247923-33-7Relevant academic research and scientific papers
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.
, 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.
Novel and efficient synthesis of tert-butyl-2-(4-(2-aminoethyl)phenylthio)- 2-methylpropanoate, a key intermediate in the synthesis of ureido thioisobutyric acid
Desai, Jigar,Argade, Anil,Gite, Sanjay,Shah, Kiran,Pavase, Laxmikant,Thombare, Pravin,Patel, Pankaj
experimental part, p. 748 - 753 (2011/03/21)
A convenient and cost-effective synthesis of pharmacologically important tert-butyl-2-(4-2-aminoethyl)phenylthio)-2-methylpropanoate from commercially available 2-2-phenyl-1-ethanol is described.
1,2,4-Triazine Derivatives, Preparation and Use Thereof in Human Therapy
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Page/Page column 19-20, (2008/12/06)
The invention concerns 3,5-dioxo-(2H,4H)-1,2,4-triazine derivatives of general formula (I), wherein: R1 and R2, identical or different, represent a branched or linear C1-C7 alkyl or alkenyl radical, a C1/s
Process for Preparing the Intermediate Compounds for Pparalpha Ligands
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Page/Page column 4, (2008/12/04)
The present invention provides a process for preparing the compounds of formula (II) according to a single reaction, which is an important intermediate compound for synthesizing GW7647 (III) and GW9578 (IV) activating Peroxisome Proliferator Activated Receptor (HPPAR α).
A facile one-pot preparation of alkyl aminoaryl sulfides for the synthesis of GW7647 as an agonist of peroxisome proliferator-activated receptor α
Ham, Jungyeob,Cho, Sung Jin,Ko, Jaeyoung,Chin, Jungwook,Kang, Heonjoong
, p. 5781 - 5784 (2007/10/03)
We have developed two simple and high yielding one-pot syntheses of alkyl aminoaryl sulfides containing a series of four-steps: in situ protection of the free amine by reaction with a Grignard reagent, halogen-lithium exchange, sulfur insertion, and a substitution reaction with various electrophiles. Through this protocol, we have successfully synthesized tert-butyl-2-[4-(2-aminoethyl) phenylsulfanyl]-2-methylpropanoate, a key intermediate for the synthesis of GW7647 and GW9578 (ureido-TiBAs), in 92% yield. Furthermore, we were able to improve the overall yield of, GW7647 to 66%, 3 times the yield previously reported.
