- Design, Synthesis, and Study of the Insecticidal Activity of Novel Steroidal 1,3,4-Oxadiazoles
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A series of novel steroidal derivatives with a substituted 1,3,4-oxadiazole structure was designed and synthesized, and the target compounds were evaluated for their insecticidal activity against five aphid species. Most of the tested compounds exhibited potent insecticidal activity against Eriosoma lanigerum (Hausmann), Myzus persicae, and Aphis citricola. Compounds 20g and 24g displayed the highest activity against E. lanigerum, showing LC50 values of 27.6 and 30.4 μg/mL, respectively. Ultrastructural changes in the midgut cells of E. lanigerum were detected by transmission electron microscopy, indicating that these steroidal oxazole derivatives might exert their insecticidal activity by destroying the mitochondria and nuclear membranes in insect midgut cells. Furthermore, a field trial showed that compound 20g exhibited effects similar to those of the positive controls chlorpyrifos and thiamethoxam against E. lanigerum, reaching a control rate of 89.5% at a dose of 200 μg/mL after 21 days. We also investigated the hydrolysis and metabolism of the target compounds in E. lanigerum by assaying the activities of three insecticide-detoxifying enzymes. Compound 20g at 50 μg/mL exhibited inhibitory action on carboxylesterase similar to the known inhibitor triphenyl phosphate. The above results demonstrate the potential of these steroidal oxazole derivatives to be developed as novel pesticides.
- Bai, Hangyu,Jiang, Weiqi,Li, Qi,Li, Tian,Ma, Shichuang,Shi, Baojun,Wu, Wenjun
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p. 11572 - 11581
(2021/10/12)
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- 5 - Alkyl - [1, 3, 4] - oxadiazole -2 - carboxylic acid alkyl ester method
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The invention discloses a synthetic method of 5-alkyl-[1,3,4]-oxadiazole-2-alkyl ester formate. The synthetic method comprises the following steps: 1, performing ammonolysis reaction on dialkyl ester oxalate and hydrazine hydrate to obtain mono alkyl ester hydrazide oxalate; 2, performing acylation reaction on the obtained mono alkyl ester hydrazide oxalate and fatty acid anhydride to obtain 2-acylhydrazino-mono alkyl ester oxalate; and 3, performing dehydration cyclization reaction on the obtained 2-acylhydrazino-mono alkyl ester oxalate to obtain a target product, namely 5-alkyl-[1,3,4]-oxadiazole-2-alkyl ester formate. The synthetic method of the 5-alkyl-[1,3,4]-oxadiazole-2-alkyl ester formate, disclosed by the invention, can avoid the use of reagents with strong toxicity and strong corrosivity by improving the process, and is novel in route, high in yield, low in raw material and solvent price, safe, simple and convenient to operate, and suitable for industrial production.
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Paragraph 0103-0108
(2019/03/02)
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- Preparation method of pyrimidinone amide type compound
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The invention discloses a pyrimidinone amide type compound and a preparation method thereof. A pyrimidinone compound is taken as a starting material and is subjected to four-step chemical conversion to obtain TN-A005 and an analogue thereof, and an intermediate can be prepared from methyl tetrazole. A one-pot method is used for feeding in the whole preparation process, post-treatment purificationof each step is recrystallization or dispersion washing, the use of means such as silica gel column chromatography is avoided, the preparation technology is greatly simplified, the preparation efficiency is improved, and the total yield can reach 50%. The method is simple and convenient in preparation steps and can improve the preparation efficiency.
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Paragraph 0042; 0043; 0046
(2018/10/19)
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- 4,5-diphenyl isoxazole derivative as well as preparation method and application thereof
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The invention discloses a 4,5-diphenyl isoxazole derivative as well as a preparation method and application thereof. Specifically, the invention relates to a 4,5-diphenyl isoxazole derivative of a structure represented by the formula (I), a stereoisomer or pharmaceutically acceptable salt of the derivative, wherein the definition of each substituent in the formula (I) is the same as that in a specification. Compounds of novel structures have the activity of inhibiting heat shock proteins HSP90, can be used for treating cancers, neurodegenerative diseases, inflammatory diseases, autoimmune diseases and ischemic brain injuries, and has wide application prospect.
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Paragraph 0173; 0174; 0175; 0176
(2017/06/02)
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- 3. 4 - diphenyl - 4H - 1, 2, 4 - triazole derivative and its preparation method and application (by machine translation)
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The invention discloses 3, 4 - diphenyl - 4H - 1, 2, 4 - triazole derivative and its preparation method and application. In particular, the invention relates to the formula (I) structure of 3, 4 - diphenyl - 4H - 1, 2, 4 - triazole derivatives, its stereoisomers or its pharmaceutically acceptable salt, formula (I) in the definition of each substituent is as defined in the specification. These structure of novel compound with heat shock protein HSP90 inhibitory activity, can be used for treating cancer, neurodegenerative diseases, inflammatory diseases, autoimmune diseases, ischemic brain injury and the like, it has broad application prospects. (by machine translation)
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Paragraph 0243; 0274; 0275; 0276
(2017/07/01)
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- COMPOUNDS AS HEPATITIS C INHIBITORS AND USES THEREOF IN MEDICINE
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Provided herein are compounds as hepatitis C inhibitors and uses thereof in medicine. Specifically, provided herein is a compound of Formula (I) or a stereoisomer, a tautomer, an enantiomer, an N-oxide, a hydrate, a solvate, a metabolite, a pharmaceutically acceptable salt or a prodrug thereof, which can be used for treating HCV infection or hepatitis C diseases. Also provided herein are a pharmaceutically acceptable composition containing such compound and a method of treating HCV infection or hepatitis C diseases comprising administering the compound or pharmaceutical composition thereof disclosed herein.
