3057-25-8

Upstream product

• 5331-43-1 N-benzyloxycarbonyl-hydrazine 
• 3057-26-9 2-(propan-2-yliden)hydrazinecarboxylic acid benzyl ester 
• 67-64-1 acetone 

Downstream Products

• 1451983-13-3 2-benzyl 1-tert-butyl 1-isopropylhydrazine-1,2-dicarboxylate 

Relevant academic research and scientific papers

BENZOINDAZOLONE COMPOUND, AND INTERMEDIATE THEREOF

The present invention relates to a benzoindazolone compound, or a pharmaceutically acceptable salt, hydrate, solvate, enantiomer, diasteromer, tautomer or prodrug thereof; and an intermediate thereof. A compound according to the present invention is used as a substrate for NQO1 to facilitate a redox reaction of NQO1, and thus is expected to be developable as a medicine for preventing or treating inflammatory diseases.

Rational Drug Design of Topically Administered Caspase 1 Inhibitors for the Treatment of Inflammatory Acne

The use of an interleukin β antibody is currently being investigated in the clinic for the treatment of acne, a dermatological disorder affecting 650M persons globally. Inhibiting the protease responsible for the cleavage of inactive pro-IL1β into active IL-1β, caspase-1, could be an alternative small molecule approach. This report describes the discovery of uracil 20, a potent (38 nM in THP1 cells assay) caspase-1 inhibitor for the topical treatment of inflammatory acne. The uracil series was designed according to a published caspase-1 pharmacophore model involving a reactive warhead in P1 for covalent reversible inhibition and an aryl moiety in P4 for selectivity against the apoptotic caspases. Reversibility was assessed in an enzymatic dilution assay or by using different substrate concentrations. In addition to classical structure-activity-relationship exploration, topical administration challenges such as phototoxicity, organic and aqueous solubility, chemical stability in solution, and skin metabolic stability are discussed and successfully resolved.

E-64c-hydrazide: A lead structure for the development of irreversible cathepsinc inhibitors

CathepsinC is a papain-like cysteine protease with dipeptidyl aminopeptidase activity that is thought to activate various granule-associated serine proteases. Its exopeptidase activity is structurally explained by the so-called exclusion domain, which blocks the active-site cleft beyond the S2 site and, with its Asp1 residue, provides an anchoring point for the Nterminus of peptide and protein substrates. Here, the hydrazide of (2S,3S)-trans-epoxysuccinyl-L-leucylamido-3-methylbutane (E-64c) (k2/Ki=140±5M-1s-1) is demonstrated to be a lead structure for the development of irreversible cathepsinC inhibitors. The distal amino group of the hydrazide moiety addresses the acidic Asp1 residue at the entrance of the S2 pocket by hydrogen bonding while also occupying the flat hydrophobic S1′-S2′ area with its leucine-isoamylamide moiety. Furthermore, structure-activity relationship studies revealed that functionalization of this distal amino group with alkyl residues can be used to occupy the conserved hydrophobic S2 pocket. In particular, the n-butyl derivative was identified as the most potent inhibitor of the series (k2/Ki=56000±1700M-1s-1).

AZA ANALOGS OF CARBOXYALKYL DIPEPTIDE DERIVATIVES AS ANTIHYPERTENSIVES

There are disclosed aza analogs of carboxyalkyl dipeptide derivatives and related compounds which are useful as converting enzyme inhibitors and as antihypertensives said compounds being represented by the general formula: STR1 wherein A and B can be joined together to form various ring structures.