- Fused Pyridine Derivatives from the Wittig Reaction of some Fluorinated Amides
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Compound 2 reacted with phosphorane 3 (R = Et) giving the quinoline derivative 5 whereas thiophenes 7 and 9 gave enamines 8 and 10 respectively with the appropriate phosphorane 3 (R = Me or Et).Pyridine derivative 11 yielded only ethyl 2-aminonicotinate with phosphorane 3 (R = Et).Compounds 8 and 10 gave the fused pyridine derivatives 14 and 15 respectively.
- Latham, Elliot J.,Murphy, Steven M.,Stanforth, Stephen P.
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Read Online
- 9- and 11-substituted 4-azapaullones are potent and selective inhibitors of African trypanosoma
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Trypanosomes from the "brucei" complex are pathogenic parasites endemic in sub-Saharan Africa and causative agents of severe diseases in humans and livestock. In order to identify new antitrypanosomal chemotypes against African trypanosomes, 4-azapaullone
- Maiwald, Franziska,Benítez, Diego,Charquero, Diego,Dar, Mahin Abad,Erdmann, Hanna,Preu, Lutz,Koch, Oliver,H?lscher, Christoph,Loa?c, Nadège,Meijer, Laurent,Comini, Marcelo A.,Kunick, Conrad
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- SYNTHESIS, X-RAY STRUCTURE ANALYSIS, AND VIBRATIONAL SPECTRAL STUDIES OF 1-(3-((6-BROMOPYRIDO[2,3-d]PYRIMIDIN-4-YL) OXY)PHENYL)-3-CYCLOPENTYLUREA
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Abstract: A new pyrido[2,3-d]pyrimidine derivative 1-(3-((6-bromopyrido[2,3-d]pyrimidin-4-yl)oxy)phenyl)-3-cyclopentylurea is designed and synthesized. The final structure is characterized by 1H, 13C, and 2D NMR, MS, FTIR. In addition, the crystal structure of the title compound is determined by X-ray diffraction. With the 6-311G(2d,p) basis set, the molecule is further explored using density functional theory (DFT) by the B3LYP method. The final results show that the DFT optimized structure of the title molecule is consistent with the crystal structure determined by X-ray diffraction. The Hirshfeld surface analysis and the 2D fingerprint plot are given to support the quantitative analysis of intermolecular interactions and contacts generated by supramolecular accumulation in crystals. The interactions of the title molecule are analyzed by the natural bond orbital analysis. Finally, the molecular electrostatic potential and frontier molecular orbitals are further investigated using DFT. [Figure not available: see fulltext.]
- Huang, Z.-Y.,Liu, C.-J.,Luo, R.-S.,Mao, S.-N.,Zhou, Z.-X.
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- Synthesis, crystal structure, and DFT study of a new pyrido[2,3-d]pyrimidine compound 1-(4-((6-bromopyrido[2,3-d]pyrimidin-4-yl)oxy) phenyl)-3-(2,4-difluorophenyl)urea
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In this study, 1-(4-((6-bromopyrido[2,3-d]pyrimidin-4-yl)oxy)phenyl)-3- (2,4-difluorophenyl) urea was synthesized. The structure of the compound was determined by mass spectrometry and 1H NMR, 13C NMR and FT-IR spectroscopy. The solid-state structure of the title compound was determined using single-crystal X-ray diffraction and the optimized molecular structure was determined using density functional theory calculations. The conformation of the most stable isomer that was calculated at room temperature was consistent with the conformation derived from X-ray diffraction. Hirshfeld surface analysis and 2D fingerprints were used to quantitatively analyze the intermolecular interactions and contacts in the crystal structure.
- Chai, Huifang,Deng, Liyuan,Hu, Weiyin,Liao, Tianhui,Sun, Hong,Wang, Zhongyuan,Zhao, Chunshen,Zhao, Xin,Zhou, Zhixu
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- Pyrido[2,3-d]pyrimidine compound as well as preparation method and application thereof
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The present invention discloses a pyrido[2,3-d]pyrimidine compound represented by a general formula I or a pharmaceutically acceptable salt thereof. The general formula I is shown as the specification, wherein R1 is selected from one of an alkylamine group of C1-C6, an alicyclic amine group of C1-C6, a heterocyclic amine group of C1-C6, and an aromatic amine group of C6-C8, and X represents a hydrogen atom or a halogen atom. According to the invention, in-vitro cell activity tests prove that the compound provided by the invention has antitumor activity and can be used for preparing medicines for treating and/or preventing various cancers caused by BRaf kinase mutation, such as melanoma, thyroid cancer, breast cancer, liver cancer, kidney cancer, colorectal cancer, pancreatic cancer, ovarian cancer, etc.
