- Synthesis of Benzyl C-Analogues of Dapagliflozin as Potential SGLT2 Inhibitors
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Sodium-glucose co-transporter (SGLT) inhibitors are a novel class of therapeutic agents for the treatment of type 2 diabetes based on blocking of renal reabsorption of glucose. Dapagliflozin, a C-aryl glucoside, has emerged as a successful drug in the market based on this concept. We have synthesized hitherto unreported C-benzyl glucoside analogues of Dapagliflozin carrying the same aglycon present in the drug. The synthetic strategy involves in situ generation of functionalized arylmagnesium bromide with Weinreb-amide (WA) functionality for the first time, and addition on to the 1-β-formyl-2,3,4,6-tetra-O-benzyl-D-glucopyranoside for the synthesis of a C-benzyl glucoside building block 16. The WA functionality therein enabled variation in the nature of the distal ring of biarylmethane aglycon for convenient access to other analogues. All the new compounds were screened for their sodium-glucose co-transporters (SGLT1 and SGLT2) inhibition activity using cell-based nonradioactive fluorescence glucose uptake assay. Among them, 14 with IC50: 0.64 nm emerged as the most potent SGLT2 inhibitor with the best selectivity for inhibition of SGLT2 (IC50:0.64 nm) over SGLT1 (IC50: 500 nm) as compare to Dapagliflozin. On the other hand, compound 15a exhibited moderate selectivity for inhibition of SGLT2 (IC50: 4.94 nm) over SGLT1 (IC50: 68.46 nm). These results presented herein amply demonstrate the promise of C-benzyl analogues of Dapagliflozin as novel SGLT2 inhibitors for future investigations.
- Aidhen, Indrapal Singh,Banerjee, Sanjay K.,Kumar, Roshan,Mukkamala, Ramesh
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- Synthesis method of 2-halogen-5-iodobenzoic acid
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The invention discloses a synthesis method of 2-halogen-5-iodobenzoic acid. The synthesis method comprises steps as follows: o-halogen benzoic acids are subjected to one-step iodo treatment in an iodio reagent, and 2-halogen-5-iodobenzoic acid is obtained. Aftertreatment comprises steps as follows: a reaction liquid is poured into a cold reductive water solution and quenched, a solvent is evaporated to dryness, recrystallization and filtration are performed, and a product can be obtained. The method is short in reaction route, simple to operate, environmentally friendly, safer and more economical and has broad application prospects.
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Paragraph 0031-0041
(2019/09/17)
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- Novel bifenthrin derivatives, and preparation method and application thereof
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The invention discloses novel bifenthrin derivatives, and a preparation method and application thereof. The novel bifenthrin derivatives have a structural formula as shown in a formula (I) which is described in the specification. In the formula (I), when R1 is H, R2 is a Cl or CF3 substituent group, and R3 is H or a substituted or unsubstituted non-heterocyclic or heterocyclic aryl group; when R1is a Cl substituted group, R 2 is H or a Cl or CF3 substituent group, and R3 is H or a substituted or unsubstituted non-heterocyclic or heterocyclic aryl group; the non-heterocyclic aryl group is a phenyl, naphthyl, anthryl, phenanthryl or pyrenyl group; and the heterocyclic aryl group is a five-to-nine-membered monocyclic or polycyclic heterocyclic aryl group with one or more O or S heteroatoms.According to the invention, a series of the novel bifenthrin derivatives are synthesized mainly by modifying and transforming ortho-position and terminal-position benzene rings on the intermediate benzene rings of bifenthrin; and the novel bifenthrin derivatives have excellent insecticidal and mosquito-killing effect on both larvae and adult mosquitoes, are significantly reduced in toxicity and improved in metabolic stability, and shows good application prospects.
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Paragraph 0067-0076
(2019/08/30)
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- Preparation method for 2-chloro-5-iodobenzoic acid
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The invention discloses a preparation method for 2-chloro-5-iodobenzoic acid. The preparation method is characterized in that cheap o-chlorobenzoic acid is taken as a starting material to obtain 2-chloro-5-iodobenzoic acid through nitration, reduction and diazotization iodination. The method shortens reaction steps, increases the yield and is suitable for industrial production.
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Paragraph 0031; 0032
(2017/07/21)
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- Late stage iodination of biologically active agents using a one-pot process from aryl amines
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A simple and effective one-pot tandem procedure that generates aryl iodides from readily available aryl amines via stable diazonium salts has been developed. The operationally simple procedure and mild conditions allow late-stage iodination of a wide range of aryl compounds bearing various functional groups and substitution patterns. A novel synthetic strategy involving the preparation of nitroaryl compounds followed by a chemoselective tin(ii) dichloride reduction and the use of the one-pot diazotisation-iodination transformation was also developed. The general applicability of this approach was demonstrated with the preparation of a number of medicinally important compounds including CNS1261, a SPECT imaging agent of the N-methyl-d-aspartate (NMDA) receptor and IBOX, a compound used to detect amyloid plaques in the brain.
- Sloan, Nikki L.,Luthra, Sajinder K.,McRobbie, Graeme,Pimlott, Sally L.,Sutherland, Andrew
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p. 54881 - 54891
(2017/12/12)
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