1159997-55-3

Upstream product

• 329-15-7 4-trifluoromethyl-phenyl acetyl chloride 
• 757880-98-1 1-(4-(trifluoromethyl)phenyl)-1,2,3,4-tetrahydroisoquinoline 
• 1159997-91-7 1-(4-(trifluoromethyl)phenyl)-3,4-dihydroisoquinoline 
• 38925-76-7 N-phenethyl-4-(trifluoromethyl)benzamide 
• 64-04-0 phenethylamine 
• 1159997-92-8 (R)-(-)-1-(4-(trifluoromethyl)phenyl)-1,2,3,4-tetrahydroisoquinoline 
• 30806-83-8 p-ethoxycarbonylphenyl isocyanate 

Downstream Products

• 1159997-56-4 (R)-4-(1-(4-(trifluoromethyl)phenyl)-1,2,3,4-tetrahydroisoquinoline-2-carboxamido)benzoic acid 

Relevant academic research and scientific papers

Optimization of potency and pharmacokinetic properties of tetrahydroisoquinoline transient receptor potential melastatin 8 (TRPM8) antagonists

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.

TRP-M8 RECEPTOR LIGANDS AND THEIR USE IN TREATMENTS

Tetrahydroisoquinoline compounds of formula (I), and compositions containing them, for the treatment of acute, inflammatory and neurophatic 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, neurophatic pain and associated hyperalgesia and allodynia, diabetic neuropathy pain, causalgia, sympathetically maintened 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 necrotising agents, hair growth, vasomotor or allergic rhinitis, bronchial disorders or bladder disorders.