- Vibrational spectroscopic studies and computational study of 4-fluoro-N-(2′-hydroxy-4′-nitrophenyl)phenylacetamide
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Fourier-transform infrared (FT-IR) and FT-Raman spectra of 4-fluoro-N-(2′-hydroxy-4′-nitrophenyl)phenylacetamide were recorded and analyzed. A surface-enhanced Raman scattering (SERS) spectrum was recorded in silver colloid. The vibrational wavenumbers an
- Mary, Y. Sheena,Yohannan Panicker,Varghese, Hema Tresa,Raju,Bolelli, Tugba Ertan,Yildiz, Ilkay,Granadeiro, Carlos M.,Nogueira, Helena I.S.
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- N-monoarylacetothioureas as potent urease inhibitors: synthesis, SAR, and biological evaluation
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A urease inhibitor with good in vivo profile is considered as an alternative agent for treating infections caused by urease-producing bacteria such as Helicobacter pylori. Here, we report a series of N-monosubstituted thioureas, which act as effective urease inhibitors with very low cytotoxicity. One compound (b19) was evaluated in detail and shows promising features for further development as an agent to treat H. pylori caused diseases. Excellent values for the inhibition of b19 against both extracted urease and urease in intact cell were observed, which shows IC50 values of 0.16 ± 0.05 and 3.86 ± 0.10 μM, being 170- and 44-fold more potent than the clinically used drug AHA, respectively. Docking simulations suggested that the monosubstituted thiourea moiety penetrates urea binding site. In addition, b19 is a rapid and reversible urease inhibitor, and displays nM affinity to urease with very slow dissociation (koff=1.60 × 10?3 s?1) from the catalytic domain.
- Fang, Hai-Lian,He, Jie-Ling,Li, Wei-Yi,Liu, Shan-Shan,Ni, Wei-Wei,Pan, Xing-Ming,Xiao, Zhu-Ping,Ye, Ya-Xi,Yi, Juan,Zhou, Mi,Zhou, Tian-Li,Zhu, Hai-Liang
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p. 404 - 413
(2020/01/03)
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- Novel quinoline derivative inhibitor
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The invention provides a novel quinoline derivative inhibitor, which has a structure represented by the following general formula (I). According to the invention, the compound provided by the invention can selectively inhibit tyrosine kinase TAM family/an
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Paragraph 0755; 0758-0761; 0808; 0810-0812
(2020/03/12)
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- Regio- and Enantioselective Formal Hydroamination of Enamines for the Synthesis of 1,2-Diamines
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The asymmetric formal hydroamination of enamines using a CuH catalyst is reported. The method provides a straightforward and efficient approach to the synthesis of chiral 1,2-dialkyl amines in good yields with high levels of enantioselectivities for a broad range of substrates, and should have significant value for the preparation of molecules bearing a 1,2-diamine motif.
- Yu, Lu,Somfai, Peter
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supporting information
p. 8551 - 8555
(2019/05/21)
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- Direct meta-C?H Perfluoroalkenylation of Arenes Enabled by a Cleavable Pyrimidine-Based Template
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The development of efficient and mild methods for the synthesis of organofluorine compounds is of foremost interest in various fields of chemistry. A direct pyrimidine-based selective meta-C?H perfluoroalkenylation of arenes involving several commercially
- Brochetta, Massimo,Borsari, Tania,Bag, Sukdev,Jana, Sadhan,Maiti, Siddhartha,Porta, Alessio,Werz, Daniel B.,Zanoni, Giuseppe,Maiti, Debabrata
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supporting information
p. 10323 - 10327
(2019/07/18)
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- TAM family kinase and/or CSF1R kinase inhibitor and application thereof
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The invention provides a novel inhibitor compound shown in a general formula (I). The compound has good kinase inhibition activity and can be used for preventing and/or treating diseases mediated by abnormal expression of TAM family kinase and/or a ligand thereof. The compound can target CSF1R kinase and can be used for preventing and/or treating diseases mediated by abnormal expression of a TAM family kinase receptor and/or a CSF1R kinase receptor and/or ligands thereof.
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Paragraph 0596; 0600-0602
(2019/08/06)
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- A O - phenylacetylamino - (4 - trifluoromethyl) salicylic amide compound and use thereof
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The invention discloses an O-phenylacetyl-(4-trifluoromethyl) salicylamide compound represented by formula (I), and applications thereof in preparing antitumor drugs.
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Paragraph 0049
(2018/03/01)
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- Enantioselective 1,2-Anionotropic Rearrangement of Acylsilane through a Bisguanidinium Silicate Ion Pair
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Highly enantioselective bisguanidinium-catalyzed tandem rearrangements of acylsilanes are reported. The acylsilanes were activated via an addition of fluoride on the silicon to form a penta-coordinate anionic silicate intermediate. The silicate then underwent alkyl or aryl group migration from the silicon atom to the neighboring carbonyl carbon atom (1,2-anionotropic rearrangement), followed by [1,2]-Brook rearrangement to provide the secondary alcohols in high yields with excellent enantioselectivities (up to 95% ee). The isolation of an α-silylcarbinol intermediate as well as DFT calculations revealed that the 1,2-anionotropic rearrangement occurred via a bisguanidinium silicate ion pair, which is the stereodetermining step. The chiral center formed is then retained without inversion through the subsequent [1,2]-Brook rearrangement. Crotyl acylsilanes were smoothly transformed into homoallylic linear crotyl alcohols with retention of E/Z geometry, and no branched alcohols were detected. This clearly suggested that the 1,2-anionotropic rearrangement occurred through a three-membered instead of a five-membered transition state.
