6141-19-1

Upstream product

• 79-03-8 propionyl chloride 
• 529-23-7 o-aminobenzaldehyde 
• 303123-94-6 N-[2-(tert-butyl-dimethyl-silanyloxymethyl)-phenyl]-propionamide 
• 552-89-6 2-nitro-benzaldehyde 
• 4403-69-4 2-amino-1-benzylamine 
• 935675-57-3 2-ethylquinazolin-1-oxide 
• 68847-33-6 2-[(1,1,2,2-tetramethyl-1-silapropoxy)methyl]phenylamine 
• 5344-90-1 2-Aminobenzyl alcohol 

Downstream Products

• 790664-38-9 N-(2-formyl-phenyl)-N-methyl-propionamide 
• 1003024-68-7 methyl 3-hydroxy-2-methylene-3-[2-(propanoylamino)phenyl]propanoate 
• 2721-59-7 3-methylcarbostyril 
• 303123-95-7 N-[2-(1-hydroxy-2-methyl-allyl)-phenyl]-propionamide 
• 303123-96-8 (RS)-1-(2'-aminophenyl)-2-methyl-prop-2-en-1-ol 

Relevant academic research and scientific papers

Cell-Active Small Molecule Inhibitors of the DNA-Damage Repair Enzyme Poly(ADP-ribose) Glycohydrolase (PARG): Discovery and Optimization of Orally Bioavailable Quinazolinedione Sulfonamides

DNA damage repair enzymes are promising targets in the development of new therapeutic agents for a wide range of cancers and potentially other diseases. The enzyme poly(ADP-ribose) glycohydrolase (PARG) plays a pivotal role in the regulation of DNA repair mechanisms; however, the lack of potent drug-like inhibitors for use in cellular and in vivo models has limited the investigation of its potential as a novel therapeutic target. Using the crystal structure of human PARG in complex with the weakly active and cytotoxic anthraquinone 8a, novel quinazolinedione sulfonamides PARG inhibitors have been identified by means of structure-based virtual screening and library design. 1-Oxetan-3-ylmethyl derivatives 33d and 35d were selected for preliminary investigations in vivo. X-ray crystal structures help rationalize the observed structure-activity relationships of these novel inhibitors.

2,4-DIOXO-QUINAZOLINE-6-SULFONAMIDE DERIVATIVES AS INHIBITORS OF PARG

The present invention relates to compounds of formula I that function as inhibitors of PARG (Poly ADP-ribose glycohydrolase) enzyme activity wherein R1a, R1b, R1c, R1d, R1e, W, X1, X2, X3, X4, X5, X6, X7, c are each as defined herein. The present invention also relates to processes for the preparation of these compounds, to pharmaceutical compositions comprising them, and to their use in the treatment of proliferative disorders, such as cancer, as well as other diseases or conditions in which PARG activity is implicated.

A new regioselective synthesis and ambient light photochemistry of quinazolin-1-oxides

Quinazolin-1-oxides were prepared by the oxidation of tetrahydroquinazolines with H2O2-tungstate and their ambient light photochemistry was investigated. Substituent effects on their photochemical cyclization and the reactions of the products 1aH-[1,2]oxazireno[2,3-a]quinazolines under photochemical and thermal conditions are reported. The cyclization of quinazolin-1-oxides and the reactions of 1aH-[1,2]oxazireno[2,3-a]quinazolines show pronounced solvent isotope and solvent effects.

Facile synthesis of 3-substituted and 1,3-disubstituted quinolin-2(1H)-ones from 2-nitrobenzaldehydes

2-Nitrobenzaldehydes were reduced with iron powder to 2-aminobenzaldehydes, which were reacted immediately with acyl chlorides to provide 2-carboxamidobenzaldehydes (1) with overall yields of 71-90 %. Reaction of 1 with base provided 3-substituted quinolin-2(1H)-ones with 63-97 % yields. Treatment of 1 with methyl iodide and base gave 1-methyl-3-substituted quinolin-2(1H)-ones with 82-95 % yields, whereas the treatment with isopropyl iodide gave 1-isopropyl-3-substituted quinolin-2(1H)-ones with 7-42 % yields.

PYRIMIDINE DERIVATIVES AS MODULATORS OF ATP-BINDING CASSETTE TRANSPORTERS

The present invention relates to compounds of Formula (I) as modulators of ATP-Binding Cassette (“ABC”) transporters or fragments thereof, including Cystic Fibrosis Transmembrane Regulator (“CFTR”), compositions thereof, and methods therewith. The present invention also relates to methods of treating ABC transporter mediated diseases using such modulators.

Chiral Acetals as Stereoinductors: Diastereoface Selective Alkylation of Dihydrobenzoxazine-Derived Amide Enolates

Novel dihydrobenzoxazine-derived acetals of type 3 have been developed for asymmetric C-alkylations of propionyl amide enolates. High stereoselectivities are obtained for amides 15 and 22 which are rationalized in terms of intramolecular metal chelate formation.