851885-41-1

Upstream product

• 100-39-0 benzyl bromide 
• 2150-44-9 1-carbomethoxy-3,5-dihydroxybenzene 
• 54915-31-0 methyl 3-(benzyloxy)-5-hydroxybenzoate 
• 851885-42-2 methyl 3-{[(1S)-1-methyl-2-(methyloxy)ethyl]oxy}-5-[(phenylmethyl)oxy]benzoate 
• 851885-40-0 methyl 6-[({3-{[(1S)-1-methyl-2-(methyloxy)ethyl]oxy}-5-[(phenylmethyl)oxy]phenyl}carbonyl)amino]pyridine-3-carboxylate 

Downstream Products

• 915949-14-3 N-(2-aminopyridin-3-yl)-3-(benzyloxy)-5-[(1S)-2-methoxy-1-methylethoxy]benzamide 
• 919784-72-8 N-(1,5-dimethyl-1H-pyrazol-3-yl)-3-{[(1S)-1-methyl-2-(methyloxy)ethyl]oxy}-5-[(phenylmethyl)oxy]benzamide 
• 915770-72-8 N-(1-ethyl-1H-pyrazol-3-yl)-3-{[(1S)-1-methyl-2-(methyloxy)ethyl]oxy}-5-[(phenylmethyl)oxy]benzamide 
• 871656-70-1 3-{[(1S)-1-methyl-2-(methyloxy)ethyl]oxy}-N-(5-methylpyrazin-2-yl)-5-[(phenylmethyl)oxy]benzamide 
• 851885-40-0 methyl 6-[({3-{[(1S)-1-methyl-2-(methyloxy)ethyl]oxy}-5-[(phenylmethyl)oxy]phenyl}carbonyl)amino]pyridine-3-carboxylate 
• 1313195-15-1 C₂₄H₂₄N₂O₈S 
• 1313195-14-0 C₂₅H₂₇N₃O₆ 
• 1313195-13-9 C₂₃H₂₁ClN₂O₆ 
• 1313195-12-8 C₂₃H₂₁ClN₂O₆ 
• 1313195-11-7 C₂₄H₂₄N₂O₇ 
• 1313195-20-8 C₂₅H₂₆N₂O₈S 
• 1313195-19-5 C₂₆H₂₉N₃O₆ 
• 854002-03-2 C₂₄H₂₃FN₂O₆ 
• 1313195-18-4 C₂₄H₂₃ClN₂O₆ 

Relevant academic research and scientific papers

Decoration of an α-Resorcylate Nucleus as Part of the Manufacture of a Glucokinase Activator

The need to define a set of processes for the manufacture of a glucokinase activator called for an evaluation of different strategies to differentiate the hydroxyls of an α-resorcylic acid derivative. While direct functionalization proved possible, it did not allow access to crystalline intermediates that offered control over the rejection of process impurities. The strategy taken forward involved the installation of a benzoyl protecting group using careful control of pH in order to achieve useful levels of selectivity. This allowed the remaining α-resorcylate hydroxyl to be functionalized using a Mitsunobu reaction, with liquid-liquid partitioning being used to separate downstream intermediates of interest away from the redox byproducts of this reaction. Downstream challenges that were overcome in order to deliver a commercially viable means of manufacturing the API included developing an amidation reaction with a poorly reactive aminopyrazine coupling partner.

Design of a potent, soluble glucokinase activator with increased pharmacokinetic half-life

The continued optimization of a series of glucokinase activators is described, including attempts to understand the interplay between molecular structure and the composite parameter of unbound clearance. These studies resulted in the discovery of a new sc

2 -HETEROCYCLYLOXYBENZOYL AMINO HETEROCYCLYL COMPOUNDS AS MODULATORS OF GLUCOKINASE FOR THE TREATMENT OF TYPE 2 DIABETES

Compounds of formula (I) wherein R1, HET-1 and HET-2 are as described in the specification, and their salts, are activators of glucokinase (GLK) and are thereby useful in the treatment of, for example, type 2 diabetes. Processes for preparing compounds of formula (I) are also described.

HETEROARYL BENZAMIDE DERIVATIVES FOR USE AS GLK ACTIVATORS IN THE TREATMENT OF DIABETES

Compounds of formula (I), wherein R1, R4, HET-1 and HET-2 are as described in the specification, and their salts and pro-drugs, are activators of glucokinase (GLK) and are thereby useful in the treatment of, for example, type 2 diabetes. Processes for preparing compounds of formula (I) are also described.

2-PHENYL SUBSTITUTED IMIDAZOL [4 , 5B] PYRIDINE/ PYRAZINE AND PURINE DERIVATIVES AS GLUCOKINASE MODULATORS

Compounds of Formula (I), wherein R1- R10, A and X1 to X3 are as described in the specification, and their salts and pro-drugs, are activators of glucokinase (GLK) and are thereby useful in the treatment of, for example, type 2 diabetes. Processes for preparing compounds of formula (I) are also described.

HETROARYL BENZAMIDE DERIVATIVES FOR USE AS GLK ACTIVATORS IN THE TREATMENT OF DIABETES

Compounds of Formula (I) wherein: R1 is hydroxymethyl; R2 is selected from -C(O)NR4R5, SO2NR4R5, S(O)pR4 and HET-2; HET-1 is a 5- or 6-membered, optionally substituted C-linked heteroaryl ring; HET-2 is a 4-, 5- or 6-membered, C- or N-linked optionally substituted heterocyclyl ring; R3 is selected from halo, fluoromethyl, difluoromethyl, trifluoromethyl, methyl, methoxy and cyano; R4 is selected from for example hydrogen, optionally substituted (1-4C)alkyl and HET-2; R5 is hydrogen or (1-4C)alkyl; or R4 and R5 together with the nitrogen atom to which they are attached may form a heterocyclyl ring system as defined by HET-3; HET-3 is for example an optionally substituted N-linked, 4, 5 or 6 membered, saturated or partially unsaturated heterocyclyl ring; p is (independently at each occurrence) 0, 1 or 2; m is 0 or 1; n is 0, 1 or 2; provided that when m is 0, then n is 1 or 2; or a salt, pro drug or solvate thereof, are described. Their use as GLK activators, pharmaceutical compositions containing them, and processes for their preparation are also described.

BENZOYL AMINO PYRIDYL CARBOXYLIC ACID DERIVATIVES USEFUL AS GLUCOKINASE (GLK) ACTIVATORS

A compound of Formula (I): Formula (I) wherein: R1 is selected from hydrogen and C1-4alkyl; R2 is selected from: R4-C(R5aR5b)- , R4=C(R6)- and R7aC(R7b

BENZOYL AMINO PYRIDIL CARBOXYLIC ACID DERIVATIVES AS GLUOKINASE ACTIVATORS

Compounds of Formula (I) wherein: R1-X- is selected from: methyl, methoxymethyl and Formula (X); R2 is selected from hydrogen, methyl, chloro and fluoro; n is 1 or 2; or a salt, pro-drug or solvate thereof, are described. Their use a