102123-80-8

Upstream product

• 2018-66-8 Z-Leu-OH 
• 543-27-1 isobutyl chloroformate 
• 53363-87-4 Z-Leu-OH*dicyclohexylamine salt 

Downstream Products

• 102123-81-9 (3-diazo-1-(S)-(2-methylpropyl)-2-oxopropyl)carbamic acid benzyl ester 
• 20898-09-3 Z-Leu-N₂H₂-Boc 
• 176664-74-7 (S)-2-((2S,3S)-2-{2-[2-((S)-2-Benzyloxycarbonylamino-4-methyl-pentanoylamino)-2-methyl-propionylamino]-acetylamino}-3-methyl-pentanoylamino)-4-methyl-pentanoic acid methyl ester 
• 176664-82-7 C₄₇H₇₇N₉O₁₂ 
• 1020082-39-6 C₁₄H₁₉N₅O₃ 
• 86910-04-5 Cbz-gLeu-CO-H 
• 118405-11-1 ((S)-4-{(S)-1-[(S)-2-((S)-1-Benzylcarbamoyl-3-methyl-butylcarbamoyl)-1-hydroxy-ethyl]-3-methyl-butylcarbamoyl}-2-hydroxy-1-isobutyl-5-phenyl-pentyl)-carbamic acid benzyl ester 
• 118405-12-2 ((S)-4-{(S)-1-[(S)-2-((S)-1-Benzylcarbamoyl-3-methyl-butylcarbamoyl)-1-hydroxy-ethyl]-3-methyl-butylcarbamoyl}-1-isobutyl-2-oxo-5-phenyl-pentyl)-carbamic acid benzyl ester 
• 118387-80-7 ((S)-4-{(S)-1-[(S)-2-((S)-1-Benzylcarbamoyl-3-methyl-butylcarbamoyl)-1-hydroxy-ethyl]-3-methyl-butylcarbamoyl}-1-isobutyl-6-methyl-2-oxo-heptyl)-carbamic acid benzyl ester 
• 118405-06-4 ((S)-4-{(S)-1-[(S)-2-((S)-1-Benzylcarbamoyl-3-methyl-butylcarbamoyl)-1-hydroxy-ethyl]-3-methyl-butylcarbamoyl}-2-hydroxy-1-isobutyl-6-methyl-heptyl)-carbamic acid benzyl ester 
• 118387-79-4 ((S)-4-{(S)-1-[(S)-2-((S)-1-Benzylcarbamoyl-3-methyl-butylcarbamoyl)-1-hydroxy-ethyl]-3-methyl-butylcarbamoyl}-1-isobutyl-2-oxo-butyl)-carbamic acid benzyl ester 
• 118405-05-3 Z-LeuΨGly-Sta-Leu-NHCH2Ph 
• 128117-73-7 2-Benzyl-2-((S)-3-benzyloxycarbonylamino-5-methyl-2-oxo-hexyl)-malonic acid 
• 118404-36-7 (2RS,5S)-2-benzyl-5-<(benzyloxycarbonyl)amino>-7-methyl-4-oxooctanoic acid 

Relevant academic research and scientific papers

Sodium borohydride reduction of carbamoyl azide function: A synthesis of N-protected N'-formyl-gem-diaminoalkyl derivatives

A simple, efficient two-step synthesis of N-protected N′-formyl-gem- diaminoalkyl derivatives is reported. The procedure involves the unprecedented reduction of the carbamoyl azide of α-N-Boc/Fmoc/Z-protected amino acids and dipeptides (Boc = tert-butoxycarbonyl, Fmoc = 9-fluorenylmethoxycarbonyl, Z = benzyloxycarbonyl) by treatment with NaBH4 at room temperature. The reaction proceeds rapidly (45 min) without detectable epimerization (by HPLC-ESI-MS analysis) and is not influenced by the nature of the starting carbamoyl azide. The 1H and 13C NMR analyses of the synthesized N-protected N′-formamides were carried out in [D 6]DMSO. The spectra exhibited the presence of two rotameric forms in solution as a result of the restricted rotation around the N-CO formyl bond. The integration of the N-CH-N protons of the two isomers showed that the cis isomer (rotamer B) was the more abundant conformer by 60 to 78 %. The reported synthesis represents the potential value of carbamoyl azides as versatile chiral starting materials for many synthetic purposes. A simple two-step synthesis of N-protected N′-formyl-gem-diaminoalkyl derivatives is reported that employs the reduction of the carbamoyl azide of N-protected amino acids and N-protected dipeptide acids with NaBH4. This racemization-free protocol is compatible with the most commonly used N-protecting groups. Copyright

Synthesis and biological evaluation of novel irreversible serine protease inhibitors using amino acid based sulfonyl fluorides as an electrophilic trap

We have designed and synthesized novel irreversible serine protease inhibitors containing aliphatic sulfonyl fluorides as an electrophilic trap. These substituted taurine sulfonyl fluorides derived from taurine or protected amino acids were conveniently s

Synthesis and biological activity of a series of potent fluoromethyl ketone inhibitors of recombinant human calpain I

