- Synthetic method of aromatic amide alkene compound
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The invention discloses a synthesis method of an aromatic amide alkene compound, which comprises the following steps: mixing a carbamyl chloride compound 1 and isopropyl magnesium bromide 2 in the presence of inert gas at low temperature, and then carrying out heating reaction to obtain the aromatic amide alkene compound 3. Compared with the prior art, the method has the advantages that the Grignard reagent isopropenyl magnesium bromide reacts with the carbamyl chloride compound, the aromatic amide alkene compound is synthesized in one step, the reaction speed is high, and the product yield is high.
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Paragraph 0037-0039
(2021/11/27)
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- Synthesis and Biological Evaluation of Celastrol Derivatives with Improved Cytotoxic Selectivity and Antitumor Activities
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Cdc37 associates kinase clients to Hsp90 and promotes the development of cancers. Celastrol, a natural friedelane triterpenoid, can disrupt the Hsp90-Cdc37 interaction to provide antitumor effects. In this study, 31 new celastrol derivatives, 2a - 2d , 3a - 3g , and 4a - 4t , were designed and synthesized, and their Hsp90-Cdc37 disruption activities and antiproliferative activities against cancer cells were evaluated. Among these compounds, 4f , with the highest tumor cell selectivity (15.4-fold), potent Hsp90-Cdc37 disruption activity (IC50= 1.9 μM), and antiproliferative activity against MDA-MB-231 cells (IC50= 0.2 μM), was selected as the lead compound. Further studies demonstrated 4f has strong antitumor activities both in vitro and in vivo through disrupting the Hsp90-Cdc37 interaction and inhibiting angiogenesis. In addition, 4f exhibited less toxicity than celastrol and showed a good pharmacokinetics profile in vivo. These findings suggest that 4f may be a promising candidate for development of new cancer therapies.
- Feng, Jia-Hao,He, Qi-Wei,Hou, Ji-Qin,Hu, Xiao-Long,Long, Huan,Wang, Bao-Lin,Wang, Hao,Wang, Quan,Wang, Rong,Ye, Wen-Cai,Zhang, Li-Xin,Zhang, Xiao-Qi
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p. 1954 - 1966
(2021/07/20)
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- N-heterocyclic (4-phenylpiperazin-1-yl)methanones derived from phenoxazine and phenothiazine as highly potent inhibitors of tubulin polymerization
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We report here a series of 27 10-(4-phenylpiperazin-1-yl)methanones derived from tricyclic heterocycles which were screened for effects on tumor cell growth, inhibition of tubulin polymerization, and induction of cell cycle arrest. Several analogues, among them the 10-(4-(3-methoxyphenyl)piperazine-1-carbonyl)-10H-phenoxazine-3-carbonitrile (16o), showed excellent antiproliferative properties, with low nanomolar GI50 values (16o, mean GI50 of 3.3 nM) against a large number (93) of cancer cell lines. Fifteen compounds potently inhibited tubulin polymerization. Analysis of cell cycle by flow cytometry revealed that inhibition of tumor cell growth was related to an induction of G2/M phase cell cycle blockade. Western blotting and molecular docking studies suggested that these compounds bind efficiently to β-tubulin at the colchicine binding site. Our studies demonstrate the suitability of the phenoxazine and phenothiazine core and also of the phenylpiperazine moiety for the development of novel and potent tubulin polymerization inhibitors.
- Prinz, Helge,Ridder, Ann-Kathrin,Vogel, Kirsten,B?hm, Konrad J.,Ivanov, Igor,Ghasemi, Jahan B.,Aghaee, Elham,Müller, Klaus
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p. 749 - 766
(2017/02/05)
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- A containing asymmetric urea functional organic siloxane and its preparation method
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The invention discloses functional organosiloxane containing asymmetrical substituted urea and a preparation method thereof. The preparation method comprises the following steps: carrying out reaction between 4, 4'-dibromodiphenylamine and triphosgene to obtain (i) N, N(/i)-di(4-bromo phenyl) carbamyl chloride; and then, carrying out reaction with 3-aminopropyl triethoxysilane to obtain functional organosiloxane, wherein the organosiloxane is the functional organosiloxane containing asymmetrical substituted urea through the verification of infrared spectrum, ultraviolet spectrum, 1H-NMR (1Hydrogen-Nuclear Magnetic Resonance) and 13C-NMR. The structure of the compound contains a plurality of functional groups such as siloxane, amide, urea groups and bromoaryl. The functional organosiloxane has a potential application value on the respects of molecular imprinting recognition materials, structural flame retardant materials, rare earth light emitting materials, white carbon black and the like. The functional organosiloxane disclosed by the invention is reasonable in synthetic line, mild in condition, easy to operate, low in cost of raw materials and high in product yield.
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Paragraph 0049; 0050
(2017/02/09)
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- Optimization of 1,2,5-thiadiazole carbamates as potent and selective ABHD6 inhibitors
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At present, inhibitors of α/β-hydrolase domain 6 (ABHD6) are viewed as a promising approach to treat inflammation and metabolic disorders. This article describes the development of 1,2,5-thiadiazole carbamates as ABHD6 inhibitors. Altogether, 34 compounds were synthesized, and their inhibitory activity was tested using lysates of HEK293 cells transiently expressing human ABHD6 (hABHD6). Among the compound series, 4-morpholino-1,2,5-thiadiazol-3-yl cyclooctyl(methyl)carbamate (JZP-430) potently and irreversibly inhibited hABHD6 (IC50 = 44 nM) and showed ～ 230-fold selectivity over fatty acid amide hydrolase (FAAH) and lysosomal acid lipase (LAL), the main off-targets of related compounds. Additionally, activity-based protein profiling indicated that JZP-430 displays good selectivity among the serine hydrolases of the mouse brain membrane proteome. JZP-430 has been identified as a highly selective, irreversible inhibitor of hABHD6, which may provide a novel approach in the treatment of obesity and type II diabetes.
- Patel, Jayendra Z.,Nevalainen, Tapio J.,Savinainen, Juha R.,Adams, Yahaya,Laitinen, Tuomo,Runyon, Robert S.,Vaara, Miia,Ahenkorah, Stephen,Kaczor, Agnieszka A.,Navia-Paldanius, Dina,Gynther, Mikko,Aaltonen, Niina,Joharapurkar, Amit A.,Jain, Mukul R.,Haka, Abigail S.,Maxfield, Frederick R.,Laitinen, Jarmo T.,Parkkari, Teija
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p. 253 - 265
(2015/02/05)
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- Asymmetric α-arylation of amino acid derivatives by clayden rearrangement of ester enolates via memory of chirality
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A method for asymmetric α-arylation of amino acid derivatives has been developed. The arylation was performed by Clayden rearrangement of ester enolates via memory of chirality to give hydantoins with an aryl-substituted tetrasubstituted carbon with up to 99% ee.
- Tomohara, Keisuke,Yoshimura, Tomoyuki,Hyakutake, Ryuichi,Yang, Pan,Kawabata, Takeo
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supporting information
p. 13294 - 13297
(2013/09/24)
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- Rhenium(I) tricarbonyl complexes of salicylaldehyde semicarbazones: Synthesis, crystal structures and cytotoxicity
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A series of N,N-disubstituted salicylaldehyde semicarbazones (SSCs), HOC6H4CHN-NHCONR2, and their rhenium(I) tricarbonyl complexes, [ReBr(CO)3(SSC)], have been synthesised and characterised by IR and 1H NMR spectroscopy. Crystallographic analysis of the complex [ReBr(CO)3(H2Bu2)] (H2Bu2 = SSC where R = Bun) showed that the SSC acts as a bidentate ligand via its imino nitrogen and carbonyl oxygen atoms. The [ReBr(CO)3(SSC)] complexes exhibit moderate to high cytotoxicities towards MOLT-4 cells (IC50 = 1-24 μM, cf. 18 μM for cisplatin), and the majority of them are virtually non-toxic against non-cancerous human fibroblasts. Apoptotic assays of [ReBr(CO) 3(H2Bnz2)] (Bnz = benzyl) revealed that it mediates cytotoxicity in MOLT-4 cells via apoptosis. The complex [ReBr(CO) 3(H2Bnz2)] reacts with guanosine by proton transfer from the phenolic OH group to N(7) of guanosine. In (CD 3)2SO, [ReBr(CO)3(H2Bnz 2)] undergoes facile conversion to the dimeric complex, [Re(CO) 3(HBnz2)]2, via bromide dissociation.