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Paragraph 0085-0086
(2021/01/12)
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- Synthesis and antitumor activity of novel pyridino[2,3-d]pyrimidine urea derivatives
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A series of novel N-(3-((6-bromopyrido[2,3-d]pyrimidin-4-yl)oxy)phenyl)pyrrolidine-1-carboxamide and 1-(3-((6-bromopyrido[2,3-d]pyrimidin-4-yl)oxy)phenyl)-3-propylurea derivatives were synthesized. Their antitumor activities against human breast carcinoma cells (MCF-7) and human colon cancer cells (HCT-116) in vitro were evaluated, using sorafenib as a positive control drug. Anticancer bioassays indicated that several compounds exhibited appreciable anticancer activity against MCF-7 and HCT-116 cells. Particularly, compounds 9g and 8b demonstrated the most significant inhibitory effect against HCT-116 and MCF-7 cells, with inhibition ratios of 25.56% and 26.46%, respectively. Additionally, the synthesized pyridine[2,3-d]pyrimidine derivatives containing a urea group moieties exhibited antitumor activities against MCF-7 and HCT-116 cells in vitro.
- Chen, Dongmei,Chen, Yumei,Yang, Di,Zheng, Zhaopeng,Zhou, Zhixu
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p. 1628 - 1636
(2021/05/19)
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- Synthesis, Crystal Structure, and DFT Study of a New Derivative of Pyrido[2,3-d]pyrimidine
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Abstract: N-{4-[(6-bromopyrido[2,3-d]pyrimidin-4-yl)oxy]phenyl}morpholine-4-carboxamide has been synthesized as a derivative of pyrido[2,3-d]pyrimidine that demonstrates antitumor, antibacterial, anti-inflammatory, and antimicrobial activities. Synthesis of the target compound based on 2-aminonicotinic acid as the starting material has included its esterification, bromination, cyclization, and substitution reactions. Structure of the product is confirmed by 1H and 13C NMR, FT-IR, and single-crystal X-ray diffraction (XRD). The optimized structure, electrostatic potential and frontier molecular orbitals (FMO) of the compound have been approached by DFT calculations. The compound demonstrates antiproliferative activity on A375 cells.
- Deng, Liyuan,Hu, Weiyin,Liao, Wanpeng,Pan, Hongyan,Sun, Hong,Zhou, Zhixu
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p. 2489 - 2496
(2022/01/22)
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- Access to pyridines via cascade nucleophilic addition reaction of 1,2,3-triazines with activated ketones or acetonitriles
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We studied the cascade nucleophilic addition reactions of 1,2,3-triazines with activated acetonitriles or ketones, which were used to construct highly substituted pyridines that are not easily accessed by conventional methods. The strategy addressed some structural diversity issues currently facing medicinal chemistry, and the resulting pyridines could be used as convenient precursors for the synthesis of related pharmaceuticals. In particular, our method was applied to the syntheses of the marketed drug etoricoxib and several biologically important molecules in a few steps.
- Zhang, Yuan,Luo, Han,Lu, Qixing,An, Qiaoyu,Li, You,Li, Shanshan,Tang, Zongyuan,Li, Baosheng
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supporting information
p. 393 - 396
(2020/05/18)
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- Synthesis method and applications of polysubstituted 2-aminopyridine derivative
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The invention belongs to the field of organic synthetic chemistry, and relates to a synthetic method and applications of a polysubstituted 2-aminopyridine derivative. According to the method, a 1,2,3-triazine compound and a cyanomethyl compound are used as substrates and are subjected to a one-step cycloaddition reaction under an alkaline condition to obtain a polysubstituted 2-aminopyridine derivative, wherein the reaction does not involve in danger and control reagents and medicines, and a simple, safe, efficient and environment-friendly strategy is provided for synthesizing the polysubstituted 2-aminopyridine derivative. According to the present invention, the obtained product is subjected to further derivatization, such that the active molecule or the drug molecule containing the 2-aminopyridine structure can be synthesized, such as active molecule SC-53606, drug molecule apatinib and nevirapine.
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Paragraph 0048-0050
(2020/04/22)
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- PROCESS FOR THE CATALYTIC DIRECTED CLEAVAGE OF AMIDE-CONTAINING COMPOUNDS
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The present invention relates to a catalytic method for the conversion of amide-containing compouds by means of a build-in directing group and upon the action of a heteronucleophilic compound (in se an amine (RNH2 or RNHR') or an alcohol (ROH) or a thiol (RSH)) in the presence of a metal catalyst to respectively esters, thioesters, carbonates, thiocarbonates and to what is defined as amide-containing compounds (such as carboxamides, urea, carbamates, thiocarbamates). The present invention also relates to these amide-containing compounds having a build-in directing group (DG), as well as the use of such directing groups in the catalytic directed cleavage of N-DG amides with the use of heteronucleophiles (in se an amine (RNH2 or RNHR') or an alcohol (ROH) or thiol (RSH)).
