- Solid-supported sulfonylhydroxylamine as an effective N-animating agent of anilines
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An effective method for the synthesis of aryl hydrazines by amination of anilines using the solid-supported phenylsulfonylhydroxylamine was described. Treatment of aniline with the solid-supported aminating agent, followed by removal of the resin, provided the corresponding hydrazine in 21% yield. The resulting hydrazines were directly adapted to the solid-phase synthesis of indoles, providing nine naltrindole derivatives varying the substituents on the aromatic rings.
- Ohno, Hiroshi,Tanaka, Hiroshi,Takahashi, Takashi
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Read Online
- Synthesis of benzofuro[3,2-b] indoline amines via deamination-interrupted Fischer indolization and their unexpected reactivity towards nucleophiles
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We report the access to the benzofuro[3,2-b]indoline framework of phalarine from benzofuran-2-ones via the Fischer indolization reaction which was interrupted at the deamination step. Unexpectedly, allyl nucleophiles did not add to the aminal position of these benzofuro[3,2-b]indoline amines but to the adjacent ring junction center in the presence of trifluoroborane to deliver 3,3-disubstituted indolines containing a difluoroboron-containing six-membered ring with fluorescence properties.
- Tomakinian, Terry,Guillot, Régis,Kouklovsky, Cyrille,Vincent, Guillaume
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Read Online
- Discovery of novel inhibitors of human phosphoglycerate dehydrogenase by activity-directed combinatorial chemical synthesis strategy
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Serine, the source of the one-carbon units essential for de novo purine and deoxythymidine synthesis plays a crucial role in the growth of cancer cells. Phosphoglycerate dehydrogenase (PHGDH) which catalyzes the first, rate-limiting step in de novo serine biosynthesis has become a promising target for the cancer treatment. Here we identified H-G6 as a potential PHGDH inhibitor from the screening of an in-house small molecule library based on the enzymatic assay. We adopted activity-directed combinatorial chemical synthesis strategy to optimize this hit compound. Compound b36 was found to be the noncompetitive and the most promising one with IC50 values of 5.96 ± 0.61 μM against PHGDH. Compound b36 inhibited the proliferation of human breast cancer and ovarian cancer cells, reduced intracellular serine synthesis, damaged DNA synthesis, and induced cell cycle arrest. Collectively, our results suggest that b36 is a novel PHGDH inhibitor, which could be a promising modulator to reprogram the serine synthesis pathway and might be a potential anticancer lead worth further exploration.
- Gou, Kun,Luo, Youfu,Luo, Yuan,Sun, Qingxiang,Tan, Yuping,Tao, Lei,Zhao, Yinglan,Zhou, Xia,Zhou, Yue,Zuo, Zeping
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- Cross-Coupling between Hydrazine and Aryl Halides with Hydroxide Base at Low Loadings of Palladium by Rate-Determining Deprotonation of Bound Hydrazine
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Reported here is the Pd-catalyzed C–N coupling of hydrazine with (hetero)aryl chlorides and bromides to form aryl hydrazines with catalyst loadings as low as 100 ppm of Pd and KOH as base. Mechanistic studies revealed two catalyst resting states: an arylpalladium(II) hydroxide and arylpalladium(II) chloride. These compounds are present in two interconnected catalytic cycles and react with hydrazine and base or hydrazine alone to give the product. The selectivity of the hydroxide complex with hydrazine to form aryl over diaryl hydrazine was lower than that of the chloride complex, as well as the catalytic reaction. In contrast, the selectivity of the chloride complex closely matched that of the catalytic reaction, indicating that the aryl hydrazine is derived from this complex. Kinetic studies showed that the coupling process occurs by rate-limiting deprotonation of a hydrazine-bound arylpalladium(II) chloride complex to give an arylpalladium(II) hydrazido complex.
- Borate, Kailaskumar,Choi, Kyoungmin,Goetz, Roland,Hartwig, John F.,Shinde, Harish,Wang, Justin Y.,Zuend, Stephan J.
