149690-05-1

Usage

Uses

Used in Pharmaceutical Industry:
Sacubitril Sodium Salt is used as an active pharmaceutical ingredient for the treatment of heart failure. It is combined with valsartan, another antihypertensive drug, to form the drug known as valsartan/sacubitril or LCZ696 during trials. This combination drug is marketed under the brand name Entresto and has been proven effective in managing heart failure conditions by reducing the strain on the heart and improving its function.

Upstream product

• 76757-90-9 N-(tert-butoxycarbonyl)-D-tyrosine methyl ester 
• 108-30-5 succinic acid anhydride 
• 149690-12-0 (2R,4S)-5-([1,1'-biphenyl]-4-yl)-4-amino-2-methylpentanoic acid ethyl ester hydrochloride 
• 149709-56-8 methyl N-(tert-butoxycarbonyl)-O-[(trifluoromethyl)sulfonyl]-D-tyrosinate 
• 149709-60-4 ethyl (2R,4S)-5-([1,1'-biphenyl]-4-yl)-4-((tert-butoxycarbonyl)amino)-2-methylpentanoate 
• 1012341-50-2 (2R,4S)-5-[(1,1‘-biphenyl)-4-yl]-4-((tert-butoxycarbonyl)amino)-2-methylpentanoic acid 
• 149709-62-6 α-ethyl (αR,γS)-γ-<(3-carboxy-1-oxopropyl)amino>-α-methyl<1,1'-biphenyl>-4-pentanoate 
• 1038924-97-8 (2R,4S)-5-([1,1'-biphenyl]-4-yl)-4-(2,5-dioxopyrrol-1-yl)-2-methyl pentanoate 

Downstream Products

• 149709-62-6 α-ethyl (αR,γS)-γ-<(3-carboxy-1-oxopropyl)amino>-α-methyl<1,1'-biphenyl>-4-pentanoate 

Relevant academic research and scientific papers

AMMONIUM CARBOXYLATE COMPOUND, CRYSTALLINE FORM, AMORPHOUS FORM AND PREPARATION METHOD THEREOF

The present disclosure belongs to the field of chemical synthesis, and in particular relates to an ammonium carboxylate compound, a crystalline form and an amorphous form, and a preparation method thereof. The present disclosure prepares the compound and the crystalline form I and its single crystal, amorphous form and crystalline form II thereof. The compound, the crystalline forms, the single crystal and the amorphous form can stably exist and exhibit good solid forms, suitable for medicine-making. Furthermore, these products possess high purity and less single impurity. Moreover, the preparation methods of the present disclosure are easy to implement due to the simple processes with mild reaction conditions, and could produce products of high yield and high purity without complex purification steps. Furthermore, the preparation methods may facilitate safety, environmental protection, and industrial production.

AMORPHOUS TRISODIUM SACUBITRIL VALSARTAN AND PROCESS FOR ITS PREPARATION

The present invention provides for crystalline Form B1 of N-(3-carboxyl-1-oxopropyl)- (4S)-(p-phenylphenylmethyl)-4-amino-2R-methyl butanoic acid ethyl ester sodium salt, crystalline Form B2 of N-(3-carboxyl-1-oxopropyl)-(4S)-(p-phenylphenylmethyl)-4- amino-2R-methyl butanoic acid ethyl ester sodium salt, a novel process for the preparation of crystalline Form B of N-(3-carboxyl-1-oxopropyl)-(4S)-(p-phenylphenylmethyl)-4- amino-2R-methyl butanoic acid ethyl ester sodium salt. The present invention also provides for crystalline Form B of (S)-N-(1 -Carboxy-2-Methyl-Prop-1-yl)-N-Pentanoyl-N-[2'-(1 H- Tetrazol-5-yl)-Biphenyl-4-yl-Methyl]-Amine disodium salt, crystalline Form P of (S)-N- (1 -Carboxy-2-Methyl-Prop-1-yl)-N-Pentanoyl-N-[2'-(1 H-Tetrazol-5-yl)-Biphenyl-4-yl- Methyl]-Amine disodium salt and processes for their preparation thereof. The present invention further provides an industrial method production of Amorphous Form of Sacubitril valsartan trisodium. The present invention also provides for amorphous solid dispersions of Sacubitril valsartan trisodium with excipients.

