Month: December 2022

Acids of the pyridazine series. I. New preparations of 3-chloro-6-pyridazinyloxyacetic acid and some of its derivatives was written by Rosseels, G.. And the article was included in Bulletin des Societes Chimiques Belges in 1964.Recommanded Product: 3-Methoxypyridazine This article mentions the following:

Treatment of dimethylaminoethylamine with chloroacetyl chloride in EtOAc at 0° led to the hydrochloride of R₂NCH₂CH₂NHCOCH₂Cl (I, R = Me), m. 121°, in 50% yield. Similarly, the hydrochloride of N,N-diethylaminoethyl-2-chloroacetamide (I, R = Et), m. 77° was prepared in 50% yield from diethylaminoethylamine. Treatment of 3,6-dichloropyridazine with glycolic acid in alk. solution afforded 65% 3-chloro-6-pyridazinyloxyacetic acid (II, R = H), m. 145°, 278 mμ (log ε 3.27). Reaction of 3-chloropyridazin-6-one with chloroacetic acid in KOH solution gave 85% 3-chloro-6-oxo-1-pyridazinylacetic acid (III, R = OH), m. 220°, k 300 mμ (log ε 3.47). Et diazoacetate reacts with 3-chloropyridazin-6-one in C₆H₆ in the presence of Cu powder to give a mixture of Et 3-chloro-6-pyridazinyloxyacetate (II, R = Et), b_0.2 120-4°, m. 67° (60%), and Et 3-chloro-6-oxo-1-pyridazinylacetate (III, R = OEt), b_0.2 131-5°, m. 78° (6.7%). The major product (II, R = Et) was identified by the similarity of its ultraviolet and infrared spectra to those of II (R = H) to which it was converted by alk. hydrolysis. Esterification of II (R = H) with EtOH and H₂SO₄ gave II (R = Et) which was identical with the product from the diazoacetate reaction. Et glycolate reacted with 3,6-dichloropyridazine to give II (R = Et) directly in 60% yield. The minor product (III, R = OEt) was similarly identified by its spectra and hydrolysis to 3-chloro-6-oxo-1-pyridazinylacetic acid (III, R = OH) which was reesterified to give III (R = OEt), which was independently prepared by the action of Et chloroacetate on 3-chloropyridazin-6-one. Attempts to chlorinate 3-oxo-6-pyridazinylacetic acid with POCla led only to 3-chloropyridazin-6-one, m. 140°. Treatment with POCl₃ of 3-hydroxy-6-oxo-1-pyridazinylacetic acid gave 3,6-dichloropyridazine. Reaction of II (R = H) with 2-chloro-1-dimethylaminoethane (IV) in iso-PrOH led, in 60% yield, to dimethylaminoethyl 3-chloro-6-pyridazinyloxyacetate (II, R = CH₂CH₂NMe₂) hydrochloride, m. 120°, X 275 mμ (log ε 3.240). Similarly, II (R = H) was converted to the hydrochloride of II (R = CH₂CH₂NEt₂), m. 118°, in 50% yield, by reaction with 2-chloro-1-diethylaminoethane (V). Treatment of III (R = OH) with IV or V led to the hydrochloride of III (R = CH₂CH₂NMe₂), m. 120°, in 60% yield or the hydrochloride of III (R = CH₂CH₂NEt₂), m. 118°, in 58% yield, resp. Reaction of IV with 3-oxo-6-pyridazinyloxyacetic acid and working up with tartaric acid led to the tartrate of dimethylaminoethyl 3-oxo-6pyridazinyloxyacetate, m. 314° (decomposition), in 50% yield. Similarly, the tartrate of dimethylaminoethyl 3-hydroxy-6-oxo-1-pyridazinylacetate, m. 310° (decomposition), was prepared in 51% yield from 3-hydroxy-6-oxo-1-pyridazinylacetic acid and IV and working up with tartaric acid. The hydrochloride of the β-dimethylaminoethylamide of 3-chloro-6-oxo-1-pyridazinylacetic acid (III, R = NHCH₂CH₂NMe₂.HCl), m. 263°, was prepared in 50% yield from I (R = Me) and 3-chloropyridazin-6-one. Similarly, III (R = NHCH₂CH₂NEt₂.HCl), m. 258°, was prepared in 50% yield from I (R = Et) and 3-chloropyridazin-6-one. In the experiment, the researchers used many compounds, for example, 3-Methoxypyridazine (cas: 19064-65-4Recommanded Product: 3-Methoxypyridazine).