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supporting information
p. 399 - 408
(2020/10/29)
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- PROCESS FOR THE SYNTHESIS OF ARYL HYDRAZINES
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The invention relates to a process for the synthesis of aryl hydrazinesof formula I or a salt thereof, which process comprises subjecting an arene of formula II to a coupling reaction with hydrazine or a derivative thereof, wherein the coupling reaction is conducted in the presence of a catalyst comprising palladium and a diphosphine ligand, wherein the phosphorus atoms are connected through two, three, four, or five atoms selected from car- bon, nitrogen, oxygen or iron, and in which the non-connecting phosphorus substituents are C1- C 10-alkyl or C3-C10-cycloalkyl, wherein the amount of Pd used is up to 0.5 mol-% relative to the amount of arene of formula II; and a base.
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Page/Page column 21-23; 25; 26; 30; 31; 34; 35
(2020/06/01)
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- Method for synthesizing 1-(2,4-dichlorophenyl)-3-methyl-4-difluoromethyl-1,2,4-triazole-5-ketone
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The invention discloses a method for synthesizing 1-(2,4-dichlorophenyl)-3-methyl-4-difluoromethyl-1,2,4-triazole-5-ketone. The method takes p-chloroaniline as a raw material, through diazotization, reduction, and salt forming, p-chlorophenylhydrazine hydrochloride is synthesized, p-chlorophenylhydrazine is obtained through alkali neutralization, under condition that tert-butyl alcohol is taken asa solvent, chlorophenylhydrazine, acetaldehyde, sodium cyanate and sodium hypochlorite are subjected to condensation, cyclisation and an oxidation reaction to generate 1-p-chlorophenyl-3-methyl-1H-1,2,4-triazole-5-ketone, and the 1-p-chlorophenyl-3-methyl-1H-1,2,4-triazole-5-ketone is subjected to salt forming, reaction with chlorodifluoromethane, and chlorination to obtain the 1-(2,4-dichlorophenyl)-3-methyl-4-difluoromethyl-1,2,4-triazole-5-ketone (a sulfentrazone intermediate). The synthetic method takes p-chloroanniline as the raw material, the synthetic method is realized by only one-time chlorination, steric hindrance for intermediate synthesis is small, and the impurity is low, so that the yield is increased; in addition, the raw materials required by the synthesis route are easilyacquired, the cost is low, the condition is mild, operation is simple, security is high, and the synthesis method is in favor of realizing industrial production.
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Paragraph 0056; 0057
(2018/03/28)
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- Lewis Acid Catalyzed Annulation of Cyclopropane Carbaldehydes and Aryl Hydrazines: Construction of Tetrahydropyridazines and Application Toward a One-Pot Synthesis of Hexahydropyrrolo[1,2- b]pyridazines
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In this report, a facile synthesis of tetrahydropyridazines via a Lewis acid catalyzed annulation reaction of cyclopropane carbaldehydes and aryl hydrazines has been demonstrated. Moreover, the generated tetrahydropyridazine further participated in a cycloaddition reaction with donor-acceptor cyclopropanes to furnish hexahydropyrrolo[1,2-b]pyridazines. We also performed these two steps in one pot in a consecutive manner. In addition, a monodecarboxylation reaction of hexahydropyrrolo[1,2-b]pyridazine was achieved with a good yield.
- Dey, Raghunath,Kumar, Pankaj,Banerjee, Prabal
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p. 5438 - 5449
(2018/05/28)
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- Synthesis method of p-chlorophenyl hydrazine
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The invention discloses a synthesis method of p-chlorophenyl hydrazine. The method comprises the following steps: (1) adding hydrazine hydrate into a four-neck flask, starting to stir and adding a hydrochloric acid solution dropwise at a certain reaction temperature to obtain a hydrazine hydrochloride solution; (2) adding p-chloroaniline into the four-neck flask, starting to stir by using glycol as a solvent, adding the hydrazine hydrochloride solution obtained in the step (1) dropwise at the reaction temperature of 100 to 120 DEG C, performing heat-insulating reflux reaction for 2 to 6 hours, and filtering, washing and drying after the reaction is finished to obtain the p-chlorophenyl hydrazine. By the method, one-step synthesis of the p-chlorophenyl hydrazine is realized by using the p-chloroaniline and the hydrazine hydrate, the yield can reach more than 85%, and the method is suitable for enterprise large-scale production; by the method provided by the invention, the tedious operation steps, such as diazotization, reduction and acidolysis, in the traditional method are avoided, and the process safety is improved; by the method, the use amount of water can be reduced, the discharge quantity of waste water is greatly reduced, waste water treatment in the later period is avoided, and the cost is reduced.
