Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: EC:2.1.1.69 (
BMT
)
2,655
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Triazolopyridine ethers with mGlu
2
positive allosteric modulator (PAM) activity are disclosed. The synthesis, in vitro activity, and metabolic stability data for a series of analogs is provided. The effort resulted in the discovery of a potent, selective, and brain penetrant lead molecule
BMT
-133218 ((+)-7m). After oral administration at 10mg/kg,
BMT
-133218 demonstrated full reversal of PCP-stimulated locomotor activity and prevented MK-801-induced working memory deficits in separate mouse models. Also, reversal of impairments in executive function were observed in rat set-shifting studies at 3 and 10mg/kg (p.o.). Extensive plasma protein binding as the result of high lipophilicity likely limited activity at lower doses. Optimized triazolopyridine ethers offer utility as mGlu
2
PAMs for the treatment of
schizophrenia
and merit further preclinical investigation.
...
PMID:Triazolopyridine ethers as potent, orally active mGlu
2
positive allosteric modulators for treating schizophrenia. 2791 48
The metabotropic glutamate receptor 5 (mGluR5) is an attractive target for the treatment of
schizophrenia
due to its role in regulating glutamatergic signaling in association with the
N
-methyl-d-aspartate receptor (NMDAR). We describe the synthesis of 1
H
-pyrazolo[3,4-
b
]pyridines and their utility as mGluR5 positive allosteric modulators (PAMs) without inherent agonist activity. A facile and convergent synthetic route provided access to a structurally diverse set of analogues that contain neither the aryl-acetylene-aryl nor aryl-methyleneoxy-aryl elements, the predominant structural motifs described in the literature. Binding studies suggest that members of our new chemotype do not engage the receptor at the MPEP and CPPHA mGluR5 allosteric sites. SAR studies culminated in the first non-MPEP site PAM, 1
H
-pyrazolo[3,4-
b
]pyridine
31
(
BMT
-145027), to improve cognition in a preclinical rodent model of learning and memory.
...
PMID:Development of 1
H
-Pyrazolo[3,4-
b
]pyridines as Metabotropic Glutamate Receptor 5 Positive Allosteric Modulators. 2799 42