3-Methoxypyridazine (cas: 19064-65-4) belongs to pyridazine derivatives. The pyridazine derivatives are mostly present in biologically active compounds and are also present with different pharmacophores. Specifically, the pyridazine moiety is an important structural feature of various pharmacologically important compounds with activities like antimicrobial, analgesic, anti-inflammatory, antiplatelet, anticancer, antisecretory, antiulcer, antidepressant, cardiotonic, vasodilator, antiarrhythmic, and hypocholesterolaemic.Recommanded Product: 3-Methoxypyridazine

Referemce:
Pyridazine – Wikipedia,
Pyridazine | C4H4N2 – PubChem

Photochemistry. VI. Photo-induced methylation of pyridazines was written by Tsuchiya, Takashi;Arai, Heihachiro;Igeta, Hiroshi. And the article was included in Chemical & Pharmaceutical Bulletin in 1972.Recommanded Product: 19064-65-4 This article mentions the following:

Irradiation of pyridazine (I, R = R1 = H) (MeOH containing 5% HCl) gave II (R = R1 = H) and III (R = R1 = H). I (R = H, R1 = Me) gave II (R = H, R1 = Me; R = Me, R1 = H) and III (R = H, R1 = Me). I (R = MeO, R1 = H) gave II (R = H, R1 = MeO; R = Me, R1 = MeO). I (R = R1 = Me) gave II (R = R1 = Me) and III (R = R1 = Me). I (R = Me, R1 = MeO) gave only II (R = Me, R1 = MeO). I (R = Me, R1 = Cl; R = R1 = Cl; R = Cl, R1 = Ph, gave the 5-methylated and 4,5-dimethylated compounds resp. I (R = Cl, R1 = H) (IV) did not give monomethylation, but gave III (R = Cl, R1 = H) (1-2%), due to decomposition of IV. In the experiment, the researchers used many compounds, for example, 3-Methoxypyridazine (cas: 19064-65-4Recommanded Product: 19064-65-4).

3-Methoxypyridazine (cas: 19064-65-4) belongs to pyridazine derivatives. Pyridazine and phthalazine have quite different spectroscopic properties compared with their isomers, pyrazine and quinoxaline. In the past decade, X-ray data were reported with regard to the characterization and structural elucidation of a number of pyridazine-metal complexes, including pyridazine ligands with zinc, nickel, copper, cadmium and ruthenium.Recommanded Product: 19064-65-4

Referemce:
Pyridazine – Wikipedia,
Pyridazine | C4H4N2 – PubChem

Ring-closing metathesis for the synthesis of heteroaromatics: evaluating routes to pyridines and pyridazines was written by Donohoe, Timothy J.;Bower, John F.;Basutto, Jose A.;Fishlock, Lisa P.;Procopiou, Panayiotis A.;Callens, Cedric K. A.. And the article was included in Tetrahedron in 2009.Application In Synthesis of 3-Methoxypyridazine This article mentions the following:

Ring-closing olefin metathesis (RCM) has been applied to the efficient synthesis of densely and diversely substituted pyridine and pyridazine frameworks. Routes to suitable metathesis precursors have been investigated and the scope of the metathesis step has been probed. The metathesis products function as precursors to the target heteroaromatic structures via elimination of a suitable leaving group, which also facilitates earlier steps by serving as a protecting group at nitrogen. Further functionalization of the metathesis products is possible both prior to and after aromatization. The net result is a powerful strategy for the de novo synthesis of highly substituted heteroaromatic scaffolds. In the experiment, the researchers used many compounds, for example, 3-Methoxypyridazine (cas: 19064-65-4Application In Synthesis of 3-Methoxypyridazine).

