共查询到20条相似文献,搜索用时 31 毫秒
1.
Hantzch’s type reaction of methyl acetopyruvate(2a), methyl 3-aminocrotonate(3) and 3-nitrobenzaldehyde(4) led to dimethyl 3-acetyl-6-methyl-4-(3′-nitrophenyl)-2,5-dicarboxylate(5a) and methyl 2,6-dimethyl-5-(1′, 2′-dioxo-2′-methoxyethyl)-4-(3′-nitrophenyl)-1,4-dihydropyridine-3-carboxylate(6a) in 26.7 and 9.2% yield, respectively. On the other hand, methyl 2,6-dimethyl-4-(3′-nitrophenyl)-1, 4-dihydropyridine 3-carboxylate(9) was acylated by ethyl oxaly chloride to give methyl 2,6-dimethyl-5-(1′,2′-dioxo-2′-ethoxyethyl)-4-(3′-nitrophenyl)-1,4-dihydropyridine-3-carboxylate(6b) in 76.8% yield. 相似文献
2.
2,6-Dimethyl-4-(3′-nitrophenyl)-3-methoxylaminocarbonyl-1,4-dihydropyridine-5-carboxylic acid methylester,3b reacted with 2-cyanoethanol or benzylalcohol to give the corresponding cyanoethylurethane compound6c in 40.6% yield and benzylurethane compound6d in 32% yield. The cyanoethylurethane6c was hydrolized in ethanolic NaOH to give 2,6-dimethyl-4-(3′-nitrophenyl)-1,4-dihydropyridine-3-amino-5-carboxylic acid 5-methyl
ester. HCl8 in 64.8% yield. Another acid hydrolysis of benzylurethane6d gave 2,6-dimethyl-4-(3′-nitrophenyl)-1,4-dihydropyridine-3-amino-5-carboxylic acid 5-methylester. HBr11 in 54.7% yield. 相似文献
3.
Jungjin Suh Bongyong Lee Changseop Kim Jongwook Lee Byungchae Kim Byunghee Han Choongsup Kim 《Archives of pharmacal research》1990,13(3):240-245
□Asymmetric 2,6-dimethyl-4-aryl-1,4-dihydropyridine-3,5-dicarboxylate with [N-(3,4-methylenedioxybenzyl)-N-methyl] aminoethyl
group as the ester moiety and related 1,4-dihydropyridine derivatives were prepared and tested for the effects on vascular
smooth muscles. 2,6-dimethyl-4-(3′-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylic acid 3-[N-(3′, 4′-methylenedioxybenzyl)-N-methyl]
aminoethyl ester 5-methyl ester (11) and 2,6-dimethyl-4-(3′-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylic acid 3-[N-2′,3′-methylenedioxybenzyl)-N-methyl]
aminoethyl ester 5-ethyl ester (15) showed potent vasodilating activities. IC50 (10−8 M) was 2.6 and 2.7 for11 and15, compared with 3.5 for nicardipine. 相似文献
4.
2,6-Dimethyl-4-(3′-nitrophenyl)-3-methoxylaminocarbonyl-1,4-dihydropyridine-5-carboxylic acid methylester,3b reacted with 2-cyanoethanol or benzylalcohol to give the corresponding cyanoethylurethane compound6c in 40.6% yield and benzylurethane compound6d in 32% yield. The cyanoethylurethane6c was hydrolized in ethanolic NaOH to give 2,6-dimethyl-4-(3′-nitrophenyl)-1,4-dihydropyridine-3-amino-5-carboxylic acid 5-methyl ester. HCl8 in 64.8% yield. Another acid hydrolysis of benzylurethane6d gave 2,6-dimethyl-4-(3′-nitrophenyl)-1,4-dihydropyridine-3-amino-5-carboxylic acid 5-methylester. HBr11 in 54.7% yield. 相似文献
5.
