Pyrazolo pyridazinones

Pyridazinone (39), prepared via reacting 37 with A/, A -dimethylace-tamide dimethyl acetal, afforded pyrazolo[4,3-c]pyridazine (38) upon treatment with hydrazine (Scheme 6) (81JHC333). 

A series of pyrazolo[3,4-, pyridazinones 430 and analogues, potentially useful as peripheral vasodilators, were synthesized and evaluated as inhibitors of PDE5 extracted from human platelets. Several of them showed ICso values in the range 0.14-1.4 pM. A good activity and selectivity profile versus PDE6 was found for compound 430 (6-benzyl-3-methyl-l-isopropyl-4-phenylpyrazolo[3,4-r/]pyridazin-7(6/7)-one). Structure-activity relationship studies demonstrated the essential role played by the benzyl group at position 6 of the pyrazolopyridazine system. Other types of pyridazinones fused with five- and six-membered heterocycles (pyrrole, isoxazole, pyridine, and dihydropyridine), as well as some open-chain models were prepared and evaluated. Besides the pyrazole, the best of the fused systems proved to be isoxazole and pyridine <2002MI227>. 

Disubstituted and 1,3,5-trisubstituted l/7-pyrazolo[3,4-d]pyridazin-4(5//)-ones (200) can be synthesized by irradiation of 5-(l-alkyl-2-alkylidenehydrazino)-4-chloro-3(2//)-pyridazinones (199) in benzene or acetone (equation 146)589. Eighteen derivatives of... 

The solid phase parallel synthesis of tetrahydroimidazo[l,2-a][l,3,5]triazepin-2-thiones and 2-imines has been reported starting from resin-bound peptides <06JCO127>. Pyrazolo[r,5 l,6]pyrimido[4,5-rf]pyridazinones with potent and selective phosphodiesterase 5 (PDEs) inhibitory activity have been described <06JMC5363>... 

Hydrazones of 4-chloro-5-hydrazino-3(2//)-pyridazinones undergo photolytic cyclization (Equation (29)) to give pyrazolo[3,4- /]pyridazinones <84JHC1249>. 

Convenient access to pyrazolo[2,3-6]pyridazinones is provided by cycH-zation of pyrazolylaminomethyleneketenes which are generated either from Meldrum s acid derivatives, such as 391 and 392, or from a range of pyrazo-lylaminoacrylates, such as 393 and 394, (Scheme 80 2015UP8). It should be noted that these are the thermodynamic products formed at higher pyrolysis temperatures, and FVP of the same precursors at lower temperatures gives the isomeric mesomeric betaines with a pyrazolotriazine structure as described in Section 5.9. 

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