- Total synthesis of (±)-tangutorine and chiral HPLC separation of enantiomers
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The first total synthesis of racemic tangutorine, a novel indole alkaloid, was performed in 7 steps. The key reactions, dithionite reduction and acidic cyclization provided easy access with good yields to the tangutorine skeleton. Comprehensive NMR spectroscopic data of new compounds are given. Chiral HPLC separation of enantiomers is reported.
- Putkonen, Tiina,Tolvanen, Arto,Jokela, Reija,Caccamese, Salvatore,Parrinello, Nunziatina
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Read Online
- Synthesis and early ADME evaluation of a novel scaffold, tetrahydro-6 h -Pyrido[3,2- B ]azepin-6-One
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The synthesis and preliminary ADME evaluation of -novel 4-(trifluoromethyl)-5,7,8,9-tetrahydro-6H-pyrido[3,2-b]azepin-6-ones is presented. The key step is a ring expansion of 4-(trifluoromethyl)-7,8- dihydroquinolin-5(6H)-ones via a Beckmann rearrangement. The rearrangement opens up possibilities to access novel unexplored scaffolds for medicinal chemistry. The biopharmaceutical profiling revealed a strong structural dependency of the druglike properties. Georg Thieme Verlag Stuttgart . New York.
- Muylaert, Koen,Jatczak, Martyna,Wuyts, Benjamin,De Coen, Laurens M.,Van Hecke, Kristof,Loones, Hans,Keemink, Janneke,García, Daniel,Mangelinckx, Sven,Annaert, Pieter,Stevens, Christian V.
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Read Online
- Efficient synthesis of decahydroacridine-1,8-diones and polyhydroquinolines using the step-wise method
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Various symmetrical and unsymmetrical decahydroacridine-1,8-dione and polyhydroquinoline derivatives were synthesized via two-step cyclocondensation reactions. The advantages of this step-wise addition of reactants in comparison with other one-pot reactions are avoiding the formation of 2 or 3 undesired by-products, therefore allowing cleaner work up of reaction. The important factor of this effective cyclocondensation method is that the prepared β-enaminone component was added dropwise to the solution, in which the Knoevenagel condensation product is slowly being formed by reaction of aldehyde molecule and 1,3-dicarbonyl compounds. The results of the proposed step-wise method are compared and discussed with those obtained in the one-pot reactions.
- Hosseininasab, Fatemeh Sadat,Memarian, Hamid Reza
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- Copper-Catalyzed Thiolation of Terminal Alkynes Employing Thiocyanate as the Sulfur Source Leading to Enaminone-Based Alkynyl Sulfides under Ambient Conditions
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A highly efficient protocol for copper-catalyzed thio-alkynylation of enaminone-based thiocyanates with terminal alkynes under mild conditions has been developed. This scalable amino group-directed thio-alkynylation proceeds in the open air with a broad substrate scope and an excellent yield. The demonstrated synthetic transformation creates the opportunity for a wide variety of sulfur-containing useful materials. Gram-scale synthesis and further synthetic transformations of alkynyl sulfides highlight the potential utility of the method.
- Chandran,Pise, Ashwini,Shah, Suraj Kumar,Rahul,Suman,Tiwari, Keshri Nath
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supporting information
p. 6557 - 6561
(2020/08/24)
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- Preparation method of 2-chloro-7, 8-dihydro-6H-quinolin-5-ketone
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The invention relates to a preparation method of 2-chloro-7, 8-dihydro-6H-quinolin-5-ketone. 2-chloro-7, 8-dihydro-6H-quinolin-5-ketone comprises preparation components of a component as shown in thedescription, anhydrous ethanol, anhydrous ammonium acetate, anhydrous sodium carbonate, methyl acrylate, DMF, acetonitrile, phosphorus oxychloride and ethyl acetate, and by adopting the preparation method, the existing situation of g-class production is overcome, so that the technical level reaches the industry leading position. Furthermore, the optimized process enables the order batch output ofa project to reach 15 kg, the product quality is improved obviously, the product purity reaches 99.5%, single impurities are lower than 0.1%, and heavy metal, burning residues and residual solvents meet the standards of pharmacopoeia. Technically, the process is optimized, therefore the overall yield of the process is increased by 30%, and the discharge of three wastes (waste water, waste gas andwaste residues) is reduced through the recovery of the solvents.
