199296-26-9

Upstream product

• 79-37-8 oxalyl dichloride 
• 252271-82-2 [(cyano-methyl-methyl)-amino]-acetic acid benzyl ester 
• 7677-24-9 trimethylsilyl cyanide 
• 2462-31-9 benzyl 2-aminoacetate hydrochloride 
• 75-07-0 acetaldehyde 
• 96042-30-7 4-(dicyanomethylene)-2-methyl-6-(p-dimethylaminostyryl)-4H-pyran 
• 1738-68-7 Gly-OBz 

Downstream Products

• 204453-16-7 [5-chloro-3-(4-methoxy-benzylamino)-6-methyl-2-oxo-2H-pyrazin-1-yl]-acetic acid benzyl ester 
• 579508-12-6 {5-chloro-6-methyl-2-oxo-3-[(5,6,7,8-tetrahydro-[1,8]naphthyridin-2-ylmethyl)-amino]-2H-pyrazin-1-yl}-acetic acid benzyl ester 
• 787607-60-7 [5-chloro-3-(4-fluoro-phenylamino)-6-methyl-2-oxo-2H-pyrazin-1-yl]-acetic acid benzyl ester 
• 369368-55-8 1-Benzyloxycarbonylmethyl-5-chloro-3-hydrazino-6-methylpyrazinone 
• 259539-01-0 Benzyl 2-[3-chloro-5-({[(2 R ,4 R)-1-cyclopentyl-4-methylpiperidinyl]methyl}amino)-2-methyl-6-oxo-1(6 H)-pyrazinyl]acetate 
• 259537-56-9 Benzyl 2-[3-[(3-[(tert-butoxycarbonyl)(methyl)amino]methylphenethyl)amino]-5-chloro-6-methyl-2-oxo-1(2 H)-pyrazinyl]acetate 
• 259537-82-1 benzyl 2-[3-chloro-5-[(3-{[(2-methoxyethyl)amino]methyl}phenethyl)amino]-2-methyl-6-oxo-1(6H)-pyrazinyl]acetate 
• 221135-89-3 3-[2-(3-Fluorophenyl)ethylamino]-1-carboxymethyl-6-methylpyrazinone 
• 199294-70-7 N-(6-amino-2-methyl-pyridin-3-ylmethyl)-2-(6-methyl-2-oxo-3-phenethylamino-2H-pyrazin-1-yl)-acetamide 
• 199296-11-2 N-(6-amino-pyridin-3-ylmethyl)-2-(6-methyl-2-oxo-3-phenethylamino-2H-pyrazin-1-yl)-acetamide 
• 1026051-67-1 [6-methyl-3-(1-methyl-2-phenyl-ethylamino)-2-oxo-2H-pyrazin-1-yl]-acetic acid 
• 454483-59-1 C₂₇H₃₈N₆O₃SSi 

Relevant academic research and scientific papers

Discovery of achiral inhibitors of the hepatitis C virus NS3 protease based on 2(1H)-pyrazinones

Herein, the design, synthesis and inhibitory potency of a series of novel hepatitis C virus (HCV) NS3 protease inhibitors are presented. These inhibitors are based on a 2(1H)-pyrazinone P3 scaffold in combination with either a P2 phenylglycine or a glycine, and they were evaluated on the wild type as well as on two resistant variants of the enzyme, A156T and D168V. Molecular modelling suggested that the aromatic side-chain of the P2 phenylglycine occupies the same space as the substituent in position 6 on the pyrazinone core. The versatile synthetic route applied for the pyrazinone synthesis made a switch between the two positions easily feasible, resulting in phenyl- or benzyl substituted pyrazinones and leaving glycine as the P2 residue. Of several P1-P1′ residues evaluated, an aromatic P1-P1′ scaffold was found superior in combination with the new P3-P2 building block. As a result, an entirely new type of achiral and rigidified inhibitors was discovered, with the best of the novel inhibitors having fourfold improved potency compared to the corresponding tripeptide lead. We consider these achiral inhibitors highly suitable as starting points for further optimization.