- Cao, Weidi,Tan, Davin,Lee, Richmond,Tan, Choon-Hong
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supporting information
p. 1952 - 1955
(2018/02/17)
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- Diastereoselective Electrophilic Trifluoromethylthiolation of Chiral Oxazolidinones: Access to Enantiopure α-SCF3 Alcohols
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Lithium imide enolates featuring Evans’ chiral oxazolidinone auxiliary were involved in diastereoselective α-trifluoromethylthiolation with electrophilic SCF3 donors. Diastereopure products were isolated and converted to enantiopure α-SCF3 alcohols without racemisation. (Figure presented.).
- Chachignon, Hélène,Kondrashov, Evgeniy V.,Cahard, Dominique
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supporting information
p. 965 - 971
(2018/01/27)
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- Heterocyclic pyrrolizinone and indolizinones derived from natural lactam as potential antifungal agents
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With the aim to develop highly potential active heterocyclic compounds, two series of multi-substituted pyrrolizinone and indolizinones derived from lactam were designed, synthesized and evaluated for their potential antifungal activities against six species of the plant pathogen fungi (Fusarium graminearum, Sclerotinia sclerotiorum, Phomopsis adianticola, Gloeosporium theae-sinensis, Alternaria tenuis Nees, Magnaporthe oryzae). The structure of all the newly molecules were confirmed by analytical spectroscopic data, including 1H NMR, 13C NMR and ESI-MS. According to the preliminary studies on bio-evaluation assay, some of the obtained compounds exhibited moderate and broad-spectrum activities against six fungi compared to the intermediates 6a, 6f and the hymexazol. Particularly, the inhibition rate of compounds 7l, 7m and 7t reached 69.25%, 74.76%, 65.38% against Phomopsis adianticola and Magnaporthe oryzae in vitro activity. Furthermore, compounds 7l and 7t displayed obviously inhibition activities against Phomopsis adianticola compared to the hymexazol. Consequently, compounds 7l and 7t with six-membered alkane ring could be used as new motifs for further investigation.
- Wang, Shuangshuang,Bao, Longzhu,Wang, Wenda,Song, Di,Wang, Jingjing,Cao, Xiufang
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p. 257 - 266
(2018/08/04)
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- Novel 4-(4-substituted amidobenzyl)furan-2(5H)-one derivatives as topoisomerase I inhibitors
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In this study, two series of novel 4-(4-substituted amidobenzyl)furan-2(5H)-one derivatives containing an α,β-unsaturated lactone fragment were synthesized and screened for Topo I inhibition and antitumor activity. The topoisomerase I inhibitory activities and cytotoxicities against three human cancer cell lines (MCF-7,Hela,A549) were evaluated. The results revealed that series 2, compounds bearing an exocyclic double bond on the furanone ring, generally showed more potent activity than series 1, compounds lacking an exocyclic double bond. Several compounds of series 2 possess significant Topo I inhibitory activity and potent antiproliferative activity against cancer cell lines. Further mechanism studies of the most active compound of series 2 (B-15) indicated that synthetic compounds can not only stabilize the drug-enzyme-DNA covalent ternary complex as well as camptothecin, but also interfere with the binding between Topo I and DNA. The binding patterns of these compounds with Topo I and structure-activity relationships are discussed.
- Peng, Cheng-Kang,Zeng, Ting,Xu, Xing-Jun,Chang, Yi-Qun,Hou, Wen,Lu, Kuo,Lin, Hui,Sun, Ping-Hua,Lin, Jing,Chen, Wei-Min
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p. 187 - 199
(2017/01/06)
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- Diphenylurea derivatives for combating methicillin- and vancomycin-resistant Staphylococcus aureus
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A new class of diphenylurea was identified as a novel antibacterial scaffold with an antibacterial spectrum that includes highly resistant staphylococcal isolates, namely methicillin- and vancomycin-resistant Staphylococcus aureus (MRSA & VRSA). Starting with a lead compound 3 that carries an aminoguanidine functionality from one side and a n-butyl moiety on the other ring, several analogues were prepared. Considering the pharmacokinetic parameters as a key factor in structural optimization, the structure-activity-relationships (SARs) at the lipophilic side chain were rigorously examined leading to the discovery of the cycloheptyloxyl analogue 21n as a potential drug-candidate. This compound has several notable advantages over vancomycin and linezolid including rapid killing kinetics against MRSA and the ability to target and reduce the burden of MRSA harboring inside immune cells (macrophages). Furthermore, the potent anti-MRSA activity of 21n was confirmed in?vivo using a Caenorhabditis elegans animal model. The present study provides a foundation for further development of diphenylurea compounds as potential therapeutic agents to address the burgeoning challenge of bacterial resistance to antibiotics.
- Eissa, Ibrahim H.,Mohammad, Haroon,Qassem, Omar A.,Younis, Waleed,Abdelghany, Tamer M.,Elshafeey, Ahmed,Abd Rabo Moustafa, Mahmoud M.,Seleem, Mohamed N.,Mayhoub, Abdelrahman S.
