ISSN:0365-6233    

DOI:10.1002/ardp.19963290102

出版商:WILEY‐VCH Verlag    

年代:1996

数据来源: WILEY

摘要:

AbstractAs an extension of our study aiming to discover a novel compound with dual activities against histamine and slow‐reacting substance (SRS), we synthesized two types of indolylpiperidine derivatives,3and4–20.Testing forin vivoantianaphylactic activity and forin vitroanti‐SRS activity revealed that (2E,4E)‐5‐(3,5‐dimethoxy‐4‐hydroxyphenyl)‐N‐(2‐(4‐(1H‐indol‐3‐yl)piperidin‐1‐yl)ethyl)‐2,4‐pentadienamide (11) exhibited potent dual activities with ED50= 0.89 mg/kg and IC50= 1.43 μM, respectively. However, the plasma concentration of unchanged11was very low when administered orally in guinea pigs. This result can be explained by fast fo

ISSN:0365-6233    

DOI:10.1002/ardp.19963290103

出版商:WILEY‐VCH Verlag    

年代:1996

数据来源: WILEY

摘要:

AbstractA number of 2‐(1,2,3,4‐tetrahydro‐1‐isoquinolyl)‐ethanol derivatives7a—ehave been synthesized in diastereomerically and enantiomerically pure form and have been evaluated for their binding affinity at μ and κ opioid receptors. The amido ketones5a—candent‐5a—c, which were accessible by employing3bandent‐3bfor Asymmetric Electrophilic Amidoalkylation reactions, served as starting compounds. Upon reduction of5a—candent‐5a—cthe amido alcoholsl‐6a—c,u‐6a—c,ent‐l‐6a—candent‐u‐6a—cwere obtained. Hydrolysis of these compounds yielded the secondary amino alcoholsl‐7a—c,u‐7a—c,ent‐l‐7a—candent‐u‐7a—cand upon reductive methylation ofl‐7b—c,u‐7b—c,ent‐l‐7b—candent‐u‐7b—cwith CH2O and NaCNBH3the tertiary amino alcoholsl‐7d—e,u‐7d—e,ent‐l‐7d—eandent‐u‐7d—ewere obtained.The binding affinities of the final compoundsl‐7a—e,u‐7a—e,ent‐l‐7a—eandent‐u‐7a—eat both the μ and the κ receptor were strongly dependent on their stereochemistry. In each case isomers exhibited higher affinity at the μ than at the κ receptor. For the secondary amino alcohols7a—cthe affinity at the μ receptor followed the stereochemical orderl‐7>ent‐l‐7>ent‐u‐7>u‐7whereas for the tertiary amino alcohols the orderl‐7>u‐7>ent‐l‐7>ent‐u‐7was found. The stereoisomersl‐7dandl‐7eof the tertiary amino alcohols were found to be the most active compounds the latter exhibitin

ISSN:0365-6233    

DOI:10.1002/ardp.19963290104

出版商:WILEY‐VCH Verlag    

年代:1996

数据来源: WILEY

摘要:

AbstractA group of racemic 3‐[2‐nitrooxyethyl(1,3‐dinitrooxy‐2‐propyl or 4‐nitrophenylethyl)] 5‐isopropyl 1,4‐dihydro‐2,6‐dimethyl‐4‐[2‐trifluoromethylphenyl (2‐nitrophenyl or 3‐nitrophenyl)]‐3,5‐pyridinedicarboxylates13–15were prepared using the Hantzsch reaction that involved the condensation of 2‐nitrooxyethyl9a, 1,3‐dinitrooxy‐2‐propyl9bor 4‐nitrophenylethyl9cacetoacetate with isopropyl 3‐aminocrotonate11and 2‐trifluoromethyl12a, 2‐nitro12bor 3‐nitro12cbenzaldehyde.In vitrocalcium channel antagonist activities were determined using a guinea pig ileum longitudinal smooth muscle assay. Compounds13–15exhibited superior, or equipotent, calcium channel antagonist activity (10−8to 10−10M range) relative to the reference drug nifedipine (IC50= 1.43 × 10−8M). The R1C‐3 ester substituent was a determinant of calcium channel antagonist activity where the potency order was CH2CH2ONO2>CH2CH2‐C6H4‐4‐NO2≥ CH(CH2ONO2)2. In contrast, the C‐4 R2‐aryl substituent (2‐CF3‐C6H4‐, 2‐O2N‐C6H4‐ or 3‐O2N‐C6H4‐) was not a major determinant of activity. Compounds13a–15a, which possess a 3‐(2‐nitrooxyethyl) ester substituent exhibit superior calcium channel antagonist smooth muscle relaxant activity (IC50= 10−10M range) relative to nifedipine, could serve as potential

ISSN:0365-6233    

DOI:10.1002/ardp.19963290105

出版商:WILEY‐VCH Verlag    

年代:1996

数据来源: WILEY

摘要:

AbstractWe synthesized several vitamin E analogues containing oxygenated functional groups in place of the 8‐methyl group which is common to all the natural vitamin E congeners, based on the hypothesis that the methyl group might be metabolically oxidized to produce active forms which might have specific functions other than the antioxidant function. All the vitamin E analogues examined had antioxidant activity. 8‐[6‐Hydroxy‐2,5,7‐trimethyl]‐2‐(4,8,12‐trimethyltridecanyl)chroman'methanol (1d) and 2,5,7‐trimethyl‐2‐(4,8,12‐trimethyltridecanyl)chroman‐6‐ol (4d) showed similar activity to α‐tocopherol. 6‐Hydroxy‐2,5,7‐trimethyl‐2‐(4,8,12‐trimethyltridecanyl) chroman‐8‐carbaldehyde (2d) and 6‐hydroxy‐2,5,7‐trimethyl‐2‐(4,8,12‐trimethyltridecanyl)chroman‐8‐carboxylic acid (3d) showed weaker activity than α‐tocopherol, but thei

ISSN:0365-6233    

DOI:10.1002/ardp.19963290106

出版商:WILEY‐VCH Verlag    

年代:1996

数据来源: WILEY

摘要:

AbstractN‐Substituted indazolones were shown to be potent anti‐inflammatory and analgesic agents in mice at 8 mg/kg. In addition, the agents were able to protect against death caused by endotoxins similar to those found in chronic infections. In part, the ability of these agents to suppress the inflammatory process is due to their blockage of cytokine release, e.g. TNFα and IL‐1, as well as their inhibition of high affinity binding to receptors on target cells of inflammation. Suppressing these receptors can be linked to the inhibition by the agents of lysosomal hydrolytic enzymes, prostaglandin cyclooxygenase and 5°‐lipoxygenase activities. Free radical generation involved in inflammation was also stabilized in the presence of most of the

ISSN:0365-6233    

DOI:10.1002/ardp.19963290107

出版商:WILEY‐VCH Verlag    

年代:1996

数据来源: WILEY

摘要:

AbstractSynthesis of the title compounds is described, starting from alkylation of the pyroglutaminol‐acetal4a[1]at the α‐lactam position C‐6 with methyl iodide. Subsequent addition of 2‐cyclohexen‐1‐one led to diastereoselective formation of the 1,2‐aldol addition product7b/7c, which after dehydratization was aromatized with DDQ to yield the 6‐methyl‐6‐phenyl derivative7h.Acetal cleavage and Jones oxidation yielded 4,4‐disubstituted, enantiomerically pure pyroglutamic acid3b.X‐ray analysis confirmed the assignment of the configuration of the new

ISSN:0365-6233    

DOI:10.1002/ardp.19963290108

出版商:WILEY‐VCH Verlag    

年代:1996

数据来源: WILEY

摘要:

AbstractOn treatment with pharmaceutically important primary 1,3‐diamines2and8as well aso‐aminobenzenesulfonamides13–15, homophthalaldehyde (1) yields the intensely blue fluorescent, heteroanellated isoquinolines5and9, as well as moderately fluorescent isoquinobenzothiadiazines

ISSN:0365-6233    

DOI:10.1002/ardp.19963290109

出版商:WILEY‐VCH Verlag    

年代:1996

数据来源: WILEY

摘要:

AbstractAKBA (acetyl‐11‐keto‐β‐boswellic acid,1) and KBA (11‐keto‐β‐BA,2) fromBoswellia serrataRoxb. andBoswellia carteriiBirdw. are direct, nonredox‐type inhibitors of 5‐lipoxygenase, the key enzyme for leukotriene biosynthesis (IC50= 1.5 and 3μM in intact neutrophils, respectively). In order to study the impact of the carboxyl function for enzyme inhibition, we synthesized novel analogues of boswellic acids. The C‐4 alcohol derivative of KBA (4) still exerted 5‐lipoxygenase inhibitory activity (IC50= 4.5 μM), whereas (8), the C‐4 alcohol analogue of β‐boswellic acid (7), the methyl ester analogue of KBA (5), and acetyl‐11‐keto‐amyrin (9) possessed no inhibitory potential in concentrations up to 50 μM. These findings reveal that a hydrophilic group at C4 in combination with an 11‐keto‐function is essential for 5

ISSN:0365-6233    

DOI:10.1002/ardp.19963290110

出版商:WILEY‐VCH Verlag    

年代:1996

数据来源: WILEY

ISSN:0365-6233    

DOI:10.1002/ardp.19963290111

出版商:WILEY‐VCH Verlag    

年代:1996

数据来源: WILEY