Medicinal Chemistry Research p. 2325 - 2335 (2015)
Update date:2022-08-28
Topics:
Hernández-Vázquez, Eduardo
Chagoya, Victoria
Adenosine, the adenine nucleoside, has demonstrated various pharmacological properties related to the treatment of relevant clinical diseases. With respect to this, one of the most fascinating biological activities of adenosine is its capacity for reversing hepatic fibrosis, which has been established in several in vitro and in vivo studies. Although adenosine seems to be a privileged compound, it lacks of metabolic stability to be considered as a drug candidate. For this reason, in this preliminary study, six prodrugs were developed in order to enhance the plasma half-life of adenosine, in which the esterification at 5′ position of adenosine was considered. According to previous works, the increase in steric hindrance at this position could develop unfavorable interactions inside adenosine deaminase (ADA) catalytic domain, which is reported as the main enzyme implicated in adenosine metabolism. Besides, molecular docking was employed to verify if the hindrance at carbinol group in the prodrugs is enough to diminish its oxidation and also to predict if compounds would be metabolized by a promiscuous esterase. Finally, the in vitro assays corroborated the theoretical findings and also indicated that the compounds are less metabolized than adenosine by ADA; in the case of compounds containing proline and thioproline progroups (4d and 4e, respectively), the reduction was more than three-fold of decrease.
View Morezhangjiagang bonded areas banggao co;ltd
website:http://www.shunchangchem.com
Contact:0086-13921972933
Address:Dongsha Chemical Zone.Zhangjiagang, Jiangsu Province
Beijing Mesochem Technology Co.,LTD
website:http://www.mesochem.com
Contact:0086-10-57862036
Address:2301, Floor 23, Building 9 Lippo Plaza, Yard 8 Ronghua Middle Road, ETDZ, Beijing, China
Henan Techway Chemical Co.,Ltd.
website:http://www.techwaychem.com
Contact:+86-371-66380080
Address:No.27 Shunhe Road,
Xinchang Yueding Chemical Co., Ltd.
Contact:86-571-56926323
Address:NO.90 BEIMENCHENGWAI CHENGGUAN TOWN XINCHANG
Puyang Huicheng Electronic Material Co., Ltd
website:http://huichengchem.weba.testwebsite.cn/index_en.html
Contact:+86-393-8910800
Address:West Section Shengli Road, Puyang457000, China
Doi:10.1016/j.tetlet.2014.10.067
(2014)Doi:10.1021/acs.joc.6b01425
(2016)Doi:10.1246/cl.2010.1127
(2010)Doi:10.1021/j100882a011
(1966)Doi:10.1002/hlca.19690520131
(1969)Doi:10.1016/j.tet.2006.11.046
(2007)