- Substituted diaryl compound and preparation method and application thereof
-
The invention relates to the field of medicinal chemistry, in particular to a substituted diaryl compound (I). The preparation method comprises the following steps: medicine preparation and medical application thereof. Test results show that the substituted diaryl compound has a good inhibition effect on human lung cancer (A549), human ovarian cancer (SKOV3), human melanoma (A375) and human colon cancer (LOVO) cells. Formula (I):
- -
-
Paragraph 0073-0075; 0076
(2021/09/15)
-
- Design, synthesis, and antibacterial evaluation of novel derivatives of NPS-2143 for the treatment of methicillin-resistant S. aureus (MRSA) infection
-
Methicillin-resistant Staphylococcus aureus (MRSA) infections are a significant global health challenge due to the emergence of strains exhibiting resistance to nearly all classes of antibiotics. This necessitates the rapid development of novel antimicrobials to circumvent this critical problem. Screening of compounds based on phenotypes is one of the major strategies for finding new antibiotics at present. Hence, we here performed a phenotypic screening against MRSA and identified NPS-2143 exhibiting activity against MRSA with an MIC value of 16 μg ml?1. In order to discover more potent anti-MRSA agents, a series of derivatives of NPS-2143 were designed and synthesized. The most promising compounds 48 and 49 exhibited favorable antimicrobial activity with an MIC value of 2 μg ml?1.
- Chen, Yao,Ju, Yuan,Li, Chungen,Yang, Tao,Deng, Yong,Luo, Youfu
-
p. 545 - 554
(2019/04/10)
-
- Design, synthesis and biological evaluation of novel desloratadine derivatives with anti-inflammatory and H1 antagonize activities
-
To improve the anti-inflammatory activity of desloratadine, we designed and synthesized a series of novel desloratadine derivatives. All compounds were evaluated for their anti-inflammatory and H1 antagonistic activities. Among them, compound 2c showed the strongest H1 antagonistic and anti-inflammatory activity. It also exhibited promising pharmacokinetic profiles and low toxicity. All these results suggest that compound 2c as a novel anti-allergic agent is worthy of further investigation.
- Li, Feng,Xu, Qinlong,Zhu, Qihua,Chu, Zhaoxing,Lin, Gaofeng,Mo, Jiajia,Zhao, Yan,Li, Jiaming,He, Guangwei,Xu, Yungen
-
-
- A facile and efficient method for synthesis of β-iodocarboxylates from terminal epoxides
-
A facile and efficient method has been developed for synthesis of β-iodocarboxylates in the presences of Ph3P/I2. Starting from epoxides, a series of β-iodocarboxylate compounds can be directly obtained in toluene media with excellent yields. Moreover, the method was successfully applied for the late-stage modification of natural products, such as isosteviol and vincamine derivatives, achieving the corresponding β-iodocarboxylates in good yields.
- Zhu, Ye-Fu,Wei, Bo-Le,Wang, Wen-Qiong,Xuan, Li-Jiang
-
supporting information
(2019/11/26)
-
- Syntheses of pterocarpenes and coumestans via regioselective cyclodehydration
-
A highly efficient synthetic route to pterocarpenes and coumestans is described. BCl3-mediated dehydrative cyclization of 1,3-diaryloxyacetones under mild conditions permitted regioselective ring closure to afford 3-((2-iodoaryloxy)methyl)benzo
- Nayak, Maloy,Jung, Youngeun,Kim, Ikyon
-
p. 8074 - 8087
(2016/09/09)
-
- Synthesis and evaluation of 4-(2-hydroxypropyl)piperazin-1-yl) derivatives as Hsp90 inhibitors
-
We previously reported 4-(3-((6-bromonaphthalen-2-yl)oxy)-2-hydroxypropyl)-N,N-dimethylpiperazine-1-sulfonamide (1) as a novel heat shock protein 90 inhibitor with moderate activity. In our ongoing efforts for the discovery of Hsp90 modulators we undertake structural investigations on 1. Series of the titled compound were designed, synthesized and evaluated. We have found that compounds with a hydroxyl group at C-4 of the aryl ring on the piperazine moiety possess Hsp90 inhibition properties. Compound 6f with improved activity could be further developed and optimized as Hsp90 inhibitor.
