- Carboxyboronate: A Versatile C1 Building Block
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The synthesis and applications of carboxy-MIDA-boronate, a novel C1 building block, are described. This molecule is accessible via a ruthenium tetraoxide-mediated cleavage of commercially available ethynyl-MIDA-boronate. In the course of this study, carboxy-MIDA-boronate was found to possess ambident reactivity towards nucleophiles. Carboxylic acid derivatization produces a broad range of previously unknown carbamoyl-, oxycarbo- and thiocarboboronates. Carboxy-MIDA-boronate and its derivatives undergo condensations to access borylated heterocycles with boron at positions that are difficult to access using alternate methods. The resulting heterocycles participate in the Suzuki–Miyaura cross-coupling reaction, enabling entry into diverse bis(heteroaryl) motifs. The carbon monoxide-releasing capacity of carboxy-MIDA-boronate was also examined and applied in palladium-catalyzed carbonylation.
- Holownia, Aleksandra,Tien, Chieh-Hung,Diaz, Diego B.,Larson, Reed T.,Yudin, Andrei K.
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- Synthesis and biological evaluation of thiabendazole derivatives as anti-angiogenesis and vascular disrupting agents
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Abstract Thiabendazole, already approved by FDA for oral use as an anti-fungal and anti-helminthic drug since 1967, has recently been repurposed as a vascular disrupting agent. By optimization of the structure of the lead compound, we successfully identified compound TBZ-19 and the new derivative is over 100-fold more potent than the lead compound against the growth of four different cell lines (A549, HCT-116, HepG2 and HUVECs). The most potent two candidates TBZ-07 and TBZ-19, exhibiting moderate inhibitory cell proliferation activity, were also verified as anti-angiogenesis and vascular disrupting agents. Therefore, TBZ-07 and TBZ-19 would be promising candidates with vasculature targeting activity and merit further development.
- Zhang, Chao,Zhong, Bo,Yang, Simin,Pan, Liangkun,Yu, Siwang,Li, Zhongjun,Li, Shuchun,Su, Bin,Meng, Xiangbao
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- Synthesis, characterization and biological evaluation of benzimidazole and benzindazole derivatives as anti-hypertensive agents
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A substituted benzimidazole and benzindazole derivatives had been synthesized having antihypertensive activity through antagonizing the angiotensin II (Ang II) receptors. The in vivo antihypertensive activity of the compounds was done with acute renal hypertension model. Two compounds TG 1 and TG 3 were found to have antihypertensive activity comparable to Telmisartan which is a prototype for Angiotensin II receptor antagonists class of drugs.In an antihypertensive study the compounds TG 1, TG 2 and TG 3 had systolic blood pressures of 147.2 mm/Hg, 168.2 mm/Hg, and 126.3 mm/Hg, respectively. This systolic blood pressure was lower than the disease control vehicle-treated rodents, which had a systolic blood pressure of 167.2 mm/Hg. The diastolic blood pressure was 119.7 mm/Hg, 124.7 mm/Hg and 88.83 mm/Hg, respectively and that of the disease control vehicle-treated rodents was 122.3 mm/Hg. TG 3 had comparable decrease in the MABP to Telmisartan. These encouraging results make compound TG 3 effective anti-hypertensive drug candidate and worthy of further investigation.
- Silky, Sethy,Mandal, Sudip Kumar,Ewies, Ewies Fawzy,Neerupma, Dhiman,Arun, Garg
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p. 3659 - 3664
(2021/07/10)
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- New synthesis method of thiabendazole
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The invention relates to a new synthetic route of a drug commonly named as thiabendazole. Thiazole-4-formaldehyde is used as a raw material, and is condensed with hydroxylamine hydrochloride to obtainthiazole-4-formaldoxime, thiazole-4-formaldoxime is subjected to chlorination by using NCS, and then reacts with aniline to obtain N-phenylthiazole-4-methylamine oxime, then N-phenylthiazole-4-methylamine oxime reacts with p-trifluoromethyl benzoyl chloride to obtain an amidoxime ester, and finally a visible-light-catalyzed free radical reaction is adopted for cyclization to obtain thiazole. According to the method, the visible-light-catalyzed free radical reaction is used to the synthesis of thiabendazole for the first time, the reaction conditions of a high temperature and a strong acid inthe traditional synthesis method are avoided, and thereby the reaction is greener and milder. The method has a broad spectrum, and can also be used for synthesis of imidazole compounds Ia-Ial.
