1396972-31-8

Upstream product

• 2592-18-9 Boc-Thr-OH 
• 74-88-4 methyl iodide 
• 4144-02-9 O-methyl-L-threonine 
• 24424-99-5 di-tert-butyl dicarbonate 
• 101-83-7 N-cyclohexyl-cyclohexanamine 
• 113525-91-0 (2S,3S)-methyl 2-[(tert-butoxycarbonyl)amino]-3-hydroxybutanoate 
• 2592-18-9 N-tert-butoxycarbonyl-L-allo-threonine 
• 2592-18-9 (2R,3S)-2-tert-butoxycarbonylamino-3-hydroxybutyric acid 
• 544480-12-8 methyl (2R,3S)-2-(tert-butoxycarbonylamino)-3-methoxybutanoate 
• 537697-28-2 O-methyl-D_S-threonine 
• 2592-18-9 (2R,3R)-allo-2-tert-butoxycarbonylamino-3-hydroxybutyric acid 
• 544480-13-9 methyl (2R,3R)-2-(tert-butoxycarbonylamino)-3-methoxybutanoate 

Downstream Products

• 537697-19-1 tert-butyl ((2R,3R)-1-hydroxy-3-methoxybutan-2-yl)carbamate 

Relevant academic research and scientific papers

The crystal structure of an isopenicillin N synthase complex with an ethereal substrate analogue reveals water in the oxygen binding site

Isopenicillin N synthase (IPNS) is a non-heme iron oxidase central to the biosynthesis of β-lactam antibiotics. IPNS converts the tripeptide δ-(l-α-aminoadipoyl)-l-cysteinyl-d-valine (ACV) to isopenicillin N while reducing molecular oxygen to water. The substrate analogue δ-(l-α-aminoadipoyl)-l-cysteinyl-O-methyl-d-threonine (ACmT) is not turned over by IPNS. Epimeric δ-(l-α-aminoadipoyl)-l-cysteinyl-O- methyl-d-allo-threonine (ACmaT) is converted to a bioactive penam product. ACmT and ACmaT differ from each other only in the stereochemistry at the β-carbon atom of their third residue. These substrates both contain a methyl ether in place of the isopropyl group of ACV. We report an X-ray crystal structure for the anaerobic IPNS:Fe(II):ACmT complex. This structure reveals an additional water molecule bound to the active site metal, held by hydrogen-bonding to the ether oxygen atom of the substrate analogue.

IMIDAZOPYRIDAZINES AS MODULATORS OF IL-17

The present application discloses compounds having the following formula: (I), or pharmaceutically acceptable salts thereof, wherein R1, R2, R3, R4 and R5 are defined in the specification, as well as methods of making and using the compounds disclosed herein for treating or ameliorating an IL-17 mediated syndrome, disorder and/or disease.

KCNT1 INHIBITORS AND METHODS OF USE

The present invention is directed to, in part, compounds and compositions useful for preventing and/or treating a neurological disease or disorder, a disease or condition relating to excessive neuronal excitability, and/or a gain-of-function mutation in a gene (e.g., KCNT1). Methods of treating a neurological disease or disorder, a disease or condition relating to excessive neuronal excitability, and/or a gain-of-function mutation in a gene such as KCNT1 are also provided herein.

Inhibitors of Memapsin 2 Cleavage for the Treatment of Alzheimer's Disease

Proteases such as memapsin 2 are important enzymes, playing roles in a variety of diseases including Alzheimer's Disease. The inventors have developed inhibitors of memapsin 2 and methods of use therefore in the treatment of disease.

BENZIIMIDAZOLE AND IMIDAZOPYRIDINE DERIVATIVES AS SODIUM CHANNEL MODULATORS

The invention relates to benzimidazole and imidazopyridine derivatives, to their use in medicine, to compositions containing them, to processes for their preparation and to intermediates used in such processes. More particularly the invention relates to new Nav1.8 modulators of formula (I) or pharmaceutically acceptable salts thereof, wherein R1, R2, R3, R4, R5, R6, R7. X and Y are as defined in the description. Nav1.8 modulators are potentially useful in the treatment of a wide range of disorders, particularly pain.

Structure-based design of highly selective β-secretase inhibitors: Synthesis, biological evaluation, and protein-ligand x-ray crystal structure

The structure-based design, synthesis, and X-ray structure of protein-ligand complexes of exceptionally potent and selective β-secretase inhibitors are described. The inhibitors are designed specifically to interact with S1′ active site residues to provide selectivity over memapsin 1 and cathepsin D. Inhibitor 5 has exhibited exceedingly potent inhibitory activity (Ki = 17 pM) and high selectivity over BACE 2 (>7000-fold) and cathepsin D (>250000-fold). A protein-ligand crystal structure revealed important molecular insight into these selectivities. These interactions may serve as an important guide to design selectivity over the physiologically important aspartic acid proteases.

Structure-activity relationships of globomycin analogues as antibiotics

Globomycin (1a), a signal peptidase II inhibitor, and its derivatives show potent antibacterial activity against Gram-negative bacteria. The synthesis and antimicrobial activity of novel globomycin analogues are reported. The hydroxyl group in the L-Ser r

Tubulin inhibitors. Synthesis and biological activity of HTI-286 analogs with B-segment heterosubstituents

Modifications of the B-segment of HTI-286 (2) produced a class of analogs incorporating heteroatom-substituents. The structure-activity relationship was studied. Analogs bearing methylsulfide and fluoride groups exhibited potency comparable to that of the parent compound HTI-286 and to paclitaxel in cytotoxicity assays against KB-3-1 cell lines. These analogs were more potent than paclitaxel against P-glycoprotein expressing KB-8-5 and KB-V1 cell lines. Several analogs showed strong inhibition of tubulin polymerization.

β-amino-α-hydroxycarboxylic acid derivatives and HIV protease inhibitors

β-Amino-α-hydroxycarboxylic acid derivatives represented by the following formula and salts thereof which are useful as human immunodeficiency virus (HIV) protease inhibitors: The compounds are effective for treating a patient suffering from AIDS and AIDS related diseases.