Discovery of a 4-aryloxy-1H-pyrrolo[3,2-c]pyridine and a 1-aryloxyisoquinoline series of TRPA1 antagonists.
A series of TRPA1 antagonists is described having a 4-aryloxy-1H-pyrrolo[3,2-c]pyridine or a 1-aryloxyisoquinoline scaffold. These compounds have high ligand efficiency and favorable physical properties and may thus serve as scaffolds for further optimization.
AstraZeneca, Department of Medicinal Chemistry, Montréal H4S 1Z9, Canada.
Yun-Jin
YJ
Hu
AstraZeneca/OmegaChem, Department of Medicinal Chemistry, Montréal H4S 1Z9, Canada.
Miguel
M
St-Onge
AstraZeneca/OmegaChem, Department of Medicinal Chemistry, Montréal H4S 1Z9, Canada.
Sébastien
S
Laliberté
AstraZeneca/OmegaChem, Department of Medicinal Chemistry, Montréal H4S 1Z9, Canada.
Frédéric
F
Vallée
AstraZeneca, Department of Medicinal Chemistry, Montréal H4S 1Z9, Canada.
Shujuan
S
Jin
Astrazeneca, DMPK, Montréal H4S 1Z9, Canada.
Leanne
L
Bedard
AstraZeneca, Department of Bioscience, Montréal H4S 1Z9, Canada.
Jean
J
Labrecque
AstraZeneca, Department of Medicinal Chemistry, Montréal H4S 1Z9, Canada. Electronic address: Jeffrey.Albert@IntelliSynRD.com.
Jeffrey S
JS
Albert
D015220:Calcium Channels; D004305:Dose-Response Relationship, Drug; D055808:Drug Discovery; D006801:Humans; D007546:Isoquinolines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D015394:Molecular Structure; D009419:Nerve Tissue Proteins / Q000037:antagonists & inhibitors*; D011725:Pyridines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D011758:Pyrroles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D000074025:TRPA1 Cation Channel; D050051:Transient Receptor Potential Channels / Q000037:antagonists & inhibitors*
D015220:Calcium Channels; D007546:Isoquinolines; D009419:Nerve Tissue Proteins; D011725:Pyridines; D011758:Pyrroles; D000074025:TRPA1 Cation Channel; C473350:TRPA1 protein, human; D050051:Transient Receptor Potential Channels
Antagonist; Ligand gated ion channel; TRPA1