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Paragraph 0026; 0035; 0036
(2020/02/20)
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- Preparation method of thiabendazole technical
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The invention provides a preparation method of a thiabendazole technical. Compared with the prior art, in the preparation method, raw materials are equally divided into multiple parts and placed in different containers for preparation, the reaction time interval of the two adjacent reaction containers is 2-4 minutes, data in the reaction is recorded in the interval time, products obtained from thecontainers with the maximum pH value and the minimum pH value are removed, the PH value of a final product is guaranteed, and product quality is ensured.
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Paragraph 0012; 0013; 0014; 0015
(2019/08/03)
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- Production raw material of thiabendazole and preparation technology of production raw material
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The invention provides a production raw material of thiabendazole. The production raw material mainly comprises components as follows: lactic acid, o-phenylenediamine, acetone, inorganic acid, potassium permanganate, bromine, ethyl acetate, formamide and phosphorus pentasulfide, wherein the mole ratio of lactic acid to o-phenylenediamine is 1:1.17; the ratio of ethyl acetate, formamide and phosphorus pentasulfide is 2:1:1. The raw material ratio is sophisticated, the adjusting range of PH value is narrowed in a preparation process, the conversation rate of a product is increased, and the quality of the product is improved.
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Paragraph 0014-0021
(2019/08/06)
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- Formation of Amidinyl Radicals via Visible-Light-Promoted Reduction of N-Phenyl Amidoxime Esters and Application to the Synthesis of 2-Substituted Benzimidazoles
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We have developed a new method for the synthesis of 2-substituted benzimidazoles via amidinyl radicals generated by visible-light-promoted reduction of N-phenyl amidoxime esters in the presence of an iridium photocatalyst. This is the first report of the use of N-phenyl amidoxime esters as amidinyl radical precursors, and the first use of substituted benzene rings as amidinyl radical acceptors. This method widens the application range of substrates and overcomes the shortcomings of the traditional methods for the synthesis of 2-substituted benzimidazoles, which requires harsh reaction conditions, involves difficult-to-prepare substituted o-phenylenediamine substrates, and produces acidic waste.
- Li, Gang,He, Ru,Liu, Qiang,Wang, Ziwen,Liu, Yuxiu,Wang, Qingmin
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p. 8646 - 8660
(2019/07/08)
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- AN IMPROVED PROCESS FOR THE PREPARATION OF THIABENDAZOLE
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The present invention relates to an improved process for preparing thiabendazole of formula (I) with high yield, high purity, in economical and commercially viable manner for agricultural and pharmaceutical use.
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Page/Page column 13
(2019/02/06)
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- A process for the preparation method of thiabendazole
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The invention relates to a new method for synthesizing thiabendazole. Acetone and chlorine are taken as starting materials to synthesize chloroacetone, chloroacetone not subjected to separation can directly react with thiocarbamide to obtain 2-Amino-4-methylthiazole which is subjected to diazotization to obtain 4-methylthiazole, and 4-methylthiazole is oxidized to produce 4-thiazolecarboxylic acid, and finally, 4-thiazolecarboxylic acid reacts with o-phenylenediamine to obtain the target object thiabendazole. The thiabendazole is a broad-spectrum anthelmintic, can repel roundworms, hookworms, whipworms, pinworms, strongyloises stercoralis and trichinization, is also a broad-spectrum efficient disinfectant and is widely used as a fruit fresh-keeping agent and a bactericidal mildew inhibitor in various fields over the past decade in China.
