132-60-5Relevant articles and documents
5-HT3 Receptor Antagonists. 3. Quinoline Derivatives Which May Be Effective in the Therapy of Irritable Bowel Syndrome
Kishibayashi, Nobuyuki,Miwa, Yoshikazu,Hayashi, Hiroaki,Ishii, Akio,Ichikawa, Shunji,et al.
, p. 3286 - 3292 (1993)
A series of quinolinecarboxylic acid derivatives has been previously described as a new class of 5-HT3 receptor antagonists due to deviation of a carbonyl moiety from the plane of an aromatic ring in their minimum-energy conformations.These derivatives were evaluated in a wrap-restraint stress-induced defecation model in rats.Reference compounds, ondansetron (1), granisetron (2), and YM060 (4), potently inhibited a stress-induced increase in stools excreted from fed rats (ID50 = 0.27, 0.12, and 0.0052 mg/kg, po, respectively).However, quinoline derivatives exhibited different activities depending on structural class. 4-Hydroxyquinoline-3-carboxylic acid derivatives 5 and 6a possess high affinity for the 5-HT3 receptor (Ki = 6.1 and 1.5 nM, respectively) and exhibit potent activity in the Bezold-Jarisch (B-J) reflex test (ED50 = 0.0017 and 0.00010 mg/kg, iv, respectively), but they did not effectively inhibit the increase in fecal pellet output at the dose of 1 mg/kg, po.On the other hand, most of 1-substituted 2-oxoquinoline-4-carboxylates 10 showed less potent activity in the B-J reflex test than 1 or 2 but inhibited restraint stress-induced defecation more potently than 1 or 2.The ID50 value of endo-8-methyl-8-azabicyclooct-3-yl 1-isobutyl-2-oxo-1,2-dihydro-4-quinolinecarboxylate 10e was 0.013 mg/kg, po.With respect to the selected compounds 6a and 10e, effects on 5-HT- and thyrotropin-releasing hormone (TRH)-induced defecation, castor oil-induced diarrhea and wrap-restraint stress-induced colonic propulsion in rats were examined.These 5-HT3 receptor antagonists did not effectively inhibit castor oil-induced diarrhea, which has been reported not to be mediated via the 5-HT3 receptor.Although 10e showed 800-fold decreased potency compared with 4 in the B-J refles test, 10e exhibited activity as potent as 4 in 5-HT- and TRH-induced defecation assays; 10e exhibited 7-fold increased potency compared with 4 in wrap-restraint stress-induced colonic propulsions.From these results, 10e appears to interact selectively with 5-HT3 receptors in the gastrointestinal system and might be effective in the therapy of irritable bowel syndrome (IBS).
Design and synthesis of novel quinoline/chalcone/1,2,4-triazole hybrids as potent antiproliferative agent targeting EGFR and BRAFV600E kinases
Mohassab, Aliaa M.,Hassan, Heba A.,Abdelhamid, Dalia,Gouda, Ahmed M.,Youssif, Bahaa G.M.,Tateishi, Hiroshi,Fujita, Mikako,Otsuka, Masami,Abdel-Aziz, Mohamed
, (2021)
New quinoline / chalcone hybrids containing 1,2,4-triazole moiety have been designed, synthesized and their structures elucidated and confirmed by various spectroscopic techniques. The designed compounds showed moderate to good activity on different NCI 60 cell lines in a single-dose assay with a growth inhibition rate ranging from 50% to 94%. Compounds 7b, 7d, 9b, and 9d were the most active compounds in most cancer cell lines with a growth inhibition percent between 77% and 94%. Newly synthesized hybrids were evaluated for their anti-proliferative activity against a panel of four human cancer cell lines. Compounds 7a, 7b, 9a, 9b, and 9d showed promising antiproliferative activities. These compounds were further tested for their inhibitory potency against EGFR and BRAFV600E kinases with erlotinib as a reference drug. The molecular docking study of compounds 7a, 7b, 9a, 9b, and 9d revealed nice fitting into the active site of EGFR and BRAFV600E kinases. Compounds 7b, 9b, and 9d displayed the highest binding affinities and similar binding pattern to those of erlotinib.
Design and Synthesis of 2,5-Disubstituted-1,3,4-Oxadiazole Hybrids Bearing Pyridine and 1,2,3-Triazole Pharmacophores
Kaushik, Reena,Kushwaha, Khushbu,Chand, Mahesh,Vashist, Monika,Jain, Subhash C.
, p. 1042 - 1047 (2017)
A novel series of 2,5-disubstituted-1,3,4-oxadiazoles decorated with two biodynamic moieties pyridine and 1,2,3-triazole have been successfully synthesized in good yields under mild reaction conditions. The synthesized compounds are valuable for biological activity exploration since three biodynamic moieties are covalently linked together in a single molecular framework. All the synthesized compounds were fully characterized by their detailed spectral studies IR, 1HNMR, 13C NMR and Mass.
PRODUCTION METHOD OF QUINOLINECARBOXAMIDE DERIVATIVE OR PRODUCTION INTERMEDIATE THEREOF
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, (2022/06/03)
Provided is a method for industrially advantageously synthesizing a production intermediate of a quinolinecarboxamide derivative or a salt thereof. The present invention provides a method for producing a quinolinecarboxylic acid derivative of formula (4) or a salt thereof, including reacting an aniline of the following formula (1), in the presence of boron trifluoride-tetrahydrofuran complex or boron trifluoride-diethyl ether complex, with an aldehyde of formula (2) and subsequently reacting the resulting compound with an α-keto acid of formula (3), wherein R1, R2, R3 and R4 are the same or different and each represent a hydrogen atom, a halogen atom, a lower alkyl group, or the like, R5 represents a hydrogen atom, a lower alkyl group, or the like, and R6 represents a hydrogen atom, a lower alkyl group, or the like.
Quinoline carboxamide core moiety-based compounds inhibit P. falciparum falcipain-2: Design, synthesis and antimalarial efficacy studies
Singh, Anju,Kalamuddin, Md,Maqbool, Mudasir,Mohmmed, Asif,Malhotra, Pawan,Hoda, Nasimul
, (2020/12/07)
Targeting Falcipain-2 (FP2) for the development of antimalarials is a promising and established concept in antimalarial drug discovery and development. FP2, a member of papain-family cysteine protease of the malaria parasite Plasmodium falciparum holds an important role in hemoglobin degradation pathway. A new series of quinoline carboxamide-based compounds was designed, synthesized and evaluated for antimalarial activity. We integrated molecular hybridization strategy with in-silico drug design to develop FP2 inhibitors. In-vitro results of FP2 inhibition by Qs17, Qs18, Qs20 and Qs21 were found to be in low micromolar range with IC50 4.78, 7.37, 2.14 and 2.64 μM, respectively. Among the 25 synthesized compounds, four compounds showed significant antimalarial activities. These compounds also depicted morphological and food-vacuole abnormalities much better than that of E-64, an established FP2 inhibitor. Overall these aromatic substituted quinoline carboxamides can serve as promising leads for the development of novel antimalarial agents.