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Paragraph 0013-0022
(2017/05/19)
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- Method for preparing p-chlorophenylhydrazine
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The invention discloses a method for preparing p-chlorophenylhydrazine. According to the method, p-chloroaniline, methyl ethyl ketazine and water are taken as raw materials, p-chlorophenylhydrazine is synthesized by reaction at a certain temperature, and ammonia and butanone generated in the reaction process can be recycled to be used for synthesizing methyl ethyl ketazine. Compared with a conventional process for preparing p-chlorophenylhydrazine through diazotization reaction, the method is mild in reaction condition, not higher in requirements for devices, fewer in reaction steps, high in yield and simple in aftertreatment, product impurities are fewer, the purity is high, the production cost is low, the process is free of generation of waste water and waste gas, and the method is a green environment-friendly novel process.
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Paragraph 0010
(2017/08/29)
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- P-chlorophenylhydrazine synthesis method
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The invention discloses a p-chlorophenylhydrazine synthesis method. The technical scheme comprises the following steps: reacting sodium hypochlorite and p-chloroaniline to prepare p-chlorphenyl monochloroamine, and reacting the p-chlorphenyl monochloroamine and ammonia to obtain p-chlorophenylhydrazine. Compared with the traditional diazo-reaction process for preparing p-chlorophenylhydrazine, the method disclosed by the invention has the advantages of mild reaction conditions, low requirements for equipment, less reaction steps, simple synthesis method, low by-product and wastewater output, low energy consumption, high yield and low production cost, thereby being an energy-saving environment-friendly new process.
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Paragraph 0007; 0008; 0009
(2017/07/21)
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- Synthesis and biological evaluation of 4-(2-fluorophenoxy)-3,3′-bipyridine derivatives as potential c-met inhibitors
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Six series of novel 4-(2-fluorophenoxy)-3,3′-bipyridine derivatives conjugated with aza-aryl formamide/amine scaffords were designed and synthesized through a structure-based molecular hybridization approach. The target compounds were evaluated for c-Met kinase inhibitory activities and cytotoxicity against four cancer cell lines (HT-29, A549, MKN-45 and MDA-MB-231) in vitro. Most compounds exhibited moderate to excellent potency, and the most promising candidate 26c (c-Met kinase IC50 = 8.2 nM) showed a 4.7-fold increase in cytotoxicity against c-Met-addicted MKN-45 cell line in vitro (IC50 = 3 nM), superior to that of Foretinib (IC50 = 23 nM). The preliminary structure-activity relationship indicated that a 1H-benzo [e] [1,3,4]thiadiazine-3-carboxamide-4,4-dioxide moiety as linker contributed to the antitumor potency.
- Zhao, Sijia,Zhang, Yu,Zhou, Hongyang,Xi, Shuancheng,Zou, Bin,Bao, Guanglong,Wang, Limei,Wang, Jiao,Zeng, Tianfang,Gong, Ping,Zhai, Xin
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- Synthesis and biological evaluation of benzimidazole phenylhydrazone derivatives as antifungal agents against phytopathogenic fungi
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A series of benzimidazole phenylhydrazone derivatives (6a-6ai) were synthesized and characterized by 1H-NMR, ESI-MS, and elemental analysis. The structure of 6b was further confirmed by single crystal X-ray diffraction as (E)-configuration. All the compounds were screened for antifungal activity against Rhizoctonia solani and Magnaporthe oryzae employing a mycelium growth rate method. Compound 6f exhibited significant inhibitory activity against R. solani and M. oryzae with the EC50 values of 1.20 and 1.85 μg/mL, respectively. In vivo testing demonstrated that 6f could effectively control the development of rice sheath blight (RSB) and rice blast (RB) caused by the above two phytopathogens. This work indicated that the compound 6f with a benzimidazole phenylhydrazone scaffold could be considered as a leading structure for the development of novel fungicides.
