1133853-58-3Relevant academic research and scientific papers
Synthesis of Tetrahydronaphthyridines from Aldehydes and HARP Reagents via Radical Pictet-Spengler Reactions
Jackl, Moritz K.,Kreituss, Imants,Bode, Jeffrey W.
supporting information, p. 1713 - 1715 (2016/05/19)
The combination of aldehydes with newly designed HARP (halogen amine radical protocol) reagents gives access to α-substituted tetrahydronaphthyridines. By using different HARP reagents, various regioisomeric structures can be prepared in a single operation. These products, which are of high value in medicinal chemistry, are formed in a predictable manner via a formal Pictet-Spengler reaction of electron-poor pyridines that would not participate in the corresponding polar reactions.
Optimization of potency and pharmacokinetic properties of tetrahydroisoquinoline transient receptor potential melastatin 8 (TRPM8) antagonists
Horne, Daniel B.,Tamayo, Nuria A.,Bartberger, Michael D.,Bo, Yunxin,Clarine, Jeffrey,Davis, Carl D.,Gore, Vijay K.,Kaller, Matthew R.,Lehto, Sonya G.,Ma, Vu V.,Nishimura, Nobuko,Nguyen, Thomas T.,Tang, Phi,Wang, Weiya,Youngblood, Beth D.,Zhang, Maosheng,Gavva, Narender R.,Monenschein, Holger,Norman, Mark H.
, p. 2989 - 3004 (2014/05/06)
Transient receptor potential melastatin 8 (TRPM8) is a nonselective cation channel expressed in a subpopulation of sensory neurons in the peripheral nervous system. TRPM8 is the predominant mammalian cold temperature thermosensor and is activated by cold temperatures ranging from 8 to 25 °C and cooling compounds such as menthol or icilin. TRPM8 antagonists are being pursued as potential therapeutics for treatment of pain and bladder disorders. This manuscript outlines new developments in the SAR of a lead series of 1,2,3,4-tetrahydroisoquinoline derivatives with emphasis on strategies to improve pharmacokinetic properties and potency. Selected compounds were profiled in two TRPM8 target-specific in vivo coverage models in rats (the icilin-induced wet dog shake model and the cold pressor test). Compound 45 demonstrated robust efficacy in both pharmacodynamic models with ED90 values 3 mg/kg.
Vanilloid receptor ligands and their use in treatments
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Page/Page column 14, (2009/04/24)
Bicyclic 3,4-fused piperidine compounds, and compositions containing them, for the treatment of acute, inflammatory and neuropathic pain, dental pain, general headache, migraine, cluster headache, mixed-vascular and non-vascular syndromes, tension headache, general inflammation, arthritis, rheumatic diseases, osteoarthritis, inflammatory bowel disorders, inflammatory eye disorders, inflammatory or unstable bladder disorders, psoriasis, skin complaints with inflammatory components, chronic inflammatory conditions, inflammatory pain and associated hyperalgesia and allodynia, neuropathic pain and associated hyperalgesia and allodynia, diabetic neuropathy pain, causalgia, sympathetically maintained pain, deafferentation syndromes, asthma, epithelial tissue damage or dysfunction, herpes simplex, disturbances of visceral motility at respiratory, genitourinary, gastrointestinal or vascular regions, wounds, burns, allergic skin reactions, pruritus, vitiligo, general gastrointestinal disorders, gastric ulceration, duodenal ulcers, diarrhea, gastric lesions induced by necrotizing agents, hair growth, vasomotor or allergic rhinitis, bronchial disorders or bladder disorders.
