Discovery of thieno[2,3-d]pyrimidin-4(3H)-one derivatives as a new class of ROCK inhibitors

Zhang, Miao; Sun, Yu-meng; Zhao, Lanying; Li, Yueshan; Wang, Yifei; Nan, Jinshan; Qiao, Zeen; Li, Linli; Yang, Shengyong

doi:10.1016/j.bmcl.2020.126966

Cited by 4 publications

(4 citation statements)

References 15 publications

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“…Similarly, the introduction of an aromatic ring at the 3-position of the 7-azaindole yielded a compound with good inhibitory activity against ROCK In a series of thieno[2,3- d ] pyrimidin-4(3 H )-one derivatives, compound 48 showed IC 50 values of 4 and 1 nM against ROCK1 and ROCK2, respectively. Compound 48 significantly inhibited the phosphorylation of signaling proteins downstream of ROCK (Figure D) …”

Section: Rock Inhibitorsmentioning

confidence: 99%

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Application and Study of ROCK Inhibitors in Pulmonary Fibrosis: Recent Developments and Future Perspectives

et al. 2023

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Rho-associated coiled-coil-containing kinases (ROCKs), serine/threonine protein kinases, were initially identified as downstream targets of the small GTP-binding protein Rho. Pulmonary fibrosis (PF) is a lethal disease with limited therapeutic options and a particularly poor prognosis. Interestingly, ROCK activation has been demonstrated in PF patients and in animal PF models, making it a promising target for PF treatment. Many ROCK inhibitors have been discovered, and four of these have been approved for clinical use; however, no ROCK inhibitors are approved for the treatment of PF patients. In this article, we describe ROCK signaling pathways and the structure–activity relationship, potency, selectivity, binding modes, pharmacokinetics (PKs), biological functions, and recently reported inhibitors of ROCKs in the context of PF. We will also focus our attention on the challenges to be addressed when targeting ROCKs and discuss the strategy of ROCK inhibitor use in the treatment of PF.

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Section: Rock Inhibitorsmentioning

confidence: 99%

“…Compound 48 significantly inhibited the phosphorylation of signaling proteins downstream of ROCK (Figure 10D). 144 5.6. Indazole-Based ROCK Inhibitors.…”

Section: Rock Inhibitorsmentioning

confidence: 99%

Application and Study of ROCK Inhibitors in Pulmonary Fibrosis: Recent Developments and Future Perspectives

et al. 2023

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“…Miao worked on lead compound 27 and discovered a series of thienopyrimidinone derivatives with potent ROCK inhibitory activity. The representative compound 28 exhibited IC 50 values of 20 and 2 nM against ROCK I and ROCK II, respectively 77 …”

Section: Synthetic Rock Inhibitorsmentioning

confidence: 99%

“…The representative compound 28 exhibited IC 50 values of 20 and 2 nM against ROCK I and ROCK II, respectively. 77…”

Section: Indazolesmentioning

confidence: 99%

Recent advances in the development of Rho kinase inhibitors (2015–2021)

Yao

2023

Medicinal Research Reviews

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Rho‐associated coiled‐coil kinases (ROCKs) are key downstream effectors of small GTPases. ROCK plays a central role in diverse cellular events with accumulating evidence supporting the concept that ROCK is important in tumor development and progression. Numerous ROCK inhibitors have been investigated for their therapeutic potential in the treatment of cancers. In this article, we review recent research progress on ROCK inhibitors, especially those with potential for the treatment of cancers, reported in the literature from 2015 to 2021. Most ROCK inhibitors show potent in vitro and in vivo antitumor activities and have potential in the treatment of cancers.

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Discovery of indoline-based derivatives as effective ROCK2 inhibitors for the potential new treatment of idiopathic pulmonary fibrosis

Wen

Peng

et al. 2023

Bioorganic Chemistry

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Discovery of thieno[2,3-d]pyrimidin-4(3H)-one derivatives as a new class of ROCK inhibitors

Cited by 4 publications

References 15 publications

Application and Study of ROCK Inhibitors in Pulmonary Fibrosis: Recent Developments and Future Perspectives

Application and Study of ROCK Inhibitors in Pulmonary Fibrosis: Recent Developments and Future Perspectives

Recent advances in the development of Rho kinase inhibitors (2015–2021)

Discovery of indoline-based derivatives as effective ROCK2 inhibitors for the potential new treatment of idiopathic pulmonary fibrosis

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