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supporting information
p. 73 - 85
(2017/03/02)
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- Facile synthesis, biological evaluation and molecular docking studies of novel substituted azole derivatives
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In this study, we synthesized the series of novel azole derivatives and evaluated for enzyme inhibition assays, corresponding kinetic analysis and molecular modeling. Among the investigated bioassays, the oxadiazole derivatives 4a-k were found potent α-glucosidase inhibitors while the Schiff base derivatives 7a-k exhibited considerable potential toward urease inhibition. The inhibition kinetics for the most active compounds were analyzed by the Lineweaver–Burk plots to investigate the possible binding modes of the synthesized compounds toward the tested proteins. Moreover, the detailed docking studies were performed on the synthesized library of 4a-k and 7a-k to study the molecular interaction and binding mode in the active site of the modeled yeast α-glucosidase and Jack Bean Urease, respectively. It could be inferred from docking results that theoretical studies are in close agreement to that of the experimental results. The structure of one of the compound 7k was characterized by the single crystal X-ray diffraction analysis in order to find out the predominant conformation of the molecules.
- Rafiq, Muhammad,Saleem, Muhammad,Jabeen, Farukh,Hanif, Muhammad,Seo, Sung-Yum,Kang, Sung Kwon,Lee, Ki Hwan
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p. 177 - 191
(2017/03/15)
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- A novel serine racemase inhibitor suppresses neuronal over-activation in vivo
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Serine racemase (SRR) is an enzyme that produces D-serine from L-serine. D-Serine acts as an endogenous coagonist of NMDA-type glutamate receptors (NMDARs), which regulate many physiological functions. Over-activation of NMDARs induces excitotoxicity, which is observed in many neurodegenerative disorders and epilepsy states. In our previous works on the generation of SRR gene knockout (Srr-KO) mice and its protective effects against NMDA- and Aβ peptide-induced neurodegeneration, we hypothesized that the regulation of NMDARs’ over-activation by inhibition of SRR activity is one such therapeutic strategy to combat these disease states. In the previous study, we performed in silico screening to identify four compounds with inhibitory activities against recombinant SRR. Here, we synthesized 21 derivatives of candidate 1, one of four hit compounds, and performed screening by in vitro evaluations. The derivative 13J showed a significantly lower IC50 value in vitro, and suppressed neuronal over-activation in vivo.
- Mori, Hisashi,Wada, Ryogo,Takahara, Satoyuki,Horino, Yoshikazu,Izumi, Hironori,Ishimoto, Tetsuya,Yoshida, Tomoyuki,Mizuguchi, Mineyuki,Obita, Takayuki,Gouda, Hiroaki,Hirono, Shuichi,Toyooka, Naoki
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p. 3736 - 3745
(2017/06/13)
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- Ruthenium-catalysed one-pot regio- and diastereoselective synthesis of pyrrolo[1,2-a] indoles via cascade C-H functionalization/annulation
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A cascade approach has been developed towards dual C-C bond formation via consecutive C-H functionalization/cyclization giving access to pyrrolo[1,2-a]indoles in a highly regio- and diastereoselective manner using catalytic [Ru(p-cymene)Cl2]2. The methodology was further expanded to attain pentacyclic structures involving manifold C-C bond creation.
- Singh, Sukhdev,Butani, Himanshu H.,Vachhani, Dipak D.,Shah, Anamik,Van Der Eycken, Erik V.
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supporting information
p. 10812 - 10815
(2017/10/10)
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- Synthesis of ortho-arylated/benzylated arylacetamide derivatives: Pd(OAc)2-catalyzed bidentate ligand-aided arylation and benzylation of the γ-C[sbnd]H bond of arylacetamides
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In this paper, we report the Pd(OAc)2/AgOAc, bidentate ligand-directed C[sbnd]H functionalization of the sp2γ-C[sbnd]H bond of arylacetamides. While, the bidentate ligand-directed site selective functionalization of the β-C[sbnd]H bond of aromatic carboxylic acid derivatives is well known, we herein, report our attempts on the Pd(II)-catalyzed, bidentate ligand-directed arylation, benzylation, alkylation, acetoxylation and hydroxylation of the sp2γ-C[sbnd]H bond of the arylacetamide systems. The arylation and benzylation of arylacetamides were successful; however, the alkylation and acetoxylation/hydroxylation of arylacetamides were not successful. Various ligands were screened to substantiate the need for the bidentate ligand in the arylation/benzylation of arylacetamides, and 8-aminoquinoline was found to be the best bidentate ligand. Several substituted aryl-/heteroaryl iodides, 4-nitrobenzyl bromide and arylacetamide substrates were used to examine their reactivity pattern and accomplish the substrate scope/generality. In general, the bidentate ligand 8-aminoquinoline-directed arylation of arylacetamides gave the corresponding ortho-diarylated arylacetamides and benzylation of arylacetamides gave the corresponding ortho-mono benzylated arylacetamides as the predominant compounds. Overall, this method has led to the synthesis of new ortho-substituted arylacetamides in good to high yields.
- Bisht, Narendra,Babu, Srinivasarao Arulananda
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p. 5886 - 5897
(2016/09/07)
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- Copper-catalyzed base-accelerated direct oxidation of C-H bond to synthesize benzils, isatins, and quinoxalines with molecular oxygen as terminal oxidant
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We describe herein an efficient and general copper (II)-catalyzed base-accelerated oxidation of the C-H bond to synthesize benzils and isatins. With similar oxidation system an efficient one-pot procedure for the synthesis of quinoxaline derivatives was realized. The two protocols feature using molecular oxygen as terminal oxidant, low catalyst loading, wide substrate scope, and high functional-group tolerance.
