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Trapidil (AR-12008) Sale

(Synonyms: 唑嘧胺; AR-12008) 目录号 : GC32458

An inhibitor of PDGF-induced activity and an antiplatelet agent

Trapidil (AR-12008) Chemical Structure

Cas No.:15421-84-8

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10mM (in 1mL Water)
¥736.00
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50mg
¥2,142.00
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产品描述

Trapidil is an inhibitor of PDGF-induced activity and an antiplatelet agent.1,2 It inhibits PDGF-induced proliferation of U251MG glioma cells and isolated rat aortic smooth muscle cells in a concentration-dependent manner. Trapidil (1 mM) inhibits platelet aggregation induced by ADP, arachidonic acid , or U-46619 in washed isolated human platelets.3 It reduces increases in intimal thickness and prevents restenosis induced by balloon angioplasty in rabbits fed a high-cholesterol diet when administered at a dose of 30 mg/kg.4

1.Kuratsu, J., and Ushio, Y.Antiproliferative effect of trapidil, a platelet-derived growth factor antagonist, on a glioma cell line in vitroJ. Neurosurg.73(3)436-440(1990) 2.Hoshiya, M., and Awazu, M.Trapidil inhibits platelet-derived growth factor-stimulated mitogen-activated protein kinase cascadeHypertension31(2)665-671(1998) 3.Mazurov, A.V., Yu, M., Leytin, V.L., et al.Decrease of platelet aggregation and spreading via inhibition of the cAMP phosphodiesterase by trapidilFEBS Lett.172(2)167-171(1984) 4.Liu, M.W., Roubin, G.S., Robinson, K.A., et al.Trapidil in preventing restenosis after balloon angioplasty in the atherosclerotic rabbitCirculation81(3)1089-1093(1990)

Chemical Properties

Cas No. 15421-84-8 SDF
别名 唑嘧胺; AR-12008
Canonical SMILES CC1=NC2=NC=NN2C(N(CC)CC)=C1
分子式 C10H15N5 分子量 205.26
溶解度 Water : ≥ 105 mg/mL (511.55 mM) 储存条件 Store at -20°C, protect from light
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5 mM 0.9744 mL 4.8719 mL 9.7437 mL
10 mM 0.4872 mL 2.4359 mL 4.8719 mL
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Research Update

An Overview on Synthetic and Medicinal Perspectives of [1,2,4]Triazolo[1,5-a]pyrimidine Scaffold

Chem Biodivers 2022 Sep;19(9):e202200291.PMID:35946991DOI:10.1002/cbdv.202200291.

[1,2,4]Triazolo[1,5-a]pyrimidine is an important heterocyclic scaffold known to have a wide range of pharmacological activities such as anticancer, antimicrobial, anti-tubercular, CB2 cannabinoid agonists, feticide, and adenosine antagonists. Several clinical trials and marketed drugs such as Trapidil, Essramycin, Pyroxsulam, DSM-265, Flumetsulam, GNF-6702, and Cevipabulin indicate the potential of [1,2,4]triazolo[1,5-a]pyrimidine moiety with various functional groups in medicinal chemistry. Herein, we represent a concise report focusing on the synthetic strategies used for diversely substituted [1,2,4]triazolo[1,5-a]pyrimidine analogs and their pharmacological applications. To the best of our knowledge, since 1980, we are the first to write a review on this emerging scaffold, which reveals the synthetic strategies, and pharmacological activities of differently substituted [1,2,4]triazolo[1,5-a]pyrimidine with special emphasis on structure-activity relationship studies.

[Trapidil after one year]

Minerva Cardioangiol 1993 May;41(5):159-66.PMID:8373465doi

Present knowledge about cerebral limb ischemia has pointed out the importance of a versatile pharmacological approach, which considers not only the hydraulic aspect of the problem through a vasodilating action, but also all the hemorheologic and hemocoagulative implications, which seem to characterize the pathology itself. For about one year Trapidil has been entering the therapeutic treatments for arterio-vascular diseases in Italy; this drug was already known and tested abroad. Trapidil has shown a more complete antithrombocytic activity than other antiaggregating drugs; as a matter of fact it inhibits the formation of TXA2 through a mechanism of receptorial antagonism and at the same time it favours an increase of prostacyclina from the arterial walls. Moreover this drug is provided with a selective inhibition of the mitogenic effects of PDGF, which occurs for the block of the receptorial binding of this factor at the level of the myointimal cells. In conclusion, in some experimental models Trapidil seems to be able to improve the hemoreologic properties of the blood. Some different clinical studies have demonstrated the therapeutic effectiveness of Trapidil. In the treating of claudication and of the pain during the rest in AOCP, we want to report two studies which have shown a general improving either of the free interval of run or a reduction of the pain. In particular the polycentric study of Bonavita has examined 200 patients afflicted with AOCP at II and III stage, who were divided into three treatment groups: Trapidil, ticlopidina and picotamide.

