- Pharmacological studies of 1-(p-chlorophenyl)propanol and 2-(1-hydroxy-3-butenyl)phenol: Two new non-narcotic analgesics designed by molecular connectivity
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Molecular topology has been applied to the design of new analgesic drugs. Linear discriminant analysis and connectivity functions were used to design two potentially suitable drugs which were synthesized and tested for analgesic properties by the acetic acid-induced abdominal constriction test in mice and the tail-flick test in rats. In mice, the compound 1-(p-chlorophenyl)propanol showed higher analgesic activity, both intraperitoneally and orally, than acetylsalicylic acid. 2-(1-Hydroxy-3-butenyl)phenol exhibited a lesser protective effect (70% of that shown by acetylsalicylic acid). In rats, acetylsalicylic acid gave the greatest protection against pain when administered intraperitoneally, while 1-(p-chlorophenyl)propanol was the most active orally. The 2-(1-hydroxy-3-butenyl)phenol, both intraperitoneally and orally, showed the least protective effect. These results demonstrated the peripheral analgesic properties of the selected compounds, thus confirming the validity of the molecular design method.
- Garcia-March,Garcia-Domenech,Galvez,Anton-Fos,De Julian-Ortiz,Giner-Pons,Recio-Iglesias
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Read Online
- MODULATORS OF HSD17B13 AND METHODS OF USE THEREOF
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The disclosure relates to compounds and pharmaceutical compositions capable of modulating the hydroxysteroid 17-beta dehydrogenase (HSD17B) family member proteins including inhibiting the HSD17B member proteins, e.g. HSD17B13. The disclosure further relates to methods of treating liver diseases, disorders, or conditions with the compounds and pharmaceutical compositions disclosed herein, in which the HSD17B family member protein plays a role.
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Paragraph 0387
(2021/01/23)
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- The Synthesis of Primary Amines through Reductive Amination Employing an Iron Catalyst
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The reductive amination of ketones and aldehydes by ammonia is a highly attractive method for the synthesis of primary amines. The use of catalysts, especially reusable catalysts, based on earth-abundant metals is similarly appealing. Here, the iron-catalyzed synthesis of primary amines through reductive amination was realized. A broad scope and a very good tolerance of functional groups were observed. Ketones, including purely aliphatic ones, aryl–alkyl, dialkyl, and heterocyclic, as well as aldehydes could be converted smoothly into their corresponding primary amines. In addition, the amination of pharmaceuticals, bioactive compounds, and natural products was demonstrated. Many functional groups, such as hydroxy, methoxy, dioxol, sulfonyl, and boronate ester substituents, were tolerated. The catalyst is easy to handle, selective, and reusable and ammonia dissolved in water could be employed as the nitrogen source. The key is the use of a specific Fe complex for the catalyst synthesis and an N-doped SiC material as catalyst support.
- B?umler, Christoph,Bauer, Christof,Kempe, Rhett
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p. 3110 - 3114
(2020/06/01)
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- Substituent effects on chiral resolutions of derivatized 1-phenylalkylamines by heptakis(2,3-di-O-methyl-6-O-tert-butyldimethylsilyl)-β-cyclodextrin GC stationary phase
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Chiral resolutions of trifluoroacetyl-derivatized 1-phenylalkylamines with different type and position of substituent were investigated by capillary gas chromatography by using heptakis(2,3-di-O-methyl-6-O-tert-butyldimethylsilyl)-β-cyclodextrin diluted in OV-1701 as a chiral stationary phase. The influence of column temperature on retention and enantioselectivity was examined. All enantiomers of meta-substituted analytes as well as fluoro-substituted analytes could be resolved. Temperature had a favorable influence on enantioselectivity for small amines with substituents at the ortho-position. The type of substituent at the stereogenic center of amines also had a crucial effect as the ethyl group led to poor enantioseparation. Among all analytes studied, trifluoroacetyl-derivatized 1-(2′-fluorophenyl)ethylamine exhibited baseline resolution with the shortest analysis time.
- Issaraseriruk, Natthapol,Sritana-anant, Yongsak,Shitangkoon, Aroonsiri
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supporting information
p. 900 - 906
(2018/05/08)
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- PROCESS FOR THE PREPARATION OF CHIRAL AMINES FROM PROCHIRAL KETONES
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There is provided a method for the preparation of an enantiomerically enriched amine from a prochiral ketone.
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Page/Page column 5; 6
(2015/12/11)
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- NITROGENATED HETEROCYCLIC COMPOUND
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The present invention provides a compound having a PDE2A selective inhibitory action, which is useful as an agent for the prophylaxis or treatment of schizophrenia, Alzheimer's disease and the like. The present invention is a compound represented by the formula (1): wherein each symbol is as described in the specification, or a salt thereof.
