- Scalable Synthetic Strategy for Unsymmetrical Trisubstituted s-Triazines
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A scalable synthetic strategy to produce a large variety of unsymmetrical trisubstituted 1,3,5-triazines was developed. This protocol applied in situ formed acyl isocyanate from amide to react with amidine, introducing two substituents to the 1,3,5-triazinone ring with a low production cost and a simple workup procedure. The scalability of this method was demonstrated by translating a small-scale procedure to a multi-kilogram-scale synthesis. Chlorination and a further coupling reaction with various nucleophiles could provide unsymmetrical trisubstituted 1,3,5-triazines bearing diverse functional groups.
- Liang, Helong,Li, Ganzhong,Zhang, Lei,Wang, Gefei,Song, Mingyu,Li, Heng,Yuan, Bingxin
-
supporting information
p. 5821 - 5825
(2021/08/01)
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- Synthetic method of substituted benzoyl isocyanate
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The invention discloses a preparation method of substituted benzoyl isocyanate, and belongs to the field of pesticide/medicine intermediates. Substituted benzoyl chloride and cyanate react in an organic solvent in the presence of a composite catalyst composed of a Lewis acid and p-toluene sulfonic acid to generate substituted benzoyl isocyanate. The method avoids the use of expensive oxalyl chloride, highly toxic phosgene, and the like, inhibits the generation of side reaction and byproduct namely cyanobenzene, selects the reaction conditions suitable for commercialization, enhances the selectivity and yield of the reaction, and reduces the generation of wastes, production cost, and environmental pollution.
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-
Paragraph 0023-0024
(2020/04/22)
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- Doramectin structural derivative and synthesis method thereof
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The invention belongs to the field of compound synthesis, and particularly relates to a Doramectin structural derivative and a synthesis method thereof. The novel Doramectin structural derivative adopts the specific technical scheme that the invention provides a series of novel Doramectin structural derivatives. Compared with a conventional chemical pesticide, the Doramectin structural derivativehas the advantages of being higher in efficiency, low in toxin, environmentally friendly, higher in applicability and the like, and is hopeful to become a new-generation green environment-friendly biological pesticide, wherein an acyl urea compound in which R is 2,6-difluorophenyl has favorable diamond-back moth resisting activity; an acyl urea compound in which R is C3H5 has favorable corn borerresisting activity; and an acyl thiourea homologues compound in which R is 2,6-difluorophenyl has favorable mythimna separata resisting activity.
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-
Paragraph 0047; 0052
(2020/03/03)
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- Design, Synthesis, and Insecticidal Activity of Novel Doramectin Derivatives Containing Acylurea and Acylthiourea Based on Hydrogen Bonding
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Our recent investigation on the insecticidal activities of several doramectin derivatives preliminarily revealed that the presence of hydrogen bonds at the C4″ position of the molecule with target protein γ-aminobutyric acid (GABA) receptor was crucial for retaining high insecticidal activity. As a continuation of our research work on the development of new insecticides, two series of novel acylurea and acylthiourea doramectin derivatives were designed and synthesized. The bioassay results indicated that the newly synthesized compounds (5o, 5t, and 6t) exhibited higher insecticidal activity against diamondback moth, oriental armyworm, and corn borer than the control compounds doramectin, commercial avermectins, chlorbenzuron, and lead compound 3g in our laboratory. Specifically, compound 5t was identified as the most promising insecticide against diamondback moth, with a final mortality rate of 80.00% at the low concentration of 12.50 mg/L, showing approximately 7.75-fold higher potency than the parent doramectin (LC50 value of 48.1547 mg/L), 6.52-fold higher potency than commercial avermectins (LC50 value of 40.5507 mg/L), and 3.98-fold higher potency than compound 3g (LC50 value of 24.7742 mg/L). Additionally, molecular docking simulations revealed that compound 5t (2.17, 2.20, 2.56, and 2.83 ?) displayed stronger hydrogen-bond action in binding with the GABA receptor, better than that of compound 5o (1.64 and 2.15 ?) and compound 6t (2.20 and 2.31 ?) at the C4″ position. This work demonstrated that these compounds containing hydrogen-bond groups might contribute to the improvement of insecticidal activity and supply certain hints toward structure optimization design for the development of new insecticides.