Trapidil induces osteogenesis by upregulating the signaling of bone morphogenetic proteins

Cell Signal 2018 Sep;49:68-78.PMID:29879471DOI:10.1016/j.cellsig.2018.06.001.

Platelet-derived growth factor receptor (PDGFR) signaling has been shown to inhibit osteogenesis. However, therapeutic efficacy of inhibiting PDGF signaling to bone regeneration in vivo and the specific mechanisms by which PDGFR signaling inhibits osteogenic differentiation remain unclear. In the present study, we examined the osteogenic effect of inhibiting PDGFR using Trapidil, a PDGFR antagonist, in vivo and in vitro, and evaluated its mechanisms. A rat calvarial defect model was analyzed by micro-computed tomography and histology to determine the pro-osteogenic effect of Trapidil in vivo. In addition, primary mouse calvarial osteoblast precursors were cultured in osteogenic differentiation medium with Trapidil to study the mechanisms. Trapidil greatly promoted bone regeneration in a rat calvarial defect model and osteogenic differentiation of calvarial osteoblast precursors. For the mechanisms, Trapidil induced phosphorylation of Smad1/5/9 and mitogen-activated protein kinase (MAPK) leading to enhance expression of Runx2, crucial transcription factor for osteogenesis. The pro-osteogenic effects of Trapidil were inhibited by LDN193189, specific inhibitor of bone morphogenetic protein (BMP) receptor, ALK2 and ALK3, and by depletion of ALK3, and treatment with noggin, an antagonist of BMPs. Moreover, Trapidil showed a synergistic effect with BMP2 on osteogenic differentiation. In conclusion, Trapidil induced BMPR activity through upregulation of BMP signaling, leading to promoted osteogenesis in vitro and in vivo. Attenuated BMPR activity may be involved in the inhibition of osteogenesis by PDGFR signaling.

Trapidil, a platelet-derived growth factor antagonist, inhibits osteoclastogenesis by down-regulating NFATc1 and suppresses bone loss in mice

Biochem Pharmacol 2013 Sep 15;86(6):782-90.PMID:23928189DOI:10.1016/j.bcp.2013.07.015.

Trapidil, a platelet-derived growth factor antagonist, was originally developed as a vasodilator and anti-platelet agent and has been used to treat patients with ischemic coronary heart, liver, and kidney disease. In this study, we investigated the effects of Trapidil on osteoclastogenesis and elucidated the possible mechanism of action of Trapidil. Trapidil strongly inhibited osteoclast formation in co-cultures of bone marrow cells and osteoblasts without affecting receptor activator of NF-魏B ligand (RANKL) or osteoprotegerin expression in osteoblasts. In addition, Trapidil suppressed RANKL-induced osteoclast formation from osteoclast precursors. Trapidil reduced RANKL-induced expression of nuclear factor of activated T cells, cytoplasmic 1 (NFATc1), a master transcription factor for osteoclastogenesis, without affecting the expression of c-Fos that functions as a key upstream activator of NFATc1 during osteoclastogenesis. Ectopic expression of a constitutively active form of NFATc1 reversed the anti-osteoclastogenic effect of Trapidil, indicating that NFATc1 is a critical target of the anti-osteoclastogenic action of Trapidil. RANKL-induced calcium oscillation and Pim-1 expression, which are required for NFATc1 induction and osteoclastogenesis, were abrogated by Trapidil. Consistent with the in vitro results, Trapidil had a potent inhibitory effect on osteoclast formation and bone resorption induced by interleukin-1 in an animal model. Taken together, our data demonstrate that Trapidil abrogates RANKL-induced calcium oscillation and Pim-1 expression required for NFATc1 induction, thereby inhibiting osteoclastogenesis.

Mechanism of cardiovascular action of Trapidil

Arzneimittelforschung 1980;30(8):1264-8.PMID:6254546doi

In anaesthetized, open-chest dogs N,N-diethyl-5-methyl[1,2,4]triazolo[1,5-alpha]pyrimidine-7-amine (Trapidil) in doses of 0.3--3 mg/kg i.v. produced increases in coronary sinus outflow and heart rate and decreases in systemic blood pressure and coronary resistance in a dose-dependent manner. Trapidil produced an increase in myocardial oxygen consumption but virtually no change in coronary arteriovenous oxygen difference. At 1.8 mg/kg i.v. of the drug coronary resistance fell to half of the pre-drug value and coronary sinus outflow almost doubled, and so did myocardial oxygen consumption. In isolated, blood-perfused dog heart preparations, Trapidil produced coronary vasodilator and positive inotropic and chronotropic effects. Theophylline produced similar effects. Trapidil was a more positive inotropic than positive chronotropic agent, and so was theophylline but to a lesser degree than Trapidil. In producing vasodilator and positive inotropic effects Trapidil was about 3 times more effective than theophylline. Trapidil and theophylline inhibited the cyclic AMP phosphodiesterase (PDE) activity in crude extracts prepared from the dog ventricular muscle. In this respect Trapidil was nearly 3 times more potent than theophylline. It is suggested that PDE inhibition would be a fundamental mechanism of action of Trapidil.