumflex coronary artery to induce thrombotic occlusion and posterolateral ischemia is initiated 1 h after the start of treatment[4]. Animal Model: Mongrel dogs of either sex, weighing 15-25 kg[3] Dosage: 0.1 mg/kg (followed by 0.02 mg/kg/h) Administration: i.v. for 5.5 hours Result: The pressor response was reduced by 87±4%.
References	[1]. Sachinidis A, et al. EXP3174, a metabolite of losartan (MK 954, DuP 753) is more potent than losartan in blockingthe angiotensin II-induced responses in vascular smooth muscle cells. J Hypertens. 1993 Feb;11(2):155-62. [2]. Inada Y, et al. Binding of KRH-594, an antagonist of the angiotensin II type 1 receptor, to cloned human and rat angiotensin II receptors. Fundam Clin Pharmacol. 2002 Aug;16(4):317-23. [3]. Richard V, et al. Comparison of the effects of EXP3174, an angiotensin II antagonist and enalaprilat on myocardial infarct size in anaesthetized dogs. Br J Pharmacol. 1993 Nov;110(3):969-74. [4]. Lynch JJ Jr, et al. 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. J Am Coll Cardiol. 1999 Sep;34(3):876-84.

Density	1.4±0.1 g/cm3
Boiling Point	707.8±70.0 °C at 760 mmHg
Melting Point	130-132ºC
Molecular Formula	C₂₂H₂₁ClN₆O₂
Molecular Weight	436.894
Flash Point	381.8±35.7 °C
Exact Mass	436.141449
PSA	109.58000
LogP	4.79
Vapour Pressure	0.0±2.4 mmHg at 25°C
Index of Refraction	1.695
Storage condition	-20°C Freezer

CHEMICAL IDENTIFICATION

RTECS NUMBER :: NI4004850

CHEMICAL NAME :: 1H-Imidazole-5-carboxylic acid, 2-butyl-4-chloro-1-((2'-(14-tetrazol-5-yl) (1,1'-biphenyl)-4-yl)methyl)-

CAS REGISTRY NUMBER :: 124750-92-1

LAST UPDATED :: 199712

DATA ITEMS CITED :: 1

MOLECULAR FORMULA :: C22-H21-Cl-N6-O2

MOLECULAR WEIGHT :: 436.94

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Intraperitoneal

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 441 mg/kg

TOXIC EFFECTS :: Sense Organs and Special Senses (Eye) - mydriasis (pupillary dilation) Behavioral - tremor Lungs, Thorax, or Respiration - respiratory depression

REFERENCE :: KSRNAM Kiso to Rinsho. Clinical Report. (Yubunsha Co., Ltd., 1-5, Kanda Suda-Cho, Chiyoda-ku, KS Bldg., Tokyo 101, Japan) V.1- 1960- Volume(issue)/page/year: 28,3959,1994

Safety Phrases	24/25

Losartan potassium

CAS#:124750-99-8

~89%

EXP 3174

CAS#:124750-92-1

Literature: SHANGHAI ALLIST PHARMACEUTICAL., INC. Patent: EP1988090 A1, 2008 ; Location in patent: Page/Page column 11 ; EP 1988090 A1

Losartan

CAS#:114798-26-4

~78%

EXP 3174

CAS#:124750-92-1

Literature: Chen, Liqin; Li, Jian; Shen, Yingzhong Patent: US2008/90885 A1, 2008 ; Location in patent: Page/Page column 2 ;

Losartan potassium

CAS#:124750-99-8

~64%

Losartan Carbox...

CAS#:114798-36-6

EXP 3174

CAS#:124750-92-1

Literature: Tetrahedron Letters, , vol. 44, # 6 p. 1149 - 1152

Precursor 2
CAS#:124750-99-8 Losartan potassium CAS#:114798-26-4 Losartan
DownStream 4
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