Biphenyl amide p38 kinase inhibitors 3: Improvement of cellular and in vivo activity

Angell, Richard; Aston, N.M.; Bamborough, Paul; Buckton, J; Cockerill, Stuart; deBoeck, Suzanne J.; Edwards, Chris D.; Holmes, Duncan S.; Jones, Katherine L.; Lainé, Dramane I.; Patel, Shila; Smee, Penny A.; Smith, Kathryn J.; Somers, Don O.; Walker, Ann L.

doi:10.1016/j.bmcl.2008.06.048

Cited by 68 publications

(66 citation statements)

References 6 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…p38α MAP kinase, a serine/threonine kinase, has been implicated in the production of inflammatory cytokines such as TNFα and IL-1β, thus making this kinase an attractive target for developing effective anti-rheumatic drugs. 94 Angell et al, 95 Leu74 and Phe169. These findings also revealed the strict steric requirements of this pocket in the enzyme.…”

Section: Iκb Kinase 2 (Ikk2) Inhibitor 64mentioning

confidence: 99%

The “Cyclopropyl Fragment” is a Versatile Player that Frequently Appears in Preclinical/Clinical Drug Molecules

2016

View full text Add to dashboard Cite

Recently, there has been an increasing use of the cyclopropyl ring in drug development to transition drug candidates from the preclinical to clinical stage. Important features of the cyclopropane ring are, the (1) coplanarity of the three carbon atoms, (2) relatively shorter (1.51 Å) C-C bonds, (3) enhanced π-character of C-C bonds, and (4) C-H bonds are shorter and stronger than those in alkanes. The present review will focus on the contributions that a cyclopropyl ring makes to the properties of drugs containing it. Consequently, the cyclopropyl ring addresses multiple roadblocks that can occur during drug discovery such as (a) enhancing potency, (b) reducing off-target effects,

show abstract

Section: Iκb Kinase 2 (Ikk2) Inhibitor 64mentioning

confidence: 99%

The “Cyclopropyl Fragment” is a Versatile Player that Frequently Appears in Preclinical/Clinical Drug Molecules

2016

View full text Add to dashboard Cite

show abstract

“…[17][18][19] Recent years have seen the discovery and exploratory development of several p38 MAPK inhibitors that may find utility in pain management. [20][21][22][23] Intrathecal administration of p38 MAPK inhibitors has consistently been shown to be efficacious in preclinical models of neuropathic pain. 9,11,24,25 Few studies, however, have been undertaken to establish the relevance of p38 MAPK inhibition in humans.…”

mentioning

confidence: 99%

A Randomized, Placebo-controlled Trial of the Analgesic Efficacy and Safety of the p38 MAP Kinase Inhibitor, Losmapimod, in Patients With Neuropathic Pain From Lumbosacral Radiculopathy

Ostenfeld¹,

Krishen

Lai³

et al. 2015

The Clinical Journal of Pain

View full text Add to dashboard Cite

show abstract

“…[33] The only chemical difference between these two is the group involved in the interaction with the LR. The more potent derivative 19 interacts with key residues Glu71 and Asp168, whereas contact with Glu71 is absent for compound 18 ( Figure 6).…”

Section: Protein Regionmentioning

confidence: 99%

A Comprehensive Structural Overview of p38α Mitogen‐Activated Protein Kinase in Complex with ATP‐Site and Non‐ATP‐Site Binders

et al. 2017

View full text Add to dashboard Cite

Herein we review all the currently available ATP‐site and non‐ATP‐site ligands bound to p38α mitogen‐activated protein kinase (MAPK) available in the RCSB Protein Data Bank (PDB). The co‐crystallized inhibitors have been classified into different families according to their experimental binding mode and chemical structure, and the ligand–protein interactions are discussed using the most representative compounds. This systematic structural analysis could provide some take‐home lessons for drug discovery programs aimed at the rational identification and optimization of new p38α MAPK inhibitors.

show abstract

Biphenyl amide p38 kinase inhibitors 3: Improvement of cellular and in vivo activity

Cited by 68 publications

References 6 publications

The “Cyclopropyl Fragment” is a Versatile Player that Frequently Appears in Preclinical/Clinical Drug Molecules

The “Cyclopropyl Fragment” is a Versatile Player that Frequently Appears in Preclinical/Clinical Drug Molecules

A Randomized, Placebo-controlled Trial of the Analgesic Efficacy and Safety of the p38 MAP Kinase Inhibitor, Losmapimod, in Patients With Neuropathic Pain From Lumbosacral Radiculopathy

A Comprehensive Structural Overview of p38α Mitogen‐Activated Protein Kinase in Complex with ATP‐Site and Non‐ATP‐Site Binders

Contact Info

Product

Resources

About