- Design, Synthesis, and Mechanism of Antiviral Acylurea Derivatives Containing a Trifluoromethylpyridine Moiety
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Novel acylurea derivatives 7a-7ab were designed and synthesized by linking the active substructures trifluoromethylpyridine and anthranilic diamide via an acylurea bridge. Most of the title compounds exhibited good activity against tobacco mosaic virus (TMV), particularly compound 7x (EC50 of 211.8 μg/mL), which showed much higher curative activity than ningnanmycin (EC50 of 389.8 μg/mL), and compound 7ab, which showed excellent inactivation activity (EC50 of 36.1 μg/mL), similar to ningnanmycin (EC50 of 23.2 μg/mL). The preliminary mechanism of these derivatives was investigated. Autodocking analysis revealed that compounds 7x and 7ab had good affinity for TMV coat protein (TMV CP), with low binding energies (-7.86 and -8.59 kcal/mol) comparable to ningnanmycin (-8.75 kcal/mol). Molecular dynamics simulation showed that compound 7x had a stable system structure with a better binding free energy (-32.94 kcal/mol) than ningnanmycin (-25.62 kcal/mol). Microscale thermophoresis showed that compound 7x bound more strongly to TMV CP (Kd of 19.8 ± 7.3 μM) than ningnanmycin (Kd of 21.2 ± 7.3 μM). Transmission electron microscopy and self-assembly experiments demonstrated that compounds 7x and 7ab significantly obstructed the self-assembly of TMV RNA and TMV CP. This new acylurea derivative has excellent antiviral activity by targeting TMV CP and inhibiting TMV self-assembly and can be considered a candidate for antiviral applications.
- Chen, Shunhong,Guo, Shengxin,Wang, Yanyan,Wei, Panpan,Wu, Jian,Zhang, Wei,Zhao, Wei
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p. 12891 - 12899
(2021/11/17)
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- Dihydroquinoline compound and preparation method and application thereof
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The invention belongs to the field of medical chemistry, relates to a dihydroquinoline compound and a preparation method and application thereof, and particularly provides a compound as shown in a formula (I) or stereoisomers, salts, solvates and crystals thereof, a preparation method of the compound, and application of the compound serving as an intermediate in preparation of medicines for treating cancers or infectious diseases. The compound provided by the invention has the advantages of high yield, purity and optical purity in preparation of medicines for treating cancers or infectious diseases, mild reaction conditions, easiness in purification, stable process and easiness in operation, and can meet industrial-scale production and application.
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Paragraph 0052-0056
(2020/06/09)
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- New spiro pyrrole[2, 1-b]quinazolone derivative, preparation method and application thereof
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The invention relates to a new spiro pyrrole[2, 1-b]quinazolone derivative, a preparation method and application thereof. The new spiro pyrrole[2, 1-b]quinazolone derivative is synthesized by using asimple method. The yield is high, the production cost is
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Paragraph 0155-0157
(2020/11/09)
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- Synthesis and structure-insecticidal activity relationship of novel phenylpyrazole carboxylic acid derivatives containing fluorine moiety
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A series of novel phenylpyrazole carboxylic acid derivatives containing fluorine moiety, i.e., diamides 11, simple aryl-bearing amides 12 and acylthioureas 14 were successfully synthesized based on the key fluoro-containing phenylpyrazole acid intermediate. The new compounds were identified and confirmed by melting point, 1H NMR, 13C NMR and elemental analysis or HRMS. The bioassay results indicated that some of the compounds possessed excellent insecticidal activities towards oriental armyworm, diamondback moth and corn borer at low concentrations. For examples, compounds 11a, 11e?g and 14b exhibited remarkable larvicidal activities with LC50 values of 0.13 ? 0.39 mg/L and 0.0002 ? 0.0014 mg/L against oriental armyworm and diamondback moth, respectively, were comparable with those of the control chlorantraniliprole. Particularly, 11e were found superior to chlorantraniliprole in oriental armyworm tests (LC50: 0.23 mg/L vs. 0.26 mg/L); 11a, 11e, 11f and 14c in diamondback moth tests with LC50 values of 0.0002 mg/L, 0.0002 mg/L, 0.0008 mg/L and 0.0005 mg/L, respectively, were more effective than that of chlorantraniliprole. In addition, 12a also showed a promising insecticidal potential and development/optimization advantage. Compounds 11a, 11e–g, 12a, 14b and 14c could be considered as possible new leading structures for further study. The SAR investigation indicated that the compounds with fluorine motif (e.g., -F, -CF2H, -CF3) held apparently favorable insecticidal potentials, which provided useful guidance for further design/development of new phenylpyrazole-containing agrochemicals.
