130497-30-2Relevant academic research and scientific papers
Orthogonal Catalysis for an Enantioselective Domino Inverse-Electron Demand Diels?Alder/Substitution Reaction
Beeck, Sebastian,Ahles, Sebastian,Wegner, Hermann A.
supporting information, (2021/12/09)
An enantioselective domino process for the synthesis of substituted 1,2-dihydronaphthalenes has been developed by the combination of chiral amines and a bidentate Lewis acid in an orthogonal catalysis. This new method is based on an inverse electron-demand Diels?Alder and a subsequent group exchange reaction. An enamine is generated in situ from an aldehyde and a chiral secondary amine catalyst that reacts with phthalazine, activated by the coordination to a bidentate Lewis acid catalyst. The absolute configuration of the product is controlled by chiral information provided by the amine. The formed ortho-quinodimethane intermediate is then transformed via a group exchange reaction with thiols. The new method shows a broad scope and tolerates a wide range of functional groups with enantiomeric ratios up to 91 : 9. All-in-all, this enantioselective synthesis tool provides an easy access to complex 1,2-dihydronaphthalenes starting from readily available phthalazine, aldehydes and thiols in a combinatorial way.
2-Aminomethyl piperidines as novel urotensin-II receptor antagonists
Jin, Jian,Wang, Yonghui,Wang, Feng,Shi, Dongchuan,Erhard, Karl F.,Wu, Zining,Guida, Brian F.,Lawrence, Sarah K.,Behm, David J.,Disa, Jyoti,Vaidya, Kalindi S.,Evans, Christopher,McMillan, Lynette J.,Rivero, Ralph A.,Neeb, Michael J.,Douglas, Stephen A.
, p. 2860 - 2864 (2008/12/22)
A series of 2-aminomethyl piperidines has been discovered as novel urotensin-II receptor antagonists. The synthesis, initial structure-activity relationships, and optimization of the initial hit that resulted in the identification of potent, cross-species active, and functional urotensin-II receptor antagonists such as 1a and 11a are described.
(2S)-1-(arylacetyl)-2-(aminomethyl)piperidine derivatives: Novel, highly selective κ opioid analgesics
Vecchietti,Giordani,Giardina,Colle,Clarke
, p. 397 - 403 (2007/10/02)
This paper describes the synthesis and structure-activity relationships as κ opioid analgesics of a novel class of 1-(arylacetyl)-2-(aminomethyl)piperidine derivatives (8). The active conformation of the pharmacophore, with a torsional angle (N1C2C7N8) of 60°, was defined with computational studies and 1H NMR. A quantitative structure-activity relationship study of the arylacetic moiety substitution indicated that the presence of an electron-withdrawing and lipophilic substituent in para and/or meta positions is required for good analgesic activity and κ affinity. The lead compounds (2S)-1-[(3,4-dichlorophenyl)acetyl]-2-(pyrrolidin-1-ylmethyl) piperidine hydrochloride (14) and (2S)-1-[[4-(trifluoromethyl)phenyl]acetyl]-2-(pyrrolidin-1- ylmethyl)piperidine hydrochloride (21) are the most κ/μ selective (respectively 6500:1 and 4100:1) and among the most potent (K(i) κ 0.24 and 0.57 nM, respectively) κ ligands identified so far. In the mouse tail flick model of antinociception, compound 14 (ED50 = 0.05 mg/kg sc) was 25 times more potent than morphine and 16 times more potent than the standard κ ligand U-50488.
