129253-02-7

Upstream product

• 13139-16-7 N-tert-butyloxy-isoleucine 
• 100-46-9 benzylamine 
• 3160-59-6 N-Cbz-L-Isoleucine 
• 3391-99-9 N-Z-L-isoleucine N-hydroxysuccinimide ester 
• 134015-91-1 C₂₁H₂₆N₂O₃ 
• 13139-16-7 N-(tert-butyloxycarbonyl)-L-isoleucine 
• 154128-82-2 Boc-Ile-NHCH₂C₆H₅ 
• 3392-08-3 tert-(butoxycarbonyl)isoleucine succinimidyl ester 

Downstream Products

• 73-32-5 L-isoleucine 
• 1067648-89-8 (2S,4S,5S)-5-azido-6-benzyloxy-4-hydroxy-2-isopropyl-hexanoic acid ((S)-1-benzylcarbamoyl-2-methyl-butyl)-amide 
• 1067648-90-1 (2S,4S,5S)-5-amino-6-benzyloxy-4-hydroxy-2-isopropyl-hexanoic acid ((S)-1-benzylcarbamoyl-2-methyl-butyl)-amide 
• 1067648-28-5 N-[(1S,2S,4S)-4-((S)-1-benzylcarbamoyl-2-methyl-butylcarbamoyl)-1-benzyloxymethyl-2-hydroxy-5-methyl-hexyl]-5-(methanesulphonyl-methyl-amino)-N'-((R)-1-phenyl-ethyl)-isophthalamide 
• 137143-95-4 (1R,2S)-2-[(1S,2S)-1-Hydroxy-3-phenyl-2-(2,2,2-trifluoro-acetylamino)-propyl]-cyclopentanecarboxylic acid ((1S,2S)-1-benzylcarbamoyl-2-methyl-butyl)-amide 
• 137143-93-2 (4S,5R)-4-Benzyl-5-[(1R,2R)-2-((1S,2S)-1-benzylcarbamoyl-2-methyl-butylcarbamoyl)-cyclopentyl]-2,2-dimethyl-oxazolidine-3-carboxylic acid benzyl ester 
• 161510-50-5 SDZ 282310 
• 276257-35-3 Boc-Pro-Ile-NHBn 
• 276257-15-9 Boc-Ala-Gly-Pro-Ile-NHBn 
• 1056671-22-7 (2S,4S,5S)-5-benzylamino-4-hydroxy-2-isopropyl-6-(naphthalen-1-ylmethoxy)-hexanoic acid ((1S,2S)-1-benzylcarbamoyl-2-methylbutyl)-amide trifluoroacetate 
• 1056671-17-0 (2S,4S,5S)-4-hydroxy-2-isopropyl-5-isopropylamino-6-(naphthalen-1-ylmethoxy)-hexanoic acid ((1S,2S)-1-benzylcarbamoyl-2-methylbutyl)-amide trifluoroacetate 
• 1056676-15-3 (2S,4S,5S)-5-azido-6-benzyloxy-4-hydroxy-2-isopropyl-hexanoic acid ((1S,2S)-1-benzylcarbamoyl-2-methyl-butyl)-amide 
• 1056674-98-6 (2S,4S,5S)-5-azido-4-hydroxy-2-isopropyl-6-[3-(3-methoxy-propoxy)-benzyloxy]-hexanoic acid ((1S,2S)-1-benzylcarbamoyl-2-methylbutyl)-amide 

Relevant academic research and scientific papers

[...] - Orn (ClCH2NH) - AA - benzylamine, its synthesis, activity and application (by machine translation)

The invention discloses the following formula of 13 for β - Carboline -3 - formyl - Orn (ClCH2 NH) - AA - NHCH2 C6 H5 (In the formula AA is selected from L - Arg, L - Asn, L - Asp, L - Glu, L - Gly, L - Ile, L - Leu, L - Met, L - Phe, L - Pro, L - Thr, L - Trp, L - Val residue), discloses a process for their preparation, discloses their inhibition of tumor cell growth, therefore this invention discloses their use as anti-tumor medicament. (by machine translation)

Benzylamide antagonists of protease activated receptor 2 with anti-inflammatory activity

Activation of protease activated receptor 2 (PAR2) has been implicated in inflammatory and metabolic disorders and its inhibition may yield novel therapeutics. Here, we report a series of PAR2 antagonists based on C-terminal capping of 5-isoxazolyl-l-cyclohexylalanine-l-isoleucine, with benzylamine analogues being effective new PAR2 antagonists. 5-Isoxazolyl-l-cyclohexylalanine-l-isoleucine-2-methoxybenzylamine (10) inhibited PAR2-, but not PAR1-, induced release of Ca2+(IC500.5 μM) in human colon cells, IL-6 and TNFα secretion (IC501-5 μM) from human kidney cells, and was anti-inflammatory in acute rat paw inflammation (ED505 mg/kg sc). These findings show that new benzylamide antagonists of PAR2 have anti-inflammatory activity.

