Discovery of 3,6-dihydroimidazo[4,5-d]pyrrolo[2,3-b]pyridin-2(1H)-one derivatives as novel JAK inhibitors

Yamagishi, Hiroshi; Shirakami, Shohei; Nakajima, Yutaka; Takahashi, Fumie; Hamaguchi, Hisao; Hatanaka, Keiko; Moritomo, Ayako; Inami, Masamichi; Higashi, Yasuyuki; Inoue, Takayuki

doi:10.1016/j.bmc.2015.05.028

Cited by 18 publications

(12 citation statements)

References 27 publications

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“…prepared a series of tricyclic dipyrrolopyridine derivatives as a novel Janus kinase (JAK) inhibitors. Thus, SNAr displacement of chloride in 6‐chloronicotinonitrile with the piperidine derivative 260 gave pyrrolopyridine derivative 261 (Scheme ) .…”

Section: Janus Kinases Inhibitorsmentioning

confidence: 99%

“…Treatment of 267 with isobutyl chloroformate resulted in pyrazolopyrrolopyridine 268 , followed by deprotection of the Bn group in the presence of 1‐chloroethyl chloroformate and the SEM group under acidic condition to afford 271 . Condensation with cyanoacetic acid gave the desired compound 272 (Scheme ) .…”

Section: Janus Kinases Inhibitorsmentioning

confidence: 99%

“…Condensation of 275 with cyanoacetic acid gave the desired compound 276 . The racemate 274 was separated by chiral column chromatography to give 274a and 274b , which were converted to 276a and 276b , respectively (Scheme ) .…”

Section: Janus Kinases Inhibitorsmentioning

confidence: 99%

“…Treatment with Zn(CN) 2 and Pd(PPh 3 ) 4 resulted in 281 , which was followed by deprotection of the Boc group and the SEM group to give 282 . Condensation with cyanoacetic acid provided the desired compound 283 (Scheme ) .…”

Section: Janus Kinases Inhibitorsmentioning

confidence: 99%

“…Deprotection of the SEM group and the Bn group provided 289 . Condensation with cyanoacetic acid gave the desired compound 290 (Scheme ) .…”

Section: Janus Kinases Inhibitorsmentioning

confidence: 99%

See 4 more Smart Citations

A Review: Synthesis and Medicinal Importance of Nicotinonitriles and Their Analogous

Gouda

Hussein

Helal

et al. 2018

Journal of Heterocyclic Chem

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Section: Janus Kinases Inhibitorsmentioning

confidence: 99%

Section: Janus Kinases Inhibitorsmentioning

confidence: 99%

Section: Janus Kinases Inhibitorsmentioning

confidence: 99%

Section: Janus Kinases Inhibitorsmentioning

confidence: 99%

“…Deprotection of the SEM group and the Bn group provided 289 . Condensation with cyanoacetic acid gave the desired compound 290 (Scheme ) .…”

Section: Janus Kinases Inhibitorsmentioning

confidence: 99%

See 3 more Smart Citations

A Review: Synthesis and Medicinal Importance of Nicotinonitriles and Their Analogous

Gouda

Hussein

Helal

et al. 2018

Journal of Heterocyclic Chem

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Ecofriendly synthesis of pyrano[2,3‐d]pyrimidine derivatives and related heterocycles with anti‐inflammatory activities

Abdelazim

Aziz

Mouneir

et al. 2020

Archiv der Pharmazie

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A versatile, efficient, clean, and facile method was used for the synthesis of pyrano[2,3‐d]pyrimidine derivatives by the one‐pot three‐component condensation reaction of thiobarbituric acid and malononitrile with p‐chlorobenzaldehyde, using Fe3O4 or ZnO or Mn3O4 as nanostructure catalysts. The catalyst could be easily recovered using an external magnet and reused for six cycles with almost a consistent activity. A series of polyheterocyclic compounds containing five and/or six rings fused with each other was designed. The anti‐inflammatory activities for some of the newly synthesized compounds were evaluated. All the synthesized compounds were characterized on the basis of their elemental analyses and spectral data.

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Exploration of 3,6-dihydroimidazo(4,5-d)pyrrolo(2,3-b)pyridin-2(1H)-one derivatives as JAK inhibitors using various in silico techniques

Jisha¹,

Aswathy²,

Masand³

et al. 2017

In Silico Pharmacol.

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This study focuses on understanding the structural features of 3,6-dihydroimidazo(4,5-d)pyrrolo(2,3-b)pyridin-2(1H)-one (dpp) derivatives to computationally identify new JAK inhibiting compounds. For the purpose, a novel virtual screening strategy, with 2D and 3D-QSAR (CoMFA and CoMSIA), data mining, pharmacophore modeling, ADMET prediction, multi-targeted protein-based docking and inverse QSAR, was employed. The 2D-QSAR equations developed for the JAK3, JAK2 and JAK1 involved five physicochemical descriptors. These descriptors correlate with the anti-RA activity with R values for JAK3, JAK2 and JAK1 are 0.9811, 0.8620 and 0.9740, respectively. The 3D-QSAR studies such as CoMFA and CoMSIA carried out through PLS analysis of the training set of JAK3, JAK2 and JAK1, gave Q values as 0.369, 0.476 and 0.490; [Formula: see text] values as 0.863, 0.684 and 0.724 and, F values as 23.098, 28.139 and 31.438, respectively. The contour maps produced by the CoMFA and CoMSIA models were used to understand the importance of hydrogen bond donor, acceptor, hydrophobic, steric and electrostatic interactions. The molecular docking studies of these selected compounds with various JAK proteins were carried out and the protein-ligand interactions were also studied. The study concluded that dpp15(s) is a highly potent JAK inhibitor with a very good predicted IC value.

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Discovery of 3,6-dihydroimidazo[4,5-d]pyrrolo[2,3-b]pyridin-2(1H)-one derivatives as novel JAK inhibitors

Cited by 18 publications

References 27 publications

A Review: Synthesis and Medicinal Importance of Nicotinonitriles and Their Analogous

A Review: Synthesis and Medicinal Importance of Nicotinonitriles and Their Analogous

Ecofriendly synthesis of pyrano[2,3‐d]pyrimidine derivatives and related heterocycles with anti‐inflammatory activities

Exploration of 3,6-dihydroimidazo(4,5-d)pyrrolo(2,3-b)pyridin-2(1H)-one derivatives as JAK inhibitors using various in silico techniques

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