E-4177

    WARNING: This product is for research use only, not for human or veterinary use.

MedKoo CAT#: 526926

CAS#: 135070-05-2

Description: E-4177 is an angiotensin type 1 receptor antagonist potentially for the treatment of hypertension. In rat adrenal cortex and liver, E4177 competitively inhibited the specific binding of 125I-[Sar1,Ile8]Ang II, with IC50 being (5.2 +/- 1.0) x 10(-8) M for the adrenal cortex and (1.2 +/- 0.3) x 10(-7) M for the liver. These IC50 values were similar to those for losartan, which showed an IC50 of (6.0 +/- 0.9) x 10(-8) M for the adrenal cortex and (1.3 +/- 0.5) x 10(-7) M for the liver. E4177 is a potent AT1 Ang II-receptor antagonist that may be clinically useful for the treatment of cardiovascular diseases such as hypertension.


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E-4177 is not in stock, but may be available through custom synthesis. For cost-effective reason, minimum 1 gram order is requested. The product will be characterized by NMR, HPLC and MS analysis. Purity (HPLC) is usually >98%. CoA, QC data, MSDS will be provided when product is successfully made. The estimated lead time is 2-3 months. Please send email to sales@medkoo.com to inquire quote.


Chemical Structure

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Theoretical Analysis

MedKoo Cat#: 526926
Name: E-4177
CAS#: 135070-05-2
Chemical Formula: C24H21N3O2
Exact Mass: 383.1634
Molecular Weight: 383.451
Elemental Analysis: C, 75.18; H, 5.52; N, 10.96; O, 8.34


Synonym: E-4177; E-4177; E4177.

IUPAC/Chemical Name: 4'-((2-cyclopropyl-7-methyl-3H-imidazo[4,5-b]pyridin-3-yl)methyl)-[1,1'-biphenyl]-2-carboxylic acid

InChi Key: VWWMGPCUZVOLLK-UHFFFAOYSA-N

InChi Code: InChI=1S/C24H21N3O2/c1-15-12-13-25-23-21(15)26-22(18-10-11-18)27(23)14-16-6-8-17(9-7-16)19-4-2-3-5-20(19)24(28)29/h2-9,12-13,18H,10-11,14H2,1H3,(H,28,29)

SMILES Code: O=C(C1=CC=CC=C1C2=CC=C(CN3C(C4CC4)=NC5=C(C)C=CN=C53)C=C2)O


Technical Data

Appearance:
Solid powder

Purity:
>98% (or refer to the Certificate of Analysis)

Shipping Condition:
Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition:
Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility:
Soluble in DMSO

Shelf Life:
>2 years if stored properly

Drug Formulation:
This drug may be formulated in DMSO

Stock Solution Storage:
0 - 4 C for short term (days to weeks), or -20 C for long term (months).

Harmonized System Code:
293490


References

1: Kuma S, Oki E, Onohara T, Komori K, Maehara Y. Angiotensin II-induced growth of vascular smooth muscle cells is associated with modulation of cell surface area and platelet-derived growth factor receptor expression. Clin Exp Pharmacol Physiol. 2007 Mar;34(3):153-60. PubMed PMID: 17250632.

2: Tanaka M, Umemoto S, Kawahara S, Kubo M, Itoh S, Umeji K, Matsuzaki M. Angiotensin II type 1 receptor antagonist and angiotensin-converting enzyme inhibitor altered the activation of Cu/Zn-containing superoxide dismutase in the heart of stroke-prone spontaneously hypertensive rats. Hypertens Res. 2005 Jan;28(1):67-77. PubMed PMID: 15969257.

3: Matsuda H, Hayashi K, Arakawa K, Naitoh M, Kubota E, Honda M, Matsumoto A, Suzuki H, Yamamoto T, Kajiya F, Saruta T. Zonal heterogeneity in action of angiotensin-converting enzyme inhibitor on renal microcirculation: role of intrarenal bradykinin. J Am Soc Nephrol. 1999 Nov;10(11):2272-82. PubMed PMID: 10541285.

4: Matsumoto K, Morishita R, Moriguchi A, Tomita N, Yo Y, Nishii T, Nakamura T, Higaki J, Ogihara T. Prevention of renal damage by angiotensin II blockade, accompanied by increased renal hepatocyte growth factor in experimental hypertensive rats. Hypertension. 1999 Aug;34(2):279-84. PubMed PMID: 10454454.

5: Uehara Y, Hirawa N, Kawabata Y, Numabe A, Gomi T, Ikeda T, Omata M. Angiotensin II subtype-1 receptor antagonists improve hemodynamic and renal changes without affecting glucose metabolisms in genetic rat model of non-insulin-dependent diabetes mellitus. Am J Hypertens. 1999 Jan;12(1 Pt 1):21-7. PubMed PMID: 10075380.