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Page/Page column 51; 53
(2017/04/11)
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- HETEROCYCLIC COMPOUNDS USEFUL AS PDK1 INHIBITORS
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The present invention provides compounds useful as inhibitors of PDK1. The present invention also provides compositions thereof, and methods of treating PDK1-mediated diseases.
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Page/Page column 101;
(2016/10/08)
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- P2X3 AND/OR P2X2/3 COMPOUNDS AND METHODS
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The present application provides novel compounds and methods for preparing and using these compounds. In one embodiment, the compounds are of the structure of formula (I), wherein R1-R4 are defined herein. In a further embodiment, these compounds are useful in method for regulating one or both of the P2X3 or P2X2/3 receptors. In another embodiment, these compounds are useful for treating pain in patients by administering one or more of the compounds to a patient.
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Paragraph 0239; 0240; 0241
(2015/07/07)
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- 2,4-DIARYL - SUBSTITUTED [1,8] NAPHTHYRIDINES AS KINASE INHIBITORS FOR USE AGAINST CANCER
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The present invention relates to novel [1,8]naphthyridine derivatives of formula (I) and to the use of such compounds in which the inhibition, regulation and/or modulation of signal transduction by ATP consuming proteins like kinases plays a role, particu
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Paragraph 0271; 0272; 0273
(2013/05/08)
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- Facile assembly of two 6-membered fused N-heterocyclic rings: A rapid access to novel small molecules via Cu-mediated reaction
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A rapid, versatile and one-pot Cu-mediated domino reaction has been developed for facile assembly of two six membered fused N-heterocyclic rings leading to novel small molecules as potential inhibitors of PDE4. The Royal Society of Chemistry.
- Adepu, Raju,Sunke, Rajnikanth,Meda, Chandana L. T.,Rambabu,Krishna, G. Rama,Reddy, C. Malla,Deora, Girdhar Singh,Parsa, Kishore V. L.,Pal, Manojit
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supporting information
p. 190 - 192
(2013/02/22)
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- Highly efficient one-pot amination of carboxylate-substituted nitrogen-containing heteroaryl chlorides via Staudinger reaction
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An efficient one-pot method for the synthesis of tert-butyl 6-aminonicotinate (5) is described. The key transformation involves displacement of the chloro group in tert-butyl 6-chloronicotinate (2) with azide followed by a Staudinger reaction. The scope of this methodology is further extended for the synthesis of a series of carboxylate-substituted heteroaryl amines. In particular, we synthesized tert-butyl carboxylate-substituted amino-pyridine, -pyridazine, and -pyrazine. In addition to one-pot conversion, short reaction time, simplicity of operation, ease of purification, and good yields are the key advantages of this methodology.
- Kandalkar, Sachin R.,Kaduskar, Rahul D.,Ramaiah, Parimi Atchuta,Barawkar, Dinesh A.,Bhuniya, Debnath,Deshpande, Anil M.
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supporting information
p. 414 - 418
(2013/02/23)
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- 2,4- DIARYL-SUBSTITUTED [1,8] NAPHTHYRIDINES AS KINASE INHIBITORS FOR USE AGAINST CANCER
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The present invention relates to novel [1,8]naphthyridine derivatives of formula (I) and to the use of such compounds in which the inhibition, regulation and/or modulation of signal transduction by ATP consuming proteins like kinases playsa role, particularly to inhibitors of TGF-beta receptor kinases, and to the use of such compounds for the treatment of kinase-induced diseases, in particular for the treatment of tumors
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Page/Page column 73
(2012/01/14)
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- Anthranilic acid-based inhibitors of phosphodiesterase: Design, synthesis, and bioactive evaluation
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Our previous studies identified two 2-benzoylaminobenzoate derivatives 1, which potently inhibited superoxide (O2-) generation induced by formyl-l-methionyl-l-leucyl-l-phenylalanine (FMLP) in human neutrophils. In an attempt to improve their activities, a series of anthranilic acid derivatives were synthesized and their anti-inflammatory effects and underlying mechanisms were investigated in human neutrophils. Of these, compounds 17, 18, 46, 49, and 50 showed the most potent inhibitory effect on FMLP-induced release of O2- in human neutrophils with IC50 values of 0.20, 0.16, 0.15, 0.06, and 0.29 μM, respectively. SAR analysis showed that the activities of most compounds were dependent on the ester chain length in the A ring. Conversely, a change in the linker between the A and B ring from amide to sulfonamide or N-methyl amide, as well as exchanges in the benzene rings (A or B rings) by isosteric replacements were unfavorable. Further studies indicated that inhibition of O2- production in human neutrophils by these anthranilic acids was associated with an elevation in cellular cAMP levels through the selective inhibition of phosphodiesterase 4. Compound 49 could be approved as a lead for the development of new drugs in the treatment of neutrophilic inflammatory diseases.