- Wang, Baolei,Wang, Hongxue,Liu, Hang,Xiong, Lixia,Yang, Na,Zhang, Yan,Li, Zhengming
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p. 739 - 745
(2019/08/20)
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- Synthesis and nematicidal activities of 1,2,3-benzotriazin-4-one containing 4,5-dihydrothiazole-2-thiol derivatives against Meloidogyne incognita
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A series of novel 1,2,3-benzotriazin-4-one derivatives containing 4,5-dihydrothiazole-2-thiol were synthesized and characterized by 1H NMR, 13C NMR, 19F NMR and HRMS. The bioassay results showed that compounds 3-(3-((4,5-dihydrothiazol-2-yl)thio)propyl)-7-methoxybenzo[d][1–3]triazin-4(3H)-one, 3-(3-((4,5-dihydrothiazol-2-yl)thio)propyl)-6-nitrobenzo[d][1–3]triazin-4(3H)-one, 7-chloro-3-(3-((4,5-dihydrothiazol-2-yl)thio)propyl)benzo[d][1–3]triazin-4(3H)-one exhibited good control efficacy against the cucumber root-knot nematode disease caused by Meloidogyne incognita at the concentration of 10.0 mg L?1 in vivo. Compound 7-chloro-3-(3-((4,5-dihydrothiazol-2-yl)thio)propyl)benzo[d][1–3]triazin-4(3H)-one showed excellent nematicidal activity with inhibition 68.3% at a concentration of 1.0 mg L?1. It suggested that the structure of 1,2,3-benzotriazin-4-one containing 4,5-dihydro-thiazole-2-thiol could be optimized further.
- Chen, Xiulei,Zhou, Zhen,Li, Zhong,Xu, Xiaoyong
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p. 194 - 200
(2019/09/13)
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- Synthesis and nematicidal evaluation of 1,2,3-benzotriazin-4-one derivatives containing piperazine as linker against Meloidogyne incognita
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To explore new skeleton with nematicidal activity, a series of novel 1,2,3-benzotriazin-4-one derivatives containing piperazine as linker were synthesized and varied fragments were also introduced to increase structure diversity of the new skeleton. Their inhibitory activities in vivo were evaluated against Meloidogyne incognita. The newly prepared compounds A6, A8, A21, A28 and A38 exhibited more than 50% inhibition at the concentration of 20 mg/L. Especially compound A6 displayed 71.4% inhibition against Meloidogyne incognita at the concentration of 20 mg/L. The nematicidal activities varied significantly depending on the types and positions of the substituents, which provided guidance for further structure modification.
- Chen, Xiulei,Jia, Haowu,Li, Zhong,Xu, Xiaoyong
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supporting information
p. 1207 - 1213
(2019/03/29)
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- Substituted pyrimidine type compound as well as preparation method and use thereof
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The invention belongs to the medical chemistry field and particularly relates to a substituted pyrimidine type compound, a preparation method thereof and use thereof as a reference substance for the qualitative and/or quantitative analysis of relevant impurities in quality research of a raw material drug of mesylate of (S)-4-amino-6-((1-(8-chloro-4-oxo-2-phenyl-1,4-dihydroquinolin-3-yl)ethyl)amino)pyrimidine-5-cyano.
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Paragraph 0034; 0035; 0036; 0037
(2019/04/14)
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- Substituted pyrimidines PI3K inhibitor a sulfonate of the crystal and its preparation method (by machine translation)
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The invention belongs to the field of medicinal chemistry, relates to substituted pyrimidines PI3K inhibitors of a sulfonate of the crystal and its preparation method, in particular of the formula I (S)- 4 - amino - 6 - ((1 - (8 - chloro - 4 - oxo - 2 - phenyl - 1, 4 - dihydroquinoline - 3 - yl) ethyl) amino) pyrimidine - 5 - cyano methanesulfonic acid salt of crystal form and its preparation method, the methanesulfonic acid salt of the crystalline form can be used for preparing and treating and/or preventing cancer, tissue hyperplasia or inflammatory disease, (by machine translation)
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Paragraph 0062; 0064-0066
(2019/04/14)
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- Officinal salts of substituted pyrimidine type PI3K inhibitor and preparation method of officinal salt
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The invention belongs to the medical chemistry field and relates to officinal salts, hydrates, solvates or crystals of a substituted pyrimidine type PI3K inhibitor and a preparation method and application of the officinal salts, the hydrates, the solvates or the crystals. The invention particularly relates to the officinal salts, hydrates, solvates or crystals of (S)-4-amino-6-((1-(8-chloro-4-oxo-2-phenyl-1,4-dihydroquinolin-3-yl)ethyl)amino)pyrimidine-5-cyano of formula (I) (shown in the description) and a preparation method of the officinal salts, the hydrates, the solvates or the crystals.The officinal salts, the hydrates, the solvates or the crystals can be used for preparing drugs for treating and/or preventing cancers, hyperblastosis or inflammatory diseases.
