Tetrahydro-5 -quinolinones

The X-ray structures of the complexes of (-l-)-huperzine A (1) and (—)-huperzine B (2) with Torpedo californica AChE were determined at 2.1 and 2.35 A resolution, respectively (152), and compared to the previously determined structure of the (—)-huperzine A complex. Recently, alkylene-linked dimers of 5-amino-5,6,7,8-tetrahydro-quinolinone (hupyridone, 254a), a fragment of huperzine A (1), were shown to serve as more potent inhibitors of AChE than (—)-huperzine A (1) and monomeric 253a. Two dimers, (5, 5 )-(—)-bis(10)-hupyridone [(NjN)- —)-254a] and (S,S)-(—)-bis(12)hupyridone [(5, S)-(—)-254b] containing, respectively, 10 and 12 methylenes in... 

Tetrahydropyrido[2,l-6][l,3]oxazine (29) afforded pyridinium bromide (30) on the action of aqueous hydrogen bromide, and no reaction occurred on treatment with NaBEL) in methanol [77JCS(P2)759]. Treatment of 3-oxo-2,3,7,8,9,10-hexahydro-l//-[l,3]oxazino[3,2-a]quinolinium chloride with ethanol yielded l-(2-carboxyethyl)-5,6,7,8-tetrahydro-2(l//)-quinolinone (69MI1). 

Tetrahydro-5-oxo-2(lH)-quinolinone (4.0mmol), 1,7-diaminoheptane (2.0 mmol) and 5 drops of HO Ac dissolved in 50 ml benzene were refluxed with azeotropic removal of water for 24 hours. The solution was cooled, concentrated, and the Schiff base used directly in Step 2. 

An efficient one-pot procedure for the synthesis of 4-aryl-8-arylidene-5,6,7,8-tetrahydro-2-quinolinones 66 has been developed by Yen and co-workers [54] based on a cyclocondensation reaction of W-ethoxycarbonylmethylpyridinium chloride with an aromatic aldehyde and cyclohexanone. The microwave-assisted (domestic microwave oven) MCR resulted in the formation of compound 66 in high yields (Scheme 50). 

Yan C-G, Cai X-M, Wang Q-F et al (2008) A novel four component one-pot access to 4, 6-diaryl-2-pyridinone and 4-aryl-5, 6, 7, 8-tetrahydro-2-quinolinones. Lett Org Chem... 

Pyrazolo[3,4-Z)]pyridines, the 7-chloro-6-fluoro-2,4-dimethylquinoline and its mercapto-thiadiazolyl or oxadiazolyl quinolines 21 were prepared via Diels-Alder reaction conversion of methyl 2-(3-oxo-3-phenylpropenylamino)benzoate into 3-benzoyl-l.S -quinolin-4-one 22 . A mixture of aniline derivatives and malonic ester gave a variety of 3-aryl-4-hydroxyquinolin-2(l//)-ones 23. Condensation of isatins with ketones afforded quinoline-4-carboxylic acids. 2-Aryl-l,2,3,4-tetrahydro-4-quinolinones 22 and carbazolylquinolone were also prepared. The substitution of 2-chloroquinoline gave the 2-substituted quinolines. Basic alumina has catalyzed the C-C bond formation between 2-hydroxy-1,4-naphthoquinone and 2-chloroquinoline derivative to give 21. Reaction of organic halides with 8-hydroxyquinolines gave the respective ethers. The azodye derivatives of 21 were prepared in the absence of solvent. Silica gel catalyzed the formation of 2-ketomethylquinolines from reaction of 2-methylquinolines with acyl chlorides. 

For l-ethoxy-4a,7,8,8a-tetrahydro- and l-ethoxy-4a,7,8,8a-tetrahydro-8a-methyl-3(4//)-iso-quinolinone, the starting trienes were synthesized and cyclized in a single vessel. The trienes were synthesized by the reaction of substituted ethyl 2-propenimidate with the appropriate... 

The oxidative aromatization of tetrahydro-5(l/f)-quinolinones and tetrahydropyrido [2,3-fif]pyrimidin-4(//)-one withpara-benzaldehydes as oxidants in NaOEt/EtOH results in the formation of the corresponding quinolone and aryl methanol because of the hydride transfer from tetrahydroquinoline to arylaldehydes during the oxidation process. The yield of the products basically depends on the substituents with -l-M effect attached to the para position of benzene rings connected to the 2- and 4-positions of the hydro-quinolinone moiety and substituents with -I effect attached to the aryl aldehydes. 

Figure 4.9 Structures of selected SARMs androgen receptor antagonists bicalutamide (1) and flutamide (2) arylpropionamide-based agonists S-1 (3), S-4 (Andarine, 4),S-22 (5) bicyclic hydantoin-derived antagonist nilutamide (6) agonists BMS-564929 (7), and 4-(7-hydroxy-l,3-dioxo-tetrahydro-pyrroIo[l,2-c]imidazoI-2-yI)-naphthaIene-l-carbo-nitrile (8) quinolinone-based SARMs LG-121071 (9), LGD-2226 (10), and bisethyl-amino-4-trifluoromethyIquinoIin-2(lH)-one (11) and tetrahydroquinoline-derived SARMs S-40503 (12), and 2-methyI-2-(8-nitro-3a,4,5,9b-tetrahydro-3H-cycIopenta[c] chinoIin-4-yI)propan-l-oI (13).

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