- Synthesis method for benzamidine derivatives
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The invention discloses a synthesis method for benzamidine derivatives. According to the synthesis method disclosed by the invention, a reaction of preparing benzamidine derivatives from benzonitrile raw materials is completed in a green and efficient manner by using an ionic liquid-supported nano-metal catalyst, and the catalyst is high in activity and recoverable. Benzamidoxime is formed from benzonitrile and hydroxylamine hydrochloride, and then benzamidine is obtained through hydrogenation reduction under the catalysis of the ionic liquid-supported nano-metal catalyst.
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Paragraph 0009
(2017/08/28)
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- Method for synthesizing benzamidine derivative
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The invention discloses a method for synthesizing a benzamidine derivative. According to the method, a reaction for preparing the benzamidine derivative from a benzonitrile raw material can be efficiently and greenly completed by use of an ionic-liquid-loaded metal nano catalyst, and the ionic-liquid-loaded metal nano catalyst has the advantages of being high in activity and recoverable. Benzamidine can be obtained by reaction of benzonitrile and hydroxylamine hydrochloride to obtainbenzamidoxime and hydrogenation reduction of the benzamidoxime in the presence of the ionic-liquid-loaded metal nano catalyst for catalysis.
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Paragraph 0009
(2017/05/16)
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- Synthesis method of benjia amidine derivative
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The invention provides a synthesis method of a benjia amidine derivative. A reaction that the benjia amidine derivative is prepared from a cyanobenzene class material is completed efficiently in an environmentally friendly manner through a metal nanometer catalyst loaded by ionic liquid, and the catalyst is high in activity and can be recycled. Cyanobenzene and hydroxylamine hydrochloride form benzamidoxime, and then benjia amidine is obtained through hydrogenation reduction under catalysis of the metal nanometer catalyst loaded by the ionic liquid.
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Paragraph 0008; 0009
(2017/08/28)
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- Synthesis method for benzamidine derivatives
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The invention discloses a synthesis method for benzamidine derivatives. According to the synthesis method disclosed by the invention, a reaction of preparing benzamidine derivatives from benzonitrile raw materials is completed in a green and efficient manner by using an ionic liquid-supported nano-metal catalyst, and the catalyst is high in activity and recoverable. Benzamidoxime is formed from benzonitrile and hydroxylamine hydrochloride, and then benzamidine is obtained through hydrogenation reduction under the catalysis of the ionic liquid-supported nano-metal catalyst.
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Paragraph 0009
(2017/05/04)
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- Structure-based design, synthesis and evaluation in vitro of arylnaphthyridinones, arylpyridopyrimidinones and their tetrahydro derivatives as inhibitors of the tankyrases
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Abstract The tankyrases are members of the PARP superfamily; they poly(ADP-ribosyl)ate their target proteins using NAD+ as a source of electrophilic ADP-ribosyl units. The three principal protein substrates of the tankyrases (TRF1, NuMA and axin) are involved in replication of cancer cells; thus inhibitors of the tankyrases may have anticancer activity. Using structure-based drug design and by analogy with known 3-arylisoquinolin-1-one and 2-arylquinazolin-4-one inhibitors, series of arylnaphthyridinones, arylpyridinopyrimidinones and their tetrahydro-derivatives were synthesised and evaluated in vitro. 7-Aryl-1,6-naphthyridin-5-ones, 3-aryl-2,6-naphthyridin-1-ones and 3-aryl-2,7-naphthyridin-1-ones were prepared by acid-catalysed cyclisation of the corresponding arylethynylpyridinenitriles or reaction of bromopyridinecarboxylic acids with β-diketones, followed by treatment with NH3. The 7-aryl-1,6-naphthyridin-5-ones were methylated at 1-N and reduced to 7-aryl-1-methyl-1,2,3,4-tetrahydro-1,6-naphthyridin-5-ones. Cu-catalysed reaction of benzamidines with bromopyridinecarboxylic acids furnished 2-arylpyrido[2,3-d]pyrimidin-4-ones. Condensation of benzamidines with methyl 1-benzyl-4-oxopiperidine-3-carboxylate and deprotection gave 2-aryl-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-ones, aza analogues of the known inhibitor XAV939. Introduction of the ring-N in the arylnaphthyridinones and the arylpyridopyrimidinones caused >1000-fold loss in activity, compared with their carbocyclic isoquinolinone and quinazolinone analogues. However, the 7-aryl-1-methyl-1,2,3,4-tetrahydro-1,6-naphthyridin-5-ones showed excellent inhibition of the tankyrases, with some examples having IC50 = 2 nM. One compound (7-(4-bromophenyl)-1-methyl-1,2,3,4-tetrahydro-1,6-naphthyridin-5-one) showed 70-fold selectivity for inhibition of tankyrase-2 versus tankyrase-1. The mode of binding was explored through crystal structures of inhibitors in complex with tankyrase-2.
