Identification of novel 2-benzyl-1-indanone analogs as interleukin-5 inhibitors

Pulla Reddy Boggu; Jungsuk Cho; Youngsoo Kim; Sang-Hun Jung

doi:10.1016/j.ejmech.2018.04.030

Identification of novel 2-benzyl-1-indanone analogs as interleukin-5 inhibitors

Eur J Med Chem. 2018 May 25:152:65-75. doi: 10.1016/j.ejmech.2018.04.030. Epub 2018 Apr 16.

Authors

Pulla Reddy Boggu¹, Jungsuk Cho¹, Youngsoo Kim², Sang-Hun Jung³

Affiliations

¹ College of Pharmacy and Institute of Drug Research and Development, Chungnam National University, Daejeon, 34134, Republic of Korea.
² College of Pharmacy, Chungbuk National University, Cheongju, 19421, Republic of Korea.
³ College of Pharmacy and Institute of Drug Research and Development, Chungnam National University, Daejeon, 34134, Republic of Korea. Electronic address: jungshh@cnu.ac.kr.

PMID: 29689475
DOI: 10.1016/j.ejmech.2018.04.030

Abstract

A novel series of 2-benzyl-1-indanone analogs were investigated as IL-5 inhibitory activity. Among the synthesized compounds, 7-(cyclohexylmethoxy)-2-(4-hydroxybenzyl)-2,3-dihydro-1H-inden-1-one (7s, 100.0% inhibition at 30 μM, IC₅₀ = 4.0 μM), and 7-(cyclohexylmethoxy)-2-(3-hydroxybenzyl)-2,3-dihydro-1H-inden-1-one (7t, 95.0% inhibition at 30 μM, IC₅₀ = 6.0 μM) showed the best inhibitory activity against IL-5. The 2-benzyl-1-indanone analogs showed moderate to strong IL-5 inhibitory activity. Especially, hydroxyl (HBD/HBA) substituent at position 3 or 4 on phenyl ring B showed potent IL-5 inhibition. Additionally, the bulky hydrophobic cyclohexylmethoxy group at position 7 of the 1-indanone ring is favorable for the inhibitory activity.

Keywords: 1-Indanone analogs; Inhibitor; Interleukin-5; SAR.

MeSH terms

Animals
Cell Line
Dose-Response Relationship, Drug
Indans / chemistry*
Indans / pharmacology*
Interleukin-5 / antagonists & inhibitors*
Mice
Molecular Structure
Structure-Activity Relationship

Substances

2-benzyl-1-indanone
Indans
Interleukin-5