- Yu, Jing-Wen,Mao, Shuai,Wang, Yong-Qiang
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supporting information
p. 1575 - 1580
(2015/03/14)
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- Designing new analogs for streamlining the structure of cytotoxic lamellarin natural products
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Despite the therapeutic potential of marine-derived lamellarin natural products, their preclinical development has been hampered by their lipophilic nature, causing very poor aqueous solubility. In order to develop more drug-like analogs, their structure was streamlined in this study from both the cytotoxic activity and lipophilicity standpoints. First, a modified total synthetic route was successfully devised to construct a library of 59 systematically designed lamellarin analogs, which were then subjected to cytotoxicity and log P determinations. Along with the 25 first-generation lamellarins previously synthesized in our laboratory, the structure-activity and structure-lipophilicity relationships were extensively evaluated. Our results clearly indicated the additional structural requirements around the lamellarin skeleton which, when combined with those reported previously, can provide invaluable guidance for further modifications to increase the aqueous solubility of these compounds.
- Tangdenpaisal, Kassrin,Worayuthakarn, Rattana,Karnkla, Supatra,Ploypradith, Poonsakdi,Intachote, Pakamas,Sengsai, Suchada,Saimanee, Busakorn,Ruchirawat, Somsak,Chittchang, Montakarn
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p. 925 - 937
(2015/03/31)
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- SPIROCYCLIC HETEROCYCLE COMPOUNDS USEFUL AS HIV INTEGRASE INHIBITORS
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The present invention relates to Spirocyclic Heterocycle Compounds of Formula (I): and pharmaceutically acceptable salts thereof, wherein A, B, X, Y, R1, R2 and R11 are as defined herein. The present invention also relates to compositions comprising at least one Spirocyclic Heterocycle Compound, and methods of using the Spirocyclic Heterocycle Compounds for treating or preventing HIV infection in a subject.
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Page/Page column 58
(2015/07/07)
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- SPIROCYCLIC HETEROCYCLE COMPOUNDS USEFUL AS HIV INTEGRASE INHIBITORS
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Disclosed are Spirocyclic Heterocycle Compounds of Formula (I) and pharmaceutically acceptable salts thereof, where A, B, X, Y, R1, R2 and R11 are as defined herein. Composition comprising at least one Spirocyclic Heterocycle Compound, and methods of using the Spirocyclic Heterocycle Compounds for treating or preventing HIV infection in a subject are also disclosed.
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Page/Page column 36
(2015/07/07)
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- Copper-mediated oxidative homocoupling and rearrangement of N-alkoxyamides: An efficient method for the preparation of aromatic esters
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N-Alkoxyamides are successfully converted into their corresponding esters in a moderate to satisfactory yields via copper-catalyzed oxidative homocoupling and Heron rearrangement. The process tolerates a wide variety of functional groups and allows the synthesis of sterically hindered ester products not readily accessible by traditional acylation chemistry. A radical-mediated pathway has been tentatively proposed for the oxidative process.
- Duan, Xiyan,Yang, Kun,Tian, Shuang,Ma, Junying,Li, Yaning,Zou, Jiao,Zhang, Dongliang,Cui, Huanqing
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supporting information
p. 4634 - 4637
(2015/07/08)
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- Ligand-Enabled Meta-C-H Alkylation and Arylation Using a Modified Norbornene
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2-Carbomethoxynorbornene is identified as a more effective transient mediator to promote a Pd(II)-catalyzed meta-C(sp2)-H alkylation of amides with various alkyl iodides as well as arylation with previously incompatible aryl iodides. The use of a tailor-made quinoline ligand is also crucial for this reaction to proceed.
- Shen, Peng-Xiang,Wang, Xiao-Chen,Wang, Peng,Zhu, Ru-Yi,Yu, Jin-Quan
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supporting information
p. 11574 - 11577
(2015/09/28)
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- Design and synthesis of thiazole derivatives as potent FabH inhibitors with antibacterial activity
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Components of fatty acid biosynthetic pathway have been identified as attractive targets for the development of new antibacterial agents. Compounds of series A (4a-4g) and series B (5a-5g) were synthesized by the formation of an amine bond between aromati
- Li, Jing-Ran,Li, Dong-Dong,Wang, Rong-Rong,Sun, Jian,Dong, Jing-Jun,Du, Qian-Ru,Fang, Fei,Zhang, Wei-Ming,Zhu, Hai-Liang
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p. 438 - 447
(2014/03/21)
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- HETEROCYCLIC COMPOUNDS FOR THE INHIBITION OF PASK
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Disclosed herein are new heterocyclic compounds of Formula IIa: and compositions thereof, and their application as pharmaceuticals for the treatment of disease. Methods of inhibiting PAS Kinase (PASK) activity in a human or animal subject are also provided for the treatment of diseases such as diabetes mellitus.
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Paragraph 0235; 0345; 0346
(2014/05/20)
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- 4-PYRIDINONETRIAZINE DERIVATIVES AS HIV INTEGRASE INHIBITORS
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The present invention relates to 4-Pyridinonetriazine Derivatives of Formula (I); and pharmaceutically acceptable salts thereof, wherein A, X, Y, R1, R2, R3 and R5 are as defined herein. The present invention also relates to compositions comprising at least one 4-Pyridinonetriazine Derivative, and methods of using the 4-Pyridinonetriazine Derivatives for treating or preventing HIV infection in a subject.
