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

共 50 条

[41] Development of Tricyclic 4,5-Dihydro-3H-pyrrolo[2,3-c]quinolin-4-ones as Potent Autotaxin Inhibitors for Pulmonary Fibrosis Treatment In Vivo
Ma, Deyi
Zhao, Bing
Yue, Lingfeng
Li, Sen
Wei, Xiujian
Jiang, Nan
Zang, Linghe
Lei, Hongrui
Zhai, Xin
JOURNAL OF MEDICINAL CHEMISTRY, 2025,
[42] Discovery of 3-({5-Chloro-1-[3-(methylsulfonyl)propyl]-1H-indol-2-yl}methyl)-1-(2,2,2-trifluoroethyl)-1,3-dihydro-2H-imidazo[4,5-c]pyridin-2-one (JNJ-53718678), a Potent and Orally Bioavailable Fusion Inhibitor of Respiratory Syncytial Virus
Vendeville, Sandrine
Tahri, Abdellah
Hu, Lili
Demin, Samuel
Cooymans, Ludwig
Vos, Ann
Kwanten, Leen
Van den Berg, Joke
Battles, Michael B.
McLellan, Jason S.
Koul, Anil
Raboisson, Pierre
Roymans, Dirk
Jonckers, Tim H. M.
JOURNAL OF MEDICINAL CHEMISTRY, 2020, 63 (15) : 8046 - 8058
[43] Heteroatom insertion into 3,4-dihydro-1H-quinolin-2-ones leads to potent and selective inhibitors of human and rat aldosterone synthase
Grombein, Cornelia M.
Hu, Qingzhong
Rau, Sabrina
Zimmer, Christina
Hartmann, Rolf W.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, 2015, 90 : 788 - 796
[44] Pyrimido [4,5-c]quinolin-1(2H)-ones as a novel class of antimitotic agents:: Synthesis and in vitro cytotoxic activity
Metwally, Kamel
Pratsinis, Harris
Kletsas, Dimitris
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, 2007, 42 (03) : 344 - 350
[45] Pyrimido[4,5-c]quinolin-1(2H)-ones as a novel class of antimitotic agents: Synthesis and in vitro cytotoxic activity
Metwally, K.
Pratsinis, H.
Kletsas, D.
PLANTA MEDICA, 2008, 74 (09) : 1147 - 1147
[46] Discovery and SAR of pyrrolo[2,1-f][1,2,4]triazin-4-amines as potent and selective PI3Kδ inhibitors
Bhide, Rajeev S.
Neels, James
Qin, Lan-Ying
Ruan, Zheming
Stachura, Sylwia
Weigelt, Carolyn
Sack, John S.
Stefanski, Kevin
Gu, Xiaomei
Xie, Jenny H.
Goldstine, Christine B.
Skala, Stacey
Pedicord, Donna L.
Ruepp, Stefan
Dhar, T. G. Murali
Carter, Percy H.
Salter-Cid, Luisa M.
Poss, Michael A.
Davies, Paul
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2016, 26 (17) : 4256 - 4260
[47] (1H-imidazo[4,5-c]pyridin-2-yl)-1,2,5-oxadiazol-3-ylamine derivatives:: Further optimisation as highly potent and selective MSK-1-inhibitors
Bamford, MJ
Bailey, N
Davies, S
Dean, DK
Francis, L
Panchal, TA
Parr, CA
Sehmi, S
Steadman, JG
Takle, AK
Townsend, JT
Wilson, DM
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2005, 15 (14) : 3407 - 3411
[48] Novel 2- and 4-Substituted 1H-Imidazo[4,5-c]quinolin-4-amine Derivatives as Allosteric Modulators of the A3 Adenosine Receptor
Kim, Yoonkyung
de Castro, Sonia
Gao, Zhan-Guo
Ijzerman, Adriaan P.
Jacobson, Kenneth A.
JOURNAL OF MEDICINAL CHEMISTRY, 2009, 52 (07) : 2098 - 2108
[49] Novel 2-and 4-substituted 1H-Imidazo[4,5-c]quinolin-4-amine derivatives as allosteric modulators of the A3 adenosine receptor
De Castro, Sonia
Kim, Yoonkyung
Gao, Zhan-Guo
Ijzerman, Adriaan P.
Jacobson, Kenneth A.
ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY, 2009, 238
[50] A NOVEL SYNTHESIS OF A 1,3-DISUBSTITUTED 1,3-DIHYDRO-2H-IMIDAZO[4,5-b]PYRIDIN-2-ONE. APPLICATION TO GW808990 A CRF1 RECEPTOR ANTAGONIST
Hayes, Jerome F.
Popkin, Matthew E.
HETEROCYCLES, 2010, 82 (01) : 297 - 303

← 1 2 3 4 5 →