100466-37-3

Upstream product

• 26830-95-5 4-methyl-2-nitrobenzonitrile 
• 89-60-1 1-chloro-4-methyl-2-nitro-benzene 
• 5326-34-1 4-Bromo-3-nitrotoluene 

Downstream Products

• 630410-23-0 4-(morpholin-4-ylmethyl)-2-nitrobenzene carbonitrile 
• 630411-43-7 (4-{[(2S)-2-(methoxymethyl)pyrrolidinyl]-methyl}-2-nitrophenyl)methylamine 
• 630411-49-3 4-{[(2R)-2-(methoxymethyl)pyrrolidinyl]-methyl}-2-nitrobenzenecarbonitrile 
• 1333470-04-4 4-(azidomethyl)-2-nitrobenzonitrile 
• 89939-36-6 4-(hydroxymethyl)-2-nitrobenzonitrile 

Relevant academic research and scientific papers

Electrostatic fields near the active site of human aldose reductase: 2. New inhibitors and complications caused by hydrogen bonds

Vibrational Stark effect spectroscopy was used to measure electrostatic fields in the hydrophobic region of the active site of human aldose reductase (hALR2). A new nitrile-containing inhibitor was designed and synthesized, and the X-ray structure of its complex, along with cofactor NADP+, with wild-type hALR2 was determined at 1.3 A resolution. The nitrile is found to be in the proximity of T113, consistent with a hydrogen bond interaction. Two vibrational absorption peaks were observed at room temperature in the nitrile region when the inhibitor binds to wild-type hALR2, indicating that the nitrile probe experiences two different microenvironments, and these could be empirically separated into a hydrogen-bonded and non-hydrogen-bonded population by comparison with the T113A mutant, in which a hydrogen bond to the nitrile is not present. Classical molecular dynamics simulations based on the structure predict a double-peak distribution in protein electric fields projected along the nitrile probe. The interpretation of these two peaks as a hydrogen bond formation-dissociation process between the probe nitrile group and a nearby amino acid side chain is used to explain the observation of two IR bands, and the simulations were used to investigate the molecular details of this conformational change. Hydrogen bonding complicates the simplest analysis of vibrational frequency shifts as being due solely to electrostatic interactions through the vibrational Stark effect, and the consequences of this complication are discussed.

Structure-activity relationships of 3,4-dihydro-1H-quinazolin-2-one derivatives as potential CDK5 inhibitors

Cyclin-dependent kinase 5 (CDK5) is a serine/threonine kinase that plays a critical role in the early development of the nervous system. Deregulation of CDK5 is believed to contribute to the abnormal phosphorylation of various cellular substrates associated with neurodegenerative disorders such as Alzheimer's disease, amyotrophic lateral sclerosis, and ischemic stroke. Acyclic urea 3 was identified as a potent CDK5 inhibitor and co-crystallographic data of urea 3/CDK2 enzyme were used to design a novel series of 3,4-dihydroquinazolin-2(1H)-ones as CDK5 inhibitors. In this investigation we present our synthetic studies toward this series of compounds and discuss their biological relevance as CDK5 inhibitors.

Acylated benzylmaltosides as inhibitors of smooth muscle cell proliferation

This invention provides smooth muscle cell proliferation inhibitors of formula I having the structure wherein R1, R2, R3, R4, and R5 are each, independently, hydrogen, acyl of 2-7 carbon atoms, haloac

2-oxo-1,3,4-trihydroquinazolinyl derivatives and methods of use

Selected compounds are effective for treatment of diseases, such as cell proliferation or apoptosis mediated diseases. The invention encompasses novel compounds, analogs, prodrugs and pharmaceutically acceptable derivatives thereof, pharmaceutical compositions and methods for prophylaxis and treatment of diseases and other maladies or conditions involving stroke, cancer and the like. The subject invention also relates to processes for making such compounds as well as to intermediates useful in such processes.

Acetal benzylmaltosides as inhibitors of smooth muscle cell proliferation

This invention provides smooth muscle cell proliferation inhibitors of formula I having the structure with the variables defined herein.

Orally available peptidic thrombin inhibitors

The present invention relates to novel thrombin inhibitors that are useful as anticoagulants. More particularly, the present invention is directed to peptide derivatives having high antithrombotic activity and high oral bioavailability.

Noncovalent tripeptidic thrombin inhibitors incorporating amidrazone, amine and amidine functions at P1

A series of noncovalent tripeptidic thrombin inhibitors incorporating amidrazone, amine and amidine functions at P1 was investigated. While the amidrazone and the amine series displayed limited oral absorption, the amidine series demonstrated generally good oral absorption and strong antithrombotic activity; the single-digit picomolar Ki achieved from this series is among the best yet reported. The present work highlights the benzamidine compound 11f (LB30812) that exhibits excellent overall profiles of potency, oral absorption and antithrombotic efficacy.

Substituted Isatoic Anhydrides: Selective Inactivators of Trypsin-like Serine Proteases

Derivatives of isatoic anhydride were prepared and tested as inhibitors of serine proteases.A number of isatoic anhydrides with positively charged substituents irreversibly inactivated several trypsin-like enzymes and preferentially inactivated trypsin over chymotrypsin.Further selectivity was obtained by introduction of an aromatic group on the N-1 position of isatoic anhydride. 7-(Aminomethyl)-1-benzylisatoic anhydride was prepared and was a selective inactivator of thrombin; thus it is possible to prepare derivatives of isatoic anhydride that are highly enzyme selective without attaching peptide recognition structures.