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Page/Page column 30; 31
(2014/07/08)
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- Use of NK-1 receptor antagonists in pruritus
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The invention relates to methods for treating pruritus with an NK-1 receptor antagonist. The invention further relates to pharmaceutical compositions comprising NK-1 receptor antagonist.
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Page/Page column 6; 7
(2014/12/12)
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- Palladium-catalyzed aryl C-H olefination with unactivated, aliphatic alkenes
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Palladium-catalyzed coupling between aryl halides and alkenes (Mizoroki-Heck reaction) is one of the most popular reactions for synthesizing complex organic molecules. The limited availability, problematic synthesis, and higher cost of aryl halide precursors (or their equivalents) have encouraged exploration of direct olefination of aryl carbon-hydrogen (C-H) bonds (Fujiwara-Moritani reaction). Despite significant progress, the restricted substrate scope, in particular noncompliance of unactivated aliphatic olefins, has discouraged the use of this greener alternative. Overcoming this serious limitation, we report here a palladium-catalyzed chelation-assisted ortho C-H bond olefination of phenylacetic acid derivatives with unactivated, aliphatic alkenes in good to excellent yields with high regio- and stereoselectivities. The versatility of this operationally simple method has been demonstrated through drug diversification and sequential C-H olefination for synthesizing divinylbenzene derivatives.
- Deb, Arghya,Bag, Sukdev,Kancherla, Rajesh,Maiti, Debabrata
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supporting information
p. 13602 - 13605
(2015/02/05)
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- Synthesis, crystal structure, anti-inflammatory and anti-hyperglycemic activities of novel 3,4-disubstituted 1,2,4-triazol-5(4H)-one derivatives
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A new series of 3,4-disubstituted 1,2,4-triazol-5(4H)-one 5a-r, bearing various methoxyphenyl, fluorophenyl, tolyl and phenyl groups, was synthesized by the dehydrocyclization of hydrazinecarboxamides 4a-r by refluxing in a 2 N sodium hydroxide solution. Hydrazinecarboxamides 4a-r was synthesized via the condensation of the corresponding aralkanoic acid hydrazides, 3a-g, with fluoro-, tolyl- and methoxyphenylisocyanates. The newly synthesized compounds (5ar) were characterized by IR, 1H NMR and 13C NMR analyses. The structure of one compound 5a was determined by single crystal X-ray diffraction analysis. All of the synthesized compounds were screened for their anti-inflammatory and anti-diabetic (α-glucosidase and α-amylase inhibition) activity to identify new drugs that might be useful in preventing damage related to diabetes and inflammation. Compounds 5j, 5k and 5m decrease the expression of type II collagen in a dose dependent manner; similarly 5l decrease the COX-2 expression of rabbit articular chondrocytes in a dose dependent manner possessing potent anti-inflammatory potential while some of derivatives including 5c, 5e, 5g and 5h cause inflammation. Meanwhile, excellent α-glucosidase and moderate α-amylase inhibitory profiles against carbohydrate modulating enzymes were demonstrated by compounds 5b, 5f, 5k and 5q compared to the reference standard acarbose, and compounds 5g, 5h, 5i, 5j, 5l and 5o exhibited moderate to low enzyme inhibition potential among the series.
- Saleem, Muhammad,Yu, Seon-Mi,Rafiq, Muhammad,Kim, Song-Ja,Seo, Sung-Yum,Lee, Ki Hwan
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p. 810 - 823
(2015/04/14)
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- Pd(ii)-catalyzed decarboxylative acylation of phenylacetamides with α-oxocarboxylic acids via C-H bond activation
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A palladium-catalyzed decarboxylative acylation of phenylacetamides with α-oxocarboxylic acids via C-H bond activation is described. This protocol provides efficient access to a range of ortho-acyl phenylacetamides, which can be easily converted to 3-isochromanone derivatives. The Royal Society of Chemistry 2013.
- Park, Jihye,Kim, Minyoung,Sharma, Satyasheel,Park, Eonjeong,Kim, Aejin,Lee, Sang Hwi,Kwak, Jong Hwan,Jung, Young Hoon,Kim, In Su
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supporting information
p. 1654 - 1656
(2013/03/14)
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- Metal-free aerobic oxidation of benzazole derivatives
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2-Benzyl benzothiazoles and benzimidazoles are easily oxidized under air and basic conditions to give the corresponding ketones in good yields. The use of palladium acetate as a catalyst has little effect and even gives, in some cases, much lower yields.
- Dos Santos, Aurelie,El Kaim, Laurent,Grimaud, Laurence
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supporting information
p. 3282 - 3287
(2013/06/05)
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- Design, synthesis and biological evaluation of novel 3,4,5-trisubstituted aminothiophenes as inhibitors of p53-MDM2 interaction. Part 2
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Five series of novel 3,4,5-trisubstituted aminothiophene derivatives and analogs were designed and synthesized based on our previous studies. All target compounds were evaluated for their p53-MDM2 binding inhibitory activities and anti-proliferation activities against A549 and PC3 tumor cell lines. Twelve compounds displayed comparable p53-MDM2 binding inhibitory activities to that of Nutlin-3. Among them, compound 7a exhibited marked binding affinity (IC 50 = 0.086 μM). In addition, most target compounds showed potent anti-proliferation activities with IC50 values at low micromolar level. A good selective profile for wild-type p53 expression cell line was also observed. Molecular docking analysis was performed as well to predict possible binding modes of target compounds with MDM2.
