710299-12-0

Upstream product

• 710299-11-9 5-[4-(tert-butyl-diphenyl-silanyloxy)-phenyl]-1-(2-chloro-phenyl)-4-methyl-1H-pyrazole-3-carboxylic acid ethyl ester 

Relevant academic research and scientific papers

PYRAZOLE DERIVATES AS CANNABINOID RECEPTOR MODULATORS

Compounds of formula (I), are cannabinoid CB1 receptors, useful, inter alia in the treatment of obesity: (I) wherein A1 is hydrogen, -COOH, or tetrazolyl, and A2 is hydrogen, -COOH, tetrazolyl, -CN, -CF3, -COR6, -SO2R6, -OR7, -NR7R8, -NHCOR6, and -NR7SO2R8 provided that one of A1 and A2 is either -COOH or tetrazolyl; p is O or 1 and A3 is phenyl or cycloalkyl, either of which is optionally substituted with R4 and/or R5; q is O or 1 ; R1 is a bond, or - (CH2)aB1(CH2)b- wherein a and b are independently O, 1 , 2 or 3 provided that a+b is not greater than 4, and B1 is -CO-, -0-, -S-, -SO-, -SO2-, -CH2-, -CHOH- or -NR7-; R2 is a bond, -(CH2)aB1 (CH2)b- or -[(CH2)aB1 (CH2)b]n-A4-[(CH2)cB2(CH2)d]m- wherein a, b, and B1 are as defined for R1; B2 is as defined for B1, c and d are independently 0,1 , 2 or 3; with the proviso that a+b+c+d is not greater than 6, n and m are independently O or 1 and A4 is a monocarbocyclic or monoheterocyclic ring, having 3 to 8 ring atoms, optionally substituted with one or more of -F, -Cl, -Br, -CN, -CF3, C1-C4 alkyl, cycloalkyl, -OR9, oxo or -NR7R8; R3 is hydrogen, C1-C4 alkyl, cycloalkyl, -CF3, -OR9, -NR7R8, -(CH2)SCOR6, -(CH2)SSO2R6, -(CH2)SNR7COR6, -(CH2)SNR7COOR8, -(CH2)SNR7SO2R6, wherein s is 1 , 2, 3 or 4; R4 and R5 independently -R9, -CN, -F, -Cl, -Br, -OR9, -NR7R8, -NR7COR6, -NR7SO2R6, -COR6, -SR9, -SOR9, -SO2R6, (C1-C4 alkyl)OR9, -(C1-C4 alkyl)NR7R8, -(C1-C4 alkyl)NR7COR6, C1-C4 alkyl)NR7COOR8, -(C1-C4 alkyl)NR7SO2R6, -(C1-C4 alkyl)COR6, -(C1-C4 alkyl)SO2R6, -NR7COOR8, or [N-(C1-C4 alkyl)]- tetrazolyl; R6 is C1-C4 alkyl, cycloalkyl, -CF3 or -NR7R8; R7 and R8 are independently hydrogen, C1-C4 alkyl or cycloalkyl and R9 is hydrogen, C1-C4 alkyl, cycloalkyl, fully or partially fluorinated C1-C4 alkyl.

Synthesis of [O-methyl-11C]1-(2-chlorophenyl)-5-(4- methoxyphenyl)-4-methyl-1H-pyrazole-3-carboxylic acid piperidin-1-ylamide: A potential PET ligand for CB1 receptors

Synthesis and in vitro evaluation of [O-methyl-11C]1-(2- chlorophenyl)-5-(4-methoxyphenyl)-4-methyl-1H-pyrazole-3-carboxylic acid piperidin-1-ylamide ([11C]-1), a potential imaging agent for CB 1 receptors using PET is described. 1-(2-Chlorophenyl)-5-(4- hydroxyphenyl)-4-methyl-1H-pyrazole-3-carboxylic acid piperidin-1-ylamide (5), the precursor for radiolabeling, was synthesized from 4-OTBDPS-propiophenone (2) in five steps with 30% overall yield. The reaction of alcohol 5 with [ 11C]MeOTf at 60°C afforded [11C]-1 with an average radiochemical yield of 14.5% (EOS) and >2000Ci/mmol specific activity. The radiotracer was found to selectively label CB1 receptors in slide-mounted sections of postmortem human brain containing prefrontal cortex as demonstrated by in vitro autoradiography using phosphor imaging.