Discovery of 1,3-dihydro-2H-imidazo[4,5-c]quinolin-2-ones based novel, potent and PI3Kδ selective inhibitors

被引：1

作者：

Bahekar, Rajesh ^{[1
]}

Dave, Bhushan ^{[1
,2
]}

Soman, Shubhangi ^{[2
]}

Pater, Dipam ^{[1
]}

Chopade, Rajendra ^{[1
]}

Funde, Radhika ^{[1
]}

Kumar, Jeevan ^{[3
]}

Sachchidanand, S. ^{[3
]}

Giri, Poonam ^{[4
]}

Chatterjee, Abhijit ^{[4
]}

Mahapatra, Jogeswar ^{[4
]}

Vyas, Purvi ^{[5
]}

Ghoshdastidar, Krishnarup ^{[5
]}

Bandyopadhyay, Debdutta ^{[5
]}

Desai, Ranjit C. ^{[1
]}

机构：

[1] Zydus Res Ctr, Dept Med Chem, NH 8A Moraiya, Ahmadabad 382210, Gujarat, India

[2] Maharaja Sayajirao Univ Baroda, Fac Sci, Dept Chem, Vadodara 390002, India

[3] Zydus Res Ctr, Dept Bioinformat, NH 8A Moraiya, Ahmadabad 382210, Gujarat, India

[4] Zydus Res Ctr, Dept Pharmacol, NH 8A Moraiya, Ahmadabad 382210, Gujarat, India

[5] Zydus Res Ctr, Dept Cell Biol, NH 8A Moraiya, Ahmadabad 382210, Gujarat, India

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2019年 / 29卷 / 11期

关键词：

PI3K inhibitors; Inflammatory and autoimmune diseases; Rheumatoid arthritis; Imidazo-quinolinones; Design; Synthesis and biological study; PHOSPHOINOSITIDE; 3-KINASE; IDELALISIB;

D O I：

10.1016/j.bmcl.2019.04.007

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

PI3K delta is implicated in various inflammatory and autoimmune diseases. For the effective treatment of chronic immunological disorders such as rheumatoid arthritis, it is essential to develop isoform selective PI3K delta inhibitors. Structure guided optimization of an imidazo-quinolinones based pan-PI3K/m-TOR inhibitor (Dactolisib) led to the discovery of a potent and orally bioavailable PI3K delta isoform selective inhibitor (10h), with an improved efficacy in the animal models.

引用

页码：1313 / 1319

页数：7

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