Calpain I, an intracellular cysteine protease, has been implicated in the neurodegeneration following an episode of stroke. In this paper, we report on a series of potent dipeptide fluoromethyl ketone inhibitors of recombinant human calpain I (rh calpain I). SAR studies revealed that while calpain I tolerates a variety of hydrophobic groups at the P1 site, Leu at P2 is preferred. However, the nature of the N-terminal capping group has a significant effect on the inhibitory activity of this series of compounds. Compound 4e [(1,2,3,4-tetrahydroisoquinolin-2-yl)carbonyl-Leu-D,L-Phe- CH2F], having a tetrahydroisoquinoline containing urea as the N-terminal capping group, is the most potent dipeptide fluoromethyl ketone inhibitor of calpain 1 (with a second-order rate constant for inactivation of 276 000 M- 1 s-1) yet reported; tripeptide 4k (Cbz-Leu-Leu-D,L-Phe-CH2F) is equipotent. A number of compounds presented in this study displayed excellent selectivity for calpain I over cathepsins B and L, two related cysteine proteases. Compounds which exhibited good inhibitory activity in the assay against isolated rh calpain I also inhibited intracellular calpain I in a human cell line. Thus, in an intact cell assay, compounds 4e and 4k inhibited calpain I with IC50 values of 0.2 and 0.1 μM, respectively. Finally, we also disclose the first example of fluorination of a dipeptide enol silyl ether to generate the corresponding dipeptide fluoromethyl ketone.

Azole endothelin antagonists. 1. A receptor model explains an unusual structure-activity profile

The pseudotetrapeptide FR-139317 is a potent and highly selective antagonist of the endothelin-A (ET(A)) receptor; however, its peptidic nature leads to poor oral absorption characteristics which make it an unlikely drug candidate. In an attempt to improv

Effect of N(α)-acyl chain length on the membrane-modifying properties of synthetic analogs of the lipopeptaibol trichogin GA IV

Trichogin GA IV, an1-residue lipopeptaibol blocked at the N-terminus by an n-octanoyl group and at the C-terminus by a 1,2-amino alcohol (L-leucinol), extracted from the fungus Trichoderma longibrachiatum, exhibits remarkable membrane-modifying properties

Peptidyl and azapeptidyl methylketones as substrate analog inhibitors of papin and cathepsin B

Peptidyl methylketones containing Phe, Tyr, Tyr(I), Tyr(I2), Leu and Ile in P2 were synthesized and tested as substrate analog revesible of papain and bovine spleen cathepsin B.The most effective cathepsin B inhibitor contained Tyr(I2) and displayed an inhibition constant of 4.7 μM at pH 6.8 and 25 deg C, while Leu or Ile gave practically inert analogs.Replacement of the amino acids in P2 with the analogues α-azaamino acids, as well as the glycine in P1 with α-azaglycine, led to complete loss of inhibiting activity.Introducing alkoxy substituents at themethyl adjacent to the ketone group generally resulted in more effective inhibitors, with inhibition constants in the micromolar range for both papin and cathepsin B. - Keywords: enzyme inhibiting activity; cysteine proptease; slow binding; peptidyl methylketone; azapeptidyl methylketone; papain; cathepsin B

Stereocontrolled synthesis of erythro N-protected α-amino epoxides and peptidyl epoxides

N-protected α-amino epoxides of erythro configuration, derived from α-amino acids, were synthesized in a stereoselective manner. The erythro (2S,3S), configuration was achieved by the synthetic sequence: amino acid -> haloketone -> halohydrin -> epoxide. A mechanistic explanation for the observed stereoselectivity is presented. This stereoselective synthetic approach was applied to the synthesis of a variety of short peptidyl epoxides, bearing a predefined absolute configuration of the chiral epoxide moiety.

Studies directed toward the design of orally active renin inhibitors. 1. Some factors influencing the absorption of small peptides

A systematic evaluation of structure-absorption relationships using a high throughput intraduodenal rat screening model has led to the delineation of a set of structural parameters that appear to govern bioavailability in a series of peptide-based renin inhibitors. Optimum structures, exemplified by 25 and 41, incorporated a single, solubilizing substituent at the C- or N- terminus combined with a lipophilic P2-site residue. Both inhibitors gave unprecedented plasma drug levels upon intraduodenal administration to monkeys, and the calculated bioavailability for 41 (14 ± 4%) is the highest reported for any peptidic renin inhibitor.

N-Haloacetyl-amino-acid amides as active-site-directed inhibitors of papain and cathepsin B

A series of N-haloacetyl-amino-acid amides were synthesized and tested as models of cysteine-protease inhibitors. They irreversibly inactivated papain and cathepsin B via a reversible enzyme-inhibitor intermediate. Apparent second-order rate constants of inactivation ranging from 65 to 16,700 M-1 s-1 were observed. Reactivity against papain, as compared to glutathione, was increased 16,400-fold for N-bromoacetyl-leucine isopentylamide and 25,700-fold for the corresponding iodoacetyl derivative; these increases are probably due to proximity effects. No inhibition of trypsin, chymotrypsin and porcine pancreatic elastase was observed. Haloacetamides represent an interesting class of easily synthesized, efficient, irreversible inhibitors of cysteine proteases, which have low non-specific alkylating properties.

Studies of anti-phospholipase A2 and anti-inflammatory activites of a synthetic nonapeptide from uteroglobin

The nonapeptide H-Met-Gln-Met-Lys-Lys-Val-Leu-Asp-Ser-OH (antiflammin), corresponding to a high amino acid similarity region of uteroglobin was prepared by solution and solid phase synthesis. The peptide do not inhibit pancreatic phospolipase A2/sub