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Paragraph 0043; 0045; 0046; 0047
(2019/04/14)
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- Acyl thiourea and acyl urea derivatives containing trifluoromethylpyridine and application thereof
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The invention discloses acyl thiourea and acyl urea derivatives containing trifluoromethylpyridine and an application thereof. A structure of the derivatives is shown in a general formula I. In the formula, definitions of R1, R2, R3, X and other groups are as shown in the description. The compound represented by the general formula I has excellent insecticidal activity, and can be used to preventand treat pests such as cotton bollworm, diamondback moth and brown planthopper, and can also be used to prevent and treat plant virus diseases such as TMV and CMV.
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Paragraph 0050-0051; 0055
(2019/12/12)
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- SUBSTITUTED PYRIMIDINE COMPOUNDS AS PHOSPHATIDYLINOSITOL 3-KINASE DELTA INHIBITOR AND USE THEREOF
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The present invention belongs to the field of medicinal chemistry, and relates to substituted pyrimidine compounds as phosphatidylinositol 3-kinase (PI3K) δ inhibitor and a use thereof. In particular, the present invention provides a compound as shown by formula I or an isomer, pharmaceutically acceptable salt, solvate or prodrug thereof, the preparation methods of same and pharmaceutical compositions containing these compounds and a use of these compounds or compositions for treating cancer, hyperblastosis diseases or inflammatory diseases. The compounds of the present invention have a good inhibiting activity on PI3Kδ and have a high selectivity. It is hoped that these will be therapeutic agents for cancer, hyperblastosis diseases or inflammatory diseases.
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Paragraph 0097; 0098
(2018/02/03)
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- Substituted pyrimidine PI3K inhibitor optical isomer and use thereof
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The invention belongs to the field of medicinal chemistry and relates to a substituted pyrimidine PI3K inhibitor optical isomer and a use thereof and specifically, provides an optical isomer shown inthe formula I or II or its hydrate, solvate, crystalline or pharmaceutically acceptable salt, its preparation method, a pharmaceutical compositions containing the optical isomer or its hydrate, solvate, crystalline or pharmaceutically acceptable salt and a use of the optical isomer or its hydrate, solvate, crystalline or pharmaceutically acceptable salt in treatment on tumor and tissue hyperplasiadiseases or inflammatory diseases. The compounds have good inhibitory activity to PI3K delta and high selectivity and are very promising as efficient and small side effect therapeutic agents for tumors, tissue proliferative diseases or inflammatory diseases.
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Paragraph 0059-0061
(2018/03/25)
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- 1,4-benzodiazepine-2,5-diones and related compounds with therapeutic properties
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The present invention provides novel chemical compounds characterized as Rho kinase (ROCK) inhibitors, methods for their discovery, and their therapeutic, research, and diagnostic use. In particular, the present invention provides 1,4-benzodiazepine-2,5-d
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Page/Page column 60; 61
(2015/09/28)
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- Recyclable (PhSe)2-catalyzed selective oxidation of isatin by H2O2: a practical and waste-free access to isatoic anhydride under mild and neutral conditions
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After a series of careful conditional optimizations and catalyst screenings, a methodology to prepare isatoic anhydrides through organoselenium-catalyzed selective oxidation of isatins by H2O2 under mild and neutral conditions was developed. The reactions were very practical because of the recyclability of the catalyst and solvent and the convenient isolation procedures of the products. This work reports the organoselenium-catalyzed oxidation of heterocycles that greatly expands the application scopes of organoselenium catalysis. It also indicates that the organoselenium catalysts are robust enough to be recycled in industrial production if suitable isolation procedures are developed.