《European Journal of Pharmacology: Molecular Pharmacology》1995,288(3):389-392
We have tested the two enantiomers of trans-azetidine-2,4-dicarboxylic acid, (2S,4S)-azetidine-2,4-dicarboxylic acid ((2S,4S)-ADA) and (2R,4R)-azetidine-2,4-dicarboxylic acid ((2R,4R)-ADA) for activity at the human metabotropic glutamate receptors mGlu1b, mGlu2, mGlu4a and mGlu5a expressed in mammalian cells. In Chinese hamster ovary (CHO) cells expressing human mGlu2 receptors, 500 μM (2S,4S)-ADA inhibited forskolin-stimulated cAMP accumulation by 33±3% while 100 μM (1S,3R)-1-Aminocyclopentane-1,3-dicarboxylic acid induced an inhibition by 66±5%. The (2R,4R)-ADA enantiomer was inactive at human mGlu2 receptors. In CHO cells expressing human mGlu4a receptors, 10 μM L-AP4 inhibited forskolin-stimulated cAMP levels by 37±4% whereas both ADA enantiomers of trans-azetidine-2,4-dicarboxylic acid (500 μM) had no such effect. In CHO cells expressing human mGlu5a receptors and L cells expressing human mGlu5a receptors, both enantiomers, applied at 500 μM or 1 mM, were ineffective in stimulating inositolmonophosphate accumulation and did not affect quisqualate-stimulated inositolmonophosphate accumulation. We conclude that (2S,4S)-azetidine-2,4-dicarboxylic acid is a weak human mGlu2 receptor agonist and that (2R,4R)-azetidine-2,4-dicarboxylic acid is inactive at human mGlu2 receptors. Trans-azetidine-2,4-dicarboxylic acid has no significant agonistic effect on human mGlu4a receptors and neither agonistic nor antagonistic effects on human mGlu1b and mGlu5a receptors. 相似文献
6.
7.
The synthesis of N′-(4-substitutedphenylsulfonyl)-2-{4-[2-(1H-indol-yl)ethyl]-3-(4-chlorobenzyl)-5-oxo-4,5-dihydro-1H-1,2,4-triazol-1-yl}acetohydrazides (3a–c), 2-{4-[2-(1H-indol-3-yl)ethyl]-3-(4-chlorobenzyl)-5-oxo-4,5-dihydro-1H-1,2,4-triazol-1-yl}-N′-aryl methylidene acetohydrazides (4a–f) and 4-[2-(1H-indol-3-yl)ethyl]-5-(4-substitutedbenzyl)-2-[(5-sulfanyl-1,3,4-oxadiazol-2-yl)methyl]-2,4-dihydro-3H-1,2,4-triazol-3-ones (5a, b) was performed starting from the corresponding acid hydrazides (2a, b) which was reported earlier. The treatment of 1,3,4-oxadiazole derivatives (5a, b) with hydrazine hydrate produced 4-amino-5-sulfanyl-4H-1,2,4-triazol-3-yl derivatives (6a, b). Then, compound 6b was converted to the corresponding Schiff base (7) by the treatment with anisaldehyde. The synthesis of 5-(4-chlorobenzyl)-4-[2-(1H-indol-3-yl)ethyl]-2-[(4-benzyl-5-oxo-4,5-dihydro-1H-1,2,4-triazol-3-yl)methyl]-2,4-dihydro-3H-1,2,4-triazol-3-one (8) and 5-(4-methylbenzyl)-4-[2-(1H-indol-3-yl)ethyl]-2-[(4-benzyl-5-oxo-4,5-dihydro-1H-1,2,4-triazol-3-yl)methyl]-2,4-dihydro-3H-1,2,4-triazol-3-one (10) was carried out by the reaction of acid hydrazides (2a, b) with aryl iso(thio)cyanates either via the formation of the intermediates (9a, b) (for 10) or direct cyclization (for 8). 1,3-Oxa(thia)zol-2(3H)-ylidene]acetohydrazide derivatives (11a, b) were obtained by the reaction of 9a, b with 4-chlorophenacyl bromide. All newly synthesized compounds were screened for their antimicrobial activities and some
of which was found to be active against the test microorganisms. 相似文献
8.
Methylation of 4-Hydroxy-2-quinolone The reaction of 4-hydroxy-2-quinolone (1a) with methyl iodide/potassium hydroxide in boiling acetone gave a mixture of 1-methyl-4-methoxy-2-quinolone (1d) , 1,3-dimethyl-4-methoxy-2-quinolone (1e) , and 1,3,3-trimethyl-2,4-dioxo-1,2,3,4-tetrahydroquinoline (2) . As by-product 2,4-dimethoxyquinoline (3) was identified. Under the same conditions 4-methoxy-2-quinolone (1c) yielded 1d, 1e, 2 and 3 , while 1-methyl-4-hydroxy-2-quinolone (1b) gave 1d, 1e and 2 . 相似文献
9.
Kai Zhou Xiao-meng Wang Yi-zhi Zhao Yong-xiao Cao Qiang Fu San-qi Zhang 《Medicinal chemistry research》2011,20(8):1325-1330
The antihypertensive activity of nitrendipine analogues can be improved by properly lengthening its alkyl chain in 3- or 5-position.
Nitrendipine and its seven analogues were synthesized, and their antihypertensive activities in spontaneously hypertensive
rats (SHR) were evaluated by ig administration. It was found that 5-n-heptyl 3-methyl 2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate [(±)-5] exhibited the strongest antihypertensive
effect amongst eight compounds. (+)-5-n-heptyl 3-methyl 2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate [(+)-5] was also prepared. Antihypertensive
activities of (±)-5 and (+)-5 in SHR were compared. The results showed that (±)-5 and (+)-5 had a higher potency than nitrendipine,
and (+)-isomer was 1.79-fold the raceme at a dose of 2 mg/kg. 相似文献
10.
Jack C. Kim 《Archives of pharmacal research》1994,17(3):204-206
A regioselective preparation of 10-methoxy-11-hydroxyaporphine (“Apocodeine,1b”) from (R,S)-10, 11-dihydroxyaporphine(apomorphine,1a) is described. The isopropylidene ketal ring of 10,11-(isopropylidenyldioxy) aporphine (2) obtained by the isopropylidenation of apomorphine, was regioselectively opened by the ten equivalent of trimethylaluminum
to give 10-hydroxy-11-t-butyloxyaporphine (3). The free 10-hydroxyl position of 3 was methylated with methyl p-toluenesulfonate/NaH, and afforded 10-methoxy-11-t-butyloxyaporphine
(4) in high yield. Selective debutylation gave the desired 10-methoxy-11-hydroxyaporphine (“apocodeine”,1b) in good yield. 相似文献
11.
Bis(2-cyanoethyl) 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate (3) reacts with sodium hydroxide solution to yield the 1-hydroxyindole-2-carboxylic acid 7 and the 9-hydroxy-beta-carboline-4-carboxylic acid 13. The structures of 7 and 13 were elucidated by derivatization and by spectroscopic methods. Bis(2-cyanoethyl) 2,6-dimethyl-4-(2-nitrosophenyl)pyridine-3,5-dicarboxylate (22) obtained by irradiation of 3 reacts with sodium hydroxide solution to give the cyclic hydroxamic acid 23 whose structure is proven by an independent synthesis. 相似文献
12.
Amides of 1-benzyl-3,7-dimethyl-4-oxo-2-thioxo-1,2,3,4- tetrahydropyrido[2,3]pyrimidine-6-carboxylic acid were obtained by the condensation of ammonia, primary and secondary cyclic amines with the corresponding acid chloride. As by - products amides of 1-benzyl-3,7-dimethyl-2,4-dioxo-1,2,3,4-tetrahydropyrido[2,3-d]pyr imidine-6- carboxylic acid were isolated as a result of desulfuration. The same reaction performed with chloride of 1-butyl-7-methyl-3-phenyl-4-oxo-2-thioxo-1,2,3,4-tetrahydropyri do[2,3- d]pyrimidine-6-carboxylic acid gave mainly the corresponding 2,4-dioxo-amides. 相似文献
13.