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Paragraph 0055; 0064; 0065; 0078; 0091; 0104
(2018/04/01)
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- Compounds and methods for treating mammalian gastrointestinal microbial infections
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Described herein are compounds, and pharmaceutically acceptable salts and prodrugs thereof, which are useful as inhibitors of IMPDH. In certain embodiments, a compound of the invention selectively inhibits a parasitic IMPDH versus a host IMPDH. Further, the invention provides pharmaceutical compositions comprising one or more compounds of the invention. The invention also relates to methods of treating various parasitic and bacterial infections in mammals. Moreover, the compounds may be used alone or in combination with other therapeutic or prophylactic agents, such as anti-virals, anti-inflammatory agents, antimicrobials and immunosuppressants.
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(2018/11/30)
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- Novel process for producing thiabendazole
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The invention discloses a process for producing thiabendazole. The process includes carrying out condensation reaction on lactic acid and o-phenylenediamine in acidic aqueous solution(with, but not limited to, hydrochloric acid); regulating pH (potential of hydrogen) values to obtain 2-alpha-hydroxyl ethyl benzimidazole; placing the 2-alpha-hydroxyl ethyl benzimidazole in a container with acetone and sulfuric acid (but not limited to sulfuric acid, or hydrochloric acid and other inorganic acid and strong acid and weak alkali salt) and carrying out oxidation reaction on the 2-alpha-hydroxyl ethyl benzimidazole and potassium permanganate (but not limited to potassium permanganate, or hydrogen peroxide and organic peroxide); carrying out extraction, desolvation and drying to obtain 2-acetyl benzimidazole; placing the 2-acetyl benzimidazole in a container with glacial acetic acid and carrying out halogenations reaction on the 2-acetyl benzimidazole and bromine (but not limited to, or chlorine and other halogens); drying filter cake to obtain 2-dibromomethane acetyl benzimidazole hydrobromide; carrying out reaction on formamide and phosphorus pentasulfide in a container with ethyl acetate to obtain thioformamide; removing phosphorus pentoxide by means of filter-press by the aid of nitrogen to obtain thioformamide/ethyl acetate solution and carrying out cyclization reaction on the thioformamide/ethyl acetate solution and 2-dibromomethane acetyl benzimidazole; purifying reaction products and regulating pH (potential of hydrogen) values to obtain the thiabendazole with the content higher than or equal to 99%. The acetone and the sulfuric acid in the corresponding container are used as solvents. The glacial acetic acid in the corresponding container is used as a solvent. The ethyl acetate in the corresponding container is used as a solvent. The process has the advantages that the cost can be lowered, risks in the aspects of safety and environmental protection can be reduced, environmental pollution can be abated, and the production efficiency can be improved; integral reaction procedures are carried out at the normal temperatures under the normal pressures, accordingly, reaction conditions are mild, the yield of the reaction at each step is quite stable, and the overall yield measured by the aid of the o-phenylenediamine can reach 75% at least.
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- A practical method, NaOCl-mediated, to prepare thiabendazoles via intramolecular amination reaction
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A series of new chlorinated thiabendazoles (6a–m) have been synthesized from readily available anilines and 4-cyanothiazole in moderate to good yields. All synthesized compounds were fully characterized using 1H NMR, 13C NMR, IR, and mass spectrometry. Additionally, the structure of the compound (6f) was confirmed by single-crystal X-ray diffraction. In addition, synthesis of 2-substituted benzimidazoles and 2-phenyl benzothiazole was investigated using our optimized conditions and the outcome is presented herein.