3-Methoxypyridazine (cas: 19064-65-4) belongs to pyridazine derivatives. Pyridazines is a six-membered nitrogen-containing significant heterocycle. It has received considerable interest because of its useful applications as natural products, pharmaceuticals, and various bioactive molecules. Specifically, the pyridazine moiety is an important structural feature of various pharmacologically important compounds with activities like antimicrobial, analgesic, anti-inflammatory, antiplatelet, anticancer, antisecretory, antiulcer, antidepressant, cardiotonic, vasodilator, antiarrhythmic, and hypocholesterolaemic.Application In Synthesis of 3-Methoxypyridazine

Referemce:
Pyridazine – Wikipedia,
Pyridazine | C4H4N2 – PubChem

Discovery of Reldesemtiv, a Fast Skeletal Muscle Troponin Activator for the Treatment of Impaired Muscle Function was written by Collibee, Scott E.;Bergnes, Gustave;Chuang, Chihyuan;Ashcraft, Luke;Gardina, Jeffrey;Garard, Marc;Jamison, Chris R.;Lu, Kevin;Lu, Pu-Ping;Muci, Alexander;Romero, Antonio;Valkevich, Ellen;Wang, Wenyue;Warrington, Jeffrey;Yao, Bing;Durham, Nickie;Hartman, James;Marquez, Anna;Hinken, Aaron;Schaletzky, Julia;Xu, Donghong;Hwee, Darren T.;Morgans, David;Malik, Fady I.;Morgan, Bradley P.. And the article was included in Journal of Medicinal Chemistry in 2021.HPLC of Formula: 33097-39-1 This article mentions the following:

Herein, the discovery of reldesemtiv I, a second-generation fast skeletal muscle troponin activator (FSTA) that increases force production at submaximal stimulation frequencies, is reported. Property-based optimization of high throughput screening hit, 4-(4-fluorobenzyl)-5-(phenethylamino)-1,2,4-thiadiazole, led to compounds with improved free exposure and in vivo muscle activation potency compared to the first-generation FSTA, tirasemtiv. The compound I demonstrated increased muscle force generation in a phase 1 clin. trial and is currently being evaluated in clin. trials for the treatment of amyotrophic lateral sclerosis. In the experiment, the researchers used many compounds, for example, 3,6-Difluoropyridazine (cas: 33097-39-1HPLC of Formula: 33097-39-1).

3,6-Difluoropyridazine (cas: 33097-39-1) belongs to pyridazine derivatives. Pyridazines is a six-membered nitrogen-containing significant heterocycle. It has received considerable interest because of its useful applications as natural products, pharmaceuticals, and various bioactive molecules. In the past decade, X-ray data were reported with regard to the characterization and structural elucidation of a number of pyridazine-metal complexes, including pyridazine ligands with zinc, nickel, copper, cadmium and ruthenium.HPLC of Formula: 33097-39-1

Referemce:
Pyridazine – Wikipedia,
Pyridazine | C4H4N2 – PubChem

Evidence for Simultaneous Dearomatization of Two Aromatic Rings under Mild Conditions in Cu(I)-Catalyzed Direct Asymmetric Dearomatization of Pyridine was written by Gribble, Michael W.;Liu, Richard Y.;Buchwald, Stephen L.. And the article was included in Journal of the American Chemical Society in 2020.Application of 19064-65-4 This article mentions the following:

Bis(phosphine) copper hydride complexes are uniquely able to catalyze direct dearomatization of unactivated pyridines with carbon nucleophiles, but the mechanistic basis for this result has been unclear. Here we show that, contrary to our initial hypotheses, the catalytic mechanism is monometallic and proceeds via dearomative rearrangement of the phenethylcopper nucleophile to a Cpara-metalated form prior to reaction at heterocycle C4. Our studies support an unexpected heterocycle-promoted pathway for this net 1,5-Cu-migration beginning with a doubly dearomative imidoyl-Cu-ene reaction. Kinetics, substituent effects, computational modeling, and spectroscopic studies support the involvement of this unusual process. In this pathway, the CuL₂ fragment subsequently mediates a stepwise Cope rearrangement of the doubly dearomatized intermediate to the give the C4-functionalized 1,4-dihydropyridine, lowering a second barrier that would otherwise prohibit efficient asym. catalysis. In the experiment, the researchers used many compounds, for example, 3-Methoxypyridazine (cas: 19064-65-4Application of 19064-65-4).