6: Nakano N, Morishita R, Moriguchi A, Nakamura Y, Hayashi SI, Aoki M, Kida I, Matsumoto K, Nakamura T, Higaki J, Ogihara T. Negative regulation of local hepatocyte growth factor expression by angiotensin II and transforming growth factor-beta in blood vessels: potential role of HGF in cardiovascular disease. Hypertension. 1998 Sep;32(3):444-51. PubMed PMID: 9740609.

7: Kim S, Izumi Y, Yano M, Hamaguchi A, Miura K, Yamanaka S, Miyazaki H, Iwao H. Angiotensin blockade inhibits activation of mitogen-activated protein kinases in rat balloon-injured artery. Circulation. 1998 May 5;97(17):1731-7. PubMed PMID: 9591768.

8: Kakiki M, Ishihara H. Pharmacokinetics, metabolism and pharmacodynamics of a benzimidazole angiotensin II type 1 receptor antagonist in the beagle dog and cynomologus monkey. Xenobiotica. 1998 Jan;28(1):77-91. PubMed PMID: 9493321.

9: Kakiki M, Morohashi K, Nomura M, Omura T, Horie T. Expression of aldosterone synthase cytochrome P450 (P450aldo) mRNA in rat adrenal glomerulosa cells by angiotensin II type 1 receptor. Endocr Res. 1997 Nov;23(4):277-95. PubMed PMID: 9430819.

10: Kim S, Wanibuchi H, Hamaguchi A, Miura K, Yamanaka S, Iwao H. Angiotensin blockade improves cardiac and renal complications of type II diabetic rats. Hypertension. 1997 Nov;30(5):1054-61. PubMed PMID: 9369255.

11: Kakiki M, Morohashi K, Nomura M, Omura T, Horie T. Regulation of aldosterone synthase cytochrome P450 (CYP11B2) and 11 beta-hydroxylase cytochrome P450 (CYP11B1) expression in rat adrenal zona glomerulosa cells by low sodium diet and angiotensin II receptor antagonists. Biol Pharm Bull. 1997 Sep;20(9):962-8. PubMed PMID: 9331977.

12: Kakiki M, Tadano K. Localization and disposition of a non-peptide angiotensin II type 1 receptor antagonist, and its glucuronide metabolite, in rat. Xenobiotica. 1997 Jul;27(7):723-32. PubMed PMID: 9253148.

13: Seki T, Yamazaki K, Kayano M. Determination of angiotensin II receptor antagonist (E4177) in human plasma and urine by high-performance liquid chromatography. J Chromatogr B Biomed Sci Appl. 1997 Jan 10;688(1):101-6. PubMed PMID: 9029319.

14: Sugano M, Makino N, Yanaga T. The effects of renin-angiotensin system inhibition on aortic cholesterol content in cholesterol-fed rabbits. Atherosclerosis. 1996 Nov 15;127(1):123-9. PubMed PMID: 9006812.

15: Makino N, Sugano M, Hata T, Taguchi S, Yanaga T. Chronic low-dose treatment with enalapril induced cardiac regression of left ventricular hypertrophy. Mol Cell Biochem. 1996 Oct-Nov;163-164:239-45. PubMed PMID: 8974063.

16: Kakiki M, Horie T. Localization of a novel non-peptide angiotensin II type 1 receptor antagonist, E4177, in rat adrenal glomerulosa. Biol Pharm Bull. 1996 Oct;19(10):1357-61. PubMed PMID: 8913512.

17: Makino N, Hata T, Sugano M, Dixon IM, Yanaga T. Regression of hypertrophy after myocardial infarction is produced by the chronic blockade of angiotensin type 1 receptor in rats. J Mol Cell Cardiol. 1996 Mar;28(3):507-17. PubMed PMID: 9011634.

18: Shimakura K, Sanaka M, Wang L, Mineshita S, Miyazaki M. Pulmonary edema induced by angiotensin II in rats. Jpn J Pharmacol. 1995 Apr;67(4):383-9. PubMed PMID: 7650872.

19: Song K, Miyazaki M, Okunishi H, Ishii K, Takai S, Shiota N, Kim S, Mendelsohn FA. Localization and quantitation of active renin in monkey kidney by radioinhibitor binding and in vitro autoradiography. Am J Hypertens. 1994 Jun;7(6):529-35. PubMed PMID: 7917151.

20: Okunishi H, Song K, Oka Y, Kobayashi T, Kawamoto T, Ishihara H, Mori N, Miyazaki M. In vitro pharmacology of a novel non-peptide angiotensin II-receptor antagonist, E4177. Jpn J Pharmacol. 1993 Jul;62(3):239-44. PubMed PMID: 8411773.