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Paragraph 0056-0065
(2018/07/30)
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- Cu catalyzed cross-dehydrogenative coupling reaction for the synthesis of 3-hydroxy-2-pyrrolidinones
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A new convenient strategy for the synthesis of 3-hydroxy-2-pyrrolidinone derivatives featuring regioselective C–C coupling has been developed. This is a Cu (II) catalyzed cross dehydrogenative coupling (CDC) involving enamino-ketones of benzyl amines and di-alkyl acetylenedicarboxylate, followed by cyclization by primary amines. TBHP (tert-butyl hydroperoxide) has been used as the oxidant to promote the coupling protocol. This synthetic route principally demonstrates the scope of CDC reaction and also applicable to gram-scale synthesis.
- Sarkar, Rajib,Mukhopadhyay, Chhanda
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p. 3069 - 3076
(2018/07/06)
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- Stable carteolol hydrochloride, preparation method thereof and eye medicine combination
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The invention relates to stable carteolol hydrochloride, a preparation method thereof and an eye medicine combination, in particular to a method for preparing carteolol hydrochloride. The method comprises the following steps of preparing 3-amino-2-cyclohexenone, tetrahydro-2,5(1H, 6H)-quinolinone, 5-hydroxy-3,4-dihydro-2(1H)-carbostyril and 5-(2,3-epoxypropoxy)-3,4-dihydro-2(1H)-carbostyril, and then the carteolol hydrochloride is obtained. Furthermore, the invention provides the carteolol hydrochloride crude medicine obtained according to the method, the eye medicine combination prepared by using the obtained carteolol hydrochloride as the crude medicine, and applications of the obtained carteolol hydrochloride to preparation of drugs for treating or preventing glaucoma or ocular hypertension. The method has excellent pharmaceutical characteristics, for example, the obtained crude medicine and a preparation has excellent stability.
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Paragraph 0120; 0123; 0135; 0144-0146; 0157; 0168; 0179
(2017/12/06)
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- Evaluation of magnetically recyclable nano-Fe3O4 as a green catalyst for the synthesis of mono- and bis-tetrahydro-4H-chromene and mono and bis 1,4-dihydropyridine derivatives
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Magnetically separable Fe3O4 nanoparticles were used as an environmental friendly catalyst for the synthesis of mono- and bis-tetrahydro-4H-chromene and mono- and bis-1,4-dihydropyridine derivatives via three-component reactions of aromatic aldehydes and malononitrile with cyclic β-dicarbonyls or cyclic β-enaminoketones respectively. These reactions were carried out in EtOH and at reflux. Fe3O4 nanoparticles can be magnetically separated from the reaction mixture by a magnet and recycled without significant loss of catalytic activity.
- Amirheidari, Bagher,Seifi, Mohammad,Abaszadeh, Mehdi
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p. 3413 - 3423
(2016/03/30)
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- Compositions for Treatment of Cystic Fibrosis and Other Chronic Diseases
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The present invention relates to pharmaceutical compositions comprising an inhibitor of epithelial sodium channel activity in combination with at least one ABC Transporter modulator compound of Formula A, Formula B, Formula C, or Formula D. The invention also relates to pharmaceutical formulations thereof, and to methods of using such compositions in the treatment of CFTR mediated diseases, particularly cystic fibrosis using the pharmaceutical combination compositions.
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Paragraph 0371
(2015/09/22)
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- Novel 5-aminotetrahydroquinoline-2-carboxylic acids and their use
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The present application relates to novel 5-amino-5,6,7,8-tetrahydroquinoline-2-carboxylic acids, to processes for their preparation, to their use for the treatment and/or prevention of diseases, and to their use for producing medicaments for the treatment and/or prevention of diseases, especially for the treatment and/or prevention of cardiovascular and cardiopulmonary disorders.
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Paragraph 0362; 0363; 0364
(2014/02/16)
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- Synthesis of chiral cyclic β-amino ketones by Ru-catalyzed asymmetric hydrogenation
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Synthesis of chiral cyclic β-amino ketones has been first reported via Ru-catalyzed asymmetric hydrogenation. High enantioselectivities were achieved by using (S)-C3-TunePhos chiral ligand (up to 94% ee).
