6-Phenyl-5 - pyridazinone

S., unpublished results Magee, P., private communication) led us to collect additional evidence for this equation. Nine more 2-phenyl-pyridazinones were synthesized and the 18 2/18 3 ratios were determined experimentally. The values ranged from -1.63 to 2.80 and a values ranged from -0.83 to 0.72 (Table IV). 

Table VII. Calculated Electron Densities of Various Differently p-Substituted 2-phenyl-pyridazinones...

As shown in Table I, presence of both the phenyl-pyridazinone norflurazon and the diphenylether oxy-fluorfen decreased the pigment content. However, a difference between these herbicides is Indicated by the... 

Primary herbicidal effects are followed by secondary ones that show up before death of the plant cell. The 70-S ribosomes of wheat chloroplasts are decreased by bleaching pyridazinones in the light, but not in the dark ( 9) A prominent mode of action is observed upon the composition of fatty acids by, e.g., BAS 13338 (SAN 9785) (24, 5), which does not substcuatially interfere with carotenoid biosynthesis. Good direct inhibition of photosynthetic electron transport (I50 3 x 10 7m) is observed with the phenylpyridazinone BAS 100822 electron transport inhibition of other phenyl-pyridazinones is less than with BAS 100822 (28). 

Okushima, H., Narimatsu, A., Kobayashi, M., Furuya, R., Tsudo, K. and Kitada, Y. 1987. A novel class of cardiotonics. Synthesis and pharmacological properties of [4-(substituted-amino)phenyl]pyridazinones and related derivatives. J. Med. Chem. 30 1157-1161. 

Athyl-l-phenyl-pyridazinon-(6)-< arbon saare-(4)-Mhyle8ter 25 It 225. 

Pyrimido[5,4-c]pyridazin-8(2i/)-one, 6- N,N-dimethylamino)-2-phenyl-synthesis, 3, 357 Pyrimido[l, 2-6]pyridazin-2-ones H NMR, 3, 333 IR spectra, 3, 335 synthesis, 3, 354, 355 Pyrimido[ 1,2-6]pyridazin-4-ones synthesis, 3, 354, 355 Pyrimido[4,5-c]pyridazinones chlorination, 3, 344 Pyrimido[4,5-d]pyridazin-5-ones... 

The patent literature covers many pyridazine derivatives claimed as blood platelet aggregation inhibitors and antithrombotic agents. The interest has been focused mainly on 6-aryl-4,5-dihydro-3(2//)-pyridazinones. In these compounds the aryl substituent has been varied within a wide range. Thus, dihydro-pyridazinones bearing a substituted or heterocycle-fused phenyl group at C-6 (60, R R2,R3 = H, alkyl Ar = substituted Ph) [34, 110-112,205-233] as well as various heteroaryl substituted congeners (61, R1, R2, R3 = H, alkyl Ar = pyridyl, thienyl, pyrrolyl, pyrazolyl) [234-241] have been prepared in search of novel antithrombotics. 

In the United States, two potent orally active positive inotropic agents, CI-914 [imazodan hydrochloride CAS 89198-09-4, (15)] and CI-930 [CAS 86798-59-6, (16)], both characterized by a 4T(l/7-imidazol-l-yl)phenyl substituent attached to C-6 of a 4,5-dihydro-3(2//)-pyridazinone system, have been developed [16]. Patents exist on compounds of this type and related unsaturated pyridazinones [17-21] and also on homologues in which the... 

Moreover, there are patents on pyridazinone-derived cardiotonic compounds in which the phenyl substituent is separated from the pyridazinone system by an alkylene or alkylidene bridge [164,165] and on various azolyl-substituted pyridylpyridazinones of type (49) [166]. Cardiovascular 6-phen-ylpyridazines of type (50) have been patented [167], In Taiwan, cyclohexyl-ammonium 3,6-pyridazinediolate (51) has been reported to show positive inotropic activity [168]. 

