60439-16-9Relevant articles and documents
Synthesis, radiolabeling and initial in vivo evaluation of [ 11C]KSM-01 for imaging PPAR-α receptors
Solingapuram Sai, Kiran Kumar,Kil, Kun-Eek,Tu, Zhude,Chu, Wenhua,Finck, Brian N.,Rothfuss, Justin M.,Shoghi, Kooresh I.,Welch, Michael J.,Gropler, Robert J.,Mach, Robert H.
supporting information, p. 6233 - 6236 (2012/10/29)
Peroxisome proliferator-activated receptor alpha (PPAR-α) is a ligand-activated nuclear receptor transcription factor that regulates the fatty acid β-oxidation. An in vitro assay identified the p-methoxy phenyl ureido thiobutyric acid derivative KSM-01 (IC50 = 0.28 ± 0.09 nM) having a higher affinity to activate PPAR-α than the PPAR-α agonist GW7647 (IC50 = 0.46 ± 0.19 nM). In this study, we report the synthesis and initial in vivo evaluation of [11C]KSM-01. The radiosynthesis was carried out by first alkylating the corresponding p-phenol precursor with [11C]MeI in DMF using NaOH, followed by deprotection of the t-butyl ester group by TFA, yielding [11C]KSM-01. SUV analysis of dynamic micro PET/CT imaging data showed that [11C]KSM-01 accumulation was ～2.0-fold greater in cardiac-specific PPAR-α overexpressing transgenic mice compared to wild-type littermates. The post-PET biodistribution studies were consistent with these results and demonstrated 2.5-fold greater radiotracer uptake in the heart of transgenic mice compared to the wild-type littermates. These results demonstrate the potential utility of PPAR-α agonists as PET radiopharmaceuticals.
Inhibitors of protein isoprenyl transferases
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, (2008/06/13)
Compounds having the formula or a pharmaceutically acceptable salt thereof wherein R1is (a) hydrogen, (b) loweralkyl, (c) alkenyl, (d) alkoxy, (e) thioalkoxy, (f) halo, (g) haloalkyl, (h) aryl-L2—, and (i) heterocyclic-L2—; R2is selected from (a) (b) —C(O)NH—CH(R14)—C(O)OR15, (d) —C(O)NH—CH(R14)—C(O)NHSO2R16, (e) —C(O)NH—CH(R14)-tetrazolyl, (f) —C(O)NH-heterocyclic, and (g) —C(O)NH—CH(R14)—C(O)NR17R18; R3is substituted or unsubstituted heterocyclic or aryl, substituted or unsubstituted cycloalkyl or cycloalkenyl, and —P(W)RR3RR3′; R4is hydrogen, lower alkyl, haloalkyl, halogen, aryl, arylakyl, heterocyclic, or (heterocyclic)alkyl; L1is absent or is selected from (a) —L4—N(R5)—L5—, (b) —L4—O—L5—, (c) —L4—S(O)n—L5— (d) —L4—L6—C(W)—N(R5)—L5—, (e) —L4—L6—S(O)m—N(R5)—L5—, (f) —L4—N(R5)—C(W)—L7—L5—, (g) —L4—N(R5)—S(O)p—L7—L5—, (h) optionally substituted alkylene, (i) optionally substituted alkenylene, (j) optionally substituted alkynylene (k) a covalent bond, (l) and (m) are inhibitors of protein isoprenyl transferases. Also disclosed are protein isoprenyl transferase inhibiting compositions and a method of inhibiting protein isoprenyl transferases.
The Copper Halide-Catalyzed Mono-Substitution of Bromine in α,ω-Dibromoalkanes by Grignard Reagents. A Reinvestigation
Andringa, H.,Hanekamp, J.,Brandsma, L.
, p. 2349 - 2351 (2007/10/02)
α,ω-Dibromoalkanes have been converted into mono-bromides R(CH2)nBr by reaction with the Grignard compounds RMgBr in THF in the presence of 5 mol percent of copper(I)bromide.In contrast to what is suggested in the original literature, this method has a limited scope.
