1010-95-3Relevant articles and documents
Temozolomide analogs with improved brain/plasma ratios – Exploring the possibility of enhancing the therapeutic index of temozolomide
Rai, Roopa,Banerjee, Monali,Wong, Darren H.,McCullagh, Emma,Gupta, Ashu,Tripathi, Shailendra,Riquelme, Eduardo,Jangir, Ramnivas,Yadav, Shyamraj,Raja, Mohd.,Melkani, Pankaj,Dixit, Vikas,Patil, Umesh,Shrivastava, Ritesh,Middya, Sandip,Olivares, Felipe,Guerrero, Javier,Surya, Arjun,Pham, Son M.,Bernales, Sebastián,Protter, Andrew A.,Hung, David T.,Chakravarty, Sarvajit
, p. 5103 - 5109 (2016)
Temozolomide is a chemotherapeutic agent that is used in the treatment of glioblastoma and other malignant gliomas. It acts through DNA alkylation, but treatment is limited by its systemic toxicity and neutralization of DNA alkylation by upregulation of the O6-methylguanine-DNA methyltransferase gene. Both of these limiting factors can be addressed by achieving higher concentrations of TMZ in the brain. Our research has led to the discovery of new analogs of temozolomide with improved brain:plasma ratios when dosed in vivo in rats. These compounds are imidazotetrazine analogs, expected to act through the same mechanism as temozolomide. With reduced systemic exposure, these new agents have the potential to improve efficacy and therapeutic index in the treatment of glioblastoma.
N6-Substituted Adenosine Receptor Agonists. Synthesis and Pharmacological Activity as Potent Antinociceptive Agents
Guengoer, Timur,Malabre, Patrice,Teulon, Jean-Marie,Camborde, Francoise,Meignen, Joelle,et al.
, p. 4307 - 4316 (2007/10/02)
Novel N6-(indol-3-yl)alkyl derivatives of adenosine were synthesized.The adenosine receptor affinity and the antinociceptive activity of these compounds were assessed in binding studies and the phenylbenzoquinone-induced writhing test.Most of these analogues exhibited a potent analgesic activity without side effects.Among them, compound 3c (UP 202-32) bound to A1 (Ki = 110 nM) and A2 (Ki = 350 nM) adenosine receptors in a specific manner since it did not interact with many other receptors, especially opioid binding sites.The antinociceptive activity in the phenylbenzoquinone assay (ED50 = 3.3 mg/kg po) was antagonized by 8-cyclopentyltheophylline, suggesting that an adenosinergic mechanism underlies the analgesic activity observed with this compound.The data obtained with these new N6-substituted adenosine receptor agonists emphasize the interest of such compounds in the treatment of pain.