- Huang, Kexuan,Guan, Zheng-Hui,Zhang, Xumu
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supporting information
p. 1686 - 1688
(2014/03/21)
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- Syntheses of quinazolinones from 2-iodobenzamides and enaminones via copper-catalyzed domino reactions
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N-Substituted 2-iodobenzamides and enaminones undergo cascade transformations to achieve quinazolinones via a copper-catalyzed Ullmann-type coupling, a Michael addition and a retro-Mannich reaction. A unique stereochemical feature of this domino process was that Z-enaminones reacted without external ligands, whereas E-enaminones required the assistance of ligands. This journal is
- Songsichan, Teerawat,Promsuk, Jaturong,Rukachaisirikul, Vatcharin,Kaeobamrung, Juthanat
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supporting information
p. 4571 - 4575
(2014/06/24)
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- Synthetic access to poly-substituted 11H-pyrido[3,2-a]carbazoles, A dna-intercalating ellipticine related structure, and their antiproliferative activity
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The facile procedure for the synthesis of the 11H-pyrido[3,2-a]carbazole structure involving the Fischer indole cyclization on tetrahydroquinolinones, available from enaminones and methyl 2-formyl-3-oxopropanoate, followed by the aromatization of the resulting 5,6-dihydro derivatives is described. This method allows for the introduction of substituents at C2, C6, and C8 to the scaffold by choice of the starting materials. In the biological testing, introduction of the phenyl group at C6 is significantly effective to improve the antiproliferative activity.
- Wu, Ming-Yu,Shaban, Elkhabiry,Switalska, Marta,Wang, Ning,Shimoda, Miho,Mizutani, Yusuke,Yoshida, Megumi,Mei, Zhen-Wu,Kawafuchi, Hiroyuki,Nokami, Junzo,Wietrzyk, Joanna,Yu, Xiao-Qi,Inokuchi, Tsutomu
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p. 1427 - 1440
(2014/07/07)
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- Development of a scalable synthesis of a vascular endothelial growth factor receptor-2 kinase inhibitor: Efficient construction of a 6-etherified [1,2,4]triazolo[1,5-a]pyridine-2-amine Core
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A practical and scalable synthesis of the vascular endothelial growth factor receptor-2 (VEGFR-2) kinase inhibitor 1 has been developed. The key features of the process development include facile preparation of the key raw material 3-amino-4- fluorophenol, chemoselective nucleophilic aromatic substitution of 5-chloro-2-nitropyridine with phenol, a safe one-pot synthesis of a substituted urea using an isothiocyanate generated in situ from inexpensive materials, and improvement of the yield of acylation in the end game. The optimized six-step synthesis afforded 1·H2O in 54% overall yield, twice as much as the yield of the original synthesis, without chromatographic purification. In addition, a robust recrystallization procedure to afford the desired crystal form of 1 was also developed.
- Ishimoto, Kazuhisa,Fukuda, Naohiro,Nagata, Toshiaki,Sawai, Yasuhiro,Ikemoto, Tomomi
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p. 122 - 134
(2014/05/20)
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- Cyclization of cyanoethylated ketones as a route to 6-substituted indole derivatives
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δ-Cyanoketones are quickly cyclized with KOtBu to 3-aminocyclohex-2-enone derivatives, which in turn will give substituted indoles when treated with oxalyl chloride. Thus, 3-amino-6,6-dimethylcyclohex-2-enone gave 3-chloro-6,6-dimethyl-2,5,6,7-tetrahydroindole-2,5-dione, whose structure was corroborated by X-ray crystallography, whereas the corresponding molecule without the blocking gem-dimethyl groups, 3-aminocyclohex-2-enone, gave via hydrogen shifts 6-chloro-3-hydroxyoxindole.
- Bergman, Jan,Stensland, Birgitta
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- Heterocyclic derivatives as metabotropic glutamate receptor modulators
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The invention relates to heterocyclic derivatives of formula I as well as their pharmaceutically acceptable salts. The invention further relates to a process for the preparation of such compounds. The compounds of the invention are mGluR5 modulators and are therefore useful for the control and prevention of acute and/or chronic neurological disorders.
