20898-44-6

Usage

InChI:InChI=1/C18H23N3O4/c1-18(2,3)25-17(24)20-15(16(22)23)9-14-11-21(12-19-14)10-13-7-5-4-6-8-13/h4-8,11-12,15H,9-10H2,1-3H3,(H,20,24)(H,22,23)/t15-/m0/s1

Upstream product

• 16832-24-9 1-benzyl-L-histidine 
• 41840-28-2 S-tert-butoxycarbonyl-4,6-dimethyl-2-mercaptopyrimidine 
• 100-39-0 benzyl bromide 
• 17791-52-5 N-(tert-butoxycarbonyl)-L-histidine 
• 620-05-3 iodomethylbenzene 

Downstream Products

• 61266-04-4 N^α-(tert-butyloxycarbonyl)-N^im-benzyl-L-histidine pentachlorophenyl ester 
• 98189-02-7 N,N-dihexadecyl-N^α-(t-butoxycarbonyl)-N^im-benzyl-L-histidinamide 
• 81019-07-0 Boc-N^im-Bzl-His-Tyr-OMe 
• 96523-67-0 Boc-His(Bzl)-Ala-OBzl 
• 81019-06-9 Boc-N^im-Bzl-His-Phe-OBzl 
• 81019-09-2 Boc-N^im-Bzl-His-D-Phe-OBzl 
• 104166-35-0 Boc-N^im-Bzl-His-Pro-Gly-Pro-OBzl 
• 104166-36-1 Boc-N^im-Bzl-His-N^im-Bzl-His-Pro-Gly-Pro-OBzl 
• 78746-24-4 N-Boc-L-(benzyl)histidyl-L-prolyl-L-phenylalanine benzyl ester 
• 81019-08-1 Boc-N^im-Bzl-His-His-OMe 
• 77119-70-1 Boc-N^im-Bzl-His-Trp-OMe 
• 221640-64-8 (2-(1-benzyl-1H-imidazol-4-yl)-1-{2-[3-(1-benzyl-1H-imidazol-4-yl)-2-tert-butoxycarbonylamino-propionylamino]-ethylcarbamoyl}-ethyl)-carbamic acid tert-butyl ester 
• 21761-38-6 N-(1-benzyl-N^α-tert-butoxycarbonyl-histidyloxy)-succinimide 
• 100223-00-5 3-(1-benzyl-1H-imidazol-4-yl)-2-tert-butoxycarbonylamino-propionic acid benzotriazol-1-yl ester 

Relevant academic research and scientific papers

Discovery of a low affinity thyrotropin-releasing hormone (TRH)-like peptide that exhibits potent inhibition of scopolamine-induced memory impairment in mice

TRH-like peptides were synthesized in which the critical N-terminus residue l-pGlu was replaced with various heteroaromatic rings, and the central residue histidine with 1-alkyl-l-histidines. All synthesized TRH-like peptides were evaluated in vitro as agonists in HEK mTRH-R1 and HEK mTRH-R2 cell lines, an expressing receptor binding assay (IC50), and cell signaling assay (EC50). The analeptic potential of the synthesized peptides was evaluated in vivo by using the antagonism of a pentobarbital-induced sleeping time. The peptides 6a, 6c and 6e were found to activate TRH-R2 with potencies (EC50) of 0.002 μM, 0.28 μM and 0.049 μM, respectively. In contrast, for signaling activation of TRH-R1, the same peptides required higher concentration of 0.414 μM, 50 μM and 19.1 μM, respectively in the FLIPR assay. The results showed that these peptides were 207, 178 and 389-fold selective towards TRH-R2 receptor subtype. In the antagonism of a pentobarbital-induced sleeping time assay, peptide 6c showed a 58.5% reduction in sleeping time. The peptide 6c exhibited high stability in rat blood plasma, a superior effect on the scopolamine-induced cognition impairment mice model, safe effects on the cardiovascular system, and general behavior using a functional observation battery (FOB).

Synthesis, receptor binding, and activation studies of N(1)-alkyl-l-histidine containing thyrotropin-releasing hormone (TRH) analogues

Thyrotropin-releasing hormone (TRH) analogues in which the N(1)-position of the imidazole ring of the centrally placed histidine residue is substituted with various alkyl groups were synthesized and studied as agonists for TRH receptor subtype 1 (TRH-R1) and subtype 2 (TRH-R2). Analogue 3 (R = C2H5) exhibited binding affinity (Ki) of 0.012 μM to TRH-R1 that is about 1.1-fold higher than that of TRH. Several analogues were found to selectively activate TRH-R2 with greater potency than TRH-R1. The most selective agonist of the series 5 [R = CH(CH3)2] was found to activate TRH-R2 with a potency (EC50) of 0.018 μM but could only activate TRH-R1 at EC50 value of 1.6 μM; that is, exhibited 88-fold greater potency for TRH-R2 versus TRH-R1. The results of this study indicate that modulation of central histidine residue is important for designing analogues which were selective agonist at TRH receptor subtypes.

Facile one-step synthesis of N-α-Boc-1-alkyl-l-histidines

A convenient one-step synthesis of N-α-Boc-1-alkyl-l-histidines 2a-f starting from Boc-l-histidine is described. N-α-Boc-l-Histidine upon direct τ(N-1) ring alkylation with various alkyl halides in the presence of sodium hydride in DMF or CH3CN easily afforded N-α-Boc-1-alkyl- l-histidines 2a-f. The reaction works equally well in either DMF or CH 3CN as solvent, however, CH3CN is preferred due to ease of reaction work-up.

Aggregation Behavior of Amphiphiles Functionalized with Dipeptide Segments and Enantioselective Ester Hydrolysis in Their Bilayer Membranes

Four amphiphiles having dipeptide segments, which consist of one histidyl residue and another amino acid residue, and the dihexadecyl moiety for the double-chain segment (N+C5AlaHis2C16, N+C5LeuHis2C16, N+C5PheHis2C16, and N+C5HisAla2C16) were synthesized, and the aggregate morphology of them was characterized by electron microscopy and differential scanning calorimetry.The amphiphiles, which have the histidyl residue bound to the dihexadecylamine component (N+C5AlaHis2C16, N+C5LeuHis2C16, and N+C5PheHis2C16) formed both multi- and single-walled aggregates in the aqueous dispersion state, while their sonicated solutions involved only single-walled vesicles.On the other hand, the amphiphile, which has the alanyl residue bound to the dihexadecylamine component (N+C5HisAla2C16) afforded tubular aggregates in the aqueous dispersion.The hydrolysis of enantiomeric esters of various hydrophobic nature, which was carried out in the single-walled vesicles, showed relatively small enantioselectivity.The reasons for such catalytic performance of the vesicles were discussed from the kinetic and mechanistic viewpoints; the kinetic analysis being carried out on the basis of the organic pseudo-phase concept.