1380698-91-8

Upstream product

• 33844-23-4 1-(2-amino-6-methoxyphenyl)ethanone 
• 75-16-1 methylmagnesium bromide 
• 4837-88-1 6-methoxy-2-nitrotoluene 
• 5460-31-1 3-nitro-o-cresol 
• 54166-96-0 methyl 2-amino-6-methoxybenzoate 
• 53967-73-0 2-nitro-6-methoxybenzoic acid 

Downstream Products

• 1380698-92-9 N-[2-(1-hydroxy-1-methylethyl)-3-(methyloxy)phenyl]acetamide 
• 697801-53-9 5-hydroxy-4,4-dimethyl-1,4-dihydro-2H-benzo[d][1,3]oxazin-2-one 
• 697801-52-8 5-methoxy-4,4-dimethyl-1,4-dihydro-2H-benzo[d][1,3]oxazin-2-one 

Relevant academic research and scientific papers

Aryl Substituted Benzimidazolones as Potent HIV-1 Non-Nucleoside Reverse Transcriptase Inhibitors

Since the discovery of HIV as the etiological agent of AIDS, the virus has infected millions of people each year. Fortunately, with the use of HAART, viremia can be suppressed to below detectable levels in the infected individuals, which significantly improves their quality of life and prevents the onset of AIDS. However, HAART is not curative and issues relating to adherence and drug resistance may lead to the re-emergence of viremia, the development of AIDS, and ultimately death. To address a pressing need for the development of new and efficacious antiretroviral agents with activity against viruses bearing prevalent resistant mutations, we have designed two generations of benzimidazolone derivatives as HIV non-nucleoside reverse transcriptase inhibitors. The first generation benzimidazolone inhibitors were found to be potent inhibitors of wild-type HIV reverse transcriptase but were ineffective in the presence of common resistance mutations such as K103N and Y181C. A second generation benzimidazolone inhibitor (compound 42) not only showed inhibitory activity against wild-type HIV but also remained active against HIV containing the K103N, Y181C, and K103N/Y181C drug resistance mutations.

Alkynyl Benzoxazines and Dihydroquinazolines as Cysteine Targeting Covalent Warheads and Their Application in Identification of Selective Irreversible Kinase Inhibitors

With a resurgence in interest in covalent drugs, there is a need to identify new moieties capable of cysteine bond formation that are differentiated from commonly employed systems such as acrylamide. Herein, we report on the discovery of new alkynyl benzoxazine and dihydroquinazoline moieties capable of covalent reaction with cysteine. Their utility as alternative electrophilic warheads for chemical biological probes and drug molecules is demonstrated through site-selective protein modification and incorporation into kinase drug scaffolds. A potent covalent inhibitor of JAK3 kinase was identified with superior selectivity across the kinome and improvements in in vitro pharmacokinetic profile relative to the related acrylamide-based inhibitor. In addition, the use of a novel heterocycle as a cysteine reactive warhead is employed to target Cys788 in c-KIT, where acrylamide has previously failed to form covalent interactions. These new reactive and selective heterocyclic warheads supplement the current repertoire for cysteine covalent modification while avoiding some of the limitations generally associated with established moieties.

HYDANTOIN DERIVATIVES USEFUL AS KV3 INHIBITORS

The invention provides compounds of formula (I): Said compounds being inhibitors of Kv3 channels and of use in the prophylaxis or treatment of related disorders.

HYDANTOIN DERIVATIVES USEFUL AS KV3 INHIBITORS

The invention provides compounds of formula (I): Said compounds being inhibitors of Kv3 channels and of use in the prophylaxis or treatment of related disorders.