- Cherfaoui, Bahidja,Guo, Tian-Kun,Sun, Hao-Peng,Cheng, Wei-Lin,Liu, Fang,Jiang, Fen,Xu, Xiao-Li,You, Qi-Dong
-
supporting information
p. 2423 - 2432
(2016/05/24)
-
- Discovery of (phenoxy-2-hydroxypropyl)piperidines as a novel class of voltage-gated sodium channel 1.7 inhibitors
-
A novel class of NaV1.7 inhibitors has been identified by high-throughput screening followed by structure activity relationship studies. Among this series of compounds, piperidine 9o showed potent human and mouse NaV1.7 inhibitory activities with fair subtype selectivity over NaV1.5. Compound 9o successfully demonstrated analgesic efficacy in mice comparable to that of the currently used drug, mexiletine, but with an expanded central nervous system safety margin.
- Suzuki, Sayaka,Kuroda, Takeshi,Kimoto, Hiroko,Domon, Yuki,Kubota, Kazufumi,Kitano, Yutaka,Yokoyama, Tomihisa,Shimizugawa, Akiko,Sugita, Ryusuke,Koishi, Ryuta,Asano, Daigo,Tamaki, Kazuhiko,Shinozuka, Tsuyoshi,Kobayashi, Hiroyuki
-
p. 5419 - 5423
(2015/11/09)
-
- Synthesis of new N-acryl-1-amino-2-phenylethanol and N-acyl-1-amino-3- aryloxypropanols and evaluation of their antihyperlipidemic, LDL-oxidation and antioxidant activity
-
As a part of our drug discovery program, we identified an alkaloidal amide i.e. Aegeline (V) isolated from the leaves of Aegle marmelos as a dual acting agent (antihyperlipidemic and antihyperglycemic). In continuation of this program, we synthesized new N-acyl-1-amino-2-alcohols (N-acrylated-1-amino-2- phenylethanol and N-acylated-1-amino-3-aryloxypropanols) via Ritter reaction and screened for their in-vivo antihyperlipdemic activity in Triton induced hyperlipidemia model, LDL-oxidation and antioxidant activity. Compounds 3, 11 and 13 showed good antihyperlipidemic activity, LDL-oxidation as well as antioxidant activity and comparable activity with marketed antidyslipidemic drug.
- Sarkar, Satinath,Sonkar, Ravi,Bhatia, Gitika,Tadigoppula, Narender
-
p. 135 - 144
(2014/05/20)
-
- Aminopropyl carbazole analogues as potent enhancers of neurogenesis
-
Neural stem cells are multipotent and self-renewing cells that can differentiate into new neurons and hold great promise for treating various neurological disorders including multiple sclerosis, Parkinson's disease, and Alzheimer's disease. Small molecules that can trigger neurogenesis and neuroprotection are particularly useful not only because of their therapeutic implications but also because they can provide an invaluable tool to study the mechanisms of neurogenesis. In this report, we have developed and screened 25 aminopropyl carbazole derivatives that can enhance neurogenesis of cultured neural stem cells. Among these analogues, compound 9 demonstrated an excellent proneurogenic and neuroprotective activity with no apparent toxicity. We believe that compound 9 can serve as an excellent lead to develop various analogues and to study the underlying mechanisms of neurogenesis.
- Yoon, Hye Jin,Kong, Sun-Young,Park, Min-Hye,Cho, Yongsung,Kim, Sung-Eun,Shin, Jae-Yeon,Jung, Sunghye,Lee, Jiyoun,Farhanullah,Kim, Hyun-Jung,Lee, Jeewoo
-
p. 7165 - 7174
(2013/11/06)
-
- Thienopyrimidines as β3-adrenoceptor agonists: Hit-to-lead optimization
-
Resulting from a vHTS based on a pharmacophore alignment on known β3-adrenoceptor ligands, an aryloxypropanolamine scaffold comprising a thienopyrimidine moiety was further optimized as a human β3-AR agonist, yielding a lead compound with an excellent cellular activity of EC50 = 20 pM, selectivity over hβ1- and hβ2-adrenoceptors and a promising safety profile.