- Wang, Weisi,Lv, Dan,Qiu, Ni,Zhang, Lei,Hu, Chunqi,Hu, Yongzhou
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p. 2886 - 2894
(2013/06/27)
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- An efficient large-scale synthesis of a naphthylacetic acid CRTH2 receptor antagonist
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An efficient and practical synthesis of a naphthylacetic acid CRTH2 receptor antagonist is reported. Michael addition of ethyl t-butyl malonate to an allenoate afforded a triester, which was selectively hydrolyzed and decarboxylated to give a benzylidenepentanedioic acid monoester. Treatment of this compound with potassium acetate and acetic anhydride produced the naphthylacetate core. The triflate of the key building block was coupled with a zinc reagent of the side chain under improved Negishi coupling conditions to afford the target product. The process was successfully scaled up to produce over 2 kg of the API.
- Shu, Lianhe,Wang, Ping,Gu, Chen,Liu, Wen,Alabanza, Lady Mae,Zhang, Yingchao
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p. 651 - 657
(2013/06/27)
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- α-Diazo-β-ketonitriles: Uniquely reactive substrates for arene and alkene cyclopropanation
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An investigation of the intramolecular cyclopropanation reactions of α-diazo-β-ketonitriles is reported. These studies reveal that α-diazo-β-ketonitriles exhibit unique reactivity in their ability to undergo arene cyclopropanation reactions; other similar acceptor-acceptor- substituted diazo substrates instead produce mixtures of C-H insertion and dimerization products. α-Diazo-β-ketonitriles also undergo highly efficient intramolecular cyclopropanation of tri- and tetrasubstituted alkenes. In addition, the α-cyano-α-ketocyclopropane products are demonstrated to serve as substrates for SN2, SN2′, and aldehyde cycloaddition reactions.
- Nani, Roger R.,Reisman, Sarah E.
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supporting information
p. 7304 - 7311
(2013/06/27)
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- USE OF THE AMINOALKYLINDOLE JWH-073-M4 AND RELATED COMPOUNDS AS NEUTRAL CB1 RECPTOR ANTAGONISTS FOR THE TREATMENT OF ALCOHOLISM, DRUG ABUSE, OBESITY, AND OBESITY-RELATED DISEASES
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Novel alkylindoles that bind tightly to cannabinoid receptors and are neutral antagonists for the cannabinoid 1 receptor and agonists for the cannabinoid 2 receptor are provided. These compounds are useful for treating alcoholism and drug abuse and for treating obesity.
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Page/Page column 52; 53
(2013/07/25)
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- Direct conversion of N -alkoxyamides to carboxylic esters through tandem nbs-mediated oxidative homocoupling and thermal denitrogenation
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Treatment of N-alkoxyamides with NBS in toluene was found to conveniently afford the corresponding carboxylic esters, including those bearing a bulky or long-chain substituent, in satisfactory to excellent yields. This approach not only represents a convenient and economic approach to a direct transformation of an alkoxyamide moiety into the carboxylic ester functional group, via oxidative homocoupling and the subsequent thermal denitrogenation, but also facilitates the synthesis of sterically hindered carboxylic esters.
- Zhang, Ningning,Yang, Rui,Zhang-Negrerie, Daisy,Du, Yunfei,Zhao, Kang
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p. 8705 - 8711
(2013/09/24)
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- Vaulted biaryls in catalysis: A structure-activity relationship guided tour of the immanent domain of the VANOL ligand
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The active site in the BOROX catalyst is a chiral polyborate anion (boroxinate) that is assembled in situ from three equivalents of B(OPh) 3 and one of the VANOL ligand by a molecule of substrate. The substrates are bound to the boroxinate by Hbonds to oxygen atoms O1-O3. The effects of introducing substituents at each position of the naphthalene core of the VANOL ligand are systematically investigated in an aziridination reaction. Substituents in the 4,4′- and 8,8′-positions have a negative effect on catalyst performance, whereas, substituents in the 7- and 7′-positions have the biggest impact in a positive direction. VANOL destination: The active site in the BOROX catalyst is a chiral polyborate anion (boroxinate; see figure) that is assembled in situ from three equivalents of B(OPh)3 and one of the VANOL ligand by a molecule of substrate. The effects of introducing substituents at each position of the naphthalene core of the VANOL ligand are systematically investigated in an aziridination reaction. Copyright
- Guan, Yong,Ding, Zhensheng,Wulff, William D.
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supporting information
p. 15565 - 15571
(2013/11/19)
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- Discovery of 4,6-substituted-(diaphenylamino)quinazolines as potent c-Src inhibitors
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A series of 4,6-substituted-(diaphenylamino)quinazolines as c-Src inhibitors have been prepared and their biological activity has also been evaluated. All the compounds displayed potential antiproliferation activities, with IC50 values ranging from 3.42 μM to 118.81 μM in five human tumor cell lines. Particularly, compound 15 exhibited higher cytotoxicity against the tested five tumor cell lines compared to the other small molecules. Generally, most of these compounds showed selectivity between the A549 cells and the other four cells, according to their corresponding IC50 values. The results obtained from the in vitro enzyme assay indicated compound 15 has remarkable inhibitory activity against c-Src kinase with an IC50 value of 27.3 nM, which is comparable to the control compounds. Furthermore, molecular docking and QSAR study by means of DS 3.5 (Discovery Studio 3.5, Accelrys, Co. Ltd) explored the binding modes and the structure and activity relationship (SAR) of these derivatives.
