- Benzoic acid derivative as well as preparation method and medicinal application thereof
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The invention discloses a benzoic acid derivative as well as a preparation method and a pharmaceutical application thereof, and belongs to the technical field of medicines. The invention specifically discloses a benzoic acid derivative represented by a co
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Paragraph 0182-0186
(2021/09/21)
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- Synthesis of novel 1,2,5-oxadiazoles and evaluation of action against Acinetobacter baumannii
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With multidrug resistant bacteria on the rise, novel antibiotics are becoming highly sought after. In 2008, eleven compounds were identified by high throughput screening as inhibitors of BasE, a key enzyme of the non-ribosomal peptide synthetase pathway found in Acinetobacter baumannii. Herein, we describe the preparation of four structurally similar heterocyclic lead compounds from that study, including one 1,2,5-oxadiazole. A further library of 30 analogues containing the oxadiazole moiety was then generated. All compounds were screened against Acinetobacter baumannii and their minimum inhibitory concentration data is reported, with (E)-3-(2-hydroxyphenyl)-N-(4-methyl-1,2,5-oxadiazol-3-yl)acrylamide 32 found to have an MIC of 0.5 mM. This work provides the foundation for further investigation of 1,2,5-oxadizoles as novel inhibitors of A. baumannii.
- Christoff, Rebecca M.,Murray, Gerald L.,Kostoulias, Xenia P.,Peleg, Anton Y.,Abbott, Belinda M.
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supporting information
p. 6267 - 6272
(2017/10/13)
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- Isoflavone amide derivatives, their preparation method and medical use
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The invention belongs to the field of medicinal chemistry, and relates to derivatives of isoflavones amides, as well as a preparation method and medical application of derivatives, in particular to the derivatives of the isoflavones amides with the general formula of (I) shown as the specification, the preparation method and the medical application of the derivatives, particularly the application of the derivatives of the isoflavones amides serving as medicaments for preventing or treating hyperlipemia, adiposis or type-II diabetes.
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Paragraph 0095
(2017/08/31)
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- Formononetin derivatives and preparation methods and medical application thereof
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The invention relates to the field of pharmaceutical chemistry, and relates to formononetin derivatives and preparation methods and medical application thereof, in particular to formononetin derivatives with the general formula as shown in (I), preparation methods thereof, pharmaceutical compositions containing the compounds and medical application of the derivatives and the pharmaceutical compositions, particularly, application of the derivatives and the pharmaceutical compositions serving as drugs for preventing or treating hyperlipidaemia or obesity or type-II diabetes. Please see the formula in the description.
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Paragraph 0087; 0088; 0089; 0096; 0097; 0098
(2017/04/29)
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- Synthesis and biological evaluation of isoflavone amide derivatives with antihyperlipidemic and preadipocyte antiproliferative activities
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A series of isoflavone amides were designed with isoflavone in place of the scaffold of 2-arylbenzoxazole as cholesterol ester transfer protein (CETP) inhibitors. Twelve new compounds were synthesized, and their inhibitory activities of CETP and preadipocyte proliferation were assayed. The hypolipidemic potency of the most effective compound HY-2c was further tested in vivo by hamster. The results indicate that HY-2c exhibited favorable antihyperlipidemic and preadipocyte antiproliferative activities.
- Wang, Wenbin,He, Yi,Xu, Pei,You, Qidong,Xiao, Hong,Xiang, Hua
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p. 4428 - 4433
(2015/08/03)
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- Synthesis, biological evaluation, and structure-activity relationships of potent noncovalent and nonpeptidic cruzain inhibitors as anti-Trypanosoma cruzi agents
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The development of cruzain inhibitors has been driven by the urgent need to develop novel and more effective drugs for the treatment of Chagas' disease. Herein, we report the lead optimization of a class of noncovalent cruzain inhibitors, starting from an inhibitor previously cocrystallized with the enzyme (Ki = 0.8 μM). With the goal of achieving a better understanding of the structure-activity relationships, we have synthesized and evaluated a series of over 40 analogues, leading to the development of a very promising competitive inhibitor (8r, IC50 = 200 nM, Ki = 82 nM). Investigation of the in vitro trypanocidal activity and preliminary cytotoxicity revealed the potential of the most potent cruzain inhibitors in guiding further medicinal chemistry efforts to develop drug candidates for Chagas' disease.
- Ferreira, Rafaela S.,Dessoy, Marco A.,Pauli, Ivani,Souza, Mariana L.,Krogh, Renata,Sales, Ana I. L.,Oliva, Glaucius,Dias, Luiz C.,Andricopulo, Adriano D.
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supporting information
p. 2380 - 2392
(2014/04/17)
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- 3-(Arylacetylamino)-N-methylbenzamides: A novel class of selective anti-Helicobacter pylori agents
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After chemical modification preceded by the random screening of our chemical library, a novel class of selective anti-Helicobacter pylori agents was generated. Consequently, the 3-(arylacetylamino)-N-methylbenzamides, which were quite easy to prepare, showed potent inhibitory activity against Helicobacter pylori but exhibited no inhibitory activity against other sorts of bacteria and fungi, e.g., Staphylococcus aureus, Bacillus subtilis, Escherichia coli, Pseudomonas aeruginosa, Bacteroides fragilis, and Candida albicans. These compounds showed potent anti-H. pylori activity under acidic conditions, whereas amoxicillin and clarithromycin decreased activity. The 3-(3-arylpropionylamino)-N-methylbenzamides, 3-(aryloxyacetylamino)-N-methylbenzamides, and (3-methylcarbamoylphenyl)carbamic acid 1-arylmethyl esters also exhibited potent anti-H. pylori activity. Finally, we selected 7n (BAS-118) as a candidate compound for further evaluation.