- Wang, Xing,Chen, Yong-Fei,Yan, Wei,Cao, Ling-Ling,Ye, Yong-Hao
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- 4-chlorophenylhydrazine phosphate preparation method
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The invention relates to a 4-chlorophenylhydrazine phosphate preparation method. The method comprises the steps of diazotization, reduction, purification and salt formation. In the diazotization and reduction steps, a reaction liquid is kept strongly acidic with concentrated hydrochloric acid, such that smooth and complete reactions are ensured. In the reduction step, zinc powder-concentrated hydrochloric acid is adopted as a reducing agent for replacing sodium thiosulfate, sodium bisulfite, stannous chloride-hydrochloric acid and the like, such that reduction performance is good, yield is high, and reaction time is shortened. Impurities such as zinc hydroxide produced in the reaction are easy to remove, such that product impurity amount is low, and product purity is high. In the salt formation step, acetone is used for leaching, such that product purity is improved, and product appearance is ensured. The preparation method has the advantages of stable and reliable process, easy operation, and high product purity (product content is no lower than 99.2% as a result of high-performance liquid chromatography). A product yield is no lower than 42%. The method can completely satisfy market demands on 4-chlorophenylhydrazine phosphate.
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Paragraph 0031-0038
(2017/03/14)
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- Diaza [1,4] Wittig-type rearrangement of N-allylic-N-Boc-hydrazines into γ-amino- N -Boc-enamines
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Diaza [1,4] Wittig-type rearrangement of N-allylic-N-Boc-hydrazines into γ-amino-N-Boc-enamines was demonstrated. The scope and limitation, experimental mechanistic studies, and a proposed reaction mechanism were also described.
- Tayama, Eiji,Kobayashi, Yoshiaki,Toma, Yuka
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supporting information
p. 10570 - 10573
(2016/09/02)
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- Remazol-Catalyzed Hydroperoxyarylation of Styrenes
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A mild photocatalytic hydroperoxyarylation of styrenes has been developed, in which a novel photocatalyst, remazol brilliant blue R (RBBR), is employed at low catalytic loading (1 mol%). The operationally easy procedure uses air as the dioxygen source. Simple mono-substituted styrenes react with aryl hydrazines in moderate-to-good yields. RBBR is proposed to act as a photosensitizer for the generation of singlet oxygen.
- Chen, Ying-Ho,Lee, Ming,Lin, Yi-Zhen,Leow, Dasheng
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supporting information
p. 1618 - 1621
(2015/08/06)
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- Synthesis of 1-(1-aryl-1H-1,2,3-triazol-4-yl)-β-carboline derivatives
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Reaction of 5-methyl-1-aryl-1H-1,2,3-triazole-4-carbocylic acid chlorides with tryptamine derivatives afforded substituted 1-aryl-N-[2-(1H-indol-3-yl) ethyl]-5-methyl-1H-1,2,3-triazole-4-carboxamides. At heating these compounds in toluene in the presence of POCl3 and P2O5 Bischler-Napieralski cyclization occurs giving 1-(1-aryl-5-methyl-1H-1,2,3- triazol-4-yl)-4,9-dihydro-3H-β-carbolines that can be transformed into β-carboline and tetrahydro-β-carboline derivatives.
- Pohodylo,Matiichuk,Obushak
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p. 275 - 279
(2014/04/17)
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- Efficient synthesis of aryl hydrazines using copper-catalyzed cross-coupling of aryl halides with hydrazine in PEG-400
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An efficient and convenient method for the synthesis of aryl hydrazines is described via copper-catalyzed cross-coupling of aryl halides with aqueous hydrazine in PEG-400. This protocol is applicable to both electron-deficient and electron-rich aryl iodides and bromides, and even to sterically hindered substrates, giving aryl hydrazines in good to excellent yields.
- Chen, Junmin,Zhang, Yimin,Hao, Wenyan,Zhang, Rongli,Yi, Fei
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p. 613 - 617
(2013/07/25)
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- Regioselective radical arylation of anilines with arylhydrazines
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Substituted 2-aminobiphenyls have been prepared from arylhydrazines and anilines via radical arylation reactions under simple oxidative conditions. The strong directing effect of the free and unprotonated amino functionality leads to high regioselectivities, and anilines have been shown to be significantly better aryl radical acceptors than nitrobenzenes or phenyl ethers. The methodology is also applicable to phenols, which react best as phenolates under strongly basic conditions. Finally, radical arylation reactions of anilines and anilinium salts under various conditions have for the first time demonstrated that regioselectivity can also be controlled through the rearomatization step and that the addition of an aryl radical to a substituted benzene might even be reversible.
- Jasch, Hannelore,Scheumann, Julia,Heinrich, Markus R.
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p. 10699 - 10706
(2013/02/25)
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- Reduction of hydrazines to amines with aqueous solution of titanium(iii) trichloride
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N-N bond cleavage in hydrazines is widely used in the preparation of amines and thus occupies a significant place in organic synthesis. In this paper, we report a new method for the reductive cleavage of N-N bonds in hydrazines by commercially available and cheap aqueous titanium(iii) trichloride. The reaction proceeds smoothly under a broad pH range from acidic to neutral and basic conditions to afford amines in good yields. This method is compatible with substrates containing functionalities such as C-C double bonds, benzyl-nitrogen bonds, benzyloxy and acyl groups. The Royal Society of Chemistry 2011.
- Zhang, Yan,Tang, Qiang,Luo, Meiming
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supporting information; experimental part
p. 4977 - 4982
(2011/08/05)
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- Synthesis and biological activity of pyrazolidine-3,5-dione substituted benzimidazole derivatives
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Condensation of o-phenylene diamine with chloro acetic acid gave 2-chloromethyl benzimdazole, which undergoes halide replacement with phenylhydrazines to give the corresponding N,N'-disubstituted hydrazines. Later these compounds were treated with diethyl malonate in presence of acetic acid to get the pyrazolidine-3,5-dione substituted benzimidazole derivatives. The synthesized compounds were subjected to microbiological screening and in vitro antiinflammatory activity.
- Tiwari, Abhishek,Tiwari, Varsha,Venkataramana,Madhavan
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experimental part
p. 1179 - 1182
(2012/01/05)
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- Methods and Compositions for Modulating P300/CBP Activity
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The present invention relates to a method for identifying compounds that modulate the activity of p300/CBP. Compounds of the invention are identified by designing or screening for a compound which binds to at least one amino acid residue of the newly identified lysine-CoA inhibitor binding site, L1 loop, electronegative pocket, or electronegative groove of the HAT domain of p300/CBP and testing the compound for its ability to modulate the activity of p300/CBP. Compositions and methods for preventing or treating diseases or disorders associated with p300/CBP are also provided as is a method for producing a semi-synthetic HAT domain.
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Page/Page column 19
(2010/09/05)
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- Synthesis and biological activity of functionalized indole-2-carboxylates, triazino- and pyridazino-indoles
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Condensation of aryl hydrazines with ethyl pyruvate gave the respective hydrazones 4-6; Fischer indolization led to substituted-1H-indole-2-carboxylic acid ethyl esters 7-9. The Mannich reaction of these compounds with formaldehyde and morpholine yielded ethyl 3-(morpholinomethyl)-substituted-1H-indole-2- carboxylates 10-12. The 5,7-dichloro-1H-indole-2-carbohydrazide 13 was cyclized with methyl orthoformate in DMF to give 6,8-dichloro[1,2,4]triazino[4,5-a]indol- 1(2H)-one 14. Vilsmeier-Haack formylation of 7-9 gave ethyl 3-formyl- substituted-1H-indole-2-carboxylates 15-17 whose 2,2′-((5-chloro-2- (ethoxycarbonyl)-1H-indol-3-yl)methylene)bis-(sulfanediyl) diacetic acid 18 was prepared. The reaction of 15 and 16 with substituted anilines by conventional and microwave methods gave ethyl 3-(N-aryliminomethyl)-5-halo-1H-indole-2- carboxylates 19-29. In a cyclocondensation reaction of 19-25 with thiolactic acid or thioglycolic acid substituted indolylthiazolidinones 30-33 were prepared. Reaction of hydrazine hydrate with 15-17 did not give the respective hydrazones but directly led to the cyclized products substituted-3H- pyridazino[4,5-b]indol-4(5H)-ones 34-36, while a reaction with 2,4-dichlorophenylhydrazine yielded the uncyclized hydrazones. The chlorination of 35 and 36 with POCl3 gave pyridazino[ 4,5-b]indoles 39 and 40, respectively; reaction of the latter compounds with morpholine gave 4-(substituted-5H-pyridazino[4,5-b]indol-4-yl)morpholine 41 and 42. Mannich reaction of 34 with formaldehyde and N-ethylpiperazine gave 8-chloro-3-((4- ethylpiperazin-1-yl)methyl)-3H-pyridazino[ 4,5-b]indol-4(5H)-one 43. The microwave assistance of selected reactions has a profound effect on the reaction speed. The structures of the new compounds were confirmed by both analytical and spectral data. Some compounds were subjected to investigations concerning their antimicrobial, tranquilizing, and anticonvulsant activities.
- El-Gendy, Adel A.,Said, Mohamed M.,Ghareb, Nagat,Mostafa, Yasser M.,El-Ashry, El Sayed H.
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experimental part
p. 294 - 300
(2009/04/11)
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- Diamine derivatives
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A compound represented by the general formula (1): Q1-Q2-T0-N(R1)-Q3-N(R2)-T1-Q4??(1) wherein R1 and R2 are hydrogen atoms or the like; Q1 is a saturated or unsaturated, 5- or 6-membered cyclic hydrocarbon group which may be substituted, or the like; Q2 is a single bond or the like; Q3 is a group in which Q5 is an alkylene group having 1 to 8 carbon atoms, or the like; and T0 and T1 are carbonyl groups or the like; a salt thereof, a solvate thereof, or an N-oxide thereof. The compound is useful as an agent for preventing and/or treating cerebral infarction, cerebral embolism, myocardial infarction, angina pectoris, pulmonary infarction, pulmonary embolism, Buerger's disease, deep venous thrombosis, disseminated intravascular coagulation syndrome, thrombus formation after valve or joint replacement, thrombus formation and reocclusion after angioplasty, systemic inflammatory response syndrome (SIRS), multiple organ dysfunction syndrome (MODS), thrombus formation during extracorporeal circulation, or blood clotting upon blood drawing.
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- DIAMINE DERIVATIVES
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A compound represented by the general formula (1):Q1-Q2-T0-N(R1)-Q3-N(R2)-T1-Q4 wherein R1 and R2 are hydrogen atoms or the like; Q1 is a saturated or unsaturated, 5- or 6- membered cyclic hydrocarbon group which may be substituted, or the like; Q2 is a single bond or the like; Q3 is a group in which Q5 is an alkylene group having 1 to 8 carbon atoms, or the like; and T0 and T1 are carbonyl groups or the like; a salt thereof, a solvate thereof, or an N-oxide thereof. The compound is useful as an agent for preventing and/or treating cerebral infarction, cerebral embolism, myocardial infarction, angina pectoris, pulmonary infarction, pulmonary embolism, Buerger's disease, deep venous thrombosis, disseminated intravascular coagulation syndrome, thrombus formation after valve or joint replacement, thrombus formation and reocclusion after angioplasty, systemic inflammatory response syndrome (SIRS), multiple organ dysfunction syndrome (MODS), thrombus formation during extracorporeal circulation, or blood clotting upon blood drawing.
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- Process for preparing arylhydrazines
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The present invention relates to a process for preparing arylhydrazines of the formula R1R2R3Ar-NH-NH2 (I) by reacting an arylhydrazinedisulfonate of the formula in which R1, R2, and R3 are identical or different and are H, C1-C4-alkyl, C1-C4-alkoxy, halogen or OH, Ar is phenyl or naphthyl, M1 and M2 are identical or different and are H, NH4, an alkali metal or +E,fra 1/2+EE alkaline earth metal and R1, R2, R3 and Ar in the formulae (I) and (II) have the same meaning, with water and an inorganic acid at from 0 to 100 DEG C. in the presence of an inert organic solvent to give the corresponding arylhydrazine salt and treating the arylhydrazine salt with a base.
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- Selective reduction of aryl diazonium fluoroborates
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Substituted aryl diazonium fluoroborates have been selectively reduced to the corresponding phenylhydrazines by using borohydride exchange resin (BER).