3-Methoxypyridazine (cas: 19064-65-4) belongs to pyridazine derivatives. The pyridazine structure is also found within the structure of several drugs such as cefozopran, cadralazine, minaprine, pipofezine, and hydralazine. Pyridazine is bioavailable (especially in the CNS) and can reduce toxicity. Pyridazine is a component of several drug molecules, and the pyridazine pharmacophore has contributed to a variety of pharmacologically active compounds.Application of 19064-65-4

Referemce:
Pyridazine – Wikipedia,
Pyridazine | C4H4N2 – PubChem

Pyridazines. I. Synthesis and nucleophilic substitution of 3-chloromethylpyridazine was written by Novitskii, K. Yu.;Sadovaya, N. K.;Kas’yanova, E. F.;Semina, L. K.. And the article was included in Khimiya Geterotsiklicheskikh Soedinenii in 1970.Recommanded Product: 27349-66-2 This article mentions the following:

To a solution of 15 ml SOCl2 in 20 ml anhydrous CHCl3 was added a solution of 12 g I (R = OH) in 60 ml anhydrous CHCl3 and the whole stirred 2 hr to yield 81% I.HCl (R = Cl) (II.HCl), m. 121-1.5° (EtOAc). This (3.3 g) in 30 ml MeOH was added dropwise to MeONa (from 1.84 g Na) in 30 ml anhydrous MeOH, and the whole stirred 30 min at room temperature and refluxed 4-5 hr to yield 76% I (R = OMe), b11 114-15°, d20 1.0978, n2oD 1.5077; picrate m. 87-8° (aqueous EtOH). Similarly was obtained 55% I (R = OEt), b7 108-9°, d20 1.0543, n20D 1.4990; picrate m. 103-4° (aqueous EtOH). To an emulsion of 0.69 g Na in 2 ml PhMe was added dropwise at 45-50° 3.3 g PhSH, stirring continued 4 hr, II (from 3.3 g II.HCl) in PhMe added, and the whole heated 2 hr on a boiling water bath to yield 96% I (R = SPh), m. 54-5.5° (petroleum ether); picrate m. 112-13° (EtOH). A mixture of 2.5 g II.HCl and 1.2 g (H2N)2CS in 300 ml anhydrous Me2CO was refluxed 10 hr to yield 92% I [R = SC(:NH)NH2.2HCl], m. 187-8° (decomposition) (hexane-MeOH). This (2.5 g) heated 1 hr on a boiling water bath with saturated K2CO3 solution gave 94% I (R = SH). II.HCl and the appropriate amine refluxed 3 hr in ether, C6H6 or in the amine gave the following I (R, b.p., mm, m.p./m.p. dipicrate, and % yield given): NEt2, 124-5°/6,-,145.5-6° (EtOH), 87; morpholino, 130-1°/1, 56-7°, 169-70° (EtOH), 85; 1 pyrrolidinyl, 115°/1.5, 51-2°, 148-9° (EtOH), 96. To a solution of 3.25 g NaCN in 5 ml H2O on a water bath was added 3.3 g II.HCl in 20 ml EtOH, and the whole refluxed 1 hr to yield 46% I (R = CN), m. 90-1° (C6H6); HCl salt m. 132-3° (EtOAc). This (1 g) in 15 ml 10% HCl heated 5 hr at 60° gave 100% I (R = H), m. 191-2° (Me2CO). In the experiment, the researchers used many compounds, for example, 3-(Chloromethyl)pyridazine hydrochloride (cas: 27349-66-2Recommanded Product: 27349-66-2).

3-(Chloromethyl)pyridazine hydrochloride (cas: 27349-66-2) belongs to pyridazine derivatives. The pyridazine derivatives are mostly present in biologically active compounds and are also present with different pharmacophores. The activity depends upon the changes of substituted groups in the pyridazine ring system resulting in different biological activities. In addition, the natural pyrimidine bases uracil, thymine, and cytosine, which are constituents of the nucleic acids, are found to be the most important naturally occurring diazines.Recommanded Product: 27349-66-2

Referemce:
Pyridazine – Wikipedia,
Pyridazine | C4H4N2 – PubChem

Syntheses of pyridazine derivatives. I. Pyridazine and its 3- and 3,6-substituted compounds was written by Itai, Takanobu;Igeta, Hiroshi. And the article was included in Yakugaku Zasshi in 1954.Recommanded Product: 3-Methoxypyridazine This article mentions the following:

