A class of novel N-(3S-1,2,3,4-tetrahydroisoquinoline-3-carbonyl)-l-amino acid derivatives: their synthesis, anti-thrombotic activity evaluation, and 3D QSAR analysis

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

“…[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. 1a), unfolded (Fig.…”

“…[15][16][17] Following this approach 3S-1,2,3,4-tetrahydro-isoqunoline-3-carbonylamino acid (THIQA), an anti-platelet aggregation compound, was modified to its dipeptide analogues to improve their permeability and consequently to enhance their anti-thrombotic activity. 9,10 In addition to a number of bioactivities, [18][19][20][21][22][23][24][25][26][27][28][29][30][31][32] tetrahydroisoquinolines were also reported as anti-platelet aggregation agents. In the mechanism investigations of anti-platelet aggregation of tetrahydroisoquinolines not only b-adrenergic/a 2 -adrenergic receptor system, 33 but also thromboxane A 2 /prostaglandin H 2 receptor system was involved.…”

“…However, due to undesirable bioavailability the antithrombotic candidates usually fail to exert therapeutic potential, which leads to the development of GPIIb/IIIa antagonists having good pharmacodynamic and pharmacokinetic property. [7][8][9][10][11][12][13][14] On the other hand, intestinal peptide transport system is particularly utilized to increase bioavailability. [15][16][17] Following this approach 3S-1,2,3,4-tetrahydro-isoqunoline-3-carbonylamino acid (THIQA), an anti-platelet aggregation compound, was modified to its dipeptide analogues to improve their permeability and consequently to enhance their anti-thrombotic activity.…”

Novel Synthetic Approaches for Bisnaphthalimidopropyl (BNIP) Derivatives as Potential Anti-Parasitic Agents for the Treatment of Leishmaniasis

“…The residue was dissolved in 50 mL EtOAc. The formed solution was washed successively with saturated aqueous solution of sodium bicarbonate (NaHCO 3 ) (30 mL × 3), 5% aqueous solution of potassium bisulfate (KHSO 4 ) (30 mL × 3), and saturated aqueous solution of sodium chloride (NaCl) (30 mL × 3), and then dried with anhydrous sodium sulfate (Na 2 SO 4 ) [40]. After filtration, the filtrate was evaporated under vacuum to give the title compound.…”

α‐N‐Protected dipeptide acids: a simple and efficient synthesis via the easily accessible mixed anhydride method using free amino acids in DMSO and tetrabutylammonium hydroxide

“…Dipeptides and small peptides have wide applications both in medicinal and synthetic chemistry. For example, they are enzyme inhibitors [1][2][3], prodrugs [4][5][6][7][8][9][10][11][12], peroxisome proliferator-activated receptor gamma antagonist [13], anti-HIV-1 [14], and chemotherapeutic metallopharmaceuticals [15][16][17][18][19][20][21]. Dipeptides are also used as additional supplementation of single important amino acid nutrients like glutamine [22][23][24][25][26][27][28][29], tyrosine [25,30,31], and cysteine [25].…”