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Paragraph 0189
(2013/11/05)
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- Synthesis and antiproliferative activity evaluation of imidazole-based indeno[1,2-b]quinoline-9,11-dione derivatives
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A series of new imidazole substituted indeno[1,2-b]quinoline-9,11-dione derivatives were synthesized and evaluated for their antiproliferative effects on HeLa, LS180, MCF-7 and Jurkat human cancer cell lines. Antiproliferative effects were evaluated using MTT assay. Prepared compounds exhibited weak to good antiproliferative activity in evaluated cell lines. Prepared compounds were more potent in Jurkat cell line when compared to LS180, HeLa and MCF-7 cell lines. Compounds 29 (IC16 = 0.7 μM) and 31 (IC16 = 1.7 μM) and 33 (IC16 = 1.7 μM) were found to be the most potent molecules on Jurkat cell lines. Moreover; it was found that some of the tested compounds bearing imidazole-2-yl moiety on the C11-position of dihydropyridine ring exhibited superior antiproliferative activity in comparison to cis-platin especially in Jurkat cell line (compounds 29, 31, and 33). It seemed that the introduction of electron-withdrawing groups on the imidazole ring enhanced the antiproliferative potential of these compounds (compounds 27, 29 and 31). The results of this study proposed that some of the imidazole substituted indeno[1,2-b]quinoline-9,11-dione compounds may act as efficient anticancer agents in vitro, emphasizing their potential role as a source for rational design of potent antiproliferative agents.
- Sarkarzadeh, Hasti,Miri, Ramin,Firuzi, Omidreza,Amini, Mohsen,Razzaghi-Asl, Nima,Edraki, Najmeh,Shafiee, Abbas
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p. 436 - 447
(2013/07/28)
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- Palladium-catalyzed oxidative annulation via C-H/N-H functionalization: Access to substituted pyrroles
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Pyrroles, ubiquitous bioactive heterocycles in nature, are readily prepared via a palladium-catalyzed oxidative annulation of cyclic trans-enamines to various internal alkynes in the absence of a directing group. Copyright
- Peng, Shiyong,Wang, Lei,Huang, Jiayao,Sun, Shaofa,Guo, Haibing,Wang, Jian
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supporting information
p. 2550 - 2557
(2013/10/21)
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- MODULATORS OF ATP-BINDING CASSETTE TRANSPORTERS
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The present invention relates to modulators of ATP-Binding Cassette (“ABC”) transporters or fragments thereof, including Cystic Fibrosis Transmembrane Conductance Regulator, compositions thereof, and methods therewith. The present invention also relates to methods of treating ABC transporter mediated diseases using such modulators.
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- METABOTROPIC GLUTAMATE RECEPTOR MODULATORS
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The invention relates to heterocyclic derivatives of formula (I) as well as their pharmaceutically acceptable salts. The invention further relates to a process for the preparation of such compounds. The compounds of the invention are mGluR5 modulators and are therefore useful for the control and prevention of acute and/or chronic neurological disorders wherein Y, W, R1, R2 and R3 are as defined in claim 1.
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Page/Page column 102-103
(2012/05/05)
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- Enaminones 12. An explanation of anticonvulsant activity and toxicity per Linus Pauling's clathrate hypothesis
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The x-ray crystal structure of 3-((5-methylisoxazol-3-yl)amino)-5- methylcyclohex-2-enone (12b) and 3-((5-methylisoxazolyl-3-yl)amino)-5,5- dimethylcyclohex-2-enone (12c) were determined and correlated to their anticonvulsant activity in mice and rats. A hypothesis for the toxicity of the analogs are advanced. In addition, a series of 5-methyl-N-(3-oxocyclohex-1-enyl) -isoxazole-3-carboxamides were synthesized and evaluated for anticonvulsant activity. These compounds were compared to the activity of the corresponding amino and aminomethyl enaminones. Additional investigation involved the synthesis and evaluation of a trifluoromethyl analog of the active isoxazole tert-butyl 4-(5-methisoxazol-3-yl-amino)-6-methyl-2-oxo-cyclohex-3-ene carboxylate (4f).
- Jackson, Patrice L.,Hanson, Clive D.,Farrell, Alanna K.,Butcher, Raymond J.,Stables, James P.,Eddington, Natalie D.,Scott
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experimental part
p. 42 - 51
(2012/07/28)
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- COMPOSITIONS FOR TREATMENT OF CYSTIC FIBROSIS AND OTHER CHRONIC DISEASES
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The present invention relates to pharmaceutical compositions comprising an inhibitor of epithelial sodium channel activity in combination with at least one ABC Transporter modulator compound of Formula A, Formula B, Formula C, or Formula D. The invention also relates to pharmaceutical formulations thereof, and to methods of using such compositions in the treatment of CFTR mediated diseases, particularly cystic fibrosis using the pharmaceutical combination compositions.
