59456-03-0Relevant academic research and scientific papers
Chromeno[3,4-c]pyridin-5-ones: Selective human dopamine D4 receptor antagonists as potential antipsychotic agents
Unangst, Paul C.,Capiris, Thomas,Connor, David T.,Heffner, Thomas G.,MacKenzie, Robert G.,Miller, Steven R.,Pugsley, Thomas A.,Wise, Lawrence D.
, p. 2688 - 2693 (2007/10/03)
The discovery of a series of chromeno[3,4-c]pyridin-5-ones with selective affinity for the dopamine D4 receptor is described. Target compounds were tested for binding to cloned human dopamine D2, D3 and D4 receptor subtypes expressed in Chinese hamster ovary (CHO) K-1 cells. Several compounds demonstrated single digit nanomolar K(i) values for binding to the D4 receptor with several hundred-fold selectivities toward the D2 and D3 receptors. A limited SAR study of this series is discussed. In a mitogenesis assay measuring [3H]thymidine uptake, the target compounds showed antagonist to weak, partial agonist activity at the D4 receptor, with intrinsic activities ranging from 0 to 35%. Compound 6, 3-benzyl-8-methyl-1,2,3,4- tetrahydrochromeno[3,4-c]pyridin-5-one, increased DOPA (L-3 4- dihydroxyphenylalanine) synthesis 84% in the hippocampus and 10% in the striatum of rat brain when dosed orally at 10 mg/kg.
3-(Aminoalkyl)-1,2,3,4-tetrahydro-5H-[1]benzopyrano[3,4-c]pyridin-5-ones as potential anticholinergic bronchodilators
Connor,Unangst,Schwender,Sorenson,Carethers,Puchalski,Brown,Finkel
, p. 683 - 688 (2007/10/02)
A series of 3-(aminoalkyl)-benzopyrano[3,4-c]pyridin-5-ones was prepared and tested as potential orally active anticholinergic bronchodilators. Inhibition of methacholine-induced collapse in guinea pigs and inhibition of pilocarpine-induced bronchoconstriction in dogs were served as in vivo models. Simultaneous measurement of salivary inhibition in the dog model allowed determination of a pulmonary selectivity ratio. The benzopyrano[3,4-c]pyridin-5-one parent ring system was prepared by Pechman condensation of phenols with a piperidine β-keto ester. Alkylation with aminoalkyl halides, or with 1-chloro-2-propanone followed by reductive amination, yielded the 3-substituted target compounds. Bronchodilator potency was related to the extent of steric crowding surrounding the side-chain terminal amine function. Addition of a methyl substituent on the carbon α to the terminal amine often increased potency or pulmonary selectivity. After secondary pharmacological evaluation, compound 7a, designated CI-923, was selected for clinical trial as a bronchodilator.
3-[2-(Mono-and dialkylamino)propyl]-1,2,3,4-tetrahydro-5H-[1]benzopyrano[3,4-C]pyridin-5-ones useful for treating bronchospastic diseases
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, (2008/06/13)
Anticholinergic 3-[2-(mono- and dialkylamino)-propyl]-1,2,3,4-tetrahydro-5H-[1]benzopyrano[3,4-c]-pyridin-5-ones useful for treating bronchospastic diseases in mammals are disclosed. Also disclosed are methods for preparing said compounds, pharmaceutical compositions containing them and methods for using said pharmaceutical compositions. A method for preparing the intermediate which is required to prepare the unsubstituted benzopyrano-[3,4-c]pyridin-5-ones of the invention is also disclosed.
Bronchodilating piperidinoethyl benzopyranopyridinones
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, (2008/06/13)
Disclosed are novel substituted benzopyranopyridines which are active as bronchodilators.