- Kumpan, Katerina,Nathubhai, Amit,Zhang, Chenlu,Wood, Pauline J.,Lloyd, Matthew D.,Thompson, Andrew S.,Haikarainen, Teemu,Lehti?, Lari,Threadgill, Michael D.
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p. 3013 - 3032
(2015/08/03)
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- Electrochemical and mARC-catalyzed enzymatic reduction of para-substituted benzamidoximes: Consequences for the prodrug concept "amidoximes instead of amidines"
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The mitochondrial amidoxime reducing component (mARC) activates amidoxime prodrugs by reduction to the corresponding amidine drugs. This study analyzes relationships between the chemical structure of the prodrug and its metabolic activation and compares its enzyme-mediated vs. electrochemical reduction. The enzyme kinetic parameters KM and Vmax for the N-reduction of ten para-substituted derivatives of the model compound benzamidoxime were determined by incubation with recombinant proteins and subcellular fractions from pig liver followed by quantification of the metabolites by HPLC. A clear influence of the substituents at position 4 on the chemical properties of the amidoxime function was confirmed by correlation analyses of 1H NMR chemical shifts and the redox potentials of the 4-substituted benzamidoximes with Hammett's σ. However, no clear relationship between the kinetic parameters for the enzymatic reduction and Hammett's σ or the lipophilicity could be found. It is thus concluded that these properties as well as the redox potential of the amidoxime can be largely ignored during the development of new amidoxime prodrugs, at least regarding prodrug activation.
- Bauch, Eva,Reichmann, Debora,Mendel, Ralf-Rainer,Bittner, Florian,Manke, Anne-Marie,Kurz, Philipp,Girreser, Ulrich,Havemeyer, Antje,Clement, Bernd
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p. 360 - 367
(2015/02/05)
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- Synthesis of p-amino-N,N′-dihydroxybenzamidine using a TBDMS protecting group protocol
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A synthetic route to p-amino-N,N′-dihydroxybenzamidine is established using a TBDMS protecting group strategy starting with p-nitrobenzhydroxamic acid chloride, which is transformed to O,O′-bis(tert-butyldimethylsilyl)- N,N′-dihydroxybenzamidine. Reduction with sodium dithionite occurs without degradation of the dihydroxyamidine functional group. Deprotection with ammonium fluoride is fast and efficient. This is important because no other possibility to synthesize this derivative has been found up to now. Furthermore, TBDMS protecting group strategy is proved to be adaptable to other substituted N,N′-dihydroxybenzamidines.
- Schwarz, Laura,Girreser, Ulrich,Clement, Bernd
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p. 3322 - 3324
(2014/06/09)
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- N-benzenesulfonyl-L-proline derivatives, method for preparing and therapeutic use
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PCT No. PCT/FR97/02049 Sec. 371 Date May 6, 1999 Sec. 102(e) Date May 6, 1999 PCT Filed Nov. 14, 1997 PCT Pub. No. WO98/24783 PCT Pub. Date Jun. 11, 1998The present invention relates to compounds selected from the group consisting of (i) the compounds of formula I: in which: X is a halogen atom or a methyl group, A is a group -N(R3)CO- or -CO-N(R3)-, B is a single bond, -CH2- or -CH2-O-, R1 is H, a C1-C3 alkyl group or a CF3 group, R2 and R3 are each independently H or a C1-C3 alkyl group, W is CH or N, and n is 2, 3, 4 or 5; and (ii) their addition salts. It further relates to the process for their preparation and to their use in therapeutics, especially for combating pathological conditions involving bradykinin.
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