Category: 171049-35-7

Potent, Orally Active GPIIb/IIIa Antagonists Containing a Nipecotic Acid Subunit. Structure-Activity Studies Leading to the Discovery of RWJ-53308 was written by Hoekstra, William J.;Maryanoff, Bruce E.;Damiano, Bruce P.;Andrade-Gordon, Patricia;Cohen, Judith H.;Costanzo, Michael J.;Haertlein, Barbara J.;Hecker, Leonard R.;Hulshizer, Becky L.;Kauffman, Jack A.;Keane, Patricia;McComsey, David F.;Mitchell, John A.;Scott, Lorraine;Shah, Rekha D.;Yabut, Stephen C.. And the article was included in Journal of Medicinal Chemistry in 1999.Computed Properties of C15H28N2O2 This article mentions the following:

Although i.v. administered antiplatelet fibrinogen receptor (GPIIb/IIIa) antagonists have become established in the acute-care clin. setting for the prevention of thrombosis, orally administered drugs for chronic use are still under development. Herein, the authors present details from the authors exploration of structure-activity surrounding the prototype fibrinogen receptor antagonist RWJ-50042, which was derived from a unique approach involving the 纬-chain of fibrinogen (Hoekstra et al. J. Med. Chem. 1995, 38, 1582). The authors analog studies culminated in the discovery of RWJ-53308 (I), a potent, orally active GPIIb/IIIa antagonist. To progress from RWJ-50042 to a suitable candidate for clin. development, the authors conducted a series of optimization cycles that employed solid-phase parallel synthesis for the rapid, efficient preparation of nearly 250 analogs, which were assayed for fibrinogen receptor affinity and inhibition of platelet aggregation induced by four different activators. This strategy produced several promising analogs for advanced study, including the 3-(3,4-methylenedioxybenzene)-尾-amino acid analog (significant improved in vivo potency) and the 3-(3-pyridyl)-尾-amino acid I (significantly improved potency, oral absorption, and duration of action). In dogs, I displayed significant ex vivo antiplatelet activity on oral administration at 1.0 mg/kg, 16% systemic oral bioavailability, minimal metabolic transformation, and an excellent safety profile. Addnl., I was efficacious in three in vivo thrombosis models: canine arteriovenous (AV) shunt (0.01-0.1 mg/kg, iv), guinea pig photoactivation-induced injury (0.3-3 mg/kg, iv), and guinea pig ferric chloride-induced injury (0.3-1 mg/kg, iv). On the basis of its noteworthy preclin. data, I was selected for clin. evaluation. In the experiment, the researchers used many compounds, for example, tert-Butyl [4,4′-bipiperidine]-1-carboxylate (cas: 171049-35-7Computed Properties of C15H28N2O2).

tert-Butyl [4,4′-bipiperidine]-1-carboxylate (cas: 171049-35-7) belongs to piperidine derivatives. Piperidine and its derivatives have become increasingly popular in many synthetic schemes. Some chemotherapeutic agents have piperidine moiety within their structure, foremost among them, vinblastine and raloxifene.Computed Properties of C15H28N2O2

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Development of Kinase Inactive PD173955 Analogues for Reducing Production of A尾 Peptides was written by Sinha, Anjana;Gindinova, Katherina;Mui, Emily;Netzer, William J.;Sinha, Subhash C.. And the article was included in ACS Medicinal Chemistry Letters in 2019.Recommanded Product: 171049-35-7 This article mentions the following:

Compound 3a, DV2-103, is a kinase inactive analog of a potent Abl1/Src kinase inhibitor, PD173955, 2. Both compounds, 2 and 3a, are known to reduce production of beta amyloid (A尾) peptide in cells and animal models. We have now prepared and evaluated a series of PD-173955 analogs, several of which reduced A尾 production potently. This occurs in cells expressing human full-length amyloid precursor protein (APP) and not in cells expressing APP 尾-C terminal fragment (APP-C99), suggesting that the kinase inactive analogs strongly affect 尾-secretase (BACE1) cleavage of APP, similarly to Gleevec. A combination of the kinase inactive analogs of PD173955 with a BACE1 inhibitor (BACEi), namely BACE IV, strongly reduced A尾 levels in cells, as noted previously with Gleevec and analogs. Several potent compounds also penetrated and accumulated in mouse brain in high nanomolar to low micromolar concentration In the experiment, the researchers used many compounds, for example, tert-Butyl [4,4′-bipiperidine]-1-carboxylate (cas: 171049-35-7Recommanded Product: 171049-35-7).

tert-Butyl [4,4′-bipiperidine]-1-carboxylate (cas: 171049-35-7) belongs to piperidine derivatives. The piperidine ring can be found not only in more than half of the currently known structures of alkaloids, but also in many natural or synthetic compounds with interesting biological activities. The piperidine and polyhydroxylated indolizidine derivatives have shown to be promising 伪-glucosidase inhibitors. The former are analogs of DNJ with an improved 伪-glucosidase inhibitory profile than that of DNJ. Boisson et al.Recommanded Product: 171049-35-7

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Development of Kinase Inactive PD173955 Analogues for Reducing Production of Aβ Peptides was written by Sinha, Anjana;Gindinova, Katherina;Mui, Emily;Netzer, William J.;Sinha, Subhash C.. And the article was included in ACS Medicinal Chemistry Letters in 2019.Recommanded Product: 171049-35-7 This article mentions the following:

Compound 3a, DV2-103, is a kinase inactive analog of a potent Abl1/Src kinase inhibitor, PD173955, 2. Both compounds, 2 and 3a, are known to reduce production of beta amyloid (Aβ) peptide in cells and animal models. We have now prepared and evaluated a series of PD-173955 analogs, several of which reduced Aβ production potently. This occurs in cells expressing human full-length amyloid precursor protein (APP) and not in cells expressing APP β-C terminal fragment (APP-C99), suggesting that the kinase inactive analogs strongly affect β-secretase (BACE1) cleavage of APP, similarly to Gleevec. A combination of the kinase inactive analogs of PD173955 with a BACE1 inhibitor (BACEi), namely BACE IV, strongly reduced Aβ levels in cells, as noted previously with Gleevec and analogs. Several potent compounds also penetrated and accumulated in mouse brain in high nanomolar to low micromolar concentration In the experiment, the researchers used many compounds, for example, tert-Butyl [4,4′-bipiperidine]-1-carboxylate (cas: 171049-35-7Recommanded Product: 171049-35-7).

tert-Butyl [4,4′-bipiperidine]-1-carboxylate (cas: 171049-35-7) belongs to piperidine derivatives. The piperidine ring can be found not only in more than half of the currently known structures of alkaloids, but also in many natural or synthetic compounds with interesting biological activities. The piperidine and polyhydroxylated indolizidine derivatives have shown to be promising α-glucosidase inhibitors. The former are analogs of DNJ with an improved α-glucosidase inhibitory profile than that of DNJ. Boisson et al.Recommanded Product: 171049-35-7

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem