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Potent antagonists of gonadotropin releasing hormone receptors derived from quinolone-6-carboxamides

SAR studies which focused upon the C-6 position of a recently described series of quinolone gonadotropin releasing hormone antagonists are reported. Synthetic access to diverse quinolone-6-carboxamides was achieved via the palladium-catalyzed amino-carbonylation reactions of iodide 4 with various amines. Amides related to 9y were especially potent, functional antagonists of rat and human GnRH receptors. (C) 2000 Elsevier Science Ltd. All rights reserved.

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Isoxazole – Wikipedia,
Isoxazole | C3H3NO – PubChem

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Room-temperature palladium-catalyzed coupling of heteroaryl amines with aryl or heteroaryl bromides

Heteroaryl amines readily undergo Buchwald-Hartwig amination reactions with a range of aryl and heteroaryl bromides at room temperature using t-BuXPhos Pd-precatalyst and NaOt-Bu. The pharmaceutically attractive biaryl amines are generally formed in short reaction times (0.5-16 h) and in good to excellent yields. Georg Thieme Verlag Stuttgart – New York.

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THERAPEUTIC COMPOUNDS AND USES THEREOF

Described herein are compounds of Formula (I) or Formula (VI), pharmaceutically acceptable salts thereof, and pharmaceutical compositions thereof. Also provided are particles (e.g., nanoparticles) comprising compounds of Formula (I) or Formula (VI) and pharmaceutical compositions thereof that are mucus penetrating. Methods of using the compounds or pharmaceutical compositions thereof for treating diseases are also provided.

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Studies with Enaminones: The reaction of enaminones with Aminoheterocycles. A route to Azolopyrimidines, Azolopyridines and Quinolines

The enaminones 1b,d,f react with 4-phenyl-3-methyl-5-pyrazoleamine 3a to yield the pyrazole derivatives 4a-c that cyclised readily on reflux in pyridine solution in presence of hydrochloric acid to yield the pyrazolo[1,5-a]pyrimidines 5a-c. Similarly 3(5)-amino-1H-triazole (3b) reacted with 1b,d,f to yield the triazolo[1,5-a]pyrimidines 5d-f. In contrast attempted condensation of the 5-tetrazoloamine (3c) with 1a,d,e resulted in its trimerisation and only triaroylbenzene 8a,d,e was isolated. The reaction of 1a,b,d with anthranilonitrile 9a and the reaction of 1a-c with the 2-aminocyclohexene thiophene-3-nitrile 10a afforded the cis enaminones 11a-c and 12a-c. Similarly, reaction of 1a-c with the methylanthranilate 9b and reaction of 1b,e with ethyl 2-aminocyclohexene thiophene-3-carboxylate 10b afforded the cis enaminones 11d-f and 12d,e respectively. Attempted cyclization of 11a-c into quinoline failed. Successful cyclization of 11d into the quinolinone 13 could be affected, on heating for five minutes in a domestic microwave oven at full power. The reaction of 1a-c,f with piperidine afforded the trans enaminones 14a-d. Similarly, trans 14e was formed from the reaction of 1b with morpholine. The coupling reaction of 1b with excess of benzene diazonium chloride afforded the formazane 16. The enaminone 2 reacted with heterocyclic amines to yield the pyridones 17,18.

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An innovation for development of Erlenmeyer-Ploechl reaction and synthesis of AT-130 analogous: A new application of continuous-flow method

The development of eco-friendly and efficient processes via one-pot multicomponent synthesis is a very attractive topic. In this work, the Erlenmeyer-Ploechl azlactone synthesis was carried out through unique, safe, fast and practical conditions without any catalyst, applying a simple microreactor and gave the corresponding products exclusively. A continuous, first microflow synthesis of N-benzoylglycine carbamide derivatives as AT-130 analogues catalyzed by Nafion-H@SPIONs was also established successfully.

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Synthesis of 3-hetaryl-1,5,3-dithiazepanes and 3-hetaryl-1,5,3- dithiazocanes in the presence of catalysts based on transition metals

Efficient procedure was developed for 3-hetaryl-1,5,3-dithiazepanes and 3-hetaryl-1,5,3-dithiazocanes preparation from hetarylamines, N,N,N?,N?-tetramethylmethanediamine, and alpha,omega- alkanedithiols (ethane-1,2-dithiol, propane-1,3-dithiol), and also by the reaction of the latter with N,N-bis(methoxymethyl)hetarylamines in the presence of catalytic quantities of transition metals salts.