- Ho, Junming,Lee, Wan Yen,Koh, Kelvin Jin Tai,Lee, Peter Peng Foo,Yan, Yaw-Kai
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- A novel and efficient strategy for the synthesis of various carbamates using carbamoyl chlorides under solvent-free and grinding conditions using microwave irradiation
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We present an efficient, fast and simple strategy of generating the intermediate carbamoyl chlorides from secondary amines using stoichiometric amounts of bis(trichloromethyl)carbonate (BTC) in solution and solvent-free conditions with excellent yields. The results obtained showed the yield increasing on whether a base was used. Finally, an efficient and rapid synthesis of variety carbamate derivatives was developed by the reaction with a high variety of different alcohols, phenols, diols and this intermediate at room temperature with grinding and in solvent-free conditions under microwave irradiation. The presence of various safe bases is shown to be effective in reducing the reaction times, increasing the yields and easing purification. The present method does not involve any hazardous phosgene.
- Zare, Hassan,Ghanbari, Mohammad Mehdi,Jamali, Marzieh,Aboodi, Abdollah
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scheme or table
p. 883 - 886
(2012/08/28)
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- Unexpected zirconium-mediated multicomponent reactions of conjugated 1,3-butadiynes and monoynes with acyl cyanide derivatives
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Going ber(zirc): Zirconium-butadiyne complexes react with acyl cyanide derivatives through diverse reaction pathways. The complexes react with two molecules of carbamoyl cyanide to form 1,4-benzodiazepin-2-one-derivatives containing azazirconacycles. Reac
- Yu, Shasha,You, Xu,Liu, Yuanhong
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supporting information
p. 13936 - 13940
(2013/01/15)
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- Discovery of novel quaternary ammonium derivatives of (3R)-quinuclidinyl carbamates as potent and long acting muscarinic antagonists
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Novel quaternary ammonium derivatives of N,N-disubstituted (3R)-quinuclidinyl carbamates have been identified as potent M3 muscarinic antagonists with long duration of action in an in vivo model of bronchoconstriction. These compounds have also presented a high level of metabolic transformation (human liver microsomes). The synthesis, structure-activity relationships and biological evaluation of these compounds are reported.
- Prat, Maria,Buil, María Antonia,Fernández, Maria Dolors,Castro, Jordi,Monleón, Juan Manuel,Tort, Laia,Casals, Gaspar,Ferrer, Manuel,Huerta, Josep Maria,Espinosa, Snia,López, Manuel,Segarra, Victor,Gavald, Amadeu,Miralpeix, Montserrat,Ramos, Israel,Vilella, Dolors,González, Marisa,Córdoba, Mnica,Cárdenas, Alvaro,Antón, Francisca,Beleta, Jorge,Ryder, Hamish
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p. 3457 - 3461
(2011/06/24)
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- Iridium-catalyzed annulation of N -arylcarbamoyl chlorides with internal alkynes
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An iridium complex successfully catalyzed the annulation of various N-arylcarbamoyl chlorides with internal alkynes to afford 2-quinolones in good to excellent yields. The present reaction is widely applicable to substrates with various functionalities. An amide-iridacycle complex was isolated, and it is likely that such an iridacycle species is a key intermediate in the catalytic reaction.
- Iwai, Tomohiro,Fujihara, Tetsuaki,Terao, Jun,Tsuji, Yasushi
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supporting information; experimental part
p. 9602 - 9603
(2010/08/22)
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- One-pot radiosynthesis of [13N]urea and [13N] carbamate using no-carrier-added [13N]NH3
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The aim of this study was to develop a practical labeling method of [ 13N]ligands using no-carrier-added [13N]NH3 with high specific activity. [13N]urea analogues [13N]1a and [13N]2a or [13N]carbamate [13N]3a were synthesized by reacting isocyanate 5a, carbamoyl chloride 6a or chloroformate 7a with [13N]NH3. The precursors 5a-7a were prepared by treating amines 8a and 9a and alcohol 10a with triphosgene in situ. These reaction mixtures were not purified and were used directly for [ 13N]ammonolysis, respectively. Using the one-pot method, we synthesized [13N]carbamazepine ([13N]4), a putative positron emission tomography ligand for brain imaging. Copyright
- Kumata, Katsushi,Takei, Makoto,Ogawa, Masanao,Kato, Koichi,Suzuki, Kazutoshi,Zhang, Ming-Rong
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experimental part
p. 166 - 172
(2010/07/02)
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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)
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- Method of generating lower alkyl and cycloalkyl isocyanates
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A method of generating lower alkyl and cycloalkyl isocyanates in situ by pyrolysis of an appropriately selected alkyl aryl urea of the formula STR1 where R1 aryl, R2 may be either alkyl, cycloalkyl or aryl, and in which R3 is the specific lower (C1 through C6) alkyl or cycloalkyl radical of the isocyanate selected to be generated.
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