1197-10-0Relevant articles and documents
Novel optimization of valmerins (tetrahydropyrido[1,2- a ]isoindolones) as potent dual CDK5/GSK3 inhibitors
Ouach, Aziz,Boulahjar, Rajaa,Vala, Christine,Bourg, Stéphane,Bonnet, Pascal,Guguen-Guillouzo, Christiane,Ravache, Myriam,Le Guevel, Rémy,Lozach, Olivier,Lazar, Sa?d,Troin, Yves,Meijer, Laurent,Ruchaud, Sandrine,Akssira, Mohamed,Guillaumet, Gérald,Routier, Sylvain
, p. 311 - 325 (2016/04/05)
An efficient synthetic strategy able to modulate the structure of the tetrahydropyridine isoindolone (Valmerin) skeleton was developed. A library of more than 30 novel final structures was generated. Biological activities on CDK5 and GSK3 as well as cellular effects on cancer cell lines were measured for each novel compound. Additionally to support the SAR, a docking study was performed. A potent GSK3/CDK5 dual inhibitor (37, IC50 CDK5/GSK3 35/7 nM) was obtained. Best antiproliferative effects were obtained on lung and prostate cell lines with IC50 Combining double low line 20 nM.
Design of glycosyltransferase inhibitors: Pyridine as a pyrophosphate surrogate
Wang, Shuai,Cuesta-Seijo, Jose A.,Lafont, Dominique,Palcic, Monica M.,Vidal, Sebastien
supporting information, p. 15346 - 15357 (2013/11/06)
A series of ten glycosyltransferase inhibitors has been designed and synthesized by using pyridine as a pyrophosphate surrogate. The series was prepared by conjugation of carbohydrate, pyridine, and nucleoside building blocks by using a combination of gly
New NO-releasing pharmacodynamic hybrids of losartan and its active metabolite: Design, synthesis, and biopharmacological properties
Breschi, Maria C.,Calderone, Vincenzo,Digiacomo, Maria,Macchia, Marco,Martelli, Alma,Martinotti, Enrica,Minutolo, Filippo,Rapposelli, Simona,Rossello, Armando,Testai, Lara,Balsamo, Aldo
, p. 2628 - 2639 (2007/10/03)
In a preliminary work, we reported two NO-sartans, possessing the characteristics of an AT1 antagonist and a "slow NO donor", obtained by adding NO-donor side chains to losartan 1. The NO release from an NO-sartan should be modulated in order to strengthen the antihypertensive activity of the native drug and to ensure additional effects, such as the antiplatelet and anti-ischemic ones. To obtain a collection of proto-typical NO-sartans, showing different rates of NO release, new NO-donor moieties have been linked to 1 or its active metabolite 2 (EXP 3174). Almost all the synthesized compounds exhibited both AT1-antagonist and NO-mediated vasorelaxing properties, with a wide range of NO-releasing rates. Further pharmacological investigation on compound 4a showed that it possessed antihypertensive and cardiac antihypertrophic effects similar to those of the reference AT1-blocking or ACE-inhibiting drugs. Furthermore, the additional anti-ischemic cardio-protective properties and antiplatelet effects of 4a have been preliminarily investigated.