- Cheng, Yih-Dih,Hwang, Tsong-Long,Wang, Han-Hsiang,Pan, Tai-Long,Wu, Chin-Chung,Chang, Wen-Yi,Liu, Yi-Ting,Chu, Tzu-Chi,Hsieh, Pei-Wen
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experimental part
p. 7113 - 7125
(2011/11/04)
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- IMIDAZO [1, 2 -A] PYRIDINES AS JNK MODULATORS
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Compounds of formula (I) modulate JNK wherein X1 and X2 are each simultaneously N or CH; X3 is CH-R2 Or N-SO2R, where R is lower alkyl; R1 is aryl or heteroaryl, substituted with 0-3 lower
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Page/Page column 26
(2010/09/17)
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- PYRIDAZINONE DERIVATIVE AND PDE INHIBITOR CONTAINING THE SAME AS ACTIVE INGREDIENT
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It is to provide a novel pyridazinone derivative represented by the following general formula (1), which is useful as a pharmaceutical and has a phosphodiesterase inhibitory action: wherein R1 represents H or C1-6 alkyl, each of R2 and R3 represents H, X, C1-6 alkoxy, Z represents O or S, and A represents AA or BB, wherein AA represents: and BB represents: wherein R4 represents H or C1-6 alkyl, and each of R5 and R6 represents C1-6 alkyl.
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Page/Page column 79-80
(2010/04/25)
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- PYRAZOLONE DERIVATIVE AND PDE INHIBITOR CONTAINING THE SAME AS ACTIVE INGREDIENT
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It is to provide a novel pyrazolone derivative represented by the following general formula (1), which is useful as a pharmaceutical and has a phosphodiesterase inhibitory action: wherein R1,R2: C1-6 alkyl; R3,R4: H, X, C1-6 alkoxy; Z:O, S; A:AA, BB, wherein AA represents wherein BB represents wherein R5: H, C1-6 alkyl ; R6,R7: C1-6 alkyl.
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Page/Page column 66
(2010/04/25)
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- BENZISOXAZOLE COMPOUND
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Disclosed is a compound represented by the general formula (I) or a salt thereof: wherein any one of R1, R2 and R3 represents a group represented by the formula: -(CH2)m-NR11R12 (wherein m is 1 or 2; and R11 and R12 independently represent a hydrogen atom or a C1-6 alkyl group or may, together with a nitrogen atom to which R11 and R12 are bound, form a 4- or 5-membered cyclic group); the remaining two or R1, R2 and R3 independently represent a group represented by the formula: -(O)n-R21 (wherein n is 0 or 1; and R21 represents a hydrogen atom, a C1-6 alkyl group, a C2-6 alkenyl group, a C2-6 alkynyl group, or the like); and R4 represents a C1-6 alkyl group which may have a substituent or the like.
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Page/Page column 155
(2009/02/10)
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- NOVEL JNK INHIBITORS
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Disclosed are substituted imidazo[1,2-a]pyridines, imidazo[1,2-a]pyrazines, imidazo[1,2-c]pyrimidines and imidazo[1,2-d]triazines compounds of the formula: (1.0) Also disclosed are methods for treating JNK1 and ERK mediated diseases using the compounds of formula 1.0.
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Page/Page column 70
(2008/12/07)
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- THERAPEUTIC AGENTS, AND METHODS OF MAKING AND USING THE SAME
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In part, the present invention is directed towards compounds with FabI inhibiting properties. Such compounds may also inhibit other enzymes, including those similar to FabI either structurally or functionally, for example, Fab K. Kits and compositions that include the disclosed compounds are also provided. Methods of treating a subject with a bacterial illness is also disclosed.