Akinori Mimura Hitomi Sumioka Katsuyoshi Matsunami Hideaki Otsuka 《Journal of natural medicines》2010,64(2):153-160
Three conjugates of the abscisic acid derivative (2Z,4E)-5-[(1S,3S,5R,8S)-3,8-dihydroxy-1,5-dimethyl-7-oxo-6-oxabicyclo[3.2.1]octan-8-yl]-3-methylpenta-2,4-dienoic acid and phenolic glucosides (1–3), and an eremophilane-type sesquiterpene glucoside (4), along with ten known compounds, were isolated from the roots of Lindera strychnifolia. The structures of all compounds were elucidated by means of spectroscopic analysis, and by application of the modified Mosher’s
method for the methyl ester of the abscisic acid derivative and the octant rule for 4. 相似文献
14.
Ibrahim Imam Ismail 《Archives of pharmacal research》1990,13(1):1-4
Reaction of propane-1,3-sultone with amines gave N-substituted aminosulphonic acids2a?i. Dehydration of2a?c with POCl3 gave the corresponding sultams3a?c. Propane-1,3-sultone1 reacted with tertury amines to give the betaiene salts4–11. 2,4-Dimethyl-1,3-butadiene-1,4-sultone12 condensed with amines to give N-substituted-2,4-dimethyl-1,3-butadiene-1,4-sultams13a and13b. The reaction of3a, 13a with hydrazine hydrate gave acid hydrazides3d or13c. Compounds3d, 13c reacted with isocyanates to yield urea derivatives14a?c, 15a?c. 相似文献
15.
V. L. Gein V. V. Yushkov N. N. Kasimova M. A. Panina N. S. Rakshina L. V. Strelkova E. V. Voronina 《Pharmaceutical Chemistry Journal》2007,41(7):367-371
1-(3-Aminopropyl)-5-aryl-4-acyl-3-hydroxy-3-pyrrolin-2-ones (I–X) were prepared via reaction of methyl acylpyruvates and a mixture of aromatic aldehyde and 1,3-diaminopropane in a 1:1:1
molar ratio. The products were converted to hydrochlorides XI–XV in 48–90% yields. 1,3-Di(4-acetyl-3-hydroxy-2-oxo-5-phenyl-3-pyrrolin-1-yl)propane (XVI) was produced in 16% yield via reaction of methyl acetylpyruvate with a mixture of benzaldehyde and 1,3-diaminopropane in
a 2:2:1 molar ratio. The biological activity of the 12 products was studied.
__________
Translated from Khimiko-Farmatsevticheskii Zhurnal, Vol. 41, No. 7, pp. 25–29, July, 2007. 相似文献
16.
Patrick R. Conlon William F. Kiesman 《Journal of labelled compounds & radiopharmaceuticals》2007,50(4):219-223
BG9928, a high affinity adenosine A1 antagonist, is currently in Phase II clinical trials for the treatment of congestive heart failure. A deuterium-labeled version of the molecule was synthesized and used as a standard for in vivo pharmacokinetic and in vitro metabolism studies. The labeled form of 3-[4-(2,6-dioxo-1,3-dipropyl-2,3,6,7-tetrahydro-1H-purin-8-yl)-bicyclo[2.2.2]oct-1-yl]-propionic acid (BG9928) was obtained in a convergent manner by joining two major building blocks: the specifically labeled heterocycle 5,6-diamino-1,3-dipropyl-1H-pyrimidine-2,4-dione ( 4 ) and the hemiester 4-(2-methoxycarbonyl-ethyl)-bicyclo[2.2.2]octane-1-carboxylic acid ( 10 ). Copyright © 2007 John Wiley & Sons, Ltd. 相似文献
17.
Two new 4-hydroxybenzyl alcohol derivatives (1 and2) were isolated from the methanol extract obtained from fresh tubers ofGastrodia elata together with 4-hydroxybenzyl methyl ether, 4-hydroxybenzyl alcohol, bis(4-hydroxyphenyl)methane, 4-hydroxybenzaldehyde,
β-sitosterol and palmitic acid.1 and2 were identified as 3-O-(4′-hydroxybenzyl)-β-sitosterol and 4-[4′-(4″-hydroxybenzyloxy) benzyloxy)benzyl methyl ether, respectively, according to
the spectroscopic data. 相似文献
18.