- Li, Jing-Ran,Li, Dong-Dong,Fang, Fei,Du, Qian-Ru,Lin, Lin,Sun, Jian,Qian, Yong,Zhu, Hai-Liang
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p. 8375 - 8386
(2013/12/04)
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- Design, synthesis, and evaluation of substituted 6-amide-4- anilinoquinazoline derivatives as c-Src inhibitors
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The 4-anilinoquinazoline scaffold has been historically used for designing EGFR/VEGFR/HER2 inhibitors while it has not been reported widely for developing c-Src inhibitors. Thus, a series of novel 4-anilinoquinazoline derivatives grafting different amide moieties at the 6-position were designed and synthesized as potential inhibitors for c-Src. In this manuscript, all of the designed compounds were screened via molecular docking using Discovery Studio 3.5 software. As expected, the results of the docking study revealed that most of these targeted compounds possessed lower binding energy than the positive control Saracatinib. Subsequently, all of the screened compounds were synthesized and evaluated for their c-Src in vitro inhibitory activities and in vitro antiproliferation assays against four human cancer cells (A549, MCF-7, HepG-2, HeLa). Among these compounds, 24 exhibited the most potent inhibitory activity against c-Src kinase as well as at the cellular level, of which the IC50 value reached up to 2.9 nM, comparable to the positive compound Saracatinib. Kinase selectivity profile also demonstrated that compound 24 showed good selectivity over several close kinase targets. These results, along with relative 3D-QSAR study, could provide an important basis for further development of compound 24 as a potent tyrosine kinase inhibitor.
- Fang, Fei,Li, Dong-Dong,Li, Jing-Ran,Sun, Jian,Du, Qian-Ru,Gong, Hai-Bin,Zhu, Hai-Liang
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p. 26230 - 26240
(2013/12/04)
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- Asymmetric hydrogenation of α- Or β-acyloxy α,β- unsaturated phosphonates catalyzed by a Rh(i) complex of monodentate phosphoramidite
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The Rh(i) complex of a monodentate phosphoramidite bearing a primary amine moiety (DpenPhos) has been disclosed to be highly efficient for the asymmetric hydrogenation of a variety of α- or β-acyloxy α,β- unsaturated phosphonates, providing the corresponding biologically important chiral α- or β-hydroxy phosphonic acid derivatives with excellent enantioselectivities (90->99% ee).
- Zhang, Jinzhu,Dong, Kaiwu,Wang, Zheng,Ding, Kuiling
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supporting information; scheme or table
p. 1598 - 1601
(2012/03/22)
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- Design, synthesis and anti-itch activity evaluation of aromatic amino acid derivatives as gastrin-releasing peptide receptor antagonists
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Eight aromatic amino acid derivatives (9a-9h) as gastrin-releasing peptide receptor (GRPR) antagonists were designed and synthesized. For the design, the tertiary structure of GRPR was predicted by blast searching in the premise of 1u19 protein as the template. Eight target compounds were docked into the binding pocket to investigate their possible binding interactions. Their anti-itch activities were tested by intrathecal injection using Kunming mice as experimental animals and chloroquine phosphate as a modeling medium. Compounds 9e and 9f significantly inhibited scratching behaviors. The anti-itch activities of these compounds decreased with the following sequence: 9e > 9f = 9d > 9b > 9g > 9a > 9h > 9c predicted by computer-aided drug design (CADD) and 9e > 9f > 9b > 9h > 9g > 9d > 9a > 9c evaluated by preliminary test. They were broadly in line with activity order pretested by CADD. It showed that the predicted tertiary structure of GRPR could be used for antipruritic drug design.
- Yao, Ri-Sheng,Li, Ting-Ting,Xu, Jun,Jiang, Lai-En,Ruan, Ban-Feng
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p. 865 - 873
(2012/10/29)
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- Hypervalent iodine catalyzed hofmann rearrangement of carboxamides using oxone as terminal oxidant
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Hofmann rearrangement of carboxamides to carbamates using Oxone as an oxidant can be efficiently catalyzed by iodobenzene. This reaction involves hypervalent iodine species generated in situ from catalytic amount of PhI and Oxone in the presence of 1,1,1,3,3,3-hexafluoroisopropanol (HFIP) in aqueous methanol solutions. Under these conditions, Hofmann rearrangement of various carboxamides affords corresponding carbamates in high yields.
- Yoshimura, Akira,Middleton, Kyle R.,Luedtke, Matthew W.,Zhu, Chenjie,Zhdankin, Viktor V.
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p. 11399 - 11404
(2013/02/23)
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- Synthesis of novel 2-[4-(4-substitutedbenzamido/phenylacetamido) phenyl]benzothiazoles as antimicrobial agents
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A new series of 2-[4-(4-substitutedbenzamido/ phenylacetamido)phenyl] benzothiazole derivatives (6a-k) were synthesized and evaluated for antibacterial and antifungal activities against Staphylococcus aureus, Bacillus subtilis, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Escherichia coli with their drug-resistant isolates and a yeast Candida albicans. Microbiological results indicated that the compounds possessed a broad spectrum of activity against the tested microorganisms at minimum inhibitory concentration (MIC) values between 100 and 6.25 lg/ml. Compounds 6d and 6k exhibited significant antibacterial activity showing 6.25 lg/ml MIC values against drugresistant S. aureus and P. aeruginosa isolates, respectively. Springer Science+Business Media, LLC 2011.
