Akebia Therapeutics, Inc.

Torcan Chemical Ltd

Alphora Research Inc.

Stealth Biotherapeutics Inc.

Aerpio Therapeutics, Inc.

Eon Labs, Inc.

Allergan, Inc.

Jan Oudenes

Boris Gorin

Craig Edward Dixon

John M Janusz

Christopher M Lanthier

James Densmore Copp

Dino Alberico

Yee-Fung Lu

Alan Quigbo Lu

Joshua Clayton

Clarke Slemon

Raymond So

Teng-Ko Ngooi

Michael E Garst

David W Old

Danny Thang Dinh

Scott M Duncan

Marc W Andersen

Ricardo Orprecio

James Denmore Copp

Elena Bejan

Elizabeth T Syage

Yong Tao

Casimir G Antczak

Fabio Eduardo Silva E Souza

Wen-Lung Yeh

Jason Edward Field

Navindra Jainarine Ramjit

Emma-Louise Moore

Graham McGowan

Fabio Souza

Walter Giust

Alan Qingbo Lu

Edward Armand Arsenault

Richard Donald Mortimer

Brian George Hochfellner

Casimir Gregory Antczak

Boris I Gorin

Alan Quigho Lu

Danielle Marie Di Donato

Disclosed are processes for preparing [(3-hydroxypyridine-2-carbonyl)amino]-alkanoic acids, derivatives, inter alia, 5-aryl substituted and 5-heteroaryl substituted [(3-hydroxypyridine-2-carbonyl]amino}acetic acids. Further disclosed are methods for making prodrugs of [(3-hydroxypyridine-2-carbonyl)-amino]acetic acids, for example, [(3-hydroxypyridine-2-carbonyl]amino}acetic acid esters and {[3-hydroxypyridine-2-carbonyl]amino}acetic acid amides. The disclosed compounds are useful as prolyl hydroxylase inhibitors or for treating conditions wherein prolyl hydroxylase inhibition is desired.

Process for preparing [(3-hydroxypyridine-2-carbonyl)amino]alkanoic acids, esters and amides

Disclosed are methods of making elamipretide (MTP-131), a peptide compound with therapeutic potential for treating various mitochondrial myopathies. The synthesis of the peptide can be achieved via the use of N-carboxyanhydride-modified amino acid residues, which increases the efficiency of the synthetic process and the purity of the peptide product generated.

N-carboxyanhydride-based-scale synthesis of elamipretide

Process for preparing [(3-hydroxypyridine-2-carbonyl)amino] alkanoic acids, esters and amides

Disclosed are processes for preparing [(3-hydroxypyridine-2-carbonyl)amino]-alkanoic acids, derivatives, inter alia, 5-aryl substituted and 5-heteroaryl substituted [(3-hydroxypyridine-2-carbonyl]amino}acetic acids. Further disclosed are methods for making prodrugs of [(3-hydroxypyridine-2-carbonyl)-amino]acetic acids, for example, {[(3-hydroxypyridine-2-carbonyl]amino}acetic acid esters and {[3-hydroxypyridine-2-carbonyl]amino}acetic acid amides. The disclosed compounds are useful as prolyl hydroxylase inhibittors or for treating conditions wherein prolyl hydroxylase inhibition is desired.

Disclosed is a process for preparing a treprostinil salt. The process involves the step of dissolving treprostinil in a water-miscible organic solvent to form a treprostinil solution. The treprostinil solution is reacted with an aqueous basic solution containing an alkali metal cation to form treprostinil salt. Allowing crystallization of the treprostinil salt to take place, and then collecting the treprostinil salt formed.

Process for treprostinil salt preparation

Disclosed herein is a process for preparing N-benzyl-3-hydroxypyridin-2-(1H)-ones that are substituted at the pyridine ring 4-position with a 4-carbamoylpiperazin-1-yl moiety.