- Bai, Ping,Cheng, Yao,Lu, Xiaoxia,Yang, Jian,Zhang, Qi,Zheng, Cheng
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p. 5806 - 5815
(2020/06/19)
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- Novel acyl carbamates and acyl / diacyl ureas show in vitro efficacy against Toxoplasma gondii and Cryptosporidium parvum
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Toxoplasma gondii and Cryptosporidium parvum are protozoan parasites that are highly prevalent and opportunistically infect humans worldwide, but for which completely effective and safe medications are lacking. Herein, we synthesized a series of novel small molecules bearing the diacyl urea scaffold and related structures, and screened them for in vitro cytotoxicity and antiparasitic activity against T. gondii and C. parvum. We identified one compound (GMG-1-09), and four compounds (JS-1-09, JS-2-20, JS-2-35 and JS-2-49) with efficacy against C. parvum and T. gondii, respectively, at low micromolar concentrations and showed appreciable selectivity in human host cells. Among the four compounds with efficacy against T. gondii, JS-1-09 representing the diacyl urea scaffold was the most effective, with an anti-Toxoplasma IC50 concentration (1.21 μM) that was nearly 53-fold lower than its cytotoxicity IC50 concentration, indicating that this compound has a good selectivity index. The other three compounds (JS-2-20, JS-2-35 and JS-2-49) were structurally more divergent from JS-1-09 as they represent the acyl urea and acyl carbamate scaffold. This appeared to correlate with their anti-Toxoplasma activity, suggesting that these compounds’ potency can likely be enhanced by selective structural modifications. One compound, GMG-1-09 representing acyl carbamate scaffold, depicted in vitro efficacy against C. parvum with an IC50 concentration (32.24 μM) that was 14-fold lower than its cytotoxicity IC50 concentration in a human intestinal cell line. Together, our studies unveil a series of novel synthetic acyl/diacyl urea and acyl carbamate scaffold-based small molecule compounds with micromolar activity against T. gondii and C. parvum that can be explored further for the development of the much-needed novel anti-protozoal drugs.
- Grooms, Gregory M.,Hernandez, Anolan Garcia,Khan, Shahbaz M.,Li, Kun,Stec, Jozef,Witola, William H.
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-
- Synthetic method for aryl formyl isocyanate
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The invention relates to a preparation method, and mainly relates to a synthetic method for aryl formyl isocyanate, which includes: (1) dropwise adding an aryl formamide solution, dissolved in an organic solvent, to a bis(trichloromethyl)carbonate solution; (2) slowly heating the mixture to a high temperature of 60-180 DEG C, and at the temperature, completely dropwise adding the rest of the bis(trichloromethyl)carbonate to the solution in the step (1) within 0.5-5 h, and then continuously performing the reaction for 1-6 h, after the reaction is finished, recycling the organic solvent, and performing pressure-reduced distillation to the organic solvent to prepare the aryl formyl isocyanate. The method overcome the problems of poor safety and high investment cost due to use of oxalyl chloride or carbonyl chloride in the prior art. The method has reasonable processes, is environment-friendly, low-cost, safe and reliable, is high in yield of the aryl formyl isocyanate, is low in generation of waste water, waste gas and solid wastes, and is suitable for industrial production.
- -
-
Paragraph 0014; 0015; 0016; 0018
(2019/01/07)
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- Dehydration of Amides to Nitriles under Conditions of a Catalytic Appel Reaction
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A highly expedient protocol for a catalytic Appel-type dehydration of amides to nitriles has been developed that employs oxalyl chloride and triethylamine along with triphenylphosphine oxide as a catalyst. The reactions are usually complete in less than 10 min with only a 1 mol % catalyst loading. The reaction scope includes aromatic, heteroaromatic, and aliphatic amides, including derivatives of α-hydroxy and α-amino acids.
- Shipilovskikh, Sergei A.,Vaganov, Vladimir Yu.,Denisova, Elena I.,Rubtsov, Aleksandr E.,Malkov, Andrei V.
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supporting information
p. 728 - 731
(2018/02/09)
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- Aroyl Isocyanates as 1,4-Dipoles in a Formal [4 + 1]-Cycloaddition Approach toward Oxazolone Construction
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A formal phosphine-mediated [4 + 1]-cycloaddition between a 1,2-dicarbonyl and an aroyl isocyanate to provide oxazolones bearing a disubstituted C5 center is described. By exploiting the carbene-like reactivity of oxyphosphonium enolates as C1 synthons and aroyl isocyanates as formal 1,4-dipoles, oxazolones and spiroooxindole oxazolones are constructed in high yields (39-99%).
- Eckert, Kaitlyn E.,Ashfeld, Brandon L.
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supporting information
p. 2315 - 2319
(2018/04/30)
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- Convenient One-Pot Two-Step Synthesis of Symmetrical and Unsymmetrical Diacyl Ureas, Acyl Urea/Carbamate/Thiocarbamate Derivatives, and Related Compounds
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A wide range of chemicals such as amides, hydrazides, amines, alcohols, carbazate, and sulfonate were reacted with acyl isocyanates generated by the reaction of primary amides with oxalyl chloride to give symmetrical and unsymmetrical diacyl urea derivatives, acyl ureas/carbamates/thiocarbamates, and related compounds. This method provides means for convenient one-pot, two-step synthesis of compounds bearing urea, carbamate, and other functional groups from cheap and commercially available starting reagents. It is expected that the results presented in this report will expand the medicinal chemist’s toolbox.
- Hernandez, Anolan Garcia,Grooms, Gregory M.,El-Alfy, Abir T.,Stec, Jozef
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p. 2163 - 2176
(2017/05/05)
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- Synthesis, antitumor activity and mechanism of action of novel 1,3-thiazole derivatives containing hydrazide–hydrazone and carboxamide moiety
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A series of novel 2,4,5-trisubstituted 1,3-thiazole derivatives containing hydrazide–hydrazine, and carboxamide moiety including 46 compounds T were synthesized, and evaluated for their antitumor activity in vitro against a panel of five human cancer cell lines. Eighteen title compounds T displayed higher inhibitory activity than that of 5-Fu against MCF-7, HepG2, BGC-823, Hela, and A549 cell lines. Especially, T1, T26 and T38 exhibit best cytotoxic activity with IC50values of 2.21?μg/mL, 1.67?μg/mL and 1.11?μg/mL, against MCF-7, BCG-823, and HepG2 cell lines, respectively. These results suggested that the combination of 1,3-thiazole, hydrazide–hydrazone, and carboxamide moiety was much favorable to cytotoxicity activity. Furthermore, the flow cytometry analysis revealed that compounds T1 and T38 could induce apoptosis in HepG2 cells, and it was confirmed T38 led the induction of cell apoptosis by S cell-cycle arrest.
- He, Haifeng,Wang, Xiaoyan,Shi, Liqiao,Yin, Wenyan,Yang, Ziwen,He, Hongwu,Liang, Ying
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supporting information
p. 3263 - 3270
(2016/07/12)
-
- Synthesis and antitumor activity of novel N-benzoyl-N'-substituted pyrimidinyl (thio)semicarbazide derivatives
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A series of substituted pyrimidinyl (thio)semicarbazide derivatives were designed and synthesized. The antitumor results showed that the activity of thiosemicarbazide compounds (series II) was generally higher than that of the corresponding semicarbazide derivatives (series I). Among them, IIk displayed higher cytotoxicity against HL-60, BGC-823 and Bel-7402 than that of adriamycin and exhibited broad in vitro cytotoxicity against 13 human tumor cell lines. Meanwhile, the cytotoxic selectivity and anti-multidrug resistance were evaluated, and IIk exhibited selective cytotoxicity against cancer cells in comparison to human normal cells and had significant anti-multidrug resistance capability. The bioassay results showed that IIk showed great promise as a potent lead compound for further antitumor discovery.
- Song, Gaopeng,Li, Jianzuo,Tian, Hao,Li, Yasheng,Hu, Dekun,Li, Ying,Cui, Zining
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p. 329 - 334
(2016/04/04)
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- Copper(II)-catalyzed enantioselective intramolecular cyclization of N-alkenylureas
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The first Cu(II)-catalyzed highly enantioselective intramolecular cyclization of N-alkenylureas was developed for the concise assembly of chiral vicinal diamino bicyclic heterocycles. Facile removal of carbonyl group of the carbamido moiety allowed for ready access to enantioenriched cyclic vicinal diamines.
- Fu, Shaomin,Yang, Honghao,Deng, Yuanfu,Jiang, Huanfeng,Zeng, Wei,Li, Guoqiang
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supporting information
p. 1018 - 1021
(2015/03/30)
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- METHODS AND COMPOSITIONS FOR SELECTIVE AND TARGETED CANCER THERAPY
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Provided herein are methods and compositions for selective and targeted cancer therapy, in particular certain benzothiophenes, benzothiazoles, oxalamides, N-acyl ureas and chromones, and their use in selectively treating certain adenocarcinomas. In some embodiments, the selective toxicity of the compounds may be mediated through SCD1 and/or CYP450 such as CYP4F11.
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Page/Page column 233
(2015/03/28)
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- Novel acylureidoindolin-2-one derivatives as dual Aurora B/FLT3 inhibitors for the treatment of acute myeloid leukemia
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A series of 6-acylureido derivatives containing a 3-(pyrrol-2- ylmethylidene)indolin-2-one scaffold were synthesized as potential dual Aurora B/FLT3 inhibitors by replacing the 6-arylureido moiety in 6-arylureidoindolin-2- one-based multi-kinase inhibitors. (Z)-N-(2-(pyrrolidin-1-yl)ethyl)-5-((6-(3-(2- fluoro-4-methoxybenzoyl)ureido)-2-oxoindolin-3-ylidene)methyl)-2, 4-dimethyl-1H-pyrrole-3-carboxamide (54) was identified as a dual Aurora B/FLT3 inhibitor (IC50 = 0.4 nM and 0.5 nM, respectively). Compound 54 also exhibited potent cytotoxicity with single-digit nanomolar IC50 values against the FLT3 mutant-associated human acute myeloid leukemia (AML) cell lines MV4-11 (FLT3-ITD) and MOLM-13 (FLT3-ITD). Compound 54 also specifically induced extrinsic apoptosis by inhibiting the phosphorylation of the Aurora B and FLT3 pathways in MOLM-13 cells. Compound 54 had a moderate pharmacokinetic profile. The mesylate salt of 54 efficiently inhibited tumor growth and reduced the mortality of BALB/c nude mice (subcutaneous xenograft model) that had been implanted with AML MOLM-13 cells. Compound 54 is more potent than sunitinib not only against FLT3-WT AML cells but also active against sunitinib-resistant FLT3-ITD AML cells. This study demonstrates the significance of dual Aurora B/FLT3 inhibitors for the development of potential agents to treat AML.
- Jagtap, Ajit Dhananjay,Chang, Pei-Teh,Liu, Jia-Rong,Wang, Hsiao-Chun,Kondekar, Nagendra B.,Shen, Li-Jiuan,Tseng, Hsiang-Wen,Chen, Grace Shiahuy,Chern, Ji-Wang
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p. 268 - 288
(2014/08/18)
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- Asymmetric auto-tandem catalysis with a planar-chiral ruthenium complex: Sequential allylic amidation and atom-transfer radical cyclization
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Ru does it all: A novel example of an asymmetric auto-tandem reaction catalyzed by a planar-chiral cyclopentadienyl-ruthenium complex is described. The reaction of allylic chloride with α-haloamides provides synthetically useful, diastereomerically and enantiomerically enriched γ-lactams with multiple stereogenic centers through one-pot sequential allylic amidation/atom-transfer radical cyclization. PG=protecting group. Copyright
- Kanbayashi, Naoya,Takenaka, Kazuhiro,Okamura, Taka-Aki,Onitsuka, Kiyotaka
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supporting information
p. 4897 - 4901
(2013/06/05)
-
- Synthesis of 1,2-diketones from β-keto nitriles via a protection-oxidative-decyanation-deprotection protocol
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A variety of 1,2-diketones were prepared from -keto nitriles via a three-step protocol including the protection of the ketones with methoxyamine, oxidative decyanation, and microwave-assisted deprotection in the final step. This approach provides a novel and efficient access to a wide scope of symmetric and unsymmetric 1,2-diketones using molecular oxygen as the oxidant in the decyanation process. Georg Thieme Verlag Stuttgart - New York.
- Liu, Yu,Yun, Xiliu,Zhang-Negrerie, Daisy,Huang, Jianhui,Du, Yunfei,Zhao, Kang
-
supporting information; experimental part
p. 2984 - 2994
(2011/11/04)
-
- One-pot addition-intramolecular N-cyclization of carbamates mediated by alkali metallic reagents as an approach to 4-(fluoroalkyl)oxazolidin-2-ones
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A mild and straightforward strategy for the synthesis of 4-(fluoroalkyl)oxazolidin-2-ones via one-pot addition-intramolecular N-cyclization of allyl carbamates with fluoroalkyl iodides is presented. The reaction proceeded in moderate to good yield through regiocontrol and an increase in the reactivity of the ambident nucleophiles by the use of alkali metallic reagents. Georg Thieme Verlag Stuttgart. New York.
- Yang, Xue-Yan,Fang, Xiang,Ju, Zheng-Hua,Hu, Yun-Li,Wu, Fan-Hong
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experimental part
p. 3627 - 3634
(2011/12/21)
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- Separating agent for enantiomeric isomers
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The present invention provides a separating agent for enantiomeric isomers exhibiting high separation power. That is, the present invention provides a separating agent for enantiomeric isomers including, as an active ingredient, a polysaccharide derivative having at least part of hydrogen atoms of hydroxyl groups of a polysaccharide such as cellulose or amylose substituted by at least one of atomic groups represented by the following general formulae (I) and (II): (in the formulae, R represents a substituted or unsubstituted aromatic group, or a linear, branched, or cyclic aliphatic group).
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Page/Page column 6
(2010/04/23)
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- Aminimides derived from benzoylformic acid esters as thermally latent base catalysts
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As a novel thermal latent anionic initiator for lower temperature applications, a new class of aminimide, 1,1-dimethyl-1-(2-hydroxypropyl)amine benzoylformimide (BFI), was synthesized from benzoylformic acid methyl ester in 95% yield, and its thermal rearrangement behavior was studied in detail. Thermal rearrangement of BFI proved to take place on heating above 80 °C via the Curtius rearrangement mechanism, generating the corresponding isocyanate, hydroxyamine, and their further reaction products. BFI proved to catalyze the polymerization of epoxides and epoxide/thiol system on heating above 80 °C. They exhibit both the long pot life and the low-temperature rapid polymerization in the presence of BFI which supported the promising applications of BFI as an efficient thermal latent base catalyst for anionically polymerizable/curable systems.
- Kirino, Manabu,Tomita, Ikuyoshi
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scheme or table
p. 8821 - 8827
(2011/11/29)
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- Synthesis of vinyl-functionalized oxazoles by olefin cross-metathesis
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(Chemical Equation Presented) A ruthenium-based catalyzed olefin cross-methathesis reaction involving 2- and 4-vinyl-functionalized oxazoles was developed. A wide range of olefinic partners was coupled in good to excellent yields and high stereoselectivities under mild conditions. This methodology offers new opportunities for the synthesis of a plethora of biologically active natural products.
- Hoffman, Thomas J.,Rigby, James H.,Arseniyadis, Stellios,Cossy, Janine
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p. 2400 - 2403
(2008/09/18)
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- Synthesis, structure and biological activity of some new aroylurea derivatives containing 1,3,4-thiadiazole
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In an extensive search for biologically active aroylurea compounds as plant growth regulators, a series of new N-aroyl-N′-[5-(E)-styryl-1,3,4- thiadiazol-2-yl]ureas have been designed and synthesized. Their structures were characterized by IR, 1H NMR, MS, elemental analysis, and single-crystal X-ray diffraction techniques. The preliminary bioassay showed that some of the title compounds exhibited good plant-growth regulating activity. Copyright Taylor & Francis Group, LLC.
- Song, Xin-Jian,Tan, Xiao-Hong
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experimental part
p. 1755 - 1765
(2009/08/15)
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- Mild and direct conversion of quinoline N-oxides to 2-amidoquinolines with primary amides
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A simple, one-pot procedure is described for the direct conversion of quinoline N-oxides to α-amidoquinolines with primary amides. This methodology is complimentary to the Abramovich reaction, which is limited to the introduction of secondary amides via imidoyl chlorides. Although reaction conditions are quite similar, omission of the base is key for successful reaction with primary amides, which were found not to proceed through the intermediacy of an imidoyl chloride but rather through an acyl isocyanate.
- Couturier, Michel,Caron, Laurence,Tumidajski, Stephanie,Jones, Kris,White, Timothy D.
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p. 1929 - 1932
(2007/10/03)
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- A novel class of potent influenza virus inhibitors: Polysubstituted acylthiourea and its fused heterocycle derivatives
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A series of polysubstituted and fused heterocycle derivatives of acylthiourea was prepared and the biological activity against influenza virus was evaluated. Of the analogues that demonstrated IC50s 0.1 μM, acylthiourea derivatives 16 and 50 were further investigated as candidates with the most potential for future development. The SAR of these compounds are discussed and they represent a novel class of highly potent and selective inhibitors of influenza virus.
- Sun, Chuanwen,Huang, Hai,Feng, Meiqing,Shi, Xunlong,Zhang, Xiaodong,Zhou, Pei
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p. 162 - 166
(2007/10/03)
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- Synthesis and evaluation of a new series of substituted acyl(thio)urea and thiadiazolo [2,3-a] pyrimidine derivatives as potent inhibitors of influenza virus neuraminidase
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A series of substituted acyl(thio)urea and 2H-1,2,4-thiadiazolo [2,3-a] pyrimidine derivatives were prepared and both of their cell culture and enzymatic activity toward influenza virus were tested. Their in vitro neuraminidase inhibitory activities were in good agreement with the corresponding activities in cultured cells and they were evaluated as potent neuraminidase inhibitors. Of the analogues that demonstrated IC50s 0.1 μM, 16 and 60 were further investigated as candidates with the most potential for future development. The molecular docking work of the representative compound was described to provide more insight into their mechanism of action and further rationalize the observations of this new series herein, which represents a novel class of highly potent and selective inhibitors of influenza virus.
- Sun, Chuanwen,Zhang, Xiaodong,Huang, Hai,Zhou, Pei
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p. 8574 - 8581
(2008/02/07)
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- Facile, one-pot synthesis of bicyclic 2-pyridones from acyl isocyanates, N-phenylmaleimide and trimethylsilyldiazomethane
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The hetero-Diels-Alder reaction of 2-substituted 4-tri- methylsiloxyoxazoles, prepared in situ from trimethylsilyldiazomethane and acyl isocyanates, with N-phenylmaleimide followed by treatment with a catalytic amount of 10-camphorsulfonic acid efficiently gave bicyclic 2-pyridones in a one-pot process. Georg Thieme Verlag Stuttgart.
- Hari, Yoshiyuki,Iguchi, Tomoe,Aoyama, Toyohiko
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p. 2147 - 2150
(2007/10/03)
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- 3-D QSAR analysis of inhibition of murine soluble epoxide hydrolase (MsEH) by benzoylureas, arylureas, and their analogues
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Two hundred and seventy-one compounds including benzoylureas, arylureas and related compounds were assayed using recombinant murine soluble epoxide hydrolase (MsEH) produced from a baculovirus expression system. Among all the insect growth regulators assayed, 18 benzoylphenylurea congeners showed weak activity against MsEH. Newly synthesized cyclohexylphenylurea, 1-benzyl-3-phenylurea, and 1,3-dibenzylurea analogues were rather potent. The introduction of a methyl group at the para-position of the phenyl ring of cyclohexylphenylurea enhanced the activity 6-fold, though similar substituent effects were not seen for any of the benzoylphenylureas. The activities of these compounds, including several previously reported compounds, such as dicyclohexylurea, diphenylurea, and their related analogues (Morisseau et al., Proc. Natl. Acad. Sci., 1999, 96, 8849), were quantitatively analyzed using comparative molecular field analysis (CoMFA), a three-dimensional quantitative structure-activity relationship (3-D QSAR) method. Both steric and electrostatic factors contributing to variations in the activity were visualized using CoMFA. CoMFA results showed that one side of the cyclohexylurea moiety having a trans-amide conformation (A-ring moiety) is surrounded by large sterically unfavorable fields, while the other side of A-ring moiety and the other cyclohexyl group (B-ring moiety) is encompassed by sterically favored fields. Electrostatically negative fields were scattered around the entire molecule, and a positive field surrounds the carbon of the carbonyl group. Hydrophobic fields were visualized using Kellogg's hydropathic interaction (HINT) in conjunction with CoMFA. Hydrophobically favorable fields appeared beside the 4- and 4'-carbon atoms of the cyclohexyl groups, and hydrophobically unfavorable fields surrounded the urea bridge. The addition of the molecular hydrophobicity, it> /it>, to CoMFA did not improve the correlation significantly. The ligand-binding interactions shown by X-ray crystallographic data were rationalized using the results of the CoMFA and HINT analyses, and the essential physicochemical parameters for the design of new MsEH inhibitors were disclosed. Copyright (C) 2000 Elsevier Science Ltd.