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Isoxazole – Wikipedia,
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Insights into the electrochemical degradation of sulfamethoxazole and its metabolite by Ti/SnO2-Sb/Er-PbO2 anode

Electrochemical degradation of sulfamethoxazole (SMX) and its metabolite acetyl-sulfamethoxazole (Ac-SMX) by Ti/SnO2-Sb/Er-PbO2 were investigated. Results indicated that the electrochemical degradation of SMX and Ac-SMX followed pseudo-first-order kinetics. The rate constants of SMX and Ac-SMX were 0.268 and 0.072 min-1 at optimal current density of 10 and 14 mA/cm2, respectively. Transformation products of SMX and Ac-SMX were identified and the possible degradation pathways, including the cleavage of S-N bond, opening ring of isoxazole and nitration of amino group, were proposed. Total organic carbon removal of SMX was nearly 63.2% after 3 h electrochemical degradation. 22.4% nitrogen of SMX was transformed to NO3-, and 98.8% sulfur of SMX was released as SO42-. According to quantitative structure-activity relationship model, toxicities of SMX and Ac-SMX to aquatic organisms significantly decreased after electrochemical degradation. Electric energy consumption for 90% SMX and Ac-SMX degradation was determined to be 0.58-8.97 and 6.88-44.19 Wh/L at different experimental conditions, respectively. Compared with parent compound SMX, the metabolite Ac-SMX is more refractory and toxic, which emphasizes the importance of taking its metabolites into account when investigating the disposal of pharmaceuticals from wastewater.

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Isoxazole – Wikipedia,
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COMPOUNDS AND METHODS FOR KINASE MODULATION, AND INDICATIONS THEREFOR

Compounds of formula I active on protein kinases are described, as well as methods of using such compounds to treat diseases and conditions associated with aberrant activity of protein kinases. Formula (I) wherein Ar is optionally substituted heteroaryl; R 2 is hydrogen, lower alkyl or halogen; U is selected from the group consisting of -S(O) 2 -, -C(X)-, -C(X)-N(R 10 )-, and -S(O) 2 -N(R 10 )-; R 3 is optionally substituted lower alkyl, optionally substituted C3.6 cycloalkyl, optionally substituted heterocycloalkyl, optionally substituted aryl or optionally substituted heteroaryl; and wherein R 1 , R 3 , R 4 , m, L 1 , X R 10 are as described herein.

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Synthesis of furo[3,2-g]chromones under microwave irradiation and their antitumor activity evaluation

A series of furo[3,2-g]chromone derivatives were synthesized via the reaction of furochromone carbaldehyde 1 with amines 3a-d and thioglycolic acid to give thiazolidinones 4a-d. The later react with benzaldehyde/thiourea or hydroxylamine and DMF-DMA in glacial acetic acid to give thiazolopyrimidines 5a-d or thiazoloisoxazoles 6a-d, respectively. Also, the synthesis of alpha-aminophosphonates via the one-pot reaction of 1 and amines 3a,b were trapped by dialkylphosphites 7a-c afforded the corresponding alpha-aminophosphonates 8a-f. Applying hexaalkyltriamidophosphites 9a,b to 1 gives alkylidenephosphorane ylides 11a,b in an open structure form. In the present investigation, the in vitro inhibition capacity of compounds (4a, 4c, 5b, 5c, 6b-d, 8a-f, and 11a) was screened in three human cancer cell lines HCT-116, MCF-7, and HepG2. The anticancer activity results revealed that 8b and 8e had more potent cytotoxic inhibition activity against HCT-116 cell line; however, all the tested compounds had obviously less cytotoxic activity against MCF-7 cell line, while 5b, 5c, and 6d were potent against HepG2 cell line compared with that of doxorubicin.

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Isoxazole – Wikipedia,
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4-Hydroxy-2H-naphtho[2,1-e]-1,2-thiazine-3-carboxamide-1,1-dioxides and salts thereof

Compounds of the formula SPC1 Wherein R1 is hydrogen, methyl or ethyl, and Ar is phenyl, 3-chlorophenyl, 3-bromophenyl, 2-fluorophenyl, 3-fluorophenyl, 4-fluorophenyl, 3-tolyl, 2-methoxyphenyl, 3-methoxyphenyl, 2-pyridyl, 4-methyl-2-pyridyl, 6-methyl-2-pyridyl, 3-hydroxy-2-pyridyl, 3-pyridyl, 4-pyridyl, 6-chloro-3-pyridazinyl, 2-pyrazinyl, 6-chloro-2-pyrazinyl, 6-chloro-4-pyrimidinyl, 2-thiazolyl, 4-methyl-2-thiazolyl, 4-ethyl-2-thiazolyl, 5-methyl-2-thiazolyl, 5-ethyl-2-thiazolyl, 4,5-dimethyl-2-thiazolyl, 4-ethyl-5-methyl-2-thiazolyl, 5-ethyl-4-methyl-2-thiazolyl, 2-benzothiazolyl, 4,5,6,7-tetrahydro-2-benzothiazolyl, 5,6-dihydro-7H-thiopyrano[4,3-d]thiazol-2-yl, 3-methyl-5-isothiazolyl, 1,3,4-thiadiazolyl, 5-methyl-1,3,4-thiadiazol-2-yl or 5-methyl-3-isoxazolyl, And non-toxic, pharmacologically acceptable salts thereof formed with an inorganic or organic base; the compounds as well as their salts are useful as inhibitors of platelet adhesion and aggregation.

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