- Patil, Vikrant,Barragan, Enrique,Patil, Shivaputra A.,Patil, Siddappa A.,Bugarin, Alejandro
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p. 3474 - 3477
(2017/08/10)
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- Synthesis and biological evaluation of novel benzimidazole derivatives and analogs targeting the NLRP3 inflammasome
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A series of benzo[d]imidazole analogues of thiabenzole were synthesized and their anti-inflammatory activities toward NLRP3 (nucleotide-binding domain leucine-rich repeat containing protein family, pyrin domain-containing 3, also known as cryopyrin or NALP3) inflammasome were evaluated in vitro. Two lead compounds, TBZ-09 and TBZ-21, were identified by anti-production of IL-1β. In the second round of biological evaluation, based on the lead, 34 more compounds were synthesized and their in vitro anti-inflammatory activities were investigated. Several compounds were identified as anti-inflammatory agents that can reduce IL-1β expression in a dose-dependent manner. A preliminary structure-activity relationship is also summarized here.
- Pan, Liangkun,Hang, Nan,Zhang, Chao,Chen, Yu,Li, Shuchun,Sun, Yang,Li, Zhongjun,Meng, Xiangbao
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- 2-heteroaryl benzimidazole derivatives as melanin concentrating hormone receptor 1 (MCH-R1) antagonists
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A novel series of 2-heteroaryl substituted benzimidazole derivatives, containing the piperidinylphenyl acetamide group at the 1-position, were synthesized and evaluated as MCH-R1 antagonists. Extensive SAR investigation probing the effects of C-2 heteroaryl group led to the identification of 2-[2-(pyridin-3-yl)ethyl] analog 3o, which exhibits highly potent MCH-R1 binding activity with an IC50 value of 1 nM. This substance 3o also has low hERG binding activity, good metabolic stability, and favorable pharmacokinetic properties.
- Lim, Chae Jo,Kim, Jeong Young,Lee, Byung Ho,Oh, Kwang-Seok,Yi, Kyu Yang
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p. 2305 - 2310
(2013/09/24)
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- Structure-activity relationship study of selective benzimidazole-based inhibitors of Cryptosporidium parvum IMPDH
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Cryptosporidium parasites are important waterborne pathogens of both humans and animals. The Cryptosporidium parvum and Cryptosporidium hominis genomes indicate that the only route to guanine nucleotides is via inosine 5′-monophosphate dehydrogenase (IMPDH). Thus the inhibition of the parasite IMPDH presents a potential strategy for treating Cryptosporidium infections. A selective benzimidazole-based inhibitor of C. parvum IMPDH (CpIMPDH) was previously identified in a high throughput screen. Here we report a structure-activity relationship study of benzimidazole-based compounds that resulted in potent and selective inhibitors of CpIMPDH. Several compounds display potent antiparasitic activity in vitro.
- Kirubakaran, Sivapriya,Gorla, Suresh Kumar,Sharling, Lisa,Zhang, Minjia,Liu, Xiaoping,Ray, Soumya S.,MacPherson, Iain S.,Striepen, Boris,Hedstrom, Lizbeth,Cuny, Gregory D.
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scheme or table
p. 1985 - 1988
(2012/04/05)
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- ALPHA-FLUOROALKYL TETRABENAZINE AND DIHYDROTETRABENAZINE IMAGING AGENTS AND PROBES
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The present invention provides novel alpha-fluoroalkyl compounds having structure I and the corresponding dihydrotetrabenazine compounds IV wherein R1 is a C1-C10 fluorinated aliphatic radical; R2 is hydrogen or a C1-C10 aliphatic radical; and R3 is hydrogen or a C1-C10 aliphatic radical. The alpha-fluoroalkyl compounds are provided in both racemic and enantiomerically enriched forms and may comprise either or both of fluorine-18 and fluorine 19. The alpha-fluoroalkyl compounds are shown to possess high affinity for VMAT-2, a biomarker implicated in human diabetes. The alpha-fluoroalkyl compounds comprising a fluorine-18 group are useful as PET imaging agents targeting the VMAT-2 biomarker. The non-radiolabled alpha-fluoroalkyl compounds are useful as probes for the discovery of PET imaging agents.
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- Pyrazolyl benzyl ether derivatives containing a fluoromethoxyimino group and use thereof as pesticides
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The invention relates to novel pyrazolyl benzyl ethers, to a plurality of processes for their preparation and to their use for controlling harmful organisms.
