Omapatrilat | CAS#167305-00-2 | Antihypertensive Agent

MedKoo Cat#: 525780 | Name: Omapatrilat

Description:

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

Omapatrilat is a novel antihypertensive agent that inhibits both neutral endopeptidase (NEP) and angiotensin converting enzyme. NEP inhibition results in elevated natriuretic peptide levels, promoting natriuresis, diuresis, vasodilation, and reductions in preload and ventricular remodeling. The drug was promoted for possible uses in congestive heart failure. Dual inhibition of angiotensin-converting enzyme (ACE) and neprilysin (NEP) by omapatrilat and related drugs produces superior antihypertensive efficacy relative to ACE inhibitors but is associated with a higher risk of life-threatening angioedema due to bradykinin elevations.

Chemical Structure

Omapatrilat

CAS#167305-00-2

Theoretical Analysis

MedKoo Cat#: 525780

Name: Omapatrilat

CAS#: 167305-00-2

Chemical Formula: C19H24N2O4S2

Exact Mass: 408.1177

Molecular Weight: 408.53

Elemental Analysis: C, 55.86; H, 5.92; N, 6.86; O, 15.67; S, 15.70

Price and Availability

Size	Price	Availability
100mg	USD 1,750.00	2 Weeks
200mg	USD 2,350.00	2 Weeks
500mg	USD 3,250.00	2 Weeks
1g	USD 5,950.00	2 Weeks

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Related CAS #

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Synonym

BMS 186716; BMS-186716; BMS186716; Vanlev; Omapatrilat

IUPAC/Chemical Name

(4S,7S,10aS)-4-((S)-2-mercapto-3-phenylpropanamido)-5-oxooctahydro-2H-pyrido[2,1-b][1,3]thiazepine-7-carboxylic acid

InChi Key

LVRLSYPNFFBYCZ-VGWMRTNUSA-N

InChi Code

InChI=1S/C19H24N2O4S2/c22-17(15(26)11-12-5-2-1-3-6-12)20-13-9-10-27-16-8-4-7-14(19(24)25)21(16)18(13)23/h1-3,5-6,13-16,26H,4,7-11H2,(H,20,22)(H,24,25)/t13-,14-,15-,16-/m0/s1

SMILES Code

O=C([C@@H]1CCC[C@](N21)([H])SCC[C@H](NC([C@@H](S)CC3=CC=CC=C3)=O)C2=O)O

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).

HS Tariff Code

2934.99.9001

More Info

Product Data

Product Data

Instruction

View handling instruction

Biological target:

Omapatrilat is a novel antihypertensive agent that inhibits both neutral endopeptidase (NEP) and angiotensin converting enzyme.

In vitro activity:

In vitro autoradiography using the specific NEP inhibitor radioligand 125I-RB104 and the specific ACE inhibitor radioligand 125I-MK351A showed omapatrilat (10 mg/kg) caused rapid and potent inhibition of renal NEP and ACE, respectively, for 24 h (P < .01). Reference: Am J Hypertens. 2000 Oct;13(10):1110-6. https://pubmed.ncbi.nlm.nih.gov/11041166/

In vivo activity:

This study examined the effects of chronic oral administration of omapatrilat (12 mg/kg/day, n=13) or placebo (n=13) for 8 weeks on aortic leakiness, atherogenesis and ANP-mediated vasorelaxation in isolated aortas in a rabbit model of atherosclerosis produced by high cholesterol diet. In HAECs, thrombin-induced increases in ECP were prevented by ANP. Omapatrilat reduced the area of increased aortic leakiness determined by Evans-blue dye and area of atheroma formation assessed by Oil-Red staining compared to placebo. Reference: Peptides. 2013 Oct;48:21-6. https://pubmed.ncbi.nlm.nih.gov/23927843/

	Solvent	mg/mL	mM
Solubility
	DMSO	30.6	75.00

Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

Preparing Stock Solutions

The following data is based on the product molecular weight 408.53 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Concentration / Solvent Volume / Mass	1 mg	5 mg	10 mg
1 mM	1.15 mL	5.76 mL	11.51 mL
5 mM	0.23 mL	1.15 mL	2.3 mL
10 mM	0.12 mL	0.58 mL	1.15 mL
50 mM	0.02 mL	0.12 mL	0.23 mL

Formulation protocol:

