Discovery of 1-Pyrimidinyl-2-Aryl-4,6-Dihydropyrrolo [3,4-d]Imidazole-5(1H)-Carboxamide as a Novel JNK Inhibitor

Jang, Miyoung; Oh, Youri; Cho, Hyunwook; Yang, Songyi; Moon, Hyungwoo; Im, Daseul; Hah, Jung‐Mi

doi:10.3390/ijms21051698

Cited by 12 publications

(2 citation statements)

References 23 publications

(23 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…To understand their binding mode and selectivity toward one of these isoforms, we performed induced fit docking of compounds 2 , 2h , 3 , and 3h with three isoforms of JNKs. While developing JNK3 inhibitors, we sought to preserve three interactions: ,,, two hydrogen bonds in the hinge region, a hydrophobic interaction of the large aromatic ring, and a hydrogen bond in the ribose pocket. Also, the nitrogen in the imidazole ring creates a water-mediated hydrogen bond with Lys93.…”

Section: Resultsmentioning

confidence: 99%

Carbamate JNK3 Inhibitors Show Promise as Effective Treatments for Alzheimer’s Disease: In Vivo Studies on Mouse Models

et al. 2023

Self Cite

View full text Add to dashboard Cite

We have been developing new inhibitors for c-Jun N-terminal kinase 3 (JNK3) as a potential treatment for Alzheimer’s disease (AD). We identified potential JNK3 inhibitors through pharmacodynamic optimization studies, including benzimidazole compounds 2 and 3, but their unreliable pharmacokinetic properties led us to develop carbamate inhibitors 2h and 3h. In vitro studies validated carbamate inhibitors 2h and 3h as potent and highly selective JNK3 inhibitors with favorable pharmacokinetic profiles. Oral administration of 2h and 3h to both APP/PS1 and 3xTg AD mouse models improved cognitive function, indicating their potential as effective treatments for Alzheimer’s disease. Carbamate JNK3 inhibitor 3h, in particular, restored cognitive function to near-normal levels in the 3xTg mice model of AD and led to pTau reduction in the hippocampal tissues of 3xTg-AD mice during in vivo behavioral evaluations. We intend to further develop these carbamate JNK3 inhibitors in preclinical studies as a potential first-in-class treatment for AD.

show abstract

Section: Resultsmentioning

confidence: 99%

Carbamate JNK3 Inhibitors Show Promise as Effective Treatments for Alzheimer’s Disease: In Vivo Studies on Mouse Models

et al. 2023

Self Cite

View full text Add to dashboard Cite

show abstract

“…Imidazole and pyridine derivatives are momentous ve and six-membered nitrogen heterocycles because of their occurrence in natural products and biologically active compounds, including hemoglobin, chlorophyll, vitamin B6, nifedipine (cardiovascular drug), and cipro oxacin (antibacterial). Imidazole is incorporated in many important biological molecules [1][2][3][4][5][6][7].…”

Section: Introductionmentioning

confidence: 99%