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- Highly enantioselective hydrogenation of quinoline and pyridine derivatives with iridium-(P-Phos) catalyst
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The use of a chiral iridium catalyst gener-ated in situ from the (cyclooctadiene)iridium chlo-ride dimer, [Ir(COD)Cl]2, the P-Phos ligand [4, 4'-bis(diphenylphosphino)-2, 2', 6, 6'-tetramethoxy-3, 3'-bi-pyridine] and iodine (I2) for the asymmetric hydroge-nation of 2, 6-substituted quinolines and trisubstituted pyridines [2-substituted 7, 8-dihydroquinolin-5(6H)-one derivatives] is reported. The catalyst worked ef-ficiently to hydrogenate a series of quinoline deriva-tives to provide chiral 1, 2, 3, 4-tetrahydroquinolines in high yields and up to 96% ee. The hydrogenation was carried out at high S/C (substrate to catalyst) ratios of 2000-50000, reaching up to 4000 h-1 TOF (turnover frequency) and up to 43000 TON (turn-over number). The catalytic activity is found to be additive-controlled. At low catalyst loadings, de-creasing the amount of additive I2 was necessary to maintain the good conversion. The same catalyst system could also enantioselectively hydrogenate tri-substituted pyridines, affording the chiral hexahydro-quinolinone derivatives in nearly quantitative yields and up to 99% ee. Interestingly, increasing the amount of I2 favored high reactivity and enantiose-lectivity in this case. The high efficacy and enantiose-lectivity enable the present catalyst system of high practical potential.
- Tang, Wei-Jun,Tan, Jing,Xu, Li-Jin,Lam, Kim-Hung,Fan, Qing-Hua,Chan, Albert S. C.
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supporting information; scheme or table
p. 1055 - 1062
(2010/06/15)
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- Highly efficient and enantioselective hydrogenation of quinolines and pyridines with Ir-Difluorphos catalyst
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The combination of the readily available chiral bisphosphine ligand Difluorphos with [Ir(COD)Cl]2 in THF resulted in a highly efficient catalyst system for asymmetric hydrogenation of quinolines at quite low catalyst loadings (0.05-0.002 mol%), affording the corresponding products with high enantioselectivities (up to 96%), excellent catalytic activities (TOF up to 3510 h-1) and productivities (TON up to 43000). The same catalyst was also successfully applied to the asymmetric hydrogenation of trisubstituted pyridines with nearly quantitative yields and up to 98% ee. In these two reactions, the addition of I2 additive is indispensable; but the amount of I2 has a different effect on catalytic performance. The Royal Society of Chemistry 2010.
- Tang, Weijun,Sun, Yawei,Lijin, Xu,Wang, Tianli,Qinghua Fan,Lam, Kim-Hung,Chan, Albert S.C.
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supporting information; scheme or table
p. 3464 - 3471
(2010/08/21)
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- Concurrent α-iodination and N-arylation of cyclic β-enaminones
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A variety of N-substituted 3-aminocyclohex-2-enones were converted into the corresponding N-arylated α-iodo enaminones in high yields via concurrent N-iodination and N-arylation mediated by ArI(OAc)2. A mechanism is postulated to account for the reaction differences between the cyclic and the acyclic -enaminones, which undergo predominant β-acetoxylation under the same reaction conditions.
- Chen, Yan,Ju, Tong,Wang, Junwei,Yu, Wenquan,Du, Yunfei,Zhao, Kang
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supporting information; experimental part
p. 231 - 234
(2010/06/15)
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- Solid-state synthesis of β-enamino ketones from solid 1,3-dicarbonyl compounds and ammonium salts or amines
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A facile amination of solid 1,3-dicarbonyl compounds with ammonium salts or amines in solid state has been achieved by mechanochemical grinding in the presence of KHSO4 and SiO2. Most of the reactions proceed smoothly at room temperature under solid-state conditions and give their corresponding β-imino derivatives in high yields. The method has the advantage of simple manipulation and mild conditions. Georg Thieme Verlag Stuttgart.