- Bandgar,Thite
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p. 635 - 639
(2007/10/03)
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- Kinetics of the Alkaline Hydrolysis of several Alkyl Phenylcarbazates
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The kinetics in 25percent (v/v) dioxane-water of the alkaline hydrolysis, followed by UV spectrometry, of several alkyl phenylcarbazates (Ar-NH-NHCOOR, with Ar = phenyl, 4-chlorophenyl, 4-fluorophenyl, 3,4-dichlorophenyl and R = methyl, ethyl, propyl, chloroethyl, trichloroethyl) are discussed.The pKa of trichloroethyl phenylcarbazate is 14.12 at 25 deg C.The pH profiles, the activation entropy of -40 cal mol-1 K-1, the kinetic solvent isotope effect, kOH-/kOD-, of 3.45, the general-base catalysis and the effect of the leaving group and of the substituent on the aromatic ring are in agreement with the involvement of a BAc2 reaction scheme.
- Safraoui, Adil,Calmon, Michelle,Calmon, Jean-Pierre
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p. 1349 - 1352
(2007/10/02)
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- Synthesis and adenosine receptor affinity of a series of pyrazolo[3,4-d]pyrimidine analogues of 1-methylisoguanosine
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Pyrazolo[3,4-d]pyrimidines are pyrazolo analogues of purines. They have been shown to be a general class of compounds which exhibit A1 adenosine receptor affinity. Two series of pyrazolo[3,4-d]pyrimidine analogues of 1-methylisoguanosine have been synthesized. The first involved substitution of the N1-position while the second involved substitution of the N5-position. Both alkyl and aryl substituents were examined. All compounds were tested for A1 adenosine receptor affinity by using a (R)-[3H]-N6-(phenylisopropyl)adenosine binding assay. The 3-chlorophenyl group showed the greatest activity in the N1-position and the butyl group produced the greatest activity in the N5-position. Combination of the best substituent in each of these positions enhanced the overall activity. The most potent compound was 4-amino-5-N-butyl-1-(3-chlorophenyl)-1H-pyrazolo[3,4-d] pyrimidin-6(5H)-one with an IC50 of 6.4 X 10-6 M. Selectivity at the receptor subclasses was examined by performing an A2 adenosine receptor affinity assay with [3H]CGS 21680. This series of compounds were slightly less potent at A2 receptors. 4-Amino-5-N-butyl-1-(3-chlorophenyl)-1H-pyrazolo[3,4-d] pyrimidin-6(5H)-one was the most potent compound with an IC50 of 19.2 X 10-6 M.
- Harden,Quinn,Scammells
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p. 2892 - 2898
(2007/10/02)
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- Thienocinnoline compounds and their pharmaceutical use
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A thienocinnoline compound of the general formula STR1 wherein R stands for hydrogen, a halogen or a lower alkyl, Ar stands for an aryl, a heteroaryl, or an aryl or a heteroaryl having as a substituent at least a halogen, a lower alkyl, a lower alkoxy, nitro, amino, hydroxy, trifluoromethyl and/or a lower alkanoylamino; and the bond between 5a-position and 6-position represents a single bond or a double bond, which is useful as an antianxiety agent, amnesia-treating drug, a brain function-activating drug, an antidementiac drug or a potentiating agent of biological protection.
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- Reduction electrochimique des sels d'aryldiazonium en milieu aqueux: II. Effet de substituants sur la stabilisation du radical libre intermediaire de reduction et sur le rendement de la synthese d'arylhydrazines primaires
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The polarographic behaviour of a series of aromatic diazonium salts , BF4- in aqueous media is reported and discussed.The half-wave potentials corresponding to the first reduction step have been correlated to Hammett substituent constant ? and are defined by the equation : E=0.14?-0.015+/-0.01 V vs SCE.Substituent effects on the yield of electrochemical synthesis on a mercury pool of by electrochemical reduction of aryldiazoniums salts 10E-3 mol.l-1 at 0 1,1 V vs.SCE are also investigated at low temperature.The best yield (70percent) are obtained with the electron donating substituents on the phenyl ring.Unfortunately, large scale electrolytic reduction of aromatic diazoniums 10E-2 mol.l-1 at -1,1 V vs SCE results in the formation of primary hydrazines in poor yields.On such a large scale, it no longer seems possible to minimize the competitive chemical side reactions.
