929016-50-2

Upstream product

• 870-46-2 t-butoxycarbonylhydrazine 
• 2043-61-0 cyclohexanecarbaldehyde 

Downstream Products

• 161968-14-5 1-[2(S)-hydroxy-3(S)-(N-(methoxycarbonyl)-(L)-valyl)amino-4-phenyl-butyl]-1-[cyclohexylmethyl]-2-[N-methoxycarbonyl-(L)-valyl]-hydrazine 
• 161852-57-9 N'-Cyclohexylmethyl-N'-[(2S,3S)-2-hydroxy-4-phenyl-3-(2,2,2-trifluoro-acetylamino)-butyl]-hydrazinecarboxylic acid tert-butyl ester 
• 161852-58-0 N'-Cyclohexylmethyl-N'-[(2R,3S)-2-hydroxy-4-phenyl-3-(2,2,2-trifluoro-acetylamino)-butyl]-hydrazinecarboxylic acid tert-butyl ester 
• 161852-59-1 1-[2(R)-hydroxy-3(S)-amino-4-phenyl-butyl]-1-[cyclohexylmethyl]-2-[tert-butoxycarbonyl]-hydrazine 
• 161852-66-0 1-[2(S)-hydroxy-3(S)-amino-4-phenyl-butyl]-1-[cyclohexylmethyl]-2-[tert-butoxycarbonyl]-hydrazine 
• 180463-04-1 {(S)-1-[N'-((2S,3S)-3-{(S)-3-Carbamoyl-2-[(quinoline-2-carbonyl)-amino]-propionylamino}-2-hydroxy-4-phenyl-butyl)-N'-cyclohexylmethyl-hydrazinocarbonyl]-2-methyl-propyl}-carbamic acid tert-butyl ester 

Relevant academic research and scientific papers

Identification of potent pyrazole based APELIN receptor (APJ) agonists

The apelinergic system comprises the apelin receptor and its cognate apelin and elabela peptide ligands of various lengths. This system has become an increasingly attractive target for pulmonary and cardiometabolic diseases. Small molecule regulators of this receptor with good drug-like properties are needed. Recently, we discovered a novel pyrazole based small molecule agonist 8 of the apelin receptor (EC50 = 21.5 μM, Ki = 5.2 μM) through focused screening which was further optimized to initial lead 9 (EC50 = 0.800 μM, Ki = 1.3 μM). In our efforts to synthesize more potent agonists and to explore the structural features important for apelin receptor agonism, we carried out structural modifications at N1 of the pyrazole core as well as the amino acid side-chain of 9. Systematic modifications at these two positions provided potent small molecule agonists exhibiting EC50 values of 100 nM. Recruitment of β-arrestin as a measure of desensitization potential of select compounds was also investigated. Functional selectivity was a feature of several compounds with a bias towards calcium mobilization over β-arrestin recruitment. These compounds may be suitable as tools for in vivo studies of apelin receptor function.

Aza-peptide analogs as potent human immunodeficiency virus type-1 protease inhibitors with oral bioavailability

A series of aza-peptide analogs with a (hydroxyethyl)hydrazine isostere has been synthesized as HIV-1 protease inhibitors using a simple synthetic scheme. Structure-activity studies based on the X-ray of a previously described inhibitor-enzyme complex led to potent inhibitors with antiviral activity in the low-nanomolar range. The S-configuration of the transition- state hydroxyl group was preferred in this series. Small modifications of the P2P3 and P2'P3' substituents had little effect on enzyme inhibition but greatly influenced the pharmacokinetic profile. As a result of these studies, the symmetrically acylated compound 8a and its close analog 24a bearing a methyl carbamate in P3 and an ethyl carbamate in P3' position were identified as potent inhibitors with plasma concentrations exceeding antiviral ED50 values 150-fold following oral application in mice.