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Paragraph 0828
(2015/03/28)
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- CYCLOBUTENEDIONE DERIVATIVES
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The present invention relates to compounds of the formula (I): to pharmaceutically acceptable salts therefore and to pharmaceutically acceptable solvates of said compounds and salts, wherein the substituents are defined herein; to compositions containing such compounds; and to the uses of such compounds in the treatment of various diseases, particularly inflammatory conditions.
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Page/Page column 71
(2010/12/17)
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- Synthesis of highly enantiomerically enriched amines by the diastereoselective addition of triorganozincates to N-(tert-butanesulfinyl)imines
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The reaction of triorganozincates with (R)-N-(tert-butanesulfinyl) imines gives the expected α-branched sulfinamides in good to excellent yields with diastereomeric ratios of up to 98:2. The N-sulfinyl group of the products can be easily removed by acidic treatment, affording the corresponding chiral primary amines in enantiomeric excesses of up to 96%. The reactivity and the selectivity shown by the triorganozincates are different from the ones observed with the corresponding Grignard reagents, which allows, in several cases, the preparation of both enantiomers of an amine from the same imine substrate. When mixed triorganozincates are used, one can take advantage of the slow transfer rate of the methyl group to use it as a non-transferable one. Both aromatic and aliphatic aldimines, as well as activated ketimines, are good substrates for these addition reactions.
- Almansa, Raquel,Guijarro, David,Yus, Miguel
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experimental part
p. 2484 - 2491
(2009/04/11)
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- Asymmetric sulfur ylide reactions with boranes: Scope and limitations, mechanism and understanding
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The reactions of aryl-stabilized sulfur ylides with organoboranes has been studied under a variety of conditions. At 5 or -78°C, the reaction with Et3B gave a mixture of the first and second homologation products, but at -100°C, only the first homologation product was obtained even with just 1.1 equiv of Et3B. Under these optimized conditions, the chiral sulfur ylides (derived from camphor sulfonic acid) with different aryl groups were reacted with Et3B to give the corresponding alcohols (95-98% yield, 96-98% ee) and amines (74-77% yield, >98% ee). The origin of the high enantioselectivity is discussed. The use of nonsymmetrical 9-BBN derivatives was also explored. It was found that whereas primary alkyl substituents gave mixtures of products derived from competing migration of the boron substituent and the boracycle, all other groups resulted in either exclusive migration of the boron substituent (Ph, hexenyl, i-Pr) or exclusive migration of the boracycle (hexynyl, cyclopropyl). The factors responsible for the outcome of the reactions involving a hindered (i-Pr) and an unhindered (propynyl) substituent were studied by DFT calculations. This revealed that, in the case of an unhindered substituent, the conformation of the ate complex is the dominant factor whereas, in the case of a hindered substituent, the barriers to interconversion between the conformers of the ate complex and subsequent migration control the outcome of the reaction.
- Fang, Guang Y.,Wallner, Olov A.,Di Blasio, Nadia,Ginesta, Xavier,Harvey, Jeremy N.,Aggarwal, Varinder K.
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p. 14632 - 14639
(2008/09/17)
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- 2-Mercaptoimidazoles, a new class of potent CCR2 antagonists
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We describe the synthesis and SAR of a new class of CCR2 antagonists based on a 2-mercaptoimidazole scaffold. The initial lead 1a was optimized to the 3,4-disubstituted analogues 1p-(S) and 1q-(S), which have IC50 values in the MCP-1 induced Ca
- Van Lommen, Guy,Doyon, Julien,Coesemans, Erwin,Boeckx, Staf,Cools, Marina,Buntinx, Mieke,Hermans, Bart,VanWauwe, Jean
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p. 497 - 500
(2007/10/03)
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- Process for hydrolyzing optically active amides
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The present invention relates to a process for hydrolyzing optically active amides to carboxylic acids and optically active amines with retention of the center of chirality, where the hydrolysis of the amides is carried out with an alkali metal or alkalin
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Page column 5-6
(2008/06/13)
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- Enantioselective addition of diethylzinc to N-diphenylphosphinoylimines employing N,N-dialkyl-1,2-diphenyl-2-aminoethanols as chiral ligands
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By fine-tuning the substituents on the nitrogen of (1S,2R) and (1R,2S)-1,2-diphenyl-2-aminoethanols, a chiral ligand 2b was obtained, which showed excellent enantioselectivity, with up to 94% e.e, for the asymmetric addition of diethylzinc to N-diphenylphosphinoylimines 1. In one example, the optically active amide 3c was converted into a new amine 5 with 98% e.e. by a reaction sequence involving Suzuki coupling and hydrolysis without racemization.
- Zhang, Xiaomei,Gong, Liuzhu,Mi, Aiqiao,Cui, Xin,Jiang, Yaozhong,C. K. Choi, Michael,S. C. Chan, Albert
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p. 6369 - 6372
(2007/10/03)
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