Process for preparing N-benzyl-3-hydroxy-4-substituted-pyridin-2-(1H)-ones

Fused cyclopentane-4-substituted 3,5-dioxalane lactone compounds useful as an intermediate in the synthesis of prostaglandin analogs are provided. The compounds have the formula A: wherein R represents an aryl group such as p-methoxyphenyl. This compound can be reacted with a lower alkyl aluminum compound to open the dioxalane ring and reduce the lactone to lactol, without over-reducing to diol. The resulting compound can be functionalized to insert chemical side groups of target prostaglandins, adding the required &#x3b1;-side chain and then the required &#x3c9;-side chain sequentially and independently of each other. The compounds and process are particularly suitable for preparing lubiprostone.

Prostaglandin synthesis and intermediates for use therein

Fused cyclopentane&#x2014;4-substituted 3,5-dioxalane lactone compounds useful as an intermediate in the synthesis of prostaglandin analogs are provided. The compounds have the formula A: wherein R represents an aryl group such as p-methoxyphenyl. This compound can be reacted with a lower alkyl aluminum compound to open the dioxalane ring and reduce the lactone to lactol, without over-reducing to diol. The resulting compound can be functionalized to insert chemical side groups of target prostaglandins, adding the required &#x3b1;-side chain and then the required &#x3c9;-side chain sequentially and independently of each other. The compounds and process are particularly suitable for preparing lubiprostone.

An individual tetrahydrocannabinol isomer of interest is separated from a mixture containing two or more such isomers, by treating the mixture with an isocyanate or isothiocyanate of formula I:R&#x2014;(CH)&#x2014;N&#x2550;C&#x2550;X&#x2003;&#x2003;(I)where R represents an aromatic ring optionally substituted with one or more electron withdrawing groups, n=0 or 1 and X is oxygen or sulphur; so as to produce a crystallizable THC carbamate of formula II: wherein X and R are as defined above, R' is a C-Calkyl group and the dotted lines indicate optional unsaturation including aromatic, separating the compound of formula II from solution in isolation of other THC derivatives, and hydrolyzing the compound of formula II to form the individual tetrahydrocannabinol isomer of interest.

Separation of tetrahydrocannabinols

Sildenafil, a known pharmaceutical chemical useful in treatment of male sexual dysfunction, is prepared by processes in which the final chemical intermediate is of significantly lower basicity than sildenafil itself, so that sildenafil can be extracted in substantially pure form from the organic reaction mixture in which it is made by adding an aqueous medium of appropriately chosen acidic pH and causing phase shift of the sildenafil to occur selectively into the aqueous phase.

Processes for preparing sildenafil

Cisapride, i.e. cis-4-amino-5-chloro-N-�1-�3-(4 fluoro-phenoxy)propyl!-3-methoxy-4-piperidinyl!-2-methoxy-benzamide, and similar benzamide derivatives, are prepared from novel 1-aryloxyalkyl- or 1-aralkyl-3-arylcarbonyloxy-4-oxo-piperidines, by nuclear substituent re arrangement involving acyl transfer under animal forming conditions, to give the corresponding 1-aryloxyalkyl- or 1-aralkyl-3-hydroxy-4-lower alkoxy-4-arylamido piperidine. This in turn is readily converted to the corresponding 3-oxo-4-arylamido-piperidine by reaction with strong organic acid, which can then be reduced, deprotected and 3-methylated to give the final compound, e.g. cisapride.

Preparation of cisapride

Cisapride, i.e. cis-4-amino-5-chloro-N-[1-[3-(4 fluoro-phenoxy)propyl]-3-methoxy-4-piperidinyl]-2-methoxy-benzamide, and similar benzamide derivatives, are prepared from novel 1-aryloxyalkyl- or 1-aralkyl-3-arylcarbonyloxy-4-oxo-piperidines, by nuclear substituent re arrangement involving acyl transfer under animal forming conditions, to give the corresponding 1-aryloxyalkyl- or 1-aralkyl-3-hydroxy-4-lower alkoxy-4-arylamido piperidine. This in turn is readily converted to the corresponding 3-oxo-4-arylamido-piperidine by reaction with strong organic acid, which can then be reduced, deprotected and 3-methylated to give the final compound, e.g. cisapride.

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Aurora, Canada

Jan Oudenes