129297-17-2Relevant articles and documents
Novel nano-materials, RGD-tetrapeptide-modified 17β-amino-11α- hydroxyandrost-1,4-diene-3-one: Synthesis, self-assembly based nano-images and in vivo anti-osteoporosis evaluation
Wang, Yuji,Wu, Jianhui,Kang, Guifeng,Zhao, Ming,Gui, Lin,Li, Ning,Peng, Li,Zhang, Xiaoyi,Li, Li,Peng, Shiqi
supporting information; experimental part, p. 4652 - 4659 (2012/06/29)
To find novel nano-materials with anti-osteoporosis activity and without side effects three novel anti-osteoporosis active amphiphiles, 17β-(RGD-AA-amido)-11α-hydroxyandrost-1,4-diene-3-one (5a: AA = Ser, 5b: AA = Val, 5c: AA = Phe), were constructed by coupling the bone resorption inhibiting active RGD-peptides and anti-osteoporosis active 17β-amino- 11α-hydroxyandrost-1,4-diene-3-one. In the solid state 5a, 5b and 5c exist as dispersed globes of 300 nm-14 μm in diameter, dispersed eggs of 110 nm-19 μm in diameter and beads of 238 nm-22 μm in diameter, respectively. In ultrapure water 1.1 μM of 5a, 5b and 5c form nano-globes of 33-400 nm, 16-278 nm and 54-187 nm in diameter, respectively. At an oral dose of 110 nmol kg -15a-c effectively inhibited mice from developing osteoporosis. In contrast to estradiol, 5a-c did not induce mice to develop endometrial hyperplasia and thrombus.
(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.
Polymer-assisted solution-phase library synthesis and crystal structure of α-ketothiazoles as tissue factor VIIa inhibitors
Parlow, John J.,Dice, Thomas A.,Lachance, Rhonda M.,Girard, Thomas J.,Stevens, Anna M.,Stegeman, Roderick A.,Stallings, William C.,Kurumbail, Ravi G.,South, Michael S.
, p. 4043 - 4049 (2007/10/03)
A solution-phase synthesis of an α-ketothiazole library of the general form D-Phe-L-AA-Arg-α-ketothiazole is described. The five-step synthesis is accomplished using a combination of polymeric reagents and polymer-assisted solution-phase purification concepts, including reactant-sequestering resins, reagent-sequestering resins, and tagged reagents. The multistep synthesis affords desired α-ketothiazole products in excellent purities and yields. A variety of L-amino acid inputs were used to probe the S2 pocket of tissue Factor VIIa enzyme to influence both potency and selectivity. An X-ray crystal structure of compound 10k bound to the TF/VIIa complex was obtained that explains the observed selectivity. The α-ketothiazoles were found to be potent, reversible-covalent inhibitors of tissue Factor VIIa, with some analogues demonstrating selectivity over thrombin.
