313653-10-0

Upstream product

• 5292-43-3 bromoacetic acid tert-butyl ester 
• 7540-51-4 (S)-3,7-dimethyl-6-octen-1-ol 
• 37577-28-9 (1S,2R)-(+)-norphedrine 
• 115109-01-8 (R)-4-methylheptanoic acid 
• 313653-16-6 methanesulfonic Acid (S)-3,7-dimethyl-oct-6-enyl Ester 
• 208836-20-8 (R)-2,6-Dimethyl-non-2-ene 
• 77943-39-6 4-methyl-5-phenyloxazolidin-2-one 
• 313653-09-7 (4R,5S)-4-methyl-3-((R)-4-methylheptanoyl)-5-phenyloxazolidin-2-one 
• 70-07-5 mephenoxalone 

Relevant academic research and scientific papers

Chemical development of an α2δ ligand, (3 S,5 R)-3-(Aminomethyl)-5-methyloctanoic acid

Three synthetic approaches, suitable for the large scale manufacture of the α2δ-ligand, (3S,5R)-3-(aminomethyl)-5-methyloctanoic acid 3, have been evaluated. The selected seven step manufacturing process has then been optimized and used to deliver over 20 kg of API; salient features of the synthesis include the use of 4,4,4-trimethoxybutyronitrile as an efficient four carbon amino acid equivalent. Highly selective kinetic resolution of the C3 stereocentre was accomplished via diastereoselective hydrolysis of a cyanoester intermediate using Amano Lipase PS-SD. Extensive process optimisation of the route starting from (R)-2-methylpentanol, led to significant improvements through telescoping, with less than 62 kg of solvent being needed to produce 1 kg of API.

Diastereoselective, large-scale synthesis of β-amino acids via asymmetric aza-Michael addition as α2δ ligands for the treatment of generalized anxiety disorder and insomnia

Scalable synthetic routes to β-amino acids 1 and 2 are presented. These two compounds, which bind to the α2δ subunit of calcium channels and have important medical applications, have been prepared on kilogram scale in our pilot plant through an improved synthesis that avoids the use of highly toxic reagents and hazardous chemistry present in the original Medicinal Chemistry route. The two chiral centers are introduced through asymmetric Michael and aza-Michael reactions with excellent diastereoselectivity.

METHODS FOR USING AMINO ACIDS WITH AFFINITY FOR THE ALPHA-2-DELTA PROTEIN

This invention relates to certain ?-amino acids that bind to the alpha-2-delta ((x2S) subunit of a calcium channel. These compounds and their pharmaceutically acceptable salts are useful in the treatment of a variety of psychiatric, pain and other disorders.

Combinations comprising alpha-2-delta ligands

The instant invention relates to a combination, particularly a synergistic combination, of an alpha-2-delta ligand and a dual serotonin-noradrenaline re-uptake inhibitor (DSNRI) or one or both of a selective serotonin re-uptake inhibitor (SSRI) and a selective noradrenaline re-uptake inhibitor (SNRI), and pharmaceutically acceptable salths thereof, pharmaceutical compositions thereof and their use in the treatment of pain, particularly neuropathic pain.

Combinations

The instant invention relates to a combination of an alpha-2-delta ligand and an AChE inhibitor for use in therapy, particularly in the treatment of pain, particularly neuropathic pain. Particularly preferred alpha-2-delta ligands are gabapentin and pregabalin. Particularly preferred ACHE inhibitors are donepezil (Aricept?), tacrine (cognex?), rivastigmine (Exelon?), physostgmine (Synapton?), galantamine (Reminyl), metrifonate (Promem), neostigmine (Prostigmin) and icopezil.

Synergistic combinations

The instant invention relates to a combination of an alpha-2-delta ligand and a PDEV inhibitor for use in therapy, particularly in the curative, prophylactic or palliative treatment of pain, particularly neuropathic pain. Particularly preferred alpha-2-delta ligands are gabapentin and pregabalin. Particularly preferred PDEV inhibitors are sildenafil, vardenafil and tadalafil.

Alpha2delta ligands for fibromyalgia and other disorders

This invention relates to a method of treating a disorder selected from OCD, agoraphobia, agoraphobia without history of panic disorder, specific phobia, social phobia, PTSD, restless legs syndrome, premenstrual dysphoric disorder, hot flashes, and fibromyalgia by administering a compound of the formula 1 or a pharmaceutically acceptable salt thereof, wherein: R1 is hydrogen, straight or branched alkyl of from 1 to 6 carbon atoms or phenyl; and R2 is straight or branched alkyl of from 4 to 8 carbon atoms, straight or branched alkenyl of from 2 to 8 carbon atoms, cycloalkyl of from 3 to 7 carbon atoms, alkoxy of from 1 to 6 carbon atoms, -alkylcycloalkyl, -alkylalkoxy, -alkyl OH, -alkylphenyl, -alkylphenoxy, or -substituted phenyl. The invention also relates to a method of treating the above disorders by administering the compound (3S, 5R)-3-Aminomethyl-5-methyl-octanoic acid

Amino acids with affinity for the alpha-2-delta-protein

This invention relates to certain β-amino acids that bind to the alpha-2-delta (α2δ) subunit of a calcium channel. These compounds and their pharmaceutically acceptable salts are useful in the treatment of a variety of psychiatric, pain and other disorders.

Method of treating tinnitus

The invention relates to a method of treating tinnitus by administering an alpha2delta ligand such as, for example, a compound of Formula and pharmaceutically acceptable salts thereof, wherein R1 is hydrogen or straight or branched lower alkyl, and n is an integer of from 4 to 6.

Mono-and disubstituted 3-propyl gamma-aminobutyric acids

The instant invention is a series of novel mono- and disubstituted 3-propyl gamma aminobutyric acids of Formula I 1The compounds are useful as therapeutic agents in the treatment of epilepsy, faintness attacks, hypokinesia, cranial disorders, neurodegenerative disorders, depression, anxiety, panic, pain, neuropathological disorders, arthritis, sleep disorders, IBS, and gastric damage. Methods of preparing the compounds and useful intermediates are also part of the invention.