Novel N-indolylmethyl substituted olanzapine derivatives: their design, synthesis and evaluation as PDE4B inhibitors

被引：34

作者：

Gorja, Dhilli Rao ^{[1
,2
]}

Mukherjee, Soumita ^{[1
]}

Meda, Chandana Lakshmi T. ^{[1
]}

Deora, Girdhar Singh ^{[1
]}

Kumar, K. Lalith ^{[1
]}

Jain, Ankit ^{[1
,3
]}

Chaudhari, Girish H. ^{[1
,3
]}

Chennubhotla, Keerthana S. ^{[1
,3
]}

Banote, Rakesh K. ^{[1
,3
]}

Kulkarni, Pushkar ^{[1
,3
]}

Parsa, Kishore V. L. ^{[1
]}

Mukkanti, K. ^{[2
]}

Pal, Manojit ^{[1
]}

机构：

[1] Inst Life Sci, Hyderabad 500046, Andhra Pradesh, India

[2] JNT Univ, Inst Sci & Technol, Div Chem, Hyderabad 500072, Andhra Pradesh, India

[3] Zephase Therapeut Pvt Ltd, Hyderabad 500046, Andhra Pradesh, India

来源：

ORGANIC & BIOMOLECULAR CHEMISTRY | 2013年 / 11卷 / 13期

关键词：

ADVANCED CANCER; PHOSPHODIESTERASE-4; SELECTIVITY; DISCOVERY; NAUSEA;

D O I：

10.1039/c3ob27424a

中图分类号：

O62 [有机化学];

学科分类号：

070303 ; 081704 ;

摘要：

A new strategy for converting antipsychotic drug olanzapine into PDE4 inhibitors is described via the design and Pd/C mediated synthesis of novel N-indolylmethyl olanzapine derivatives. One compound showed good inhibition (IC50 1.1 mu M) and >10 fold selectivity towards PDE4B over D that was supported by docking studies. This compound also showed significant inhibition of TNF-alpha and no major toxicities in cell lines and a zebrafish embryo model except the teratogenic effects to be re-assessed in rodents.

引用

页码：2075 / 2079

页数：5

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