1. Rabkin SW, Klassen SS. Omapatrilat enhances adrenomedullin's reduction of cardiomyocyte cell death. Eur J Pharmacol. 2007 May 21;562(3):174-82. doi: 10.1016/j.ejphar.2007.01.056. Epub 2007 Feb 8. PMID: 17343842. 2. Burrell LM, Droogh J, Man in't Veld O, Rockell MD, Farina NK, Johnston CI. Antihypertensive and antihypertrophic effects of omapatrilat in SHR. Am J Hypertens. 2000 Oct;13(10):1110-6. doi: 10.1016/s0895-7061(00)01185-7. PMID: 11041166. 3. Aksakalli-Magden ZB, Ugan RA, Toktay E, Halici Z, Cadirci E. Potential role of angiotensin converting enzyme/neprilysin pathway and protective effects of omapatrilat for paracetamol‑induced acute liver injury. Exp Ther Med. 2022 Dec 12;25(1):66. doi: 10.3892/etm.2022.11765. PMID: 36605526; PMCID: PMC9798151. 4. Ichiki T, Izumi R, Cataliotti A, Larsen AM, Sandberg SM, Burnett JC Jr. Endothelial permeability in vitro and in vivo: protective actions of ANP and omapatrilat in experimental atherosclerosis. Peptides. 2013 Oct;48:21-6. doi: 10.1016/j.peptides.2013.07.020. Epub 2013 Aug 6. PMID: 23927843; PMCID: PMC3787947.

In vitro protocol:

In vivo protocol:

1. Aksakalli-Magden ZB, Ugan RA, Toktay E, Halici Z, Cadirci E. Potential role of angiotensin converting enzyme/neprilysin pathway and protective effects of omapatrilat for paracetamol‑induced acute liver injury. Exp Ther Med. 2022 Dec 12;25(1):66. doi: 10.3892/etm.2022.11765. PMID: 36605526; PMCID: PMC9798151. 2. Ichiki T, Izumi R, Cataliotti A, Larsen AM, Sandberg SM, Burnett JC Jr. Endothelial permeability in vitro and in vivo: protective actions of ANP and omapatrilat in experimental atherosclerosis. Peptides. 2013 Oct;48:21-6. doi: 10.1016/j.peptides.2013.07.020. Epub 2013 Aug 6. PMID: 23927843; PMCID: PMC3787947.

