- Synthesis and biological evaluation of novel 8-morpholinoimidazo[1,2-a]pyrazine derivatives bearing phenylpyridine/phenylpyrimidine-carboxamides
-
Herein we designed and synthesized three series of novel 8-morpholinoimidazo[1,2-a] pyrazine derivatives bearing phenylpyridine/phenylpyrimidine-carboxamides (compounds 12a-g, 13a-g and 14a-g). All the compounds were evaluated for their IC50 values against three cancer cell lines (A549, PC-3 and MCF-7). Most of the target compounds exhibited moderate cytotoxicity against the three cancer cell lines. Two selected compounds 14b, 14c were further tested for their activity against PI3Kα kinase, and the results indicated that compound 14c showed inhibitory activity against PI3Kα kinase with an IC50 value of 1.25 μM. Structure-activity relationships (SARs) and pharmacological results indicated that the replacement of the thiopyranopyrimidine with an imidazopyrazine was beneficial for the activity and the position of aryl group has a significant influence to the activity of these compounds. The compounds 13a-g in which an aryl group substituted at the C-4 position of the pyridine ring were more active than 12a-g substituted at the C-5 position. Moreover, the cytotoxicity of compounds 14a-g bearing phenylpyrimidine-carboxamides was better than that of the compounds 12a-g, 13a-g bearing phenylpyridine-carboxamides. Furthermore, the substituents on the benzene ring also had a significant impact on the cytotoxicity and the pharmacological results showed that electron donating groups were beneficial to the cytotoxicity.
- Xu, Shan,Sun, Chengyu,Chen, Chen,Zheng, Pengwu,Zhou, Yong,Zhou, Hongying,Zhu, Wufu
-
-
Read Online
- Heterocyclic-pyrimindine or pyrazine compound containing biarylamide structure and application thereof
-
The invention discloses a heterocyclic-pyrimindine or pyrazine compound containing a biarylamide structure. The heterocyclic-pyrimindine or pyrazine compound is as shown in a general formula I or II, wherein the general formula I and the general formula II are shown in the description. The heterocyclic-pyrimindine or pyrazine compound containing the biarylamide structure, and pharmaceutically acceptable salts, hydrates or solvates thereof are used as active components, and are mixed with a pharmaceutically acceptable carrier or excipient to prepare a composition; and the composition is prepared into clinically acceptable preparations. The compound provided by the invention can be used for treating and/or preventing proliferative diseases, and treating and/or preventing prostate cancer, lung cancer and cervical cancer.
- -
-
Paragraph 0140; 0141
(2017/07/22)
-
- Synthesis and Antibronchospastic Activity of 8-Alkoxy- and 8-(Alkylamino)imidazopyrazines
-
Theophylline still occupies a dominant place in asthma therapy.Unfortunatly its adverse central nervous system (CNS) stimulant effects can dramatically limit its use, and adjustments in the dosage are often needed.We have synthesized a new series of imidazopyrazine derivatives which are much more potent bronchodilators than theophylline in vivo and do not exhibit the CNS stimulatory profile.In vitro studies on isolated rat uterus and guinea pig trachea confirm the high potentialities of these derivatives. 6-Bromo-8-(methylamino)imidazopyrazine-3-carbonitrile (23) is identified as the most potent compound of the series.As i n the case of theophylline, phosphodiesterase inhibition appears unlikely to be the unique mechanism of the action of this series of heterocycles.
- Bonnet, Pierre A.,Michel, Alain,Laurent, Florence,Sablayrolles, Claire,Rechencq, Eliane,et al.
-
p. 3353 - 3358
(2007/10/02)
-
- 8-alkylaminoimidazo(1,2-a)pyrazines and derivatives, their preparation and their application in therapy
-
STR1 Novel 8-alkylamino-imidazo(1,2-a)pyrazines of formula (I) show advantages pharmacological activities. They can be used for medical products in human and veterinary therapy in the field of applications of antispasmodics, uterine relaxants, bronchodila
- -
-
-
