167316-06-5

Upstream product

• 53267-93-9 O-methyl-N-tert-butoxycarbonyl-L-tyrosine 
• 2491-20-5 L-alanine methyl ester hydrochloride 
• 74-88-4 methyl iodide 
• 188966-57-6 Boc-L-Tyr-L-Ala-OMe 
• 4326-36-7 (S)-N-(tert-butoxycarbonyl)tyrosine methyl ester 
• 3417-91-2 L-tyrosine methyl ester HCl 
• 60-18-4 L-tyrosine 
• 94790-24-6 (S)-methyl 2-((tert-butoxycarbonyl)amino)-3-(4-methoxyphenyl)propanoate 
• 6230-11-1 O-Methyltyrosine 
• 24424-99-5 di-tert-butyl dicarbonate 

Downstream Products

• 944059-32-9 C₁₉H₂₇N₂O₆I 
• 167316-07-6 BOC-D-Ala-L-Ala-L-Tyr(OMe)-L-Ala-OMe 
• 167316-05-4 BOC-D-Ala-L-Ala-L-Tyr(OMe)-L-Ala-OH 
• 161635-05-8 BOC-D-Ala-L-Ala-L-Tyr(OMe)-L-Ala-OC₆F₅ 
• 137606-77-0 RA-VII 
• 911675-93-9 N-Boc-3-iodo-Tyr(Me)-Ala-7-bromo-Trp-OMe 
• 944059-35-2 N-Boc-3-iodo-Tyr(Me)-Ala-OH 
• 133859-29-7 N-(O⁴-methyl-L-tyrosyl)-L-alanine methyl ester 
• 167316-10-1 BOC-D-alanyl-L-alanyl-O⁴-methyl-L-tyrosyl-L-alanyl-L-tyrosyl-N,O⁴-dimethyl-L-tyrosine cyclic 5⁴<*>6³ ether, methyl ester 
• 167316-08-7 BOC-D-alanyl-L-alanyl-O-methyl-L-tyrosyl-L-alanyl-N-methyl-L-tyrosyl-N,O⁴-dimethyl-L-tyrosine cyclic 5⁴<*>6³ ether, methyl ester 
• 167316-11-2 BOC-D-alanyl-L-alanyl-O⁴-methyl-L-tyrosyl-L-alanyl-N-methyl-L-tyrosyl-O⁴-methyl-L-tyrosine cyclic 5⁴<*>6³ ether, methyl ester 
• 167316-13-4 BOC-D-alanyl-L-alanyl-O⁴-methyl-L-tyrosyl-L-alanyl-L-tyrosyl-O⁴-methyl-L-tyrosine cyclic 5⁴<*>6³ ether, methyl ester 
• 167316-16-7 C₄₄H₅₆N₆O₁₂ 
• 167316-19-0 C₄₃H₅₄N₆O₁₂ 

Relevant academic research and scientific papers

Synthesis and conformation studies of rubiyunnanin B analogs

Five new analogs 4-8 of rubiyunnanin B (1), mainly modified on the tetrapeptide subunit, were synthesized. These agents 4-8 were substituted d-Ala-l-Ala-l-Tyr(OMe)-l-Ala, d-Ala-l-Ala-l-Phe-l-Ala, d-Ala-l-Ala-l-Try-l-Ala, d-Ala-l-Ala-l-Pro-l-Ala, and d-Ala-l-Ala-l-Ala for the d-Ala-l-Ala-l-N-Me-Tyr(OMe)-l-Ala tetrapeptide subunit. Unlike the natural product, the synthetic agents 4-8 adopt only a single solution conformation, and the central peptide bond in the cyclodityrosine subunit of compounds 4-8 adopt trans stereochemistry. Cytotoxic activities of analogs 4-8 against three human cancer cell lines including A549, BGC-823, and HeLa were evaluated and all the five synthesized peptides exhibited no effects against the test cell lines. These compounds were also evaluated for their antiinsulin resistance and insulin sensitizing activities and none of them showed activity in these assays.

Synthesis and conformational characterization of diketopiperazines bearing a benzyl moiety

Diketopiperazines bearing a benzyl moiety with different para-substituents were synthesized and analyzed by 1HNMR spectroscopy. All of these diketopiperazines were found to adopt a folded conformation according to the upfield chemical shift of the cis-proton (cis to the benzyl moiety) due to a shielding effect in the 1HNMR spectra. An intramolecular CH-π interaction appears to be an important factor for the folded conformation due to the effects of para-substituents on the benzyl group.

