Dataset Information

Discovery of Novel 5-(Piperazine-1-carbonyl)pyridin-2(1H)-one Derivatives as Orally eIF4A3-Selective Inhibitors.

ABSTRACT: Starting from our previous eIF4A3-selective inhibitor 1a, a novel series of (piperazine-1-carbonyl)pyridin-2(1H)-one derivatives was designed, synthesized, and evaluated for identification of orally bioavailable probe molecules. Compounds 1o and 1q showed improved physicochemical and ADMET profiles, while maintaining potent and subtype-selective eIF4A3 inhibitory potency. In accord with their promising PK profiles and results from initial in vivo PD studies, compounds 1o and 1q showed antitumor efficacy with T/C values of 54% and 29%, respectively, without severe body weight loss. Thus, our novel series of compounds represents promising probe molecules for the in vivo pharmacological study of selective eIF4A3 inhibition.

SUBMITTER: Mizojiri R

PROVIDER: S-EPMC5642020 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Discovery of Novel 5-(Piperazine-1-carbonyl)pyridin-2(1H)-one Derivatives as Orally eIF4A3-Selective Inhibitors.

Mizojiri Ryo R Nakata Daisuke D Satoh Yoshihiko Y Morishita Daisuke D Shibata Sachio S Iwatani-Yoshihara Misa M Kosugi Yohei Y Kosaka Mai M Takeda Junpei J Sasaki Shigekazu S Takami Kazuaki K Fukuda Koichiro K Kamaura Masahiro M Sasaki Shinobu S Arai Ryosuke R Cary Douglas R DR Imaeda Yasuhiro Y

ACS medicinal chemistry letters 20170908 10

Starting from our previous eIF4A3-selective inhibitor 1a, a novel series of (piperazine-1-carbonyl)pyridin-2(1H)-one derivatives was designed, synthesized, and evaluated for identification of orally bioavailable probe molecules. Compounds 1o and 1q showed improved physicochemical and ADMET profiles, while maintaining potent and subtype-selective eIF4A3 inhibitory potency. In accord with their promising PK profiles and results from initial in vivo PD studies, compounds ...[more]

PMID: 29057054

Dataset Information

Discovery of Novel 5-(Piperazine-1-carbonyl)pyridin-2(1H)-one Derivatives as Orally eIF4A3-Selective Inhibitors.

Publications

Discovery of Novel 5-(Piperazine-1-carbonyl)pyridin-2(1<i>H</i>)-one Derivatives as Orally eIF4A3-Selective Inhibitors.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Similar Datasets

Discovery of Pyridinyl Acetamide Derivatives as Potent, Selective, and Orally Bioavailable Porcupine Inhibitors.
| S-EPMC4948009 | biostudies-literature

Discovery of 3-alkoxyamino-5-(pyridin-2-ylamino)pyrazine-2-carbonitriles as selective, orally bioavailable CHK1 inhibitors.
| S-EPMC3506129 | biostudies-literature

4-Hy-droxy-6-methyl-pyridin-2(1H)-one.
| S-EPMC3790402 | biostudies-literature

3,5-Dinitro-pyridin-4(1H)-one monohydrate.
| S-EPMC2960580 | biostudies-other

Discovery of Substituted 1H-Pyrazolo[3,4-b]pyridine Derivatives as Potent and Selective FGFR Kinase Inhibitors.
| S-EPMC4904267 | biostudies-literature

Exploration of 3,6-dihydroimidazo(4,5-d)pyrrolo(2,3-b)pyridin-2(1H)-one derivatives as JAK inhibitors using various in silico techniques.
| S-EPMC5639824 | biostudies-literature

6-Bromo-3-methyl-1H-imidazo[4,5-b]pyridin-2(3H)-one.
| S-EPMC2979211 | biostudies-literature

6-Bromo-1,3-dimethyl-1H-imidazo[4,5-b]pyridin-2(3H)-one.
| S-EPMC3007224 | biostudies-literature

1-Acetyl-6-bromo-1H-imidazo[4,5-b]pyridin-2(3H)-one.
| S-EPMC3120304 | biostudies-literature

1,3-Diallyl-6-bromo-1H-imidazo[4,5-b]pyridin-2(3H)-one.
| S-EPMC3213442 | biostudies-literature