- Bolelli, Kayhan,Yalcin, Ismail,Ertan-Bolelli, Tugba,?zgen, Selda,Kaynak-Onurdag, Fatma,Yildiz, Ilkay,Aki, Esin
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p. 3818 - 3825
(2013/02/23)
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- Deracemization of α-aryl hydrocoumarins via catalytic asymmetric protonation of ketene dithioacetals
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An unprecedented catalytic asymmetric protonation of ketene dithioacetals is described. Various racemic α-aryl hydrocoumarin derivatives are transformed into enantioenriched dithioacetal-protected hydrocoumarins in the presence of a chiral Br?nsted acid catalyst. A newly developed phosphoric acid, featuring the 3,5-bis(pentafluorothio)phenyl (3,5-(SF5) 2C6H3) substituent, is introduced. The obtained products can be easily converted into either hydrocoumarins or the corresponding chromans via simple hydrolysis or hydrogenation, respectively.
- Lee, Ji-Woong,List, Benjamin
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supporting information
p. 18245 - 18248
(2013/01/15)
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- ACYLTHIOUREA COMPOUND OR SALT THEREOF, AND USE THEREOF
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To provide an antitumor agent which exhibits excellent c-Met inhibitory effect and mitigates side effects by virtue of selectively affecting to tumor cells in which c-Met is specifically expressed. The invention provides an acylthiourea compound represent
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Page/Page column 11; 12
(2011/02/26)
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- Synthesis, biological evaluation and molecular docking studies of 1,3,4-thiadiazole derivatives containing 1,4-benzodioxan as potential antitumor agents
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A series of 1,3,4-thiadiazole derivatives containing 1,4-benzodioxan (2a-2s) have been synthesized to screen for FAK inhibitory activity. Compound 2p showed the most potent biological activity against HEPG2 cancer cell line (EC50 = 10.28 μg/mL
- Sun, Juan,Yang, Yu-Shun,Li, Wei,Zhang, Yan-Bin,Wang, Xiao-Liang,Tang, Jian-Feng,Zhu, Hai-Liang
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scheme or table
p. 6116 - 6121
(2011/10/31)
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- COMPOUNDS AND METHOD FOR TREATMENT OF HIV
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The invention relates to a compound of Formulae I and/or II: Formula I Formula II and/or a pharmaceutically-acceptable salt, hydrate, solvate, tautomer, optical isomer, E-isomer, Z-isomer, or combination thereof; X is selected from Se, N-OH, NH, NO2
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Page/Page column 70-71
(2011/10/13)
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- Structural diversity-guided convenient construction of functionalized polysubstituted butenolides and lactam derivatives
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A molecular diversity-oriented convenient access to multi-substituted butenolides and lactam scaffolds via four different methods from various phenylacetic acid derivatives is described. The target molecules have been identified on the basis of analytical spectra data, and are useful synthons in the fields of medicine and agrochemicals.
- Ke, Shaoyong,Zhang, Ya-Ni,Shu, Wenming,Zhang, Zhigang,Shi, Liqiao,Liang, Ying,Wang, Kaimei,Yang, Ziwen
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experimental part
p. 1071 - 1079
(2012/03/12)
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- Process development and pilot-scale synthesis of new cyclization conditions of substituted phenylacetamides to tetrahydroisoquinoline-2-ones using Eaton's reagent
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Tetrahydroisoquinoline is a ubiquitous structural framework presented in numerous pharmacologically relevant molecules. Although accessible by the Pictet-Spengler cyclization, conditions commonly used for such cyclizations are often difficult to implement on scale. Herein, we report the development of a scaleable approach utilizing Eaton's reagent for the cyclization of substituted phenylacetamide analogues to tetrahydroisoquinoline-2-one. The development, optimization, and safety hazard evaluations, which outline the benefits and ease of workup of this new process, are discussed.
- Ulysse, Luckner G.,Yang, Qiang,McLaws, Mark D.,Keefe, Daniel K.,Guzzo, Peter R.,Haney, Brian P.
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experimental part
p. 225 - 228
(2010/04/29)
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- NAPHTHYLACETIC ACIDS
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The invention is concerned with the compounds of formula I: and pharmaceutically acceptable salts and esters thereof, wherein W, X, Y, and R1-R7 are defined in the detailed description and claims. In addition, the present invention relates to methods of manufacturing and using the compounds of formula I as well as pharmaceutical compositions containing such compounds. The compounds of formula I are antagonists or partial agonists at the CRTH2 receptor and may be useful in treating diseases and disorders associated with that receptor such as asthma.
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Page/Page column 32
(2010/06/13)
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- Synthesis and PGE2 production inhibition of 1H-furan-2,5-dione and 1H-pyrrole-2,5-dione derivatives
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3,4-Diphenyl-substituted 1H-furan-2,5-dione and 1H-pyrrole-2,5-dione derivatives were synthesized and evaluated for the inhibitory activities on LPS-induced PGE2 production in RAW 264.7 macrophage cells. Both 1H-furan-2,5-dione and 1H-pyrrole-2,5-dione rings as main scaffolds were easily obtained using one of three synthetic methods. Among the compounds investigated, 1H-3-(4-sulfamoylphenyl)-4-phenyl-pyrrole-2,5-dione (6l) showed a strong inhibitory activity (IC50 = 0.61 μM) of PGE2 production.
- Moon, Jong Taik,Jeon, Ji Young,Park, Hang Ah,Noh, Young-Soo,Lee, Kyung-Tae,Kim, Jungahn,Choo, Dong Joon,Lee, Jae Yeol
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scheme or table
p. 734 - 737
(2010/06/22)
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