19.
Six sesquiterpene derivatives, 2,3-dihydro-7-methoxy-2S*, 3R*-dimethyl-2-[4,8-dimethyl-3(E),7-nonadienyl]furo[3,2-c]coumarin (1) and 2,3-dihydro-7-methoxy-2R*,3R*-dimethyl-2-[4,8-dimethyl-3(E),7-nonadienyl]furo[3,2-c]coumarin (2), nerolidol (3), 1-(2,4-dihydroxyphenyl)-3,7,11-trimethyl-3-ninyl-6(E),10-dodecadien-1-one (4), 1-(2,4-dihydroxyphenyl)-3,7-dimethyl-3-vinyl-8-(4-methyl-2-furyl)-6(E)-octen-1-one (5) and dshamirone (6) were isolated from an 80% aqueous methanol extract of the roots of Ferula fukanensis. The sesquiterpenoids inhibited nitric oxide (NO) production and inducible NO synthase gene expression by a murine macrophage-like cell line (RAW 264.7) [1], which was activated by lipopolysaccharide and recombinant mouse interferon-. 相似文献
20.
Grażyna Chłoń-Rzepa Paweł Żmudzki Grzegorz Satała Beata Duszyńska Anna Partyka Dagmara Wróbel Magdalena Jastrzębska-Więsek Anna Wesołowska Andrzej J. Bojarski Maciej Pawłowski Paweł Zajdel 《Pharmacological reports : PR》2013,65(1):15-29
BackgroundOur previous studies in a group of arylpiperazine derivatives of 1,3-dimethyl-3,7-dihydro-purine-2,6-diones, aimed at chemical diversification of the purine-2,6-dione by introduction of hydrophobic substituent in a 7- or 8- position or elongation of the linker length between arylpiperazine and purine core, allowed a selection of potent 5-HT1A, 5-HT2A and 5-HT7 receptor ligands displaying anxiolytic and antidepressant properties. Continuing our research in this field, in the present studies we designed a new series of 8-aminoalkylamino (15–35) and 8-arylpiperazinylpropoxy (36–42) derivatives of 7-substituted 1,3-dimethyl-3,7-dihydropurine- 2,6-dione as potential 5-HT1A, 5-HT2A and 5-HT7 receptor ligands with potential psychotropic activity.MethodsRadioligand binding assays were employed for determining the affinity and the selectivity profile of the synthesized compounds for native 5-HT1A, 5-HT2A, and cloned 5-HT6 and 5-HT7 receptors. The functional activity of the selected compounds at 5-HT1A and 5-HT2A receptors was tested in the commonly used in vivo models. Antidepressant and anxiolytic properties were evaluated in the forced swim (FST) and the four-plate test (FPT) in mice, respectively.ResultsAmong the evaluated series, selected 7-benzyl-8-((4-(4-(3-chlorophenyl)piperazin-1-yl)butyl)amino)-1,3-dimethyl- 1H-purine-2,6(3H,7H)-dione (21), a mixed 5-HT1A/5-HT2A/5-HT7 receptor ligand, produced an antidepressant-like effect in FST, and exerted anxiolytic-like activity in FPT. Another pharmacologically evaluated compound 42 (a mixed 5-HT1A/5-HT7 ligand) slightly, but non-significantly attenuated the immobility time of mice in FST and was devoid of activity in FPT.ConclusionsStudy revealed advantage of mixed 5-HT1A/5-HT2A/5-HT7 receptor ligands over 5-HT1A/5-HT7 agents to display antidepressant- and anxiolytic-like activity. Modification of arylalkyl/allyl substituent in position 7 of purine-2,6-dione opens possibility for designing new 5-HT ligands with preserved π electron system and lower molecular weight. 相似文献