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- Protective agents for wood
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Solvent-free coating materials and treating agents used as water-based wood or material protective agents containing emulsifiable binding agents, quaternary ammonium compounds and optional additional active agents. The wood or material protective agents are non-flammable and enable a uniform distribution of the binding agent and the quaternary ammonium compounds in the substrates. As a result, the quaternary ammonium compounds function as a dissolving mediator for the binding agents which are dispersed in water without opacifying effects and are used as a biocide. The agents can additionally absorb water-insoluble organic biocides without impairing the homogeneity or stability of the formulation of the homogeneity of the distribution in the substrate.
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- Wood preservatives
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Wood preservatives having biocidal properties which include quaternary ammonium compounds of general formula (I): wherein R1 is a C8-18-alkyl group or an optionally substituted benzyl group, R2 is a C8-18-alkyl group, R3 is a C1-4-alkyl group or a group of the formula —[CH2—CH2—O]n—H, R4 is a C1-4-alkyl group, n is a number from 0.5 to 8, preferably from 1 to 5, and A?is the anion of an organic carboxylic acid which contains 2 to 12 C atoms and carries at least one hydroxyl, amino or sulfonic acid group. The wood preservatives also penetrate deeply into the wood without the use of pressure, and have only a mild corrosive action on metals. Furthermore, a process for treating timbers with these compositions, concentrates for the preparation thereof, the use of new and known quaternary ammonium compounds in wood preservatives and new quaternary ammonium compounds and their use as biocides.
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- Iminoacetic acid amides and their use as pest control agents
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PCT No. PCT/EP96/04345 Sec. 371 Date Apr. 15, 1998 Sec. 102(e) Date Apr. 15, 1998 PCT Filed Oct. 7, 1996 PCT Pub. No. WO97/14673 PCT Pub. Date Apr. 24, 1997Iminoacetamides of the formula (I) in which A represents a single bond or optionally substituted alkylene, Q represents oxygen or sulphur, R1 represents respectively optionally substituted cycloalkyl, cycloalkenyl, aryl or heterocyclyl, R2 represents respectively optionally substituted alkyl, alkenyl, alkinyl, cycloalkyl, cycloalkenyl, aryl or heterocyclyl, R3 represents hydrogen or respectively optionally substituted alkyl, alkenyl, alkinyl or cycloalkyl, R4 represents respectively optionally substituted cycloalkyl, cycloalkenyl, aryl or heterocyclcyl a process for their preparation, pesticidal compositions containing them, and their use for controlling pests.
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- Microbicidal benzotriazoles
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Novel benzotriazoles of the formula STR1 in which R, X1, X2, X3, X4 and Y have the meanings given in the description, and their acid addition salts and metal salt complexes, a process for the preparation of these substances and their use as microbicides in crop protection and in material protection.
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- Halogen alkenyl azolyl microbicides
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Novel halogenoalkenyl-azolyl derivatives of the formula STR1 in which R1 represents optionally substituted alkyl, optionally substituted alkenyl, optionally substituted cycloalkyl, optionally substituted aryl or represents optionally substituted heteroaryl, R2 represents alkyl, halogenoalkyl, 1-hydroxyalkyl, 2-hydroxyalkyl, 1-hydroxyhalogenalkyl, 1-alkenyl or 2-alkenyl, X1 represents fluorine, chlorine, bromine or iodine, X2 represents fluorine, chlorine, bromine or iodine, and Y represents nitrogen or a CH group, and addition products thereof with acids or metal salts are very active as microbicides in plant protection and in the protection of materials.
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- Acylated 5-aminopyrazoles and the use thereof to combat animal parasites
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The present invention relates to new acylated 5-aminopyrazoles of the formula (I) STR1 in which R1, R2, R3, R4 and R5 have the meaning given in the description, to processes for their preparation and to their use as pesticides.