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Page/Page column 64; 134
(2008/06/13)
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- NOVEL IMIDAZO[1,2-a]PYRIDINE CANNABINOID RECEPTOR LIGANDS AND PHARMACEUTICAL COMPOSITIONS CONTAINING THEM
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The present invention relates to novel imidazo[1,2-a]pyridine cannabinoid receptor ligands, in particular cannabinoid 1 (CB1) or cannabinoid 2 (CB2) receptor ligands, and uses thereof for treating diseases, conditions and/or disorders modulate by a cannab
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Page/Page column 37
(2008/06/13)
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- Synthesis and SAR of 5-, 6-, 7- and 8-aza analogues of 3-aryl-4-hydroxyquinolin-2(1H)-one as NMDA/glycine site antagonists
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A series of 5-, 6-, 7- and 8-aza analogues of 3-aryl-4-hydroxyquinolin-2(1H)-one was synthesized and assayed as NMDA/glycine receptor antagonists. The in vitro potency of these antagonists was determined by displacement of the glycine site radioligand [3H]5,7-dicholorokynurenic acid ([3H]DCKA) in rat brain cortical membranes. Selected compounds were also tested for functional antagonism using electrophysiological assays in Xenopus oocytes expressing cloned NMDA receptor (NR) 1A/2C subunits. Among the 5-, 6-, 7-, and 8-aza-3-aryl-4-hydroxyquinoline-2(1H)-ones investigated, 5-aza-7-chloro-4-hydroxy-3-(3-phenoxyphenyl)quinolin-2-(1H)-one (13i) is the most potent antagonist, having an IC50 value of 110 nM in [3H]DCKA binding and a Kb of 11 nM in the electrophysiology assay. Compound 13i is also an active anticonvulsant when administered systemically in the mouse maximum electroshock-induced seizure test (ED50 = 2.3 mg/kg, IP).
- Zhou, Zhang-Lin,Navratil, James M.,Cai, Sui Xiong,Whittemore, Edward R.,Espitia, Stephen A.,Hawkinson, Jon E.,Tran, Minhtam,Woodward, Richard M.,Weber, Eckard,Keana, John F.W.
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p. 2061 - 2071
(2007/10/03)
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- Pyrido[2,3-d]pyrimidin-4(3H)-one derivatives and 1,2,3,4-tetrahydropyrido[2,3-d]pyrimidine derivatives: Synthesis and in vitro study of their activity against platelet aggregation
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Some new derivatives of pyrido[2,3-d]pyrimidin-4(3H)-one A and 1,2,3,4-tetrahydro-pyrido[2,3-d]pyrimidines B were prepared. The study of their in vitro antiaggregating activity showed that the compounds A possessed an inhibitory potency when aggregation w
- Hou,Gravier,Casadebaig,Dupin,Bernard,Boisseau
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p. 719 - 722
(2007/10/03)
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- SYNTHESIS OF PYRROLOQUINOLINE AND PYRROLONAPHTHYRIDINE BY AN INTRAMOLECULAR CYCLISATION REACTION
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4-methylthiopyrrolonaphthyridine and pyrroloquinoline were prepared by an intramolecular cyclisation in acidic media of 1-methylsulfinyl-1-methylthio-2-ethylene.
- Cardinaud, Isabelle,Gueiffier, Alain,Debouzy, Jean-Claude,Milhavet, Jean-Claude,Chapat, Jean-Pierre
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p. 2513 - 2522
(2007/10/02)
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- Nitrogen Bridgehead Compounds. Part 42. Cyclization of Diethyl 2-(2-Pyridylaminomethylene)-succinates and -glutarates in Ethanolic Sodium Ethoxide
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2-(Pyridylaminomethylene)-succinates (1) and -glutarates (2) were treated with ethanolic sodium ethoxide solution.The succinates (1) gave, in reversible reactions, pyridopyrimidines (3) and pyridylpyrrolinones (5), and also underwent Z-E geometric isomerization.The cyclizations (Z)-(1) to (3) and (E)-(1) to (5) were more rapid than the isomerization of (1).Thus, short (1-min) reactions starting from (Z)-(1) produced the pyridopyrimidine (3) and those from (E)-(1) the pyridylpyrrolinone (5) in good yield.Longer (15-min) reactions yielded equilibrium mixtures, consisting mainly of pyridylpyrrolinones (5).Substituents at position 6 of the pyridine ring inhibited the formation of the pyridopyrimidines, whereas those at position 3 hindered or inhibited the formation of the pyridylpyrrolinones.The unsubstituted glutarate (2a) formed the pyridopyrimidine (4a) whereas the 6-substituted ones did not yield any cyclic product.Results of the sodium ethoxide ring closure were compared with those of the previously studied POCl3 - PPA and thermal cyclizations.
- Vasvari-Debreczy, Lelle,Hermecz, Istvan,Meszaros, Zoltan
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p. 1799 - 1804
(2007/10/02)
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