84552-93-2Relevant academic research and scientific papers
(3S)-N-(l-Aminoacyl)-1,2,3,4-tetrahydroisoquinolines, a class of novel antithrombotic agents: Synthesis, bioassay, 3D QSAR, and ADME analysis
Zheng, Meiqing,Zhang, Xiaoyi,Zhao, Ming,Chang, Heng Wei,Wang, Wei,Wang, Yuji,Peng, Shiqi
experimental part, p. 9574 - 9587 (2009/04/06)
To increase antithrombotic activity, 3S-tetrahydroisoquinoline-3-carboxylic acid (1) was modified with natural amino acids to form 19 novel dipeptide analogs, 3S-tetrahydroisoquinoline-3-carboxyamino acids (5a-s), targeting the intestinal peptide transport system. In vitro assay of 5a-s indicated that their potencies for inhibiting adenosine diphosphate (ADP), arachidonic acid (AA), platelet-activating factor (PAF), and thrombin (TH)-induced platelet aggregations were higher than that of 1. Additionally, in vivo assay of 5a-s indicated that their potencies for inhibiting thrombogenesis in rats were also higher than that of 1. Among the candidates, 5h with Ser attachment showed the most impressive features for further development. According to molecular field analysis based Cerius2 QSAR module, two equations (r, 0.961 and 0.988) correlating the structures with both in vitro and in vivo activities of 5a-s were established. ADMET calculations predict higher intestinal absorption for compounds 5a-s. Further investigation with 5h as a lead compound is underway.
Application of an automated synthesis suite to parallel solution-phase peptide synthesis
Kuroda,Hattori,Fujioka,Cork,Kitada,Sugawara
, p. 1147 - 1154 (2007/10/03)
An in-house developed automated synthesis suite was used to prepare a library of 72 tetrapeptide derivatives, the starting materials for pharmaceutically attractive pentapeptides, employing a convergent strategy. An initial set of 18 dipeptides were synth
USE OF POLYMERIC ACTIVATED ESTERS BASED ON 1-HYDROXYBENZOTRIAZOLE IN PEPTIDE SYNTHESIS
Grigor'ev, E. I.,Zhil'tsov, O. S.A
, p. 1774 - 1777 (2007/10/02)
A further study was made of the possibility of using polymeric activated esters based on 1-hydroxybenzotriazole in the peptide synthesis as illustrated by the synthesis of the model dipeptides N-tert-butyloxycarbonylalanylphenylalanine methyl ester and N-benzyloxycarbonylvalylglycine methyl ester.A series of negative qualities, which make their use difficult, were noticed in these ethers.A more convenient modification of the already known method for the production of the esters is proposed.In this method 3-nitro-4-chlorobenzyl alcohol, which is the key product forthe production of 1-hydroxybenzotriazole fixed on a polystyrene matrix, can be synthesized with a high yield and a high degree of purity by the reduction of the corresponding aldehyde with aluminum isopropoxide.
Synthesis of a proposed antigenic hexapeptide from Escherichia coli K88 protein fimbriae.
Meldal,Kindtler
, p. 235 - 241 (2007/10/02)
The hexapeptide Boc-Asp-Asp-Tyr-Arg-Gln-Lys-OMe is assembled by stepwise synthesis in solution with an overall yield of 44%. N alpha-boc-amino acids, protected with benzyl or benzyloxycarbonyl groups in the side-chains, are coupled as active estes of 1-hydroxybenzotriazole in mixtures of dichloromethane and N,N-dimethylformamide. N alpha-deprotection is accomplished with trifluoroacetic acid. Finally, hydrogenation with palladium on charcoal and ammonium formate produces the pure hexapeptide. A new one-pot synthesis of Boc-Arg(Z2) is described, and the use of this derivative in peptide coupling is studied. The synthetic peptide was coupled to BSA and used in direct immunication of rabbits.
Synthesis of a putative antigenic heptapeptide from Escherichia coli K88 ab protein fimbriae.
Meldal
, p. 250 - 256 (2007/10/02)
The heptapeptide Tyr-Arg-Glu-Asp-Met-Glu-Tyr-OMe, spanning region 213-219 of Escherichia coli K88 ab protein fimbriae, was synthesized with an overall yield of 37% using dicyclohexylcarbodiimide (DCC) and 1-hydroxybenzotriazole (HOBt) preactivation in all condensation reactions. The C-terminal was protected as the methyl ester. The protection scheme of N alpha-tert-butyloxycarbonyl-(Boc) and benzyl-(Bzl) or benzyloxycarbonyl (Z) groups for side chain protection was found to be orthogonal when a mixture of trifluoroacetic acid (TFA), phenol (PhOH) and p-cresol (CrOH) was used for repetitive deprotection. The final deprotection of Boc-Tyr(Bzl)-Arg(Z2)-Glu(Bzl)-Asp(Bzl)-Met-Glu(Bzl+ ++)-Tyr(Bzl)-OMe (17) was accomplished in 80% yield by prolonged treatment with hydrogen fluoride, dimethyl sulfide, p-cresol and p-thiocresol. The BSA-linked synthetic peptide was used in immunisation experiments on rabbits.
