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1.
Bioorg Med Chem ; 23(1): 66-72, 2015 Jan 01.
Article in English | MEDLINE | ID: mdl-25496808

ABSTRACT

Mitochondrial uncoupling is one of the therapeutic strategies used to control energy metabolism in various metabolic diseases and in obesity. Ppc-1 (1), a prenylated quinolinecarboxylic acid isolated from cellular slime molds, shows uncoupling activity in vitro and anti-obesity activity in vivo. In this study, we synthesized Ppc-1 (1) and its derivatives, and revealed the structure-activity relationship of uncoupling activities. The triprenylated compound 18 showed mitochondrial uncoupling activity that was more potent than that of Ppc-1 (1). Compound 18 also suppressed weight gain in mice without undesired effects such as lesions on tissues. These results indicate that compound 18 could be used as a seed compound for new anti-obesity drugs.


Subject(s)
Anti-Obesity Agents/chemical synthesis , Anti-Obesity Agents/pharmacology , Obesity/drug therapy , Quinolinic Acids/chemical synthesis , Quinolinic Acids/pharmacology , Animals , Anti-Obesity Agents/chemistry , Mice , Mice, Inbred ICR , Mitochondria/drug effects , Mitochondria/metabolism , Obesity/metabolism , Prenylation , Quinolinic Acids/chemistry , Structure-Activity Relationship , Uncoupling Agents/chemical synthesis , Uncoupling Agents/chemistry , Uncoupling Agents/pharmacology
2.
Chemistry ; 12(17): 4523-35, 2006 Jun 02.
Article in English | MEDLINE | ID: mdl-16619313

ABSTRACT

The unique electron-transport and emissive properties of tris(8-quinolinolate) aluminum(III) (Alq(3)) have resulted in extensive use of this material for small molecular organic light-emitting diode (OLED) fabrication. So far, efforts to prepare stable and easy-to-process red/green/blue (RGB)-emitting Alq(3) derivatives have met with only a limited success. In this paper, we describe how the electronic nature of various substituents, projected via an arylethynyl or aryl spacer to the position of the highest HOMO density (C5), may be used for effective emission tuning to obtain blue-, green-, and red-emitting materials. The synthetic strategy consists of four different pathways for the attachment of electron-donating and electron-withdrawing aryl or arylethynyl substituents to the 5-position of the quinolinolate ring. Successful tuning of the emission color covering the whole visible spectrum (lambda=450-800 nm) was achieved. In addition, the photophysical properties of the luminophores were found to correlate with the Hammett constant of the respective substituents, providing a powerful strategy with which to predict the optical properties of new materials. We also demonstrate that the electronic nature of the substituent affects the emission properties of the resulting complex through effective modification of the HOMO levels of the quinolinolate ligand.


Subject(s)
Aluminum/chemistry , Electrons , Organometallic Compounds/chemistry , Quinolinic Acids/chemistry , Electrochemistry , Electron Transport , Light , Organometallic Compounds/chemical synthesis , Quinolinic Acids/chemical synthesis , Semiconductors , Spectrum Analysis
3.
Bioorg Med Chem ; 12(24): 6465-72, 2004 Dec 15.
Article in English | MEDLINE | ID: mdl-15556764

ABSTRACT

Additional structural modifications of the new chemical entity, 2,8-dicyclopentyl-4-methylquinoline (DCMQ; MIC=6.25 microg/mL, M. tuberculosis H37Rv) resulted in the synthesis of four new series of the ring-substituted quinolinecarbohydrazides (series 1-4) constituting 22 analogues. All new derivatives were evaluated for in vitro antimycobacterial activities against drug-sensitive M. tuberculosis H37Rv strain. Certain ring-substituted-2-quinolinecarbohydrazide analogues described herein showed good inhibitory activity. In particular, analogues 4-(1-adamantyl)-2-quinolinecarbohydrazide (2d), 4,5-dicyclopentyl-2-quinolinecarbohydrazide (2e), 4,8-dicyclopentyl-2-quinolinecarbohydrazide (2f), and 4,5-dicyclohexyl-2-quinolinecarbohydrazide (2g) have exhibited the MIC value of 6.25 microg/mL. Further investigation of the most suitable lead prototype, 4-(1-adamantyl)-2-quinolinecarbohydrazide (2d, series 1) led to the synthesis of N2-alkyl/N2,N2-dialkyl/N2-aryl-4-(1-adamantyl)-2-quinolinecarboxamides (series 5) consisting of 13 analogues. Some of the synthesized carboxamides 7a, 7h, and 7m reported herein have exhibited excellent antimycobacterial activities in the range of 6.25-3.125 microg/mL against drug-sensitive and drug-resistant M. tuberculosis H37Rv strains.


Subject(s)
Anti-Bacterial Agents/chemical synthesis , Mycobacterium tuberculosis/drug effects , Quinolinic Acids/chemical synthesis , Amides , Anti-Bacterial Agents/pharmacology , Dose-Response Relationship, Drug , Drug Resistance, Bacterial , Microbial Sensitivity Tests , Quinolinic Acids/pharmacology , Structure-Activity Relationship
6.
J Med Chem ; 22(1): 44-8, 1979 Jan.
Article in English | MEDLINE | ID: mdl-106118

ABSTRACT

Structural modification of 3,4-dihydro-4-oxoquinazoline-2-carboxylic acid leading to ethyl 3,4-dihydro-4-oxopyrimido[4,5-b]quinoline-2-carboxylate, a new prototype with oral antiallergy activity of the disodium cromoglycate type, is described. This prototype is 10 times more potent than disodium cromoglycate in the rat passive cutaneous anaphylaxis test. Structure-activity studies indicate that a carboxylic acid moiety directly attached to the 2 position of the pyrimidine ring is most favorable for intravenous activity while esters of this acid are preferred for oral activity. The oral activity of ethyl 3,4-dihydro-4-oxopyrimido[4,5-b]quinoline-2-carboxylate (ED50 = 3 mg/kg) places this ester among the more potent orally active antiallergy agents reported to date.


Subject(s)
Passive Cutaneous Anaphylaxis/drug effects , Pyridines/chemical synthesis , Quinolinic Acids/chemical synthesis , Animals , Anti-Inflammatory Agents , Cromolyn Sodium/pharmacology , Histamine Antagonists , Male , Quinolinic Acids/pharmacology , Rats , Structure-Activity Relationship
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