- Tasler, Stefan,Baumgartner, Roland,Ammendola, Astrid,Schachtner, Josef,Wieber, Tanja,Blisse, Marcus,Rath, Sandra,Zaja, Mirko,Klahn, Philipp,Quotschalla, Udo,Ney, Peter
-
scheme or table
p. 6108 - 6115
(2010/11/19)
-
- Directed evolution of an enantioselective epoxide hydrolase: Uncovering the source of enantioselectivity at each evolutionary stage
-
Directed evolution of enzymes as enantioselective catalysts in organic chemistry is an alternative to traditional asymmetric catalysis using chiral transition-metal complexes or organocatalysts, the different approaches often being complementary. Moreover, directed evolution studies allow us to learn more about how enzymes perform mechanistically. The present study concerns a previously evolved highly enantioselective mutant of the epoxide hydrolase from Aspergillus niger in the hydrolytic kinetic resolution of racemic glycidyl phenyl ether. Kinetic data, molecular dynamics calculations, molecular modeling, inhibition experiments, and X-raystructural work for the wild-type (WT) enzyme and the best mutant revea l the basis of the large increase in enantioselectivity (E = 4.6 versus E = 115). The overall structures of the WT and the mutant are essentially identical, but dramatic differences are observed in the active site asrevealed by the X-ray structures. All of the experimental and computati onal results support a model in which productive positioning of the preferred (S)-glycidyl phenyl ether, but not the (R)-enantiomer, forms the basis of enhanced enantioselectivity. Predictions regarding substrate scope and enantioselectivity of the best mutant are shown to be possible.
- Reetz, Manfred T.,Bocola, Marco,Wang, Li-Wen,Sanchis, Joaquin,Cronin, Annette,et al.
-
supporting information; experimental part
p. 7334 - 7343
(2009/10/17)
-
- Jacobsen-type enantioselective hydrolysis of aryl glycidyl ethers. 31P NMR analysis of the enantiomeric composition of oxiranes
-
The enantioselective partial hydrolysis of a number of racemic aryl glycidyl ethers in the presence of chiral Co(salen)-catalyst was studied. The enantiomeric composition of the isolated (R)-aryl glycidyl ethers was analyzed by 31P NMR using optically active substituted 2-chloro-1,3,2- dioxaphospholanes. A synthesis of β-adrenoblocking agents (S)-toliprolol and (S)-moprolol based on the simultaneously obtained (S)-3-aryloxypropane-1,2- diols was proposed.
- Bredikhin,Strunskaya,Novikova,Azancheev,Sharafutdinova,Bredikhina
-
p. 213 - 218
(2007/10/03)
-
- Enantioselective parallel synthesis using polymer-supported chiral Co(salen) complexes
-
(matrix presented) The kinetic resolution of epoxides with phenols catalyzed by a polymer-supported Co(salen) complex is applied to the first enantioselective catalytic synthesis of parallel libraries. The corresponding 1-aryloxy-2-alcohols are obtained i
- Peukert, Stefan,Jacobsen, Eric N.
-
p. 1245 - 1248
(2008/02/09)
-
- Crown Cation Complex Effects. 20. Syntheses and Cation Binding Properties of Carbon-Pivot Lariat Ethers
-
In an effort devise synthetic cation binders that will mimic the behavior of naturally occuring ionophores such as valinomycin, we have prepared approximately 30 macrocyclic (crown) polyethers bearing flexible side chains attached to the macro ring at carbon.In many of these "carbon-pivot" compounds, the side chain contains one or more neutral donor groups that, if in a suitable geometrical arrangement, may provide additional solvation to the macro-ring-bound cation.Although such donors often enhanced the cation binding ability, overall, the increases in stability constants were modest.The physical resemblance and concept of "roping and tying" the cation suggest the name "lariat ethers".Syntheses of these molecules and binding by them of Na+ and K+ cations are reported and conclusions drawn about the structural requirements and cation binding efficacy of these materials.
- Dishong, Dennis M.,Diamond, Craig J.,Cinoman, Michael I.,Gokel, Geoge W.
-
p. 586 - 593
(2007/10/02)
-