41010-46-2

Upstream product

• 1027575-24-1 3-(Phenylmethyl)-2,3-dihydro-2-oxo-1H-imidazo<4,5-b>pyridine-1-carboxylic acid ethyl ester 
• 100-46-9 benzylamine 
• 140-75-0 para-fluorobenzylamine 
• 32282-07-8 N²-benzyl-2,3-pyridinediamine 
• 530-62-1 1,1'-carbonyldiimidazole 
• 103409-28-5 2,3-Dihydro-2-oxo-1H-imidazo<4,5-b>pyridine-1-carboxylic acid ethyl ester 
• 16328-62-4 1,3-dihydro-imidazo[4,5-b]pyridin-2-one 
• 5470-18-8 2-Chloro-3-nitropyridine 
• 6298-19-7 2-chloro-3-aminopyridine 
• 57-13-6 urea 

Downstream Products

• 263759-71-3 3-benzyl-2-chloro-3H-imidazo[4,5-b]pyridine 
• 250342-75-7 3-benzyl-2-(4'-methoxy-biphenyl-4-yl)-3H-imidazo[4,5-b]pyridine 

Relevant academic research and scientific papers

Design, synthesis and characterization of novel N-heterocyclic-1-benzyl-1H-benzo[d]imidazole-2-amines as selective TRPC5 inhibitors leading to the identification of the selective compound, AC1903

The transient receptor potential cation channel 5 (TRPC5) has been previously shown to affect podocyte survival in the kidney. As such, inhibitors of TRPC5 are interesting candidates for the treatment of chronic kidney disease (CKD). Herein, we report the synthesis and biological characterization of a series of N-heterocyclic-1-benzyl-1H-benzo[d]imidazole-2-amines as selective TRPC5 inhibitors. Work reported here evaluates the benzimidazole scaffold and substituents resulting in the discovery of AC1903, a TRPC5 inhibitor that is active in multiple animal models of CKD.

Synthesis of 1-and 3-substituted imidazo[4,5-b]pyridin-2-ones

1-and 3-Substituted imidazo[4,5-b]pyridin-2-ones were synthesized by heating equimolar amounts of 3-amino-2-chloropyridine or 2-chloro-3- methylaminopyridine, urea, and the corresponding arylamine at 150-210°C. The reaction of 3-amino-2-chloropyridine wit

BIPHENYL OXO-ACETIC ACIDS USEFUL IN THE TREATMENT OF INSULIN RESISTANCE AND HYPERGLYCEMIA

This invention provides compounds of Formula (I) having the structure wherein A is (a) or (b); B is carbon or nitrogen; D is oxygen, sulfur, or nitrogen; E is carbon or nitrogen; Y is a bond, methylene, C(O), or CH(OH); R is alkyl containing 1 to 12 carbons, aryl of 6-12 carbon atoms, arylalkyl of 7-15 carbon atoms, halogen, carboxaldehyde, trifluoromethyl, alkoxy of 1-6 carbon atoms, 2,2-dimethyl-1,3-benzodioxole, Het-alkyl wherein the alkyl moiety contains 1-6 carbon atoms, or aryl of 6-10 carbon atoms which is mono-, di-, or tri- substituted with halogen, trifluoromethyl, or alkoxy of 1-6 carbon atoms; Het is (c) (d); G is oxygen, sulfur or nitrogen; R and R are each, independently, hydrogen, alkyl of 1-6 carbon atoms, alkoxy of 1-6 carbon atoms, halogen, trifluoromethyl; R and R are each, independently, hydrogen, halogen, alkyl of 1-6 carbon atoms, aryl of 6-10 carbon atoms, trifluoromethyl, alkoxy of 1-6 carbon atoms, nitro, amino, carboalkoxy, carbamide, carbamate, urea, alkylsulfoamide, arylsulfoamide, cycloakyl of 3-8 carbon atoms, -NR(CH2)mCO2H, pyrrolidinone, a heterocyclic ring containing 5 to ring 7 atom rings having 1 to 3 heteroatoms selected from oxygen, nitrogen, or sulfur, or aryl of 6-10 carbon atoms mono-, di-, or tri-substituted with trifluoromethyl, alkyl of 1-6 carbon atoms or, alkoxy of 1-6 carbon atoms; R is hydrogen, alkyl of 1-6 carbon atoms, -CH(R)R, -C(CH2)nCO2R, -C(CH3)2CO2R, -CH(R)(CH2)nCO2R, -CH(R)C6H4CO2R; R is alkylene of 1 to 3 carbon atoms; R is hydrogen or alkyl of 1 to 6 carbon atoms; R is hydrogen, alkyl of 1-6 carbon atoms, aryl of 6-12 carbon atoms, aralkyl of 6-12 carbon atoms, cycloalkyl of 3-8 carbon atoms, phthalic acid, or Q-alkyl wherein the alkyl moiety contains 1-6 carbon atoms; Q is (e), (f), (g), or (h); W is oxygen, sulfur, or nitrogen; R is -CO2R, -CONHR, tetrazole, -PO3R; R is hydrogen, alkyl of 1-6 carbon atoms, aryl of 7-15 carbon atoms, or aralkyl of 7-15 carbon atoms; R is hydrogen, alkyl, aryl of 6-12 carbon atoms, aralkyl of 7-15 carbon atoms; m = 1-3; n = 1-6; with the proviso that when R is halogen, Y is a bond; or a pharmaceutically acceptable salt thereof, which are useful in treating metabolic disorders related to insulin resistance or hyperglycemia.