- Xu, Shi-Liang,Li, Cheng-Ping,Li, Jing-Hua
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experimental part
p. 818 - 822
(2009/07/18)
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- (1,4-DIAZA-BICYCLO[3.2.2]NON-6-EN-4-YL)-HETEROCYCLYL-METHANONE LIGANDS FOR NICOTINIC ACETYLCHOLINE RECEPTORS, USEFUL FOR THE TREATMENT OF DISEASE
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The present invention relates generally to the field of ligands for nicotinic acetylcholine receptors (nACh receptors), activation of nACh receptors, and the treatment of disease conditions associated with defective or malfunctioning nicotinic acetylcholine receptors, especially of the brain. Further, this invention relates to novel compounds, which act as ligands for the a7 nACh receptor subtype, methods of preparing such compounds, compositions containing such compounds, and methods of use thereof. The novel compounds include compounds of formula I: (I) wherein X, R1, and R2 are as herein defined.
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Page/Page column 60; 61
(2009/05/30)
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- Partially saturated indeno[1,2-b]indole derivatives via deoxygenation of heterocyclic α-hydroxy-N,O-hemiaminals
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A series of 3-aminocyclohex-2-enones were reacted with indane-1,2,3-trione monohydrate (ninhydrin) yielding 4b,9b-dihydroxyindeno[ 1,2-b]indoles that were deoxygenated to indeno[1,2-b]indoles. Georg Thieme Verlag Stuttgart.
- Hemmerling, Hans-Joerg,Reiss, Guido
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experimental part
p. 985 - 999
(2009/12/01)
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- Heterodimers and Methods of Using Them
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Novel heterodimers of tetrahydroacridines and tetrahydroquinolinones are disclosed. The heterodimers are capable of acting as both acetylcholinesterase inhibitors and N-methyl-D-aspartate (NMDA) receptor antagonists. The heterodimers may be used to improve cognitive defects via treatment or prevention in both humans and non-humans.
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Page/Page column 11
(2008/12/07)
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- A practical and one-pot procedure for the synthesis of 3-amino-2- cyclohexen-1-one from 3-aminophenol
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A simple, totally catalytic, and environmentally benign process for the synthesis of 3-amino-2-cyclohexen-1-one using 10% Pd/C-catalyzed hydrogenation has been developed.
- Sajiki, Hironao,Ikawa, Takashi,Hirota, Kosaku
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p. 219 - 220
(2012/12/24)
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- Efficient synthesis of β-amino-α,β-unsaturated carbonyl compounds
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A versatile and high-yielding procedure for the synthesis of β-enamino esters and β-enaminones is presented: in the presence of tetraethyl orthosilicate, a number of highly functional β-enamino esters were obtained; this method provided an alternative for the formation of β-amino-α,β-unsaturated carbonyl compounds with mild and functional group compatible reaction conditions. The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2005.
- Zhao, Yuanhong,Zhao, Jingfeng,Zhou, Yongyun,Lei, Ze,Li, Liang,Zhang, Hongbin
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p. 769 - 772
(2007/10/03)
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- A hetero Diels-Alder approach to the synthesis of the first angucyclinone and angucycline 5-aza-analogues
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The synthesis of two new heterodienes and their regioselective [4+2]cycloaddition reactions with several bromo-naphthoquinones allowed us to prepare the first angucyclinone and angucycline 5-aza-analogues.
- Collet, Sylvain C.,Rémi, Jean-Fran?ois,Cariou, Claire,La?b, Samia,Guingant, André Y.,Quang Vu, Nguyen,Dujardin, Gilles
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p. 4911 - 4915
(2007/10/03)
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- SAR studies of 3-cyclopropanecarbonyloxy-2-cyclohexen-1-one as inhibitors of 4-hydroxyphenylpyruvate dioxygenase
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Various 3-cyclopropanecarbonyloxy-2-cyclohexen-1-one 1 derivatives have been synthesized and tested as inhibitors of 4-hydroxyphenylpyruvate dioxygenase (4-HPPD) from pig liver. The inhibition results indicated that well-positioned dicarbonyl groups as well as the cyclopropyl group of 1 were essential for potent inhibition. Substitution at the 2-position of the ring system has a significant effect on inhibitor potency, while the 5-position can undergo substantial variations and retain inhibitor potency. In the compounds examined, 2-chloro substituted 12 is the best inhibitor of all with IC50 of 15 nM, the rest of the synthesized analogues were less potent inhibitors than the parent compound.