A straightforward microwave method for rapid synthesis of N-1, C-6 functionalized 3,5-dichloro-2(1H)-pyrazinones

A rapid and versatile one-pot, 2 × 10 min microwave protocol for the preparation of N-1 and C-6 decorated 3,5-dichloro-2(1H)-pyrazinones was developed. Comparable reaction sequences using classical conditions require about 1-2 days of heating. The α-amino

Novel pyrazinone inhibitors of mast cell tryptase: Synthesis and SAR evaluation

In this manuscript, the synthesis and SAR evaluation of a novel pyrazinone class of tryptase inhibitors is described. Chemical optimization of the P1 and P4 groups led to the identification of 7p (Ki = 93 nM) as a potent inhibitor of mast cell tryptase.

Substituted hydrazinyl heteroaromatic inhibitors of thrombin

Compounds of the invention are active as inhibitors of Thrombin and are useful in treating disease states in mammals which are characterized by abnormal thrombosis and have the following structure: as described herein.

Design, parallel synthesis, and crystal structures of pyrazinone antithrombotics as selective inhibitors of the tissue factor VIIa complex

Structure-based drug design (SBDD) and polymer-assisted solution-phase (PASP) library synthesis were used to develop a series of pyrazinone inhibitors of the Tissue Factor/Factor VIIa (TF/VIIa) complex. The crystal structure of a tripeptide-α-ketothiazole complexed with TF/VIIa was utilized in a docking experiment to identify the pyrazinone core as a starting scaffold. The pyrazinone core could orient the substituents in the correct spatial arrangement to probe the S1, S2, and S3 pockets of the enzyme. A multistep PASP library synthesis was designed to prepare the substituted pyrazinones varying the P1, P2, and P3 moieties. Hundreds of pyrazinone TF/VIIa inhibitors were prepared and tested in several serine protease enzyme assays involved in the coagulation cascade. The inhibitors exhibited modest activity on TF/VIIa with excellent selectivity over thrombin (IIa) and Factor Xa. The structure-activity relationship of the pyrazinone inhibitors will be discussed and X-ray crystal structures of selected compounds complexed with the TF/VIIa enzyme will be described. This study ultimately led to the synthesis of compound 34, which exhibited 16 nM (IC50) activity on TF/VIIa with >6250x selectivity vs Factor Xa and thrombin. This potent and highly selective inhibitor of TF/VIIa was chosen for preclinical, intravenous proof-of-concept studies to demonstrate the separation between antithrombotic efficacy and bleeding side effects in a nonhuman primate model of electrolytic-induced arterial thrombosis.

Cyclic oxyguanidine pyrazinones as protease inhibitors

Cyclic oxyguanidine pyrazinone compounds are described, including compounds of the Formula I: wherein R3, R4, R5, W, and A are as set forth in the specification, as well as hydrates, solvates or pharmaceutically acceptable

Non-covalent thrombin inhibitors featuring P3-heterocycles with P1-monocyclic arginine surrogates

Investigations on P2-P3-heterocyclic dipeptide surrogates directed towards identification of an orally bioavailable thrombin inhibitor led us to pursue novel classes of achiral, non-covalent P1-arginine derivatives. The design, synthesis, and biological activity of inhibitors NC1-NC30 that feature three classes of monocyclic P1-arginine surrogates will be disclosed: (1) (hetero)aromatic amidines, amines and hydroxyamidines, (2) 2-aminopyrazines, and (3) 2-aminopyrimidines and 2-aminotetrahydropyrimidines.

Thrombin inhibitors

Compounds of the invention are useful in inhibiting thrombin and associated thrombotic occlusions having the following structure:

ANTITHROMBOTIC AGENTS

Compounds of formula (I): Are antithrombotic agents, having utility in a variety of therapeutic areas including the prevention and/or treatment of deep vein thrombosis (DVT) after surgery, major medical illness, paralysis, malignancy, prolonged immobilisa