- Hamet-Elfakir, Claire,Caullet, ClAude
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p. 687 - 692
(2007/10/02)
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- MECHANISM OF THE FISCHER INDOLE SYNTHESIS. QUANTUM-CHEMICAL INTERPRETATION OF THE REARRANGEMENT OF SUBSTITUTED CYCLOHEXANONE ARYLHYDRAZONES TO TETRAHYDROCARBAZOLES
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Calculations of a number of model structures within the scheme of Fischer indole synthesis were made on the basis of a bonding variant of perturbation theory in the self-consistent-field (SCF) MO LCAO method.A quantum-chemical interpretation of the effect of substituents on the course of the thermal process is given.The kinetics of the thermal and acid-catalyzed indolization of substituted cyclohexanone arylhydrazones to tetrahydrocarbazoles were studied by spectrophotometry.It was shown that the experimental data are in satisfactory agreement with the calculated values. It was concluded that a concerted mechanism ( a -sigma-tropic shift) for the step involving the formation of a carbon-carbon bond in the Fischer reaction is preferred.
- Visotskii, Yu. B.,Przheval'skii, N. M.,Zemskii, B. P.,Grandberg, I. I.,Kostromina, L. Yu.
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p. 713 - 722
(2007/10/02)
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- AN EFFICIENT METHOD FOR THE CONVERSION OF ARYLHYDRAZINES INTO 2-ARYL-4,4-DIALKYLSEMICARBAZIDES
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Arylhydrazines are converted into 2-aryl-4,4-dialkylsemicarbazides by subsequent reaction with chloroformate, phosgene, dialkylamine, and alkaline hydrolysis.
- Pilgram, K. H.
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p. 697 - 706
(2007/10/02)
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- Antiimplantation Agents: Part I - 1-Arylthiosemicarbazides
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Several 1-arylthiosemicarbazides, 2-arylhydrazinothiazolines and 2-arylhydrazinodihydrothiazines have been examined for their antiimplantation activity in rats.Among the active compounds, 4-methyl-1-(3,5-bistrifluoromethylphenyl)thiosemicarbazide (3, C 2696-Go) and the corresponding 4,4-dimethyl (47), ethyl (4), n-butyl (5) and allyl (6) derivatives completely inhibit implantation at doses 10, 3, 20, 20 and 30 mg/kg respectively.The 3,4-dichlorophenyl analogue (32) is effective at a dose of 30 mg/kg. 2-(3,5-Bistrifluoromethylphenyl)hydrazinothiazoline (51) and the corresponding dihydrothiazine (63) show a weaker activity.The biological profile of C 2696-Go has been investigated in detail.It appears to prevent implantation by its antiuterotropic activity and ability to inhibit desiduoma formation.
- Nagarajan, K.,Talwalker, P.K.,Kulkarni, C.L.,Venkateswarlu, A.,Prabhu, S.S.,Nayak, G.V.
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p. 1243 - 1257
(2007/10/02)
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- Pyrazoloquinolines
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2-Aryl-pyrazolo[4-3-c]quinolin-3-ones, e.g. those of the formula STR1 and pharmaceutically acceptable acyl derivatives or salts thereof, are psychoactive agents useful in the treatment of anxiety or depression.
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- Phenyl-1,2,3,4-tetrahydrocarbazoles and use thereof
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This application relates to phenyl-substituted 1,2,3,4-tetrahydrocarbazoles and to their use as anti-depressant agents useful in the treatment of mental depression of either endogenous or reactive nature.
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- Carbazole methyl malonates
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A process for the preparation of α-methyl-carbazole-2-acetic acids, which comprises reacting an α-methyl-3-oxocyclohexane malonic acid di-lower alkyl ester with a substituted phenylhydrazine, and thereafter sequentially oxidizing and hydrolyzing the reaction product to obtain the desired acid, is described.
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- Process for producing 3-anilino-5-pyrazolones
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A process for producing a 3-anilino-5-pyrazolone which comprises reacting a β-anilino-β-alkoxy-acrylate with a hydrazine in the presence of a compound having a pKa of about 8 up to about 14.
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