Novartis Ag

Novartis Pharmaceuticals Corporation

David Hook

Matthias Napp

Bernhard Wietfeld

Erhard Bappert

Liladhar Murlidhar Waykole

Jianguang Zhou

Bernhard Riss

Bernard Riss

Yunzhong Li

Gottfried Sedelmeier

Antonio Zanotti-Gerosa

Thomas Ruch

Daniel Kaufmann

Lech Andrzej Ciszewski

Jonathan Medlock

Markus Bänziger

Steven Hawker

Philippe Polleux

Jie Ku

Markus Krumme

Paul Allen Sutton

Ulrich Meier

Bin Hu

Matthias Lotz

Gordon Stout

Massimo Moratto

Florian Karl Kleinbeck

Joerg Ogorka

Jean-Paul Mutz

Steffen Lang

Norbert Rasenack

Elodia Di Renzo

Jim Parks

Fabian Weber

Patrick Tritschler

Stefan Steigmiller

Hendrik Schneider

Jan Schlomach

Sibylle Mueller

Markus Banziger

The invention relates to polymorphic forms of the calcium salt of N-(3-carboxyl-1-oxopropyl)-(4S)-(p-phenylphenylmethyl)-4-amino-(2R)-methyl butanoic acid ethyl ester. The calcium salt of N-(3-carboxyl-1-oxopropyl)-(4S)-(p-phenylphenylmethyl)-4-amino-(2R)-methyl butanoic acid ethyl ester is useful in the treatment of various conditions and disorders responsive to the inhibition of neutral endopeptidases.

Sacubitril calcium salts

A method of preparing a pharmaceutical product comprises the steps of (a) providing a neat active pharmaceutical ingredient (API) complying with at least five of the following parameters determined by using a FT4 powder rheometer: (i) specific basic flow energy of at most 60 mJ/g; (ii) stability index of 0.75 to 1.25; (iii) specific energy of at most 10 mJ/g; (iv) major principle stress at 15 kPa of at most 40; (v) flow function at 15 kPa of at least 1.3; (vi) consolidated bulk density at 15 kPa of at least 0.26 g/mL; (vii) compressibility of at most 47%; and (viii) wall friction angle of at most 40&#xb0;; (b) dispensing the neat API of step (a) into a bottom part of a pharmaceutical carrier using a vacuum assisted metering and filling device; and (c) encapsulating the bottom part, thereby producing a pharmaceutical product.

Method for preparing a pharmaceutical product

The invention relates to a new process for producing useful intermediates for the manufacture of NEP inhibitors or prodrugs thereof, in particular NEP inhibitors comprising a &#x3b3;-amino-&#x3b4;-biphenyl-&#x3b1;-methylalkanoic acid, or acid ester, backbone, such as N-(3-carboxyl-1-oxopropyl)-(4S)-(p-phenylphenylmethyl)-4-amino-(2R)-methyl butanoic acid ethyl ester or salt thereof.

Process for the preparation of intermediates useful for the manufacture NEP inhibitors

The invention relates to a new process for producing NEP inhibitors or prodrugs thereof, in particular NEP inhibitors comprising a &#x3b3;-amino-&#x3b4;-biphenyl-&#x3b1;-methylalkanoic acid, or acid ester, backbone. In detail, the new processes, according to the present invention, are ultimately related to the synthesis of intermediates to prepare the above NEP inhibitors, namely compounds according to formula (1), or salt thereof, wherein R1 and R2 are, independently of each other, hydrogen or a nitrogen protecting group, and R3 is a carboxyl group or an ester group, preferably carboxyl group or alkyl ester.

Intermediates for producing NEP inhibitors or prodrugs thereof

The invention relates to a new process for producing useful intermediates for the manufacture of NEP inhibitors or prodrugs thereof, in particular NEP inhibitors comprising a g-amino-d-biphenyl-a-methylalkanoic acid, or acid ester, backbone, such as N-(3-carboxyl-1-oxopropyl)-(4S)-(p-phenylphenylmethyl)-4-amino-(2R)-methyl butanoic acid ethyl ester or salt thereof.

Intermediates of neutral endopeptidase inhibitors and preparation method thereof

Processes for producing NEP inhibitors or prodrugs thereof

The present invention relates to pyrrolidin-2-ones according to the formula (1), or salts thereof, wherein R1 is hydrogen or a nitrogen protecting group, methods for their preparation and their use in the preparation of NEP-inhibitors, particularly in the preparation of N-(3-carboxyl-1-oxopropyl)-(4S)-(p-phenylphenylmethyl)-4-amino-(2R)-methyl butanoic acid ethyl ester or salt thereof.

Process for preparing 5-biphenyl-4-amino-2-methyl pentanoic acid

The invention relates to a new process for producing useful intermediates for the manufacture of NEP inhibitors or prodrugs thereof, in particular NEP inhibitors comprising a -amino- -biphenyl- -methylalkanoic acid, or acid ester, backbone, such as N-(3-carboxyl-1-oxopropyl)-(4S)-(p-phenylphenylmethyl)-4-amino-(2R)-methyl butanoic acid ethyl ester or salt thereof.

The invention relates to a process for producing a compound according to formula (i)  

Process for preparing biaryl substituted 4-amino butyric acid or derivatives thereof and their use in the production of NEP inhibitors

Process for the preparation of intermediates for the manufacture of NEP inhibitors

Processes

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Rheinfelden, Switzerland

David Hook