Inhibitors of indoleamine 2,3-dioxygenase and methods of their use
A C1-C6, alkyl technology, applied in the field of enzymatically active compounds, can solve problems such as different functions
- Summary
- Abstract
- Description
- Claims
- Application Information
AI Technical Summary
Problems solved by technology
Method used
Image
Examples
preparation example Construction
[0170] The preparation of prodrugs is well known in the art and described, for example, in King, F.D., ed., Medicinal Chemistry: Principles and Practice , The Royal Society of Chemistry, Cambridge, UK (2nd edition, reprinted, 2006); Testa, B. et al., Hydrolysis in Drug and Prodrug Metabolism. Chemistry, Biochemistry and Enzymology , VCHA and Wiley-VCH, Zurich, Switzerland (2003); Wermuth, C.G., ed., The Practice of Medicinal Chemistry , 3rd Edition, Academic Press, San Diego, CA (2008).
[0171] The present invention is intended to include all isotopes of atoms present in the compounds of the present invention. Isotopes include those atoms having the same atomic number but different mass numbers. By way of general example and not limitation, isotopes of hydrogen include deuterium and tritium. Isotopes of carbon include 13 C and 14 c. Isotopically-labeled compounds of the invention can generally be prepared by conventional techniques known to those skilled in the...
Embodiment 1
[0295] Example 1 4-((1s,4s)-4-(( R )-1-(5-(4-chlorophenyl)-4 H -1,2,4-triazol-3-yl)ethyl)cyclohexyl)-6-fluoroquinoline
[0296] Intermediate 1M (17.71 mg, 0.093 mmol) and 4-chlorobenzamidine hydrochloride (17.7 mg, 0.093 mmol) in pyridine (1 mL) and TEA (0.065 mL, 0.464 mmol) were mixed in a sealed tube. The reaction mixture was purged with a stream of nitrogen for 1 minute, then sealed and heated at 110°C overnight. The reaction mixture was cooled and washed with ethyl acetate and saturated NH 4 Cl solution was diluted. The organic layer was separated and concentrated in vacuo. The residue was dissolved in MeOH and purified by preparative HPLC. Fractions containing the desired product were combined and dried by centrifugal evaporation to give Example 1 (10.8 mg, 0.024 mmol, 31% yield). LC-MS analysis: C 25 h 24 ClFN 4 Calculated value 434.17, measured value [M+H] 435.3, T r = 1.58 min (method B).
[0297]
Embodiment 2
[0299] 2-(4-fluorophenyl)-5-(( R )-1-((1s,4s)-4-(6-fluoroquinolin-4-yl)cyclohexyl)ethyl)-1,3,4-oxadiazole
[0300]
[0301] 4-Fluorobenzamidine hydrochloride (17.6 mg, 0.100 mmol) and (R)-2-((1s,4S)-4-(6-fluoroquinolin-4-yl) ring in a sealed tube A reaction mixture of hexyl)propionohydrazide 2HCl salt (30 mg, 0.077 mmol) in pyridine (1 mL) and TEA (0.065 mL, 0.464 mmol) was purged with nitrogen, then heated at 120 °C overnight. The reaction mixture was cooled and washed with ethyl acetate and NH 4 Cl solution was diluted. The organic layer was separated and concentrated in vacuo. The residue was dissolved in MeOH and purified by preparative HPLC / MS to give Example 2 (6.5 mg, 0.015 mmol, 20% yield). LC-MS analysis: C 25 h 23 f 2 N 3 O calculated value 419.18, measured value [M+H] 420.3, T r = 1.67 min (method B).
[0302]
PUM
Login to View More Abstract
Description
Claims
Application Information
Login to View More