- Yu, Lei,Ye, Jianqing,Zhang, Xu,Ding, Yuanhua,Xu, Qing
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p. 4830 - 4838
(2015/10/05)
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- COMPOUNDS FOR THE PREVENTION AND TREATMENT OF CARDIOVASCULAR DISEASE
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Disclosed are novel compounds that are useful for regulating the expression of apolipoprotein A-I (ApoA-l), and their use for the treatment and prevention of cardiovascular disease and related disease states, including cholesterol- or lipid-related disorders, such as, for example, atherosclerosis. Also disclosed are pharmaceutical compositions comprising the novel compounds.
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Page/Page column 71-73
(2010/08/04)
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- PIPERIDINE DERIVATIVES HAVING CCR3 ANTAGONISM
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The invention provides low molecular compounds having activity which inhibits binding of CCR3 ligands to CCR3 on target cells, i.e. CCR3 antagonists. The invention also provides compounds represented by formula (I) below, pharmaceutically acceptable acid adducts thereof, or pharmaceutically acceptable C1-C6 alkyl adducts thereof, as well as pharmaceutical compositions comprising them as effective ingredients, which are useful for treatment or prevention of diseases associated with CCR3, such as asthma and allergic rhinitis.
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- Pyridazinedione compounds useful in treating neurological disorders
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The present invention relates to pyridazino[4,5-b]quinolines, and pharmaceutically useful salts thereof, which are excitatory amino acid antagonists and which are useful when such antagonism is desired such as in the treatment of neurological disorders. The invention further provides pharmaceutical compositions containing pyridazino[4,5-b]quinolines as active ingredient, and methods for the treatment of neurological disorders.
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- Process for preparing 3-chloroanthranilic alkyl esters of high purity from 3-chloroanthranilic acid
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Process for preparing 3-chloroanthranilic alkyl esters by reacting 3-chloroanthranilic acid, in an inert solvent, with from 0.8 to 5 parts by weight of phosgene, and reacting the 3-chloroisatoic anhydride which is formed with an alkanol, where appropriate in the presence of an esterification catalyst, to give the 3-chloroanthranilic alkyl ester.
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- Preparation of a mixture of an alkyl 3-chloroanthranilate and an alkyl 6-chloroanthranilate
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A mixture of an alkyl 3-chloroanthranilate and an alkyl 6-chloroanthranilate, with a particular molar ratio of the components, is prepared by (a) reacting 3-chlorophthalic anhydride with ammonia, an alkali metal hydroxide and an alkali metal hypochlorite or (b) converting 3-chlorophthalic anhydride to 3-chlorophthalimide followed by reaction of the latter with an alkali metal hydroxide and an alkali metal hypochlorite, and, finally, esterifying the mixture of 5-chloroisatoic anhydride and 8-chloroisatoic anhydride, obtained by method (a) or method (b), with an alkanol. The compounds obtainable by the process of the invention are valuable starting materials for the preparation of dyes, crop protection agents and scents.
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- Amino-benzoic acid amides
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Compounds of the formula STR1 wherein (A) WHEN THE AMINO-SUBSTITUENT IS IN THE P-POSITION WITH RESPECT TO THE CARBONYL GROUP, R1 is chlorine in the o-position with respect to the carbonyl group, R2 is hydrogen, and R3 is ethylamino, cyclopentylamino, cyclohexylamino, cycloheptylamino, N-methyl-cyclohexylamino, benzylamino or 1-ethyl-pyrrolidyl-(2)-aminomethyl, or (b) when the amino-substituent is in the o--, m-- or p-position with respect to the carbonyl group, R1 is hydrogen, chlorine or bromine, R2 is trifluoromethyl, nitro or, when R4 is 1-(alkyl of 1 to 3 carbon atoms)-pyrrolidyl or 1-(alkyl of 1 to 3 carbon atoms)-piperidyl, also fluorine, chlorine, bromine or methyl, R3 is (alkyl of 1 to 5 carbon atoms)-amino, (cycloalkyl of 3 to 7 carbon atoms)-amino, benzylamino, quinuclidinyl-amino or --NH--(CH2)n --R4 where R4 is pyridyl, 1-(alkyl of 1 to 3 carbon atoms)-pyrrolidyl, 1-(alkyl of 1 to 3 carbon atoms)-piperidyl or, when n is 2 or 3, also imidazolonyl, pyrrolidino, piperidino or morpholino, and n is 0, 1, 2 or 3, And non-toxic, pharmacologically acceptable acid addition salts thereof; the compounds as well as their salts are useful as anxiolytics, anticonvulsives, antiemetics and antiulcerogenics.
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