The pharmacokinetics of amezinium metilsulphate in man have been reported [413-415]. The first step of metabolism consists in demethylation affording the pharmacologically inactive, uncharged 5-amino-2-phenyl-3(2//)-pyridazinone hydroxylated pyridazinones and sulphuric acid conjugates thereof have been isolated [413],... 

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. 

The annelation of benzo rings on pyridazines was covered in CHEC-II(1996) <1996CHEC-II(6)1>. Maes and Matyus reported new examples in their synthesis of the dibenzo[// ]phthalazin-l(27r)-one and dibenzo[//]cinnolin-3(27/)-one skeleton. Palladium-catalyzed intramolecular arylation of 2-benzyl-5-(2-bromophenyl)-4-phenylpyridazin-3(2//)-one yielded 2-benzyldibenzo[/,4]phthalazin-l(2//)-one. The synthesis of this new tetracyclic pyridazinone from 2-benzyl-5-(2-aminophenyl) -phenylpyridazin-3(2//)-one via a Pschorr-type reaction was also investigated. Similarly, the con-stmction of 2-methyldibenzo[/, ]cinnolin-3(2//)-one from 2-methyl-5-(2-bromophenyl)-6-phenylpyridazin-3(27T)-one and 2-methyl-5-(2-aminophenyl)-6-phenyl-pyridazin-3(2//)-one was performed <2003T5919>. 

In a similar manner, aldazines afford pyridazinones 317 (Scheme 7.104). 1,3-Diazadienes such as l-aryl-4-(dimethylamino)-2-phenyl-l,3-diaza-l,3-butadienes or l-aryl-4-(dimethylamino)-2-methylthio-l,3-diaza-l,3-butadienes react with oxazolones and give rise to pyrimidin-6-ones 319 and 320 as single diastereo-... 

The synthesis of pyrrolo[2,3- 7 pyridazines can be achieved by starting either with pyridazine, a tetrazine, or a pyrrole. Pyridazinone 80 reacts with bromomethyl derivatives to give poor yields of 81 <1996H(43)1863> (Equation 34), while 5-acetyl-2-methyl-4-nitro-6-phenyl-3(2//)-pyridazinone, after treatment with sarcosine ethyl ester for a brief time at room temperature, followed by acid hydrolysis afforded a good yield of 82 (70%) <1994S669>. 

On the other hand, reaction of 5-acetyl-2-methyl-4-nitro-6-phenyl-3(2//)-pyridazinone 287 with A -methyl-/3-alaninenitrile afforded the 4-(2-cyanoethyl) derivative 288, which was cyclized by heating with sodium ethoxide in ethanol to the pyrido[2,3-rflpyridazine 289 (Equation 22) <1994S669>. 

Arylidene-substituted Meldrum s acids 290 were reacted with 5-amino-6-phenyl-3(2//)-pyridazinone 291 to yield 4-aryl-2,5-dioxo-8-phenyl-l,2,3,4,5,6-hexahydropyrido[2,3-r/]pyridazines 292 in one step in good yields... 

C, Inhibition of photosynthesis at photosystem II 1,3,5-Triazines Triazinones Uracils Pyridazinone Phenyl carbamates 5... 

Reaction of the 2-acetoxy-3(2//)-furanones (526) with monosubstituted hydrazines gives good yields of the pyridazinium-5-olates (527) together with varying amounts of isomeric products. Alkyl derivatives (527 R = alkyl) have also been prepared by base-catalyzed alkylation (Mel, Me2SO4, PhCH2Cl) of 3-methyl-6-phenyl-5-ethoxycarbonyl-4( 1 //)-pyridazinone. Reduction of the diphenyl compound 527 (R = Ar = Ph) by zinc and hydrochloric acid gives 3-ethoxycarbonyl-5-hydroxy-5-methyl-l,2-diphenyl-2-pyrrolin-4-one (528 R = Ar = Ph) (Scheme 21... 

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)... 

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