- Lin, Yung-Lung,Wu, Chung-Shieh,Lin, Shean-Woei,Huang, Jian-Lin,Sun, Yang-Sheng,Yang, Ding-Yah
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p. 685 - 690
(2007/10/03)
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- Synthesis, characterization and anticonvulsant activity of enaminones. Part 6: Synthesis of substituted vinylic benzamides as potential anticonvulsants
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A comparison of enaminones from various unsubstituted and p-substituted benzamides to the analogous benzylamines has been undertaken with the aim of elucidating the essential structural parameters necessary for anticonvulsant activity. Initial studies on methyl 4-N-(benzylamino)-6-methyl-2-oxocyclohex- 3-en-1-oate, 3a, 3-N-(benzylamino)cyclohex-2-en-1-one, 3p, and 5,5-dimethyl- 3-N-(benzylamino)-cyclohex-2-en-1-one, 3r indicated that benzylamines possessed significant anti-maximal electroshock seizure (MES) activity. Evaluation of the analogous benzamides revealed significant differences in anticonvulsant activity, these differences were most probably related to the differences in their three-dimensional structures. (C) 1999 Elsevier Science Ltd.
- Foster, James E.,Nicholson, Jesse M.,Butcher, Raymond,Stables, James P.,Edafiogho, Ivan O.,Goodwin, Angela M.,Henson, Michael C.,Smith, Carlynn A.,Scott
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p. 2415 - 2425
(2007/10/03)
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- The improved preparation of 7,8-dihydro-quinoline-5(6H)-one and 6,7- dihydro-5H-1-pyrindin-5-one
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Compounds 7,8-dihydroquinoline-5(6H)-one (3) and 6,7-dihydro-5H-1- pyrindin-5-one (5) are formed by new methods from 1,3-diketone compound, ammonium acetate and 1,1,3,3-tetraethoxylpropane.
- Huang, Yanhe,Hartmann, Rolf W.
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p. 1197 - 1200
(2007/10/03)
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- Preparation of optically active spiro-hydantoins
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This invention relates to the preparation of preparing optically-active asymmetric spiro-hydantoin compounds, which are known to be of value in the medical control of certain chronic diabetic complications arising from diabetes mellitus. This invention also includes within its scope certain corresponding novel amino and hydantoic acid compounds and the cinchonine salt of optically active hydantoic acid, which are used as intermediates in the aforesaid process.
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- Method for manufacturing 3-amino-2-cyclohexene-1-one, and a novel polymer ingredient and its preparation
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A method of manufacturing 3-amino-2-cyclohexene-1-one by hydrogenating m-phenylenediamene to produce a novel intermediate salt of 3-amino-2-cyclohexene-1-imine followed by hydrolysis to produce 3-amino-2-cyclohexene-1-one. The novel intermediate 3-amino-2-cyclohexene-1-imine has also be isolated.
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- Novel resolution process for racemic spiro-hydantoins
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A novel three-step process for resolving a racemic spiro-hydantoin compound into its optical antipodes is disclosed, which involves (1) reacting said racemic compound with an optically-active asymmetric isocyanate of the formula RNCO, wherein R is (S)- or (R)-1-phenylethyl or (S) or (R)-1-(1-naphthyl)ethyl, to form the corresponding diastereomeric uredio compound; (2) separating the resulting diastereomeric mixture into its component parts, and (3) thereafter converting the separated ureido diastereomers obtained in step (b) to the corresponding asymmetric hydantoin compounds by treatment with an alkali metal lower alkoxide (C1 -C4), followed by acidification, whereupon the desired optical isomer is obtained. The final products so obtained, such as (4S)-(+)-6-fluoro-2,3-dihydro-spiro[4H-1-benzopyran-4,4'-imidazolidine]-2', 5'-dione (sorbinil) and (5'S)-3'-chloro-5', 6', 7', 8'-tetra-hydro-spiro[imidazolidine-4,5'-quinoline]-2,5-dione, are known to be useful in preventing or alleviating certain chronic diabetic complications. The aforementioned diastereomeric uredio intermediates are novel compounds.
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- 2-(2-aryl-2-oxoalkylidene) analogs of-3,5-pyridinedicarboxylic acid dialkyl esters useful for treatment of cardiovascular disorders
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The present invention are 2-(2-aryl-2-oxo-alkylidene) analogs of 1,2,3,4-tetrahydropyridine-3,5-pyridinecarboxylic acids and particularly esters thereof having valuable calcium antagonist and positive inotropic activity useful in the treatment of cardiovascular disorders, pharmaceutical compositions and methods of use therefor.
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