Novel benzofuran and benzothiophene biphenyls as inhibitors of protein tyrosine phosphatase 1B with antihyperglycemic properties

Insulin resistance in the liver and peripheral tissues, together with a pancreatic cell defect, are the common causes of Type 2 diabetes. It is now appreciated that insulin resistance can result from a defect in the insulin receptor signaling system, at a site post binding of insulin to its receptor. Protein tyrosine phosphatases (PTPases) have been shown to be negative regulators of the insulin receptor. Inhibition of PTPases may be an effective method in the treatment of Type 2 diabetes. We have identified two novel series of benzofuran/benzothiophene biphenyl oxo-acetic acids and sulfonyl- salicylic acids as potent inhibitors of PTP1B with good oral antihyperglycemic activity. To assist in the design of these inhibitors, crystallographic studies have attempted to identify enzyme inhibitor interactions. Resolution of crystal complexes has suggested that the inhibitors bind to the enzyme active site and are held in place through hydrogen bonding and van der Waals interactions formed within two hydrophobic pockets. In the oxo-acetic acid series, hydrophobic substitutents at position-2 of the benzofuran/benzothiophene biphenyl framework interacted with Phe182 of the catalytic site and were very critical to the intrinsic activity of the molecule. The hydrophobic region of the catalytic-site pocket was exploited and taken advantage by hydrophobic substituents at either the α-carbon or the ortho aromatic positions of the oxo-acetic acid moiety. Similar ortho aromatic substitutions on the salicylic acid-type inhibitors had no effect, primarily due to the different orientation of these inhibitors in the catalytic site. The most active inhibitors of both series inhibited recombinant human PTP1B with phosphotyrosyl dodecapeptide TRDI(P)YETD(P)Y(P)YRK as the source of the substrate with IC50 values in the range of 20-50 nM. Compound 68 was one of the most active compounds in vivo, normalizing plasma glucose levels at the 25 mg/kg dose (po) and the 1 mg/kg dose (ip). Compound 68 was also selective against several other PTPases.

Regiospecific functionalization of 1,3-dihydro-2H-benzimidazol-2-one and structurally related cyclic urea derivatives

Methods for selectively protecting one of the degenerate nitrogen atoms of the cyclic urea derivatives 1,3-dihydro-2H-benzimidazol-2-one (6a), 1,3-dihydro-2H-imidazo[4,5-b]pyridin-2-one (11), 1,3-dihydro-2H-imidazo[4,5-b]quinolin-2-ones (20), 1,3-dihydro-