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Paragraph 00194
(2016/09/22)
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- Hydroxyl may not be indispensable for raltegravir: Design, synthesis and SAR Studies of raltegravir derivatives as HIV-1 inhibitors
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A series of raltegravir derivatives 20-42 were prepared and systematically evaluated for their anti-HIV activity. The bioassay results showed that most of the compounds possess good to excellent anti-HIV activity. Especially, compounds 25 and 35 with subpicomole IC50 values seemed to be the most potent anti-HIV agents among all of the reported synthesized compounds. These compounds may therefore be considered as new potent anti-HIV agents. The 5-hydroxyl modification of raltegravir derivatives significantly increased the anti-HIV activity, which indicates that the hydroxyl may not be indispensable for raltegravir. The introducing of acyl at 5-position of raltegravir derivatives is favorable for antiviral activity. In addition, a high-throughput cell-based assay method with pseudotyped virus stocks was developed and used to identify HIV inhibitors.
- Wang, Ziwen,Wang, Mingxiao,Yao, Xue,Li, Yue,Qiao, Wentao,Geng, Yunqi,Liu, Yuxiu,Wang, Qingmin
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experimental part
p. 361 - 369
(2012/06/30)
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- Development of a second-generation, highly efficient manufacturing route for the HIV integrase inhibitor raltegravir potassium
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A manufacturing route for the synthesis of raltegravir potassium 1 was developed via a thermal rearrangement of amidoxime DMAD adducts 6 to construct the key, highly functionalized hydroxypyrimidinone core 7. Utilizing this route 1 was prepared in nine linear chemical steps with 22% overall yield. A second-generation synthesis was subsequently developed that solved the key chemical, productivity, and environmental impact issues of the initial synthesis. Highlights of the new synthesis include a highly selective methylation, 3-4-fold higher productivity, and a 65% reduction of combined organic and aqueous waste produced. The efficient second-generation manufacturing route provides raltegravir potassium 1 in 35% overall yield.
- Humphrey, Guy R.,Pye, Philip J.,Zhong, Yong-Li,Angelaud, Remy,Belyk, Kevin M.,Maligres, Peter E.,Miller, Ross A.,Reamer, Robert A.,Askin, David,Mancheno, Danny E.,Weissman, Steven A.
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experimental part
p. 73 - 83
(2011/09/16)
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- NOVEL PYRIMIDINECARBOXAMIDE DERIVATIVES
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This disclosure relates to novel HIV integrase inhibitors their derivatives, pharmaceutically acceptable salts, solvates, and hydrates thereof. This disclosure also provides compositions comprising a compound of this disclosure and the use of such compositions in methods of treating HIV infections.
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Page/Page column 12
(2009/07/02)
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- TASTE-MASKED TABLETS AND GRANULES
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Orally administered, taste-masked tablets and granules contain (a) a hydroxypyrimidinone carboxamide, a hydroxy-tetrahydropyridopyrimidinone carboxamide, or a related carboxamide compound, or a pharmaceutically acceptable salt thereof, (b) a taste-masking polymer, (c) a superdisintegrant, and optionally other excipients. The carboxamide compound is an HIV integrase inhibitor, and the tablets and granules are suitable for use in the inhibition of HIV integrase, the treatment or prophylaxis of HIV infection, and the treatment or prophylaxis or delay in the onset of AIDS.
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Page/Page column 36-37
(2008/06/13)
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- Potassium salt of an HIV integrase inhibitor
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Potassium salts of Compound A and methods for their preparation are disclosed, wherein Compound A is of formula: Compound A is an HIV integrase inhibitor useful for treating or prophylaxis of HIV infection, for delaying the onset of AIDS, and for treating or prophylaxis of AIDS.
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Page/Page column 24-25
(2010/11/08)
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- PHARMACEUTICAL COMPOSITION CONTAINING AN ANTI-NUCLEATING AGENT
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Pharmaceutical compositions suitable for oral administration in solid dosage forms are described. The compositions comprise an effective amount of a drug compound in the form of a salt, wherein the drug salt is characterized by conversion to a less soluble form of the drug compound under certain pH conditions, and an anti-nucleating agent.
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Page/Page column 34-35
(2010/11/08)
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- PHARMACEUTICAL FORMULATION CONTAINING A RELEASE RATE CONTROLLING COMPOSITION
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Pharmaceutical formulations suitable for oral administration in solid dosage forms are described. The compositions comprise an effective amount of a base salt of a compound of Formula (I) and a release rate controlling composition comprising a solubilizing agent, a gelling agent, and a water soluble filler; wherein R1, R2, R3 and R4 are defined herein. The formulations are suitable for use in the inhibition of HIV integrase, the treatment and prophylaxis of HIV infection, and the treatment, prophylaxis and delay in the onset of AIDS.
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Page/Page column 30-31
(2010/11/08)
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- USE OF ATAZANAVIR FOR IMPROVING THE PHARMACOKINETICS OF DRUGS METABOLIZED BY UGT1A1
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A method for improving the pharmacokinetics of an orally administered drug that is directly metabolized by UGT1A1 comprises orally administering to a mammal in need of treatment with the drug a combination of the drug or a pharmaceutically acceptable salt thereof and atazanavir or a pharmaceutically acceptable salt thereof.
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Page/Page column 35-36
(2010/11/08)
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