Pyridazinone ring

A similar strategy was used for the modification of zomepirac, basically a COX-1 selective drug. The desired COX-2 selectivity was achieved by replacing the acetic acid group by other moieties such as a pyridazinone ring or an N-acyl aminosulfonyl phenyl group to yield RS-57067 and RS-1048934, respectively (Barnett et al., 2000)... 

Betti, L., Corelli, F., Floridi, M., Giannaccini, G., Maccari, L., Manetti, F., Strappaghetti, G., Botta, M. aj-Adrenoceptor antagonists. 6. Structural optimization of pyridazinone-arylpiperazines. Study of the influence on affinity and selectivity of cyclic substituents at the pyridazinone ring and alkoxy groups at the arylpipera-zine moiety. /. Med. Chem. 2003, 46, 3555-3558. 

Since kinetic data are scarce, a comparison of relative reactivities of halogen atoms at different positions in the pyridazine or pyridazinone ring is difficult. The differences in reactivities which will be referred to are based on synthetic work. 

Attempts to hydrolyse the carbamate (9.3) under alkaline conditions gave an unexpected product which is formed by displacement of the fluorine (or less readily, chlorine) atom and formation of a pyridazinone ring. Optimum yields of this product were developed. 

A primary amino group, after diazotization, reacts with an a-ketophosphorane function to form a pyridazinone ring but the triphenylphosphine moiety is retained and can be removed by heating with aqueous alkali. 

Investigation of chemical properties of the synthesized indolopyrridazinone derivatives was carried out by the considered authors, as well as of other papers, with the purpose of changing the funetions of carbonyl groups and aromatization of pyridazinone ring. 

Pyridine and pyridazinone rings appear in compounds (97)" and (98), " the indole ring features in a series of compounds of type (99)," and a diazepinone ring in the thiopyran (100)." ... 

Pyridazinones may undergo ring contraction to pyrroles, pyrazoles and indoles, the process being induced either by an acid or base. The structure of the final product is strongly dependent on the reaction conditions. For example, 4,5-dichloro-l-phenylpyridazin-6(lFT)-one rearranges thermally to 4-chloro-l-phenylpyrazole-5-carboxylic acid (12S), while in aqueous base the corresponding 4-hydroxy acid (126) is formed (Scheme 40). 

Acrylic acid, -(3-benzo[f>]thienyl)-a -mercapto-reaction with iodine, 4, 764 Acrylic acid, o -cyano-y3-(2-thienyl)-ring opening, 4, 807 Acrylic acid, -formyl-in pyridazinone synthesis, 3, 46 Acrylic acid, furyl-rotamers, 4, 545 synthesis, 4, 658 Acrylic acid, 2-hydroxybenzoyl-chroman-4-one synthesis from, 3, 850 Acrylic acid, 5-(l-propynyl)-2-thienyl-methyl ester occurrence, 4, 909 Acrylonitrile... 

Mannich reactions, 3, 21 polymers, 1, 288 ring contraction, 3, 29 Pyridazinones, amino-diazotization, 3, 35 reaction... 

JOC6503>, and new pyridazino-psoralens 15 were prepared via a furan ring expansion reaction <05T4805>. The reaction of 3-acetylcoumarins with alloxan followed by NH2NH2 easily produced 3-(2-oxo-2//-chromen-3-yl)-6//,8//-pyrimido[4,5-c]pyridazine-5,7-diones <05JHC1223>. Furano- and pyrano[2,3-c]pyridazines 17 and 18a,b as well as substituted quinolines were conveniently prepared from pyridazinone 16 and vinyl- and allyltriphenyl-phosphonium salts <05HAC56>. 

A variety of tricylic compounds [indenopyridazinones (19)] have been prepared as rigid structural modifications of compounds like CI-930 (16) [28,29]. Most of them have been found to retain the positive inotropic and direct vasodilator activity of the freely rotating pyridazinones [28]. Also, hydrazinopyridazines of type (20) have been investigated as structural analogues of CI-914 and Cl-930, respectively. Whereas considerable inotropic activity has been observed in this series as well, ring closure to triazolo[4,3-h]pyridazines resulted in significantly less potent compounds [30]. 

Five new pyridazinones were synthesized with substitutions in the two-position of the phenyl ring as given in Table II. Using the Hansch approach, correlations were made between the experimentally determined 18 2/18 3 ratios and the values and a,a values taken out of the data collection of Hansch and Leo (15) (Table II and Equations 1-3). The hydrophobic parameter is derived from the 1-octanol/water partition coefficient and o is the Hammett electronic parameter. 

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