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- Termite-controlling agent composition
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Combating termites with a composition comprising (a) at least one compound of the formula STR1 wherein, R denotes a hydrogen atom, acyl, alkyl or optionally substituted heteroarylalkyl, A denotes a hydrogen atom, alkyl or a bivalent group which binds to B, D denotes alkyl, --S--R1, STR2 or bivalent group or atom which binds to A. wherein R1 or R2 each independently denotes a hydrogen atom, acyl, alkyl or optionally substituted heteroarylalkyl. Y denotes =N-- or STR3 wherein T1 denotes a hydrogen atom or optionally substituted alkyl, and X denotes an electron attracting group, and (b) a pyrethoid compound.
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- Substituted tetrahydro-5-nitro-pyrimidines
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The present invention relates to novel substituted in that one tetrahydro-5-nitro-pyrimidine of the formula (I), according to claim 1, STR1 in which n, R1, R2 have the meaning given in the description, to a process for its preparation and to its use for combating animal pests, especially insects, arachnids and nematodes, which are encountered in agricultural, in forestry, in the protection of stored products and of materials and, in the hygiene sector.
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- Antibacterial and antifungal polyacetal resin composition
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Antibacterial and antifungal polyacetal resin compositions include a polyacetal base resin, and an antibacterial and/or antifungal effective amount between about 0.1 to about 5 parts by weight, per 100 parts by weight of the polyacetal base resin, of at least one antibacterial and antifungal agent which contains a metal ion selected from among silver, copper and zinc ions.
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- Process for preparing thiabendazole
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Process for preparing 2-(4-thiazolyl)-1H-benzimidazole (generic name: thiabendazole) by the acid-catalyzed condensation of o-phenyldiamine and 4-cyanothiazole in solution in water or mixtures of water with miscible co-solvents (solvents which upon mixing with water in all proportions form a homogeneous mixture, as well as, other partially miscible solvents which upon mixing with water in some proportions form a homogeneous mixture under the reaction conditions of the process of this invention).
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- Preparation of high purity thiabendazole
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Process for preparing 2-(4'-thiazolyl)-benzimidazole (generic name: thiabendazole) by the acid-catalyzed condensation of o-phenylenediamine and 4-cyanothiazole using as a solvent polar organic compounds in which the reactants, catalysts and impurities are soluble, and the product, thiabendazole, is substantially insoluble.
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- 1,5-diphenyl-3-formazancarbonitril parasiticides
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The present invention is directed to the use of 1,5-diaryl-3 -formazancarbonitrile compounds for the control of parasites in vertebrate animals.
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- Process for formulating a synthetic drug for use in animal feed, and resulting formulation
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A method of formulating a synthetic drug for use in animal feed, for the purpose of reducing carry-over of the synthetic drug to subsequent lots of animal feed in the feed mill.
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- Triazolylthiophosphoric acid esters
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Triazolylthiophosphonic esters corresponding to the formula SPC1 Wherein R1 represents a phenyl radical which is substituted by one or more fluorine, bromine and/or iodine atoms, by lower alkyl, lower alkoxy, lower alkylthio, lower trihalogenoalkyl, lower alkyl-SO, lower alkyl-SO2 or O2 N groups, which may be the same or different, or by at least one chlorine and at least one fluorine, bromine or iodine atom, one lower alkyl, lower alkoxy, lower alkylthio, lower trihalogenoalkyl, lower alkyl-SO, lower alkyl-SO2 or O2 N group, or represents an unsubstituted or halogenated and/or alkoxylated phenyl-lower alkyl radical or diphenylmethyl, and one of the symbols R2 and R3 represents hydrogen or a lower alkyl radical and the other represents the radical EQU1 wherein R4 represents a lower alkyl radical or the phenyl radical and R5 represents a lower alkyl radical their manufacture and their use in pest control.
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- Condensation products
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Formamidine compounds of the formula EQU1 or WHEREIN R1 represents a substituted or unsubstituted phenyl radical, R2 represents hydroogen, alkyl, alkenyl or alkinyl and R3 represents acyl their manufacture and their use in pest control.
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