- Nakagawa, Yoshiaki,Wheelock, Craig E.,Morisseau, Christophe,Goodrow, Marvin H.,Hammock, Bruce G.,Hammock, Bruce D.
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p. 2663 - 2673
(2007/10/03)
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- A new approach to the stereoselective total synthesis of isotopically labeled D-ribo-phytosphingosine
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We describe a novel stereoselective total synthesis of D-ribo-[1,1-2H- 1,2-13C]phytosphingosine (12). Chirality at the incipient C-4 position was derived from asymmetric dihydroxylation of 1-hexadecene. The remaining chiral centers were formed by Sharpless epoxidation of an allylic alcohol, followed by benzoylcarbamate cyclization to furnish a 2-amino-1,3,4-triol derivative with the desired stereochemistry. The 2H and 13C labels were introduced by Horner-Emmons condensation of 13C-labeled triethyl phosphonoacetate, followed by reduction of the resulting carboxylic ester with AlCl3/LiAlD4. Mass spectral results indicated the suitability of 12 as an internal standard for analyses by the isotope dilution method.
- Li, Shengrong,Pang, Jihai,Wilson, William K.,Schroepfer Jr., George J.
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p. 1697 - 1707
(2007/10/03)
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- Method of preparing acylisocyanates
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The invention relates to a novel process for the preparation of acyl isocyanates which consists in reacting oxalyl chloride with an N-trialkylsilylcarboxamide or an N,N-bis(trialkylsilyl)carboxamide. The process makes it possible to obtain acyl isocyanates in good yield, in particular acyl isocyanates derived from aliphatic amides, and under simplified reaction conditions.
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-
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- Novel carbamates as potent histamine H3 receptor antagonists with high in vitro and oral in vivo activity
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The known histamine H3 receptor antagonists burimamide, thioperamide, clobenpropit, and a related homohistamine thioamide derivative were taken as templates in search for new leads. Novel histamine H3 receptor antagonists structurally described as carbamate derivatives of 3-(1H-imidazol-4- yl)propanol were prepared in high yields by treatment of the alcohol with corresponding isocyanates or carbamoyl chlorides and investigated for their H3 receptor antagonist activity. Different chain lengths and various substituents possessing different electronic and steric parameters were introduced and structure-activity relationships established. In different functional tests, the new antagonists showed high H3 receptor antagonist potencies in vitro (-log K(i) values of 6.4-8.4) at synaptosomes of rat cerebral cortex and low activities at histamine H1 and H2 receptor subtypes. They were also screened for their central in vivo activity in mice after peroral administration. The most promising compounds (2, 16, 19) showed ED50 values of about 1-2 mg/kg and thus are potential drugs for the therapy of H3 receptor dependent diseases. Some of the novel carbamate derivatives are H3 receptor selective compounds with high in vitro and in vivo activity.
- Stark, Holger,Purand, Katja,Ligneau, Xavier,Rouleau, Agnès,Arrang, Jean-Michel,Garbarg, Monique,Schwartz, Jean-Charles,Schunack, Walter
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p. 1157 - 1163
(2007/10/03)
-
- Convenient synthesis of 4-methylene-2-oxazolidinones and 4-methylenetetrahydro-1,3-oxazin-2-ones via transition-metal catalyzed intramolecular addition of nitrogen atom to actylenic triple bond
-
2-Propynyl tosylcarbamates 1 undergo cyclization smoothly by the catalysis of CuCl/Et3N or AgNCO/Et3N to furnish 4-methylene-2-oxazolidinones 2 in good yields. The similar cyclization of the N-acyl derivatives of 1 (PhCO, MeCO, EtOCO, etc.) is catalyzed effectively by AgNCO/t-BuOK. These reactions accommodate a variety of substituents at C1 and C3 of 2-propyn-1-ol and provide (Z)-2 as single stereoisomers. The scope of the cyclization of 3-butynyl carbamates is rather limited, and in general only N-tosyl derivatives of terminally unsubstituted 3-butyn-1-ols undergo cyclization to give 4-methylenetetrahydro-1,3-oxazin-2-ones in synthetically useful yields by the catalysis of AgNCO/Et3N or AgNCO/t-BuOK.
- Tamaru,Kimura,Tanaka,Kure,Yoshida
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p. 2838 - 2849
(2007/10/02)
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- Nitrosations with hydrazine derivative, VI: Novel reaction of oral antidiabetics of the sulfonylsemicarbazide type under nitrosating conditions
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Oral antidiabetics of the sulfonylsemicarbazide type like Tolazamide (1) and Glisoxepide (2) were transformed under mild nitrosating conditions, even nearly physiological in vitro conditions, to sulfonyl triazenes 3a, b by a novel reaction pathway. Model compounds with N4-Acyl-semicarbazide structure 4 showed different reaction behaviour yielding carbonamides 5 and nitrosamines 6.
- Hanefeld,Hartmann
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p. 925 - 927
(2007/10/02)
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- Ozonolysis of 5-Bromo- and 5-Ethoxy-2-phenyloxazoles. The Products and the Reaction Mechanism
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The ozonolysis of 2-phenyloxazoles having the good leaving group as an anion at C-5 position gave mainly N-benzoylisocyanate (2) with the formation of carbon dioxide.
- Kashima, Choji,Arao, Hideki
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p. 805 - 807
(2007/10/02)
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- Synthesis and anthelmintic activity of 3'-benzoylurea derivatives of 6-phenyl-2,3,5,6-tetrahydroimidazo[2,1-b]thiazole
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Reaction of 3-amino derivatives of the nematocides tetramisole and levamisole with variously substituted benzoylisocyanates gave a series of benzoylureas I which were tested for activity against helminths and ectoparasites. Compounds bearing 2,6-difluoro and 4-trifluoromethyl substituents had potent nematocidal activity in both mice and sheep. No antiectoparasitic activity was observed.
- Weikert,Bingham Jr.,Emanuel,Fraser-Smith,Loughhead,Nelson,Poulton
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p. 1630 - 1633
(2007/10/02)
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- Process for the preparation of acyl isocyanates
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The invention relates to a process for the preparation of acyl isocyanates of formula STR1 in which R is an alkyl radical, a substituted or unsubstituted naphthyl or phenyl radical or a substituted or unsubstituted aromatic heterocyclic radical, which con
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- A FACILE SYNTHESIS OF N'-BENZOYL THIOPHOSPHORYLUREAS
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Twelve title compounds 3a-l were synthesized by nucleophilic addition of thiophosphoramide 1 to benzoylisocyanate 2.The yield of compounds 3a-f and 3g-l is 72-83percent and 18-33percent.
- Liu, Zhaojie,Li, Xianfeng,Zhang, Jinglin
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p. 1189 - 1196
(2007/10/02)
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- CONDENSATION OF ACYL CHLORIDE ON SODIUM CYANATE : PREPARATION OF ACYL ISOCYANATES
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The catalytic effects of various metal halides and solvents on the reaction of benzoyl chloride with sodium cyanate were studied.It has been found that SnCl4, and ZnCl2 catalyze the reaction to give the corresponding acyl isocyanates in good yields.The scope of the reaction was studied and a number of aroyl isocyanates and their derivatives were prepared.A few non aromatic isocyanates and their derivatives were also prepared.
- Deng, M. Z.,Caubere, P.,Senet, J. P.,Lecolier, S.
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p. 6079 - 6086
(2007/10/02)
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- ADDITION OF PYRIDINE AND ISOQUINOLINE TO BENZOYLCARBONITRILE OXIDE
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Addition of pyridine to benzoylcarbonitrile oxide affords a fragile zwitterionic adduct, which slowly reverts to the addends, leading ultimately to benzoyl isocyanate and products deriving from it.A moderately stable cycloadduct is obtained in the reaction with isoquinoline.
- Caramella, P.,Bandiera, T.,Albini, F. Marinone,Gamba, A.,Corsaro, A.,Perrini, G.
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p. 4917 - 4926
(2007/10/02)
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- N-BENZOYLCARBAMATE CYCLIZATIONS
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The anion of an alcohol derived N-benzoylcarbamate may be used to deliver nitrogen intramolecularly to electrophilic centers.This allows the stereocontrolled synthesis of a variety of amino-alcohol and amino-diol derivatives.
- Knapp, Spencer,Kukkola, Paivi J.,Sharma, Shashi,Pietranico, Sherrie
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p. 5399 - 5402
(2007/10/02)
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- CYCLOFUNCTIONALISATION REACTIONS OF EPOXYALCOHOL DERIVATIVES. 3. CYCLISATION-ACYL MIGRATION OF N-BENZOYLCARBAMATES TO STEREODEFINED OXAZOLIDINONES. A NEW, DIASTEREOSPECIFIC ROUTE TO THIAMPHENICOL.
