Derivatives of 7-amino-1,2,3,4-tetrahydroisoquinoline and isophthalic acids as novel fibrinogen receptor antagonists

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

“…40,41 Our assay indicates that the IC 50 values of THIQA against platelet aggregation induced by ADP and AA are 0.55 and 0.45 lM, respectively. The IC 50 values of THIQA are 182-491 and 7-311-fold lower than that of the mentioned tetrahydroisoquinolines.…”

“…According to the literature some representatives of tetrahydroisoquinolines such as Higenamine, YS-49 and YS-51, effectively inhibit ADP-induced platelet aggregations and the IC 50 values range from 3.3 to 800 lM, 40,41,43 which are 1520-214477-fold higher than 8a-t. Therefore 2,3-diamino acid modification of THIQA greatly enhances the in vitro anti-platelet aggregation potency.…”

“…[34][35][36] Based on these investigations some derivatives of benzyltetrahydroisoquinoline alkaloid were reported having anti-platelet aggregation activities. [37][38][39][40] In the previous paper, we used THIQA as the anti-thrombotic lead, introducing amino acid into its 2-or 3-position, and prepared two series of pseudopeptides 3S-N-(L-amino-acyl)-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acids (9a-t), 9 as well as 3S-1,2,3,4-tetrahydroisoquinoline-3-carbonylamino acids (10a-t). 10 In our preinvestigation it was found that a folded (Fig.…”

Design, synthesis, and testing of an isoquinoline-3-carboxylic-based novel anti-tumor lead

“…[1][2][3] Certain isoquinoline alkaloids can inhibit a number of cancer-related enzymes, including inosine 5 0 -monophosphate dehydrogenase, 4 Pfmrk, 5 P-glycoprotein, 6 kinase B/Akt, 7 cyclin dependent kinase 4, 8 topoisomerase I, 9 TRPV1, 10 IkB kinase-b, 11 caspase-3, 12 and mammalian sterile 20 kinase. 13 Isoquinolines alkaloids have attracted considerable attention for use as antitumor agents, since the isolation of naphthyridinomycin in 1974.…”

2-Substituted (S)-2-(3,3-dimethyl-1-oxo-10,10a-dihydroimidazo[1,5-b]isoquinolin-2(1H,3H,5H)-yl)acetic acids: Conformational prediction, synthesis, anti-thrombotic and vasodilative evaluation

“…[14][15][16] Based on these receptor systems the design of tetrahydroisoquinolines attracts many interests. [17][18][19][20] In our previous work, (S)-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid (TIC) was used as a lead and C-and/or N-terminal amino acid modifications were performed. [21][22][23] In this continuing work on the modification of TIC with a substituted-dihydroimidazole functional group, seventeen novel 2-substituted (S)-2-(3,3-dimethyl-1-oxo-10,10a-dihydroimidazo [1,5-b]isoquinolin-2(1H,3H, 5H)-yl)acetic acids (5a-q) were synthesized, and evaluated in an in vitro anti-platelet aggregation assay, and an in vivo antithrombotic model.…”