STABLE AMORPHOUS FORM OF SACUBITRIL VALSARTAN TRISODIUM COMPLEX AND PROCESSES FOR PREPARATION THEREOF

The present invention relates to stable amorphous form of sacubitril valsartan trisodium complex and its solid dispersion compounds, processes for their preparation and pharmaceutical composition comprising the same. The present invention also relates to an improved process for the preparation of sacubitril sodium and its use in the preparation of sacubitril valsartan trisodium complex.

Sacubitril sodium salt crystal form (II) and preparation method of same

The invention discloses a sacubitril sodium salt crystal form (II), wherein a X-ray powder diffraction pattern of the sacubitril sodium salt has characteristic diffraction peaks at the following 2[theta] values: 3.05 +/- 0.2 degrees, 10.58 +/- 0.2 degrees, 11.36 +/- 0.2 degrees, 19.40 +/- 0.2 degrees, 19.88 +/- 0.2 degrees and 21.48 +/- 0.2 degrees or has characteristic diffraction peaks at the following 2[theta] values: 6.17 +/- 0.2 degrees, 12.38 +/- 0.2 degrees, 12.68 +/- 0.2 degrees and 22.02+/- 0.2 degrees; or the sacubitril sodium salt has the characters that are represented as the X-raypowder diffraction pattern in the figure (1). The invention also provides a preparation method of the sacubitril sodium salt crystal form (II).

Sacubitril sodium salt, eutectic mixture of sacubitril free acid and acetic acid, crystal form of eutectic mixture, and preparation method and use of crystal form

The invention relates to sacubitril sodium salt shown in a formula (IV), a eutectic mixture of sacubitril free acid and acetic acid, a crystal form of the eutectic mixture, a preparation method of thecrystal form, and a method for preparing LCZ696 by using the eutectic mixture with the crystal form. The eutectic mixture provided by the invention can form the stable crystal form, and does not easily absorb moisture; the eutectic mixture is better in thermal stability, convenient for purification of sacubitril, convenient to store and beneficial to synthesis of LCZ696. Furthermore, the eutecticmixture provided by the invention can be directly used for preparing the LCZ696 without needing additional ion exchange, and helps to control the type and content of the counter cations.

CRYSTALLINE FORM OF SACUBITRIL HEMISODIUM SALT, PREPARATION METHOD THEREOF, AND PHARMACEUTICAL COMPOSITION COMPRISING THE SAME

The present invention relates to a crystalline saccharide hemin sodium salt, a process for producing the same, and a pharmaceutical composition containing the same. The crystalline saccharide heminate salt according to the present invention exhibits excellent thermal stability and water stability, and can be mass-produced with uniform quality, thereby being preferably included as an active ingredient of a pharmaceutical composition for treating or preventing cardiovascular diseases.COPYRIGHT KIPO 2018

SACUBITRIL CONJUGATE, PREPARATION METHOD THEREOF, AND PHARMACEUTICAL COMPOSITION COMPRISING THE SAME

The present invention relates to a sacubitril conjugate, a manufacturing method thereof and a pharmaceutical composition comprising the same. The sacubitril conjugate according to the present invention exhibits excellent thermal stability and water stability, and can be mass-produced with uniform quality, and thus is preferably included as an active ingredient of a pharmaceutical composition for treating or preventing cardiovascular diseases.COPYRIGHT KIPO 2018

NEW CRYSTAL FORM OF SACUBITRIL SODIUM SALTS

The present invention relates to the field of pharmaceutical synthesis, in particular to the new crystal forms A, B, C, D and E of sacubitril sodium salts and a preparation method thereof. The pharmaceutical composition can be used, for example, for the prevention or treatment of neprilysinase-related diseases or disorders, and is mainly used for heart failure, hypertension, and cardiomyopathy.

Method for preparing Sacubitril sodium salt and application thereof

The present invention discloses a preparation method and an application of Sacubitril sodium salt, which is a NEP inhibitor. The said method can effectively control impurities, such as lactams and diacids, to below 0.05%, and thus improving product purity. The product is in a solid form, and thus greatly facilitates storage and transportation.

Preparation method of AHU sodium salt crystal form

The invention discloses a preparation method of AHU sodium salt crystal form, comprising three stages: Stage 1: synthesis of AHU1; Stage 2: synthesis of AHU2 calcium salt; and Stage 3: preparation of the AHU sodium salt crystal form. Water solubility of the AHU sodium salt crystal form prepared by the above preparation method is greatly enhanced in comparison with water solubility of free acid. The product belongs to an easily-soluble substance and is made into a solid preparation. Water solubility of the product is greatly improved, and a greater advantage can be provided for easier absorption of the product.