1: Schmedt Auf der Günne W, Zhao Y, Hedderich J, Gohlke P, Culman J. Omapatrilat: penetration across the blood-brain barrier and effects on ischaemic stroke in rats. Naunyn Schmiedebergs Arch Pharmacol. 2015 Sep;388(9):939-51. doi: 10.1007/s00210-015-1126-1. Epub 2015 May 8. PubMed PMID: 25953200. 2: Dalzell JR, Seed A, Berry C, Whelan CJ, Petrie MC, Padmanabhan N, Clarke A, Biggerstaff F, Hillier C, McMurray JJ. Effects of neutral endopeptidase (neprilysin) inhibition on the response to other vasoactive peptides in small human resistance arteries: studies with thiorphan and omapatrilat. Cardiovasc Ther. 2014 Feb;32(1):13-8. doi: 10.1111/1755-5922.12053. PubMed PMID: 24138103. 3: Ichiki T, Izumi R, Cataliotti A, Larsen AM, Sandberg SM, Burnett JC Jr. Endothelial permeability in vitro and in vivo: protective actions of ANP and omapatrilat in experimental atherosclerosis. Peptides. 2013 Oct;48:21-6. doi: 10.1016/j.peptides.2013.07.020. Epub 2013 Aug 6. PubMed PMID: 23927843; PubMed Central PMCID: PMC3787947. 4: Palaniyappan A, Uwiera RR, Idikio H, Menon V, Jugdutt C, Jugdutt BI. Attenuation of increased secretory leukocyte protease inhibitor, matricellular proteins and angiotensin II and left ventricular remodeling by candesartan and omapatrilat during healing after reperfused myocardial infarction. Mol Cell Biochem. 2013 Apr;376(1-2):175-88. doi: 10.1007/s11010-013-1565-2. Epub 2013 Jan 30. PubMed PMID: 23361363. 5: Hegde LG, Yu C, Renner T, Thibodeaux H, Armstrong SR, Park T, Cheruvu M, Olsufka R, Sandvik ER, Lane CE, Budman J, Hill CM, Klein U, Hegde SS. Concomitant angiotensin AT1 receptor antagonism and neprilysin inhibition produces omapatrilat-like antihypertensive effects without promoting tracheal plasma extravasation in the rat. J Cardiovasc Pharmacol. 2011 Apr;57(4):495-504. doi: 10.1097/FJC.0b013e318210fc7e. PubMed PMID: 21297495. 6: Yamazaki T. [Omapatrilat for treatment of heart failure]. Nihon Rinsho. 2007 May 28;65 Suppl 5:173-5. Review. Japanese. PubMed PMID: 17571381. 7: Lobo M, Patel J, Kamins G, Francis R, Breza B, Jerzewski R. Interaction of omapatrilat with FD&C Blue No. 2 lake during dissolution of modified release tablets. Int J Pharm. 2007 Jul 18;339(1-2):168-74. Epub 2007 Mar 4. PubMed PMID: 17398043. 8: Wong V, Szeto L, Uffelman K, Fantus IG, Lewis GF. Enhancement of muscle glucose uptake by the vasopeptidase inhibitor, omapatrilat, is independent of insulin signaling and the AMP kinase pathway. J Endocrinol. 2006 Aug;190(2):441-50. PubMed PMID: 16899577. 9: Loch D, Hoey A, Brown L. Attenuation of cardiovascular remodeling in DOCA-salt rats by the vasopeptidase inhibitor, omapatrilat. Clin Exp Hypertens. 2006 Jul;28(5):475-88. PubMed PMID: 16820344. 10: Basso N, Paglia N, Cini R, Inserra F, Terragno NA. Effect of omapatrilat on the aging process of the normal rat. Cell Mol Biol (Noisy-le-grand). 2005 Nov 8;51(6):557-64. Review. PubMed PMID: 16309580. 11: Ishimura K, Nishikimi T, Akimoto K, Ono H, Kangawa K, Matsuoka H. Renoprotective effect of long-term combined treatment with adrenomedullin and omapatrilat in hypertensive rats. J Hypertens. 2005 Dec;23(12):2287-96. PubMed PMID: 16269971. 12: Sulpizio AC, Pullen MA, Edwards RM, Louttit JB, West R, Brooks DP. Mechanism of vasopeptidase inhibitor-induced plasma extravasation: comparison of omapatrilat and the novel neutral endopeptidase 24.11/angiotensin-converting enzyme inhibitor GW796406. J Pharmacol Exp Ther. 2005 Dec;315(3):1306-13. Epub 2005 Sep 6. PubMed PMID: 16144980. 13: Lapointe N, Parker TG, Tsoporis JN, Nguyen QT, Marcotte F, Adam A, Lou I, Rouleau JL. Effects of the vasopeptidase inhibitor omapatrilat on peri- and postmyocardial infarction in Zucker lean rats. Can J Cardiol. 2005 Mar;21(3):291-7. PubMed PMID: 15776120. 14: Perlini S. The potential advantage of omapatrilat: dual anti-fibrotic and anti-inflammatory effects in one single molecule. J Hypertens. 2005 Feb;23(2):273-5. PubMed PMID: 15662213. 15: Abassi ZA, Yahia A, Zeid S, Karram T, Golomb E, Winaver J, Hoffman A. Cardiac and renal effects of omapatrilat, a vasopeptidase inhibitor, in rats with experimental congestive heart failure. Am J Physiol Heart Circ Physiol. 2005 Feb;288(2):H722-8. Epub 2004 Oct 21. PubMed PMID: 15498826. 16: Kothny W, Kaaden R, Ludwig P, Chase D, Krekler M. Trial logistics, implementation, and conduct of the OCTAVE mega study in Germany. Prospective, randomised, double-blind study to compare the efficacy and tolerability of omapatrilat and enalapril. Arzneimittelforschung. 2004;54(8):474-9. PubMed PMID: 15460215. 17: Graham D, Hamilton C, Beattie E, Spiers A, Dominiczak AF. Comparison of the effects of omapatrilat and irbesartan/hydrochlorothiazide on endothelial function and cardiac hypertrophy in the stroke-prone spontaneously hypertensive rat: sex differences. J Hypertens. 2004 Feb;22(2):329-37. PubMed PMID: 15076191. 18: Persson J, Morsing P, Grände PO. Vasopeptidase inhibition with omapatrilat increases fluid and protein microvascular permeability in cat skeletal muscle. J Hypertens. 2004 Mar;22(3):637-44. PubMed PMID: 15076171. 19: Cheng TO. Is omapatrilat a novel therapy of the past rather than the future? Drugs. 2004;64(6):630-1; author reply 631. PubMed PMID: 15018594. 20: McKinnell RM, Fatheree P, Choi SK, Gendron R, Jendza K, Olson Blair B, Budman J, Hill CM, Hegde LG, Yu C, McConn D, Hegde SS, Marquess DG, Klein U. Discovery of TD-0212, an Orally Active Dual Pharmacology AT1 Antagonist and Neprilysin Inhibitor (ARNI). ACS Med Chem Lett. 2018 Dec 3;10(1):86-91. doi: 10.1021/acsmedchemlett.8b00462. PMID: 30655952; PMCID: PMC6331171.