Mechanistic implications of the enantioselective addition of alkylzinc reagents to aldehydes catalyzed by nickel complexes with α-amino amide ligands

The enantioselective alkylation of aldehydes catalysed by nickel(ii)-complexes derived from α-amino amides was studied by means of density functional theory (DFT) and ONIOM (B3LYP:UFF) calculations. A mechanism was proposed in order to investigate the origin of enantioselectivity. The chirality-determining step for the alkylation was the formation of the intermediate complexes with the involvement of a 5/4/4-fused tricyclic transition state. The predominant products predicted theoretically were of (S)-configuration, in good agreement with experimental observations. The scope of the reaction was examined and high yields and enantioselectivities were observed for the enantioselective addition of Et2Zn and Me2Zn to aromatic and aliphatic aldehydes.

C2 symmetrical nickel complexes derived from α-amino amides as efficient catalysts for the enantioselective addition of dialkylzinc reagents to aldehydes

A series of C2 symmetrical 1:2 Ni:L complexes derived from α-amino amides were studied for the enantioselective addition of dialkylzinc reagents to aldehydes. Different structural elements on the ligands seem to play an important role in determining the observed enantioselectivity. Through optimization of structure and reaction conditions, the best ligand provided secondary alcohols in excellent yields (up to 98%) and enantioselectivity of up to 99% ee for (R)-enantiomer. A transition state model has been proposed to explain the observed enantioselectivities based on computational calculations at the DFT level. Very interestingly, calculations suggest a coordination model of the aldehyde to the metal complex through association of a lone pair of the carbonyl oxygen to the hydrogen atom of an amino group.

NEW COMPOUNDS

The invention provides compounds of the formula I wherein Q is aryl or heterocyclyl any of which is optionally substituted; Z is O, S, NRa or S(=O)p; Y is NH, NHNH, CH2NH, O, S or S(=O)p; n is 0, 1, 2 or 3; m is 0, 1 or 2; p is 1 or 2; Ra is H or C1-C4alkyl; R1 is hydrogen, C1-C6alkyl, C0-C3alkanediylC3-C7cycloalkyl, C0-C3alkanediylaryl or C0- C3alkanediylheterocyclyl; R2 is hydrogen or C1-C6alkyl; X' is hydrogen, fluoro, hydroxy, amino or C1-C6alkoxy; X" is hydrogen, or when X' is fluoro, then X" may also be fluoro; R3is C1-C6alkyl; R4' is C1-C6alkyl; R4" is H or C1-C6alkyl; or R4' and R4" together with the carbon atom to which they are attached define a C3-C6cycloalkyl; W is C1-C6alkyl, C3-C7cycloalkyl, aryl or heterocyclyl any of which is optionally substituted; or a pharmaceutically acceptable salt, hydrate or N-oxide thereof. The compounds of the invention are inhibitors of aspartyl proteases such as renin and are among other things useful for the treatment of conditions associated with activities of the RAS, such as hypertension, heart failure and renal insufficiency.

AMIDE DERIVATIVES AS INHIBITORS OF ASPARTYL PROTEASES

The invention provides compounds of the formula (I). N-oxides, addition salts, quaternary amines, metal complexes, stereochemically isomeric forms and metabolites thereof, wherein W is H, C1-C6alkyl, C3-C6cycloalkyl, aryl or heterocyclyl; Q is aryl or heterocyclyl; A is a five or six membered saturated, partially unsaturated or aromatic ring; D is formula (II) or formula (III); and the other variables are as defined in the specification. The compounds of the invention are inhibitors of aspartyl proteases such as renin and BACE and are among other things useful for the treatment and/or prophylaxis of conditions associated with activities of the RAS, such as hypertension, heart failure and renal insufficiency and for the treatment and or prophylaxis of conditions associated with BACE activity such as of Alzheimer's disease.

Development of Potent Inhibitors of Botulinum Neurotoxin Type B

Botulinum neurotoxins are the most potent toxins known to date. They are zinc-metalloproteases able to cleave selectively an essential component of neurotransmitter exocytosis, causing the syndrome of botulism characterized by a flaccid paralysis. There is a great interest in designing antagonists of the action of these toxins. One way is to inhibit their catalytic activity. In this study, we report the design of such inhibitors directed toward BoNT/B. A study of the S1 subsite specificity, using several β-amino thiols, has shown that this subsite prefers a p-carboxybenzyl moiety. The specificity of the S1′ and S2′ subsites was studied using two libraries of pseudotripeptides containing the S1 synthon derived from the best β-amino thiol tested. Finally, a selection of various non natural amino acids for the recognition of the "prime" domain led to the most potent inhibitor of BoNT/B described to date with a Ki value of 20 nM.

New strategies for an efficient removal of the 9- fluorenylmethoxycarbonyl (Fmoc) protecting group in the peptide synthesis

The aluminium trichloride/toluene system is investigated as a novel, unusual and straightforward reagent for the removal of the 9- fluorenylmethoxycarbonyl (Fmoc) protecting group in the solution peptide synthesis. This procedure avoids any undesired side reactions, such as the frequently observed inversion of the amino acid configuration.

Amino acid derivatives

Compounds of the formula wherein R1 represents alkoxycarbonyl, aralkoxycarbonyl, alkanoyl, aralkanoyl, aroyl, cycloalkylcarbonyl, heterocyclylcarbonyl, heterocyclyl-alkanoyl, 6-(dibenzylcarbamoyl)-4-oxohexanoyl or an acyl group of an α-amino acid in which