China
Africa
Explore chapters and articles related to this topic
The Labeling of Peptides with Positron-Emitting Radionuclides: The Importance of PET in Cancer Diagnosis
Published in Marco Chinol, Giovanni Paganelli, Radionuclide Peptide Cancer Therapy, 2016
Stefano Papi, Nicoletta Urbano, Esteban R. Obenaus, Marco Chinol
Downer in 1997 studied the reactivity of [18F]fluorophenacylbromide ([18F]FPB) for radiolabeling peptides (57), but their data suggested that octreotide was not a suitable target for labeling with [18F]FPB. The same year Wester studied the pharmacokinetics of 2-[18F]fluoropropionyl-D-Phe1-octreo-tide; although tumor uptake was rapid, the short tumor residence time and its hepatobiliary excretion imposed further developments, to obtain a more hydrophilic derivative (58). In 2001 Okarvi (59) published an extensive overview of the progress in [18F]-labeling of peptide radiopharmaceuticals; among the different methods cited, he enlightened the importance of [18F]SFB obtained via TSTU; nevertheless, the [18F]fluorobenzoyl- and [18F]fluoropropionyl-octreotide so far studied showed unfavourable biological properties, claiming an improvement in pharmacokinetic behaviour of [18F]-octreotide analogs. In 2002 Southcliffe-Goulden and colleagues (60) published a rapid solid phase synthesis and fluorination method of linear peptides, using [18F]fluorobenzoic acid and HATU/DIPEA for coupling (Fig. 4). They achieved 80–90% RCY (decay corrected), with a radiochemical purity greater than 95% in an overall synthesis time of 20 minutes; however tumor uptake of these [18F]fluorobenzoyl-peptides was still not selective.
Design, synthesis, and biological evaluation of biotinylated colchicine derivatives as potential antitumor agents
Published in Journal of Enzyme Inhibition and Medicinal Chemistry, 2022
Chao Wang, Yujing Zhang, Zeyu Wang, Yuelin Li, Qi Guan, Dongming Xing, Weige Zhang
The synthetic route for biotin-conjugates is depicted in Scheme 1. According to Bagnato’s method, Deac was synthesised in three steps26. The key intermediates 15, 16, 17, and 18 were synthesised according to the established procedures9,13,27,28. At first, commercially available 2,2′-disulfanediyldiethanol (14) was treated with 4-nitrophenyl carbonochloridate in THF containing Et3N to obtain 15, and then 15 was reacted with Deac to generate key intermediate 16. Finally, the intermediate 16 was coupled with biotin to obtain Deac-SS-Biotin in the presence of DCC and DMAP. Furthermore, Deac-Biotin was obtained from the reaction of Deac and biotin in the presence of HATU and TEA. In addition, desacetylcolchicine derivatives 17 were prepared from Deac as reported by means of treatment with corresponding anhydrides, and then 17 was coupled with biotin hydrazine (18) in the presence of EDCI, HOBt, and DMAP to obtain Deac-CC-Biotins (11).
Identification of probe-quality degraders for Poly(ADP-ribose) polymerase-1 (PARP-1)
Published in Journal of Enzyme Inhibition and Medicinal Chemistry, 2020
Zhimin Zhang, Xinyue Chang, Chixiao Zhang, Shenxin Zeng, Meihao Liang, Zhen Ma, Zunyuan Wang, Wenhai Huang, Zhengrong Shen
The syntheses of the presented final compounds were outlined in Figure 3. Compound a-1 was carried out by the reaction of commercially available 8-((tert-butoxycarbonyl)amino)octanoic acid and lenalidomide in the presence of HATU (a polypeptide condensation reagent) and trimethylamine. Boc deprotection of a-1 led to the key intermediate b-1. Compounds a-2 and a-3 were synthesised using the procedure described for the synthesis of compound a-1. The synthesis process began with the displacement of the commercially available dimethyl phosphite to o-phthalaldehydic acid and generated the corresponding phosphonate c in 89% yield. Addition of 2-fluoro-5-formylbenzonitrile to c led to the formation of benzalphthalide d in 84% yield as a mixture of E/Z isomers. The mixture of E and Z isomers were treated with hydrazine hydrate to produce the phthalazinone core. Base hydrolysis of the pendant nitrile provided the second key carboxylic acid intermediate e. The final compounds 1–3 were obtained by coupling of e and b-1–b-3 under HATU condition in 45–53% yield.
Design, synthesis and biological evaluation of novel 1H-1,2,4-triazole, benzothiazole and indazole-based derivatives as potent FGFR1 inhibitors viafragment-based virtual screening
Published in Journal of Enzyme Inhibition and Medicinal Chemistry, 2020
Jian Liu, Yu Wen, Lina Gao, Liang Gao, Fengjun He, Jingxian Zhou, Junwei Wang, Rupeng Dai, Xiaojing Chen, Di Kang, Lihong Hu
The preparation of target compounds 9a-t, 12a-d and 18a-c was described in Schemes 1–3. Compounds 9a-t were synthesised from starting material 4-fluorobenzoate (1) and 4-bromo-2-fluorobenzonitrile (2) through seven steps. The nucleophilic substitution reactions of 4-fluorobenzoate with various piperazines afforded the methyl ester 2 intermediate, which then could hydrolysis to carboxylic acid 3. Subsequently, the carboxylic acid 3 was condensed with HATU to provide the activated ester reagent 4. Meanwhile, the intermediate 5 could be condensed by 4-bromo-2-fluorobenzonitrile 1 with hydrazine. Then nitrogen atom at the 1-position of 1H-indazol-3-amine scaffold 5 was protected by BOC group. The key intermediate 8 was obtained by condensation of 4 and 7 in the presence of NaH. Treatment of the intermediate 8 with various substituted-phenylboronic acid under Suzuki coupling condition26 of Pd(dppf)Cl2 and Cs2CO3 in refluxing dioxane/water gave target compounds. According to the similar synthetic route, compounds 12a-d were synthesised from the starting material 6-bromobenzo[d]thiazol-2-amine (10) through two steps.