2,3-Diamino acid modifying 3S-tetrahydroisoquinoline-3-carboxylic acids: Leading to a class of novel agents with highly unfolded conformation, selective in vitro anti-platelet aggregation and potent in vivo anti-thrombotic activity

Zhang, Xiaoyi; Wang, Wei; Cheng, Shenling; Zhao, Ming; Zheng, Meiqing; Chang, Hsiao-Huang; Wu, Jianhui; Peng, Shiqi

doi:10.1016/j.bmc.2010.01.009

Cited by 20 publications

(2 citation statements)

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“…TICs and their N -acyl analogs have been frequently studied, and numerous derivatives have been reported as antithrombotic, anticancer, hypoglycemic, and antiviral agents (Figure ). − Interestingly, in contrast to TIC, the biological properties of the corresponding homological tetrahydrobenzo[ d ]azepines-2-carboxylic acids and their derivatives are practically unknown.…”

Section: Introductionmentioning

confidence: 99%

Synthesis of Polycyclic Tetrahydroisoquinolines and Tetrahydrobenzo[d]azepines from Polymer-Supported Allylglycine

Králová

Soural

2022

J. Org. Chem.

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Herein, we report a multistep synthesis of polycyclic tetrahydroisoquinolines and tetrahydrobenzo [d]azepines starting from Wang resin-immobilized allylglycine. After sulfonylation with 2/4-nitrobenzenesulfonyl chlorides, Mitsunobu alkylation with various phenylalkynols yielded the corresponding (phenylprop-2yn-1-yl)-sulfonamides. "Interior" ring-closure enyne metathesis (RCEM) using a Grubbs catalyst second generation (Ru2) yielded functionalized tetrahydroisoquinoline/tetrahydrobenzo[d]azepine intermediates. "East-side" [4 + 2] cycloaddition with representative dienophiles was followed by the "west-side" construction of different heterocycles using various electrophiles to finally furnish a set of novel molecular frameworks bearing fused [6 + 6] or [6 + 7] rings. The developed methodology enables the facile parallel synthesis of novel, pharmacologically promising compounds derived from privileged scaffolds.

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Section: Introductionmentioning

confidence: 99%

Synthesis of Polycyclic Tetrahydroisoquinolines and Tetrahydrobenzo[d]azepines from Polymer-Supported Allylglycine

Králová

Soural

2022

J. Org. Chem.

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“…For instance, targeting Arg-Gly-Asp-Ser, thymopentin and Lys(Pro-Ala-Lys) were used to carry dexamethasone, 1,2 VEGF-siRNA/nanodiamond, 3,4 1,1-dimethyl tetrahydro-βcarboline-3-carboxylic acid, 5 and 6,7-dihydroxy-1,1-dimethy l-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid (IQCA), 6 respectively. [14][15][16][17][18][19] According to the advantage of Ser, Ala and Thr in enhancing the anti-thrombotic activity of IQCA, 20 residues of the most important amino acid residues of the pocket (Fig. [14][15][16][17][18][19] According to the advantage of Ser, Ala and Thr in enhancing the anti-thrombotic activity of IQCA, 20 residues of the most important amino acid residues of the pocket (Fig.…”

Section: Introductionmentioning

confidence: 99%

IQCA-TASS: a nano-scaled P-selectin inhibitor capable of targeting thrombus and releasing IQCA/TARGD(S)S in vivo

Zhu

Zhao

et al. 2017

J. Mater. Chem. B

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Thrombosis seriously threatens human health worldwide. Tetrahydroisoquinoline-3-carboxylic acid (IQCA) is an antithrombotic agent, while Thr-Ala-Arg-Gly-Asp(Ser)-Ser (TASS) can target thrombus. In the discovery of nano-delivery system for targeting thrombus tetrahydroisoquinoline-3-carbonyl-Thr-Ala-Arg-Gly-Asp(Ser)-Ser (IQCA-TASS) was designed here. In vitro IQCA-TASS acted on P-selectin and down-regulated P-selectin expression. The IC 50 values of IQCA-TASS against the platelet aggregation induced by four aggregators were less than 0.45 nM.In vivo IQCA-TASS targeted thrombus, released IQCA and TASS inside thrombus, showed dose-dependent anti-thrombotic action, of which the minimal effective dose was 1 nmol/kg, and showed anti-inflammatory action. Even the dose been up to 1 μmol/kg, a dose of 1000 times of the minimal effective dose, IQCA-TASS still induced no toxic reaction. In rat plasma IQCA-TASS forms the nanoparticles of less than 41 nm in diameter. The interactions of the nanoparticles with both resting and activated platelets were imaged. In conclusion, IQCA-TASS should be a safe nano-medicine capable of targeting thrombus and releasing the anti-thrombotic/anti-inflammatory pharmacophores in the disease site.

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Tetrahydroisoquinolines

2018

Privileged Structures in Drug Discovery

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2,3-Diamino acid modifying 3S-tetrahydroisoquinoline-3-carboxylic acids: Leading to a class of novel agents with highly unfolded conformation, selective in vitro anti-platelet aggregation and potent in vivo anti-thrombotic activity

Cited by 20 publications

References 44 publications

Synthesis of Polycyclic Tetrahydroisoquinolines and Tetrahydrobenzo[d]azepines from Polymer-Supported Allylglycine

Synthesis of Polycyclic Tetrahydroisoquinolines and Tetrahydrobenzo[d]azepines from Polymer-Supported Allylglycine

IQCA-TASS: a nano-scaled P-selectin inhibitor capable of targeting thrombus and releasing IQCA/TARGD(S)S in vivo

Tetrahydroisoquinolines

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