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N-Benzoylcarbamates formed in situ from 2,3-epoxyalcohols and PhCONCO undergo clean to C-2 cyclisation followed by N to O acyl migration on treatment with catalytic sodium imidazolide or other bases.Subsequent benzoate cleavage (NaOMe) is accompanied by equilibration of the N-unsubstituted oxazolidinones; cleavage without significant isomerisation is achieved with MeLi or Zn(BH4)2.This methodology is applied in a diastereospecific, 6-step conversion of methyl 4-bromophenyl sulfonate to racemic Thiamphenicol.
- McCombie, S. W.,Nagabhushan, T. L.
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p. 5395 - 5398
(2007/10/02)
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- Reactions of (E)-1-Methoxy-1-trimethylsiloxyprop-1-ene with Acyl Isocyanates and Acyl Isothiocyanates
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Reaction of aryl acyl,and alkyl acyl isocyanates with (E)-1-methoxy-1-trimethylsiloxyprop-1-ene affords high yields of various methyl 3-acylamino-2-methyl-3-oxopropanoates.The corresponding acyl isothiocyanates give a variety of products depending on the structure of the isothiocyanate.
- Cambie, Richard C.,Davis, Paul F.,Rutledge, Peter S.,Woodgate, Paul D.
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p. 2073 - 2084
(2007/10/02)
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- Reactions de cycloaddition entre acyl (ou thioacyl) isocyanates (ou isothiocyanates) et isocyanates (ou isothiocyanates)
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cycloaddition of an acylisocyanate (1a-1f) to an isocyanate (2a-2c) affords 2,4-dioxo-3,4-dihydro-1,3,5-2H-oxadiazine (4a-4j). Kinetic addition is observed with chloroacetyl (1g) or phenoxyacetyl (1h) isocyanate and methyl isocyanate (2a) to yield a dioxoazetidine (3a and 3b respectively).The reaction of N-dimethylcarbamoyl isothiocyanate (1c) with aromatic isocyanate (2c) or isothiocyanates (2d and 2e) is a cycloaddition too, yielding thioxo (4k) and dithioxo-oxadiazines (4l and 4m).But with the aliphatic isocyanates (2a and 2b) we have observed a preliminary rearrangement of N-dimethylcarbamoyl isothiocyanate 1i to N-dimethylthiocarbamoyl isocyanate 1j and we have obtained 1,3,5-2H-thiadiazines (4n and 4p). Type 1 compounds Acylisocyanates X = Y = O R1 = a : phenyl; b : 3-nitrophenyl; c : 4-nitrophenyl; d : 4-chloro-3,5-dinitrophenyl; e : 4-chloro-2-methylphenoxymethyl; f : 2',4',5'-trichloro-1-phenoxyethyl; g : chloromethyl; h : phenoxymethyl.For R1 = N-dimethyl : N-dimethylcarbamoyl isothiocyanate : i : X = O Y = S; N-dimethylthiocarbamoyl isocyanate : j : X = S Y = O; N-dimethylthiocarbamoyl isothiocyanate : k : X = Y = S.Type 2 compounds Isocyanates Z = O R2 = a : methyl; b : ethyl; c : phenyl; Isothiocyanates Z = S R2 = d : phenyl; e : 4-fluorophenyl.Type 3 compounds Dioxoazetidines X = Y = Z = O R2 = methyl R1 = a : chloroacetyl; b : phenoxyacetyl.Type 4 compounds 1,3,5-2H-oxadiazines X = Y = Z = O R1 = phenyl R2 = a : methyl; b : ethyl; c : phenyl; R2 = methyl R1 = d : 3-nitrophenyl; e : 4-nitrophenyl; f : 4-chloro-3,5-dinitrophenyl; g : 4-chloro-2-methylphenoxymethyl; h : 2',4',5'-trichlorophenoxyethyl; i : chloromethyl; j : phenoxymethyl.For R1 = N-dimethyl : 4-thioxo-1,3,5-oxadiazines : X = Z = O Y = S R2 = k : phenyl 2,4-dithioxo-1,3,5-2H-oxadiazines : X = O Y = Z = S R2 = l : phenyl; m : 4-fluorophenyl. 1,3,5-2H-thiadiazines : X = S Y = Z = O R2 = n : methyl; p : ethyl.
- Ratton, Serge,Moyne, Jose,Longeray, Remi
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- Reaction of Guanidinium Salts with Alkyl Bromides and Acid Chlorides
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The guanidinium salt 1a reacts with alkyl bromides 2a-g and acid chlorides 2h-k to give the nitriles 3a-g and the acyl cyanides 3h-k, respectively.Acyl isocyanates 4a,b have been obtained from the guanidinium cyanate 1d and the acid chlorides 2h,l.Reaction of the alkyl bromides 2b,c,m,n and acid chlorides 2h,l with the guanidinium thiocyanate 1e affords alkyl thiocyanates 5a-d and acyl isothiocyanates 6a,b, respectively.
- Kantlehner, Willi,Kapassakalidis, Johannis J.,Speh, Peter,Braeuner, Hans-Juergen
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p. 389 - 393
(2007/10/02)
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