- Ando,Kawamura,Chiba
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p. 4468 - 4474
(2007/10/03)
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- Generation of monospecific nanomolar tyrosine kinase inhibitors via a chemical genetic approach
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Selective protein kinase inhibitors are highly sought after as tools for studying cellular signal transduction cascades, yet few have been discovered due to the highly conserved fold of kinase catalytic domains. Through a combination of small molecule syn
- Bishop, Anthony C.,Kung, Chi-Yun,Shah, Kavita,Witucki, Laurie,Shokat, Kevan M.,Liu, Yi
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p. 627 - 631
(2007/10/03)
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- Bicyclic N-hydroxyurea inhibitors of 5-lipoxygenase: Pharmacodynamic, pharmacokinetic, and in vitro metabolic studies characterizing N-hydroxy-N-(2,3-dihydro-6-(phenylmethoxy)-3-benzofuranyl)urea
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A series of N-hydroxyurea derivatives have been prepared and examined as inhibitors of 5-lipoxygenase. Oral activity was established by examining the inhibition of LTB4 biosynthesis in an ex vivo assay in the mouse. The pharmacodynamic performance in the mouse of selected compounds was assessed using an ex vivo LTB4 assay and an adoptive peritoneal anaphylaxis assay at extended pretreat times. Compounds with an extended duration of action were reexamined as the individual enantiomers in the ex vivo assay, and the (S) enantiomer of N-hydroxy-N-[2,3-dihydro-6-(phenylmethoxy)-3-benzofuranyl]urea, (+)-1a (SB 202235), was selected as the compound with the best overall profile. Higher plasma concentrations and longer plasma half-lives were found for (+)-1a relative to its enantiomer in the mouse, monkey, and dog. In vitro metabolic studies in mouse liver microsomes established enantiospecific glucuronidation as a likely mechanism for the observed differences between the enantiomers of 1a. Enantioselective glucuronidation favoring (-)-1a was also found in human liver microsomes.
- Adams, Jerry L.,Garigipati, Ravi S.,Sorenson, Margaret,Schmidt, Stanley J.,Brian, William R.,Newton, John F.,Tyrrell, Kathy A.,Garver, Eric,Yodis, Lee A.,Chabot-Fletcher, Marie,Tzimas, Maritsa,Webb, Edward F.,Breton, John J.,Griswold, Don E.
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p. 5035 - 5046
(2007/10/03)
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- SYNTHESIS OF NEW N-ACYL DERIVATIVES OF DL-TRANS-1,2-AMINOCYCLOHEXANOL
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New amide derivatives of Dl-trans-1,2-aminocyclohexanol, with a potential action on the cardiovascular system, were obtained.Keywords: N-acyl derivatives of DL-trans-1,2-aminocyclohexanol, elemental analysis, 1H NMR.
- Pekala, Elzbieta,Gajewczyk, Leonard,Marona, Henryk
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p. 339 - 342
(2007/10/02)
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- Acylated amine compounds which are useful fungicigal agents
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A compound selected from the group consisting of a compound of the formula STR1 wherein R1 is selected from the group consisting of Ar-O- and aryl, polyaryl and condensed polyaryl unsubstituted or substituted and heterocycle unsubstituted or substituted, Ar is aryl of 6 to 14 carbon atoms unsubstituted or substituted, heteroaryl unsubstituted or substituted and heterocyclic unsubstituted or substituted, W is selected from the group comsisting of --(CH2)n1 --or --(CH2)n2 --NY--(CH2)n3, n1, n2 and n3 are individually integers from 2 to 6, Y is selected from the group consisting of hydrogen, alkyl of 1 to 12 carbon atoms, aryl of 6 to 12 carbon atoms and aralkyl of 7 to 14 carbon atoms unsubstituted or substituted, --COOAlk and --COR2, Alk is alkyl of 1 to 12 carbon atoms, R2 is selected from the group consisting of alkyl of 1 to 12 carbon atoms, alkenyl and alkynyl of 2 to 12 carbon atoms, aryl of 6 to 14 carbon atoms, aralkyl of 7 to 18 carbon atoms unsubstituted or substituted and heterocyclic unsubstituted or substituted, Z is selected from the group consisting of hydrogen, STR2 R2 is alkyl of 1 to 12 carbon atoms or aralkyl of 7 to 18 carbon atoms, Alk' is alkyl of 1 to 12 carbon atoms, ArAlk is aralkyl of 7 to 18 carbon atoms, R2 ' is R2, R3 and R3 ' are selected from the group consisting of aryl substituted or unsubstituted, heteroaryl substituted or unsubstituted, heterocyclic unsubstituted or substituted and R1 with the proviso that Z is not hydrogen when W is --(CH2)3 --and R1 is 2,4-dichlorophenoxy and their non-toxic, pharmaceutically acceptable acid addition salts having fungicidal activity.
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- 7-((substituted)amino)-8-((substituted)carbonyl)-methylamino)-1-oxaspiro(4,5)decanes as analgesic agents
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Substituted phenoxy-, 1-, and 2-naphthalenyloxy-, indenyl-, indolyl-, benzofuranyl-, and benzo[b]thiofuranylcarboxamides of 7,8-(substituted-diamino)-1-oxaspiro[4.5]decanes are useful as analgesic agents. A method of making the compounds, pharmaceutical compositions employing the compounds, and a method of alleviating pain in warm-blooded animals are also disclosed.
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