Etamicastat Free Base | CAS# 760173-05-5 (free base) | dopamine β-hydroxylase (DBH) inhibitor

MedKoo Cat#: 414103 | Name: Etamicastat Free Base

Description:

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

Etamicastat Free Base is a novel peripherally selective dopamine β-hydroxylase (DBH) inhibitor being developed by Bial-Portela and Ca, S.A. for treatment of hypertension and congestive heart failure.

Chemical Structure

Etamicastat Free Base

CAS#760173-05-5 (free base)

Theoretical Analysis

MedKoo Cat#: 414103

Name: Etamicastat Free Base

CAS#: 760173-05-5 (free base)

Chemical Formula: C14H15F2N3OS

Exact Mass: 311.0904

Molecular Weight: 311.35

Elemental Analysis: C, 54.01; H, 4.86; F, 12.20; N, 13.50; O, 5.14; S, 10.30

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Related CAS #

677773-32-9 (HCl) 760173-05-5 (free base)

Synonym

Etamicastat Free Base

IUPAC/Chemical Name

5-(2-Aminoethyl)-1-((3R)-6,8-difluoro-3,4-dihydro-2H-chromen-3-yl)-1,3-dihydro-2h-imidazole-2-thione

InChi Key

CWWWTTYMUOYSQA-LLVKDONJSA-N

InChi Code

InChI=1S/C14H15F2N3OS/c15-9-3-8-4-11(7-20-13(8)12(16)5-9)19-10(1-2-17)6-18-14(19)21/h3,5-6,11H,1-2,4,7,17H2,(H,18,21)/t11-/m1/s1

SMILES Code

S=C1NC=C(CCN)N1[C@H]2COC3=C(C=C(F)C=C3F)C2

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

To be determined

Shelf Life

>2 years if stored properly

Drug Formulation

To be determined

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:

Etamicastat (BIA 5-453) is a potent and reversible dopamine-β-hydroxylase (DBH) inhibitor with an IC50 value of 107 nM.

In vitro activity:

TBD

In vivo activity:

Systolic blood pressure also measured under anesthesia, 9 or 18 h after gavage administration of 10 mg/kg etamicastat, was decreased in D2−/− mice to levels similar to those in D2+/+ littermates (Figure 1A). Diastolic blood pressures, which were increased in D2−/− mice relative to their D2+/+ littermates (91±1 vs 68±2 mmHg; P<0.05), were normalized at 9 h (D2−/−: 72±5; D2+/+: 72±1 mmHg) and 18 h (D2−/−: 75±3; D2+/+: 76±4 mmHg) after the administration of etamicastat. Reference: Hypertens Res. 2018 Jul; 41(7): 489–498. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6503839/

Preparing Stock Solutions

The following data is based on the product molecular weight 311.35 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. Armando I, Asico LD, Wang X, Jones JE, Serrão MP, Cuevas S, Grandy DK, Soares-da-Silva P, Jose PA. Antihypertensive effect of etamicastat in dopamine D2 receptor-deficient mice. Hypertens Res. 2018 Jul;41(7):489-498. doi: 10.1038/s41440-018-0041-5. Epub 2018 Apr 13. PMID: 29654295; PMCID: PMC6503839. 2. Igreja B, Wright LC, Soares-da-Silva P. Sustained high blood pressure reduction with etamicastat, a peripheral selective dopamine β-hydroxylase inhibitor. J Am Soc Hypertens. 2016 Mar;10(3):207-16. doi: 10.1016/j.jash.2015.12.011. Epub 2015 Dec 19. PMID: 26803288.

In vitro protocol:

TBD

In vivo protocol:

1: Armando I, Asico LD, Wang X, Jones JE, Serrão MP, Cuevas S, Grandy DK, Soares-da-Silva P, Jose PA. Antihypertensive effect of etamicastat in dopamine D2 receptor-deficient mice. Hypertens Res. 2018 Jul;41(7):489-498. doi: 10.1038/s41440-018-0041-5. Epub 2018 Apr 13. PMID: 29654295; PMCID: PMC6503839. 2: Loureiro AI, Bonifácio MJ, Fernandes-Lopes C, Igreja B, Wright LC, Soares-da- Silva P. Etamicastat, a new dopamine-ß-hydroxylase inhibitor, pharmacodynamics and metabolism in rat. Eur J Pharmacol. 2014 Oct 5;740:285-94. doi: 10.1016/j.ejphar.2014.07.027. Epub 2014 Jul 21. PMID: 25058908. 3: Almeida L, Nunes T, Costa R, Rocha JF, Vaz-da-Silva M, Soares-da-Silva P. Etamicastat, a novel dopamine β-hydroxylase inhibitor: tolerability, pharmacokinetics, and pharmacodynamics in patients with hypertension. Clin Ther. 2013 Dec;35(12):1983-96. doi: 10.1016/j.clinthera.2013.10.012. Epub 2013 Dec 2. PMID: 24296323. 4: Loureiro AI, Soares-da-Silva P. Distribution and pharmacokinetics of etamicastat and its N-acetylated metabolite (BIA 5-961) in dog and monkey. Xenobiotica. 2015;45(10):903-11. doi: 10.3109/00498254.2015.1024780. Epub 2015 Apr 14. PMID: 25869244. 5: Loureiro AI, Fernandes-Lopes C, Bonifácio MJ, Wright LC, Soares-da-Silva P. N-acetylation of etamicastat, a reversible dopamine-β-hydroxylase inhibitor. Drug Metab Dispos. 2013 Dec;41(12):2081-6. doi: 10.1124/dmd.113.053736. Epub 2013 Sep 6. PMID: 24013186. 6: Pires NM, Loureiro AI, Igreja B, Lacroix P, Soares-da-Silva P. Cardiovascular safety pharmacology profile of etamicastat, a novel peripheral selective dopamine-β-hydroxylase inhibitor. Eur J Pharmacol. 2015 Mar 5;750:98-107. doi: 10.1016/j.ejphar.2015.01.035. Epub 2015 Jan 30. PMID: 25641747. 7: Igreja B, Pires NM, Bonifácio MJ, Loureiro AI, Fernandes-Lopes C, Wright LC, Soares-da-Silva P. Blood pressure-decreasing effect of etamicastat alone and in combination with antihypertensive drugs in the spontaneously hypertensive rat. Hypertens Res. 2015 Jan;38(1):30-8. doi: 10.1038/hr.2014.143. Epub 2014 Oct 9. PMID: 25298210. 8: Loureiro AI, Rocha JF, Fernandes-Lopes C, Nunes T, Wright LC, Almeida L, Soares-da-Silva P. Human disposition, metabolism and excretion of etamicastat, a reversible, peripherally selective dopamine β-hydroxylase inhibitor. Br J Clin Pharmacol. 2014 Jun;77(6):1017-26. doi: 10.1111/bcp.12274. PMID: 24168152; PMCID: PMC4093927. 9: Vaz-da-Silva M, Nunes T, Rocha JF, Falcão A, Almeida L, Soares-da-Silva P. Effect of food on the pharmacokinetic profile of etamicastat (BIA 5-453). Drugs R D. 2011;11(2):127-36. doi: 10.2165/11587080-000000000-00000. PMID: 21548660; PMCID: PMC3585837. 10: Igreja B, Wright LC, Soares-da-Silva P. Sustained high blood pressure reduction with etamicastat, a peripheral selective dopamine β-hydroxylase inhibitor. J Am Soc Hypertens. 2016 Mar;10(3):207-16. doi: 10.1016/j.jash.2015.12.011. Epub 2015 Dec 19. PMID: 26803288.