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sacubitril

sacubitril
sacubitril structure
CAS No.
1038924-61-6
Chemical Name:
sacubitril
Synonyms
sacubitril;sacubitril ISO 9001:2015 REACH;(S)-5-[(biphenyl-4-yl)Methyl]pyrrolidin-2-one;(S)-5-([1,1'-biphenyl]-4-ylMethyl)pyrrolidin-2-one;2-Pyrrolidinone, 5-([1,1'-biphenyl]-4-ylmethyl)-, (5S)-
CBNumber:
CB62721013
Molecular Formula:
C17H17NO
Formula Weight:
251.32
MOL File:
1038924-61-6.mol

sacubitril Properties

Boiling point:
473.6±24.0 °C(Predicted)
Density 
1.117±0.06 g/cm3(Predicted)
pka
16.31±0.40(Predicted)
FDA UNII
17ERJ0MKGI
NCI Drug Dictionary
sacubitril

sacubitril price More Price(2)

Manufacturer Product number Product description CAS number Packaging Price Updated Buy
Chemenu CM198982 (S)-5-([1,1''-biphenyl]-4-ylmethyl)pyrrolidin-2-one 95% 1038924-61-6 1g $435 2021-12-16 Buy
Crysdot CD11361443 (S)-5-([1,1'-Biphenyl]-4-ylmethyl)pyrrolidin-2-one 95+% 1038924-61-6 1g $460 2021-12-16 Buy

sacubitril Chemical Properties,Uses,Production

Description

Sacubitril is a neprilysin inhibitor prodrug developed by Novartis that was approved as part of an orally administered supramolecular sodium salt complex with the angiotensin receptor blocker (ARB) valsartan in the U.S. and EU in 2015. Sacubitril/valsartan (also known as LCZ-696) is a first-in-class dual angiotensin receptor blocker neprilysin inhibitor (ARNI) marketed for the treatment of chronic heart failure with reduced ejection fraction (HFrEF). It represents a novel mechanistic approach to targeting HFrEF and is the first pharmacologic agent approved for HFrEF since 2004. Sacubitril is metabolized by enzymatic conversion of the ethyl ester to the active diacid (LBQ-657, structure not disclosed), which inhibits neprilysin and prevents endogenous natriuretic peptide degradation. Neprilysin inhibitors like sacubitril are not effective as monotherapy and need to be combined with a reninangiotensin aldosterone system (RAAS) inhibitor such as valsartan. Notably, dual neprilysin and angiotensin-converting enzyme (ACE) inhibition, as in omapatrilat, was found to be associated with an increased risk of life-threatening angioedema due to increased bradykinin levels. In phase III clinical trials, sacubitril/ valsartan displayed a superior safety profile to enalapril, with a 20% decrease in heart failure hospitalizations or cardiovascular death and a 16% reduction in the risk of death from any cause. Sacubitril/valsartan is now recommended as the standard of care for HFrEF as an alternative to ACEs and ARBs.

Chemical Synthesis

Several routes to sacubitril, particularly to advanced intermediates, have been published in the primary and patent literature.23 They differ generally in their choice of chiral pool starting material and their approach to introduction of the second stereocenter. The industrial scale synthesis of intermediate 47 has been reported. Accordingly, addition of the cuprate of biaryl bromide 41 to (S)-epichlorohydrin 42 followed by subjection to HCl provided chloropropanol 43 in 92% yield and 99% ee. Next, a Mitsunobu reaction involving succinimide 44 followed by treatment with refluxing HCl and NaOH generated the corresponding aminoalcohol, which was isolated via crystallization as the HCl salt prior to Boc protection to give N-Boc aminoalcohol 45 in >99% ee. Alcohol 45 was then carried through a four-step process to give acid 47 in 75% yield, starting with oxidation of the alcohol to the corresponding aldehyde with TEMPO/NaOCl. The organic phase was carried forward directly into a Wittig reaction with ylide 46, generating an α,β-unsaturated ester which was hydrolyzed to acid 47 with LiOH in an ethanol/water mixture. Interestingly, a separate patent disclosed the stereoselective hydrogenation of the trisubstituted olefin 47, in which subjection of 47 to catalytic [Ru(p-cymene)I2]2 and chiral phosphine ligand Mandyphos SL-M004-1 (48) under 40 bar of hydrogen gas in warm ethanol delivered 49 in 99:1 dr before recrystallization.
Subsequently, activation of the acid as the acid halide through the use of thionyl chloride and ethanol not only reestablished the ethyl ester but removed the Boc group, revealing a primary amine which then reacted with succinic anhydride to ultimately deliver sacubitril (V). The freebase form of sacubitril does not readily crystallize; the isolation of a number of pharmaceutically acceptable salts of sacubitril via crystallization, most preferably the calcium salt 50 or sodium salts, have been reported.
Preparation of the sacubitril/valsartan supramolecular complex (trisodium salt, hemihydrate) has been described on a kilo-scale from sacubitril calcium salt via neutralization to the freebase and subsequent complexation with valsartan in iPrOAc/ acetone. Addition of NaOH and crystallization then provided the desired trisodium salt hemihydrate.

sacubitril Preparation Products And Raw materials

Raw materials

Preparation Products


sacubitril Suppliers

Global( 39)Suppliers
Supplier Tel Fax Email Country ProdList Advantage
Henan Tianfu Chemical Co.,Ltd.
0371-55170693
0371-55170693 info@tianfuchem.com China 22607 55
career henan chemical co
+86-0371-55982848
sales@coreychem.com China 29954 58
Biochempartner
0086-13720134139
candy@biochempartner.com CHINA 968 58
Chongqing Chemdad Co., Ltd
+86-13650506873
sales@chemdad.com CHINA 37282 58
Shanghai Rochi Pharmaceutical Co.,Ltd.
15000076078 0086-21-38751876
info@rochipharma.com CHINA 432 58
Dideu Industries Group Limited
029-88380327
Service@dideu.com CHINA 30014 58
Dayang Chem (Hangzhou) Co.,Ltd.
17705817739 +86-571-88938639
+86-571-88938652,+86-571- 88492614 info@dycnchem.com CHINA 52932 58
sgtlifesciences pvt ltd
+917013299288
dj@sgtlifesciences.com China 12386 58
Amadis Chemical Company Limited
0086-571-89925085
0086-571-89925065 sales@amadischem.com China 132148 58
Chemwill Asia Co.,Ltd. 86-21-51086038
86-21-51861608 chemwill_asia@126.com;sales@chemwill.com;chemwill@hotmail.com;chemwill@gmail.com CHINA 23975 58

View Lastest Price from sacubitril manufacturers

Image Release date Product Price Min. Order Purity Supply Ability Manufacturer
2021-10-28 sacubitril
1038924-61-6
US $1.10 / g 1g 99.00% 100 Tons Min Dideu Industries Group Limited
2019-07-06 sacubitril
1038924-61-6
US $1.00 / KG 1KG 99% 100kg Career Henan Chemical Co
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