Linear TMC-95-based proteasome inhibitors

We have designed and evaluated 45 linear analogues of the natural constrained cyclopeptide TMC-95A. These synthetically less demanding molecules are based on the tripeptide sequence Y-N-W of TMC-95A. Structural variations in the amino acid side chains and

COMPOUNDS USEFUL AS MODULATORS OF THE PROTEASOME ACTIVITY

The present invention relates to the use of compounds of the following general formula (I): wherein no is 0 or 1, and when no is 1, X = CH2 or X = NCH2C6H5; R1 is OH, or a OR10 group, or a group of formula NH-(CH2)n1-R11; R2 is H, or an alkyl group, or a group of formula (CH2)n2-(CO)n3-NR13R14; R3 is H, or an alkyl group; R4 is H, or Boc, or Z; R5 is H, or Boc, or Z ; R6 is a OR16 group; R7 and R8 are H, or a halogen atom, as modulators of the proteasome activity, in the frame of the preparation of a medicament useful for the prevention or treatment of diseases wherein the proteasome is involved, or the preparation of cosmetic compositions, or of phytosanitary compositions.

Semisynthesis of an analogue of antitumor bicyclic hexapeptide RA-VII by fixing the Ala-2/Tyr-3 bond to cis by incorporating a triazole cis-amide bond surrogate

We prepared an analogue of an antitumor bicyclic hexapeptide RA-VII whose amide configuration between residues 2 and 3 was fixed to cis by incorporating a triazole cis-amide bond surrogate. This analogue was shown, by NMR studies, to take almost the same

N-Desmethyl derivatives of deoxybouvardin and RA-VII: Synthesis and evaluation

The synthesis of the complete set of seven N-desmethyl derivatives of RA-VII (8) are described. Thus, the synthesis of the four 14-membered cycloisodityrosine derivatives 21-24 and their coupling with the two tetrapeptides 32 and 33 followed by formation of the 18-membered ring with macrocyclization provided the full set of seven desmethyl derivatives 14-20 of RA-VII (8). The solution phase conformational properties of 8 and 14-20 were examined by 1D and 2D 1H NMR to reveal the role of N-methylation on the key conformational aspects of the natural agents. In contrast to each of the simple cycloisodityrosine derivatives 21-24 which adopt a single, rigid solution conformation possessing a secondary or tertiary trans amide central to the 14-membered ring, the natural agents including 8 adopt a single predominant solution conformation (83-88%) that corresponds closely to the X-ray structure conformation which possesses an inherently disfavored cis C30-N29 tertiary amide central to the 14-membered cycloisodityrosine subunit. Moreover, this cis amide is the predominant conformation (85-95%) observed with N29-desmethyl RA-VII (14) indicating that even a secondary C30-N29 amide adopts this inherently disfavored cis amide stereochemistry. The minor conformation of 8 observed in solution (12-17%) is shown to be derived from a minor cis C8-N9 tertiary amide which was not observed with its conversion to a secondary amide. Both N9-desmethyl RA-VII (15) and N9,N29-desmethyl RA-VII (18) adopt exclusively a single solution conformation that corresponds to the major solution conformations of 8 and 14. This conformation contains a characteristic cis C30-N29 amide central to a type VI β-turn and the cycloisodityrosine subunit, a trans C8-N9 amide central to a typical type II β-turn capped with a tight Ala4-NH-O=C-Ala1 hydrogen bond, and a trans C14-N15 N-methyl amide. In sharp contrast, removal of the N15 methyl group within 16, 17, 19, and 20 results in the adoption of solution conformations possessing the inherently favored trans C30-N29 amide central to the cycloisodityrosine 14-membered subunit. Thus, the N15-methyl group within 8 is responsible for the agents adoption of the disfavored cis C30-N29 amide central to the cycloisodityrosine subunit. Importantly, preceding studies have defined the cycloisodityrosine subunit of 8 as the pharmacophore and, in a reversal of the initially assigned roles, revealed that it is the tetrapeptide housed in the 18-membered ring that induces and maintains the rigid, normally inaccessible cis C30-N29 amide conformation within the 14-membered cycloisodityrosine subunit. The studies detailed herein reveal that it is the N15-methyl group that induces this conformational preference for the disfavored cis C30-N29 amide and that its removal results in a major conformational change with adoption of the trans C30-N29 amide and a loss of biological activity. Thus, the N15-methyl group is essential for maintenance of the conformational and biological properties of 8; the N9-methyl group is not essential, and its removal leads to exclusive population of a single biologically active conformation; and the N29-methyl group once thought essential to the adoption of the C30-N29 cis amide is not essential, and its removal does not alter the conformational or biological properties of 8.