Catalytic reduction of 5 g. 3,6-dichloropyridazine (I) in 50 ml. MeOH and 6 ml. concentrated NH₄OH with Pd-C (6 g. C and 15 ml. 1% PdCl₂) absorbed required amount of H in 30 min.; the solution filtered, made alk. with NH₄OH, the MeOH removed, the residue with Et₂O filtered and the filtrate distilled gave 2.5 g. pyridazine (II), b₁₆ 87-8° [picrate, m. 169° (decomposition); II.HgCl₂, columns, m. 178° (decomposition)]. Na (1 mole) in 15-20 volumes alc. (or phenol) and 1 mole I were heated 1-2 hrs. on a water bath, the excess alc. removed, the residue with water extracted with Et₂O and distilled to give 3-alkoxy-6-chloropyridazine (III) (alkoxy groups, m.ps. and yields given): MeO (IIIa), plates, m. 91°, 81.8%; EtO, leaves, m. 63° (from petr. ether), 87.5%; Me₂CHO, leaves, m. 83° (from petr. ether), 80%; PhO (IIIb), needles, m. 71° (from MeOH), 60%; PhCH₂O, leaves, m. 77° (from petr. ether), 68%; Et₂NCH₂CH₂O, b₉ 155-7° (picrate, m. 143°), 60%; similarly, 2 moles Na in 10-20 volumes alc. and 1 mole I heated 1-2 hrs. on a water bath and the product treated as above gave 3,6-dialkoxypyridazine (IV) (alkoxy group, m.ps. and yields given): MeO, plates, m. 106° (from water), 77%; EtO, columns, m. 48° (from dilute MeOH), 81%; Me₂CHO, b₇ 108-11° (bath temperature), 58%; CH₂:CHCH₂O, leaves, m. 50° (from dilute MeOH), 79%; PhCH₂O, leaves, m. 136° (from MeOH), 41%; Et₂NCH₂CH₂O, b₄ 190-200° (bath temperature) (picrate, m. 159°), 63%; PhO, needles, m. 140° (from dilute MeOH), 69%. Na (0.2 g.) in 5 ml. MeOH, 1 g. PhSH in 5 ml. MeOH and 1.3 g. I in 5 ml. MeOH heated 2 hrs. on a water bath, the MeOH removed, the residue extracted with Et₂O gave 0.8 g. 3-PhS analog of III, needles, m. 82°. Similarly, 0.35 g. Na in 5 ml. alc., 2 g. PhSH and 1 g. I gave 1.1 g. 3,6-(PhS)2 analog of IV, columns, m. 78°; 2 g. piperidine in 5 ml. C₆H₆ and 0.5 g. I refluxed 2.5 hrs., the product washed with dilute NaOH, the piperidine removed and the residue recrystallized from petr. ether gave 0.5 g. 3-piperidyl analog (V), of III, needles, m. 78°. V (0.2 g.) and 1 g. piperidine in a sealed tube heated 5 hrs. at 160° and the product treated as above gave 0.15 g. 3,6-dipiperidylpyridazine, needles, m. 115°; 2 g. IIIa in 1 ml. NH₄OH and 30 ml. MeOH reduced with Pd-C and H, the product made alk. with NH₄OH, the MeOH removed, the residue extracted with Et₂O gave 1 g. 3-methoxypyridazine, b₃ 85-6° (picrate, m. 111°). Similarly, catalytic reduction of 0.8 g. IIIb in 0.4 ml. NH₄OH and 20 ml. MeOH with Pd-C gave 0.6 g. 3-phenoxypyridazine, needles, m. 74-5°. V (2 g.) in 1.5 ml. NH₄OH and 30 ml. MeOH reduced with Pd-C and H gave 1.4 g. 3-piperidylpyridazine, b₁₄ 180-1° (picrate, columns, m. 153°). In the experiment, the researchers used many compounds, for example, 3-Methoxypyridazine (cas: 19064-65-4Recommanded Product: 3-Methoxypyridazine).

3-Methoxypyridazine (cas: 19064-65-4) belongs to pyridazine derivatives. The pyridazine derivatives are mostly present in biologically active compounds and are also present with different pharmacophores. Pyridazine is bioavailable (especially in the CNS) and can reduce toxicity. Pyridazine is a component of several drug molecules, and the pyridazine pharmacophore has contributed to a variety of pharmacologically active compounds.Recommanded Product: 3-Methoxypyridazine

Referemce:
Pyridazine – Wikipedia,
Pyridazine | C4H4N2 – PubChem

Discovery and Characterization of Selective and Ligand-Efficient DYRK Inhibitors was written by Henderson, Scott H.;Sorrell, Fiona;Bennett, James;Fedorov, Oleg;Hanley, Marcus T.;Godoi, Paulo H.;Ruela de Sousa, Roberta;Robinson, Sean;Ashall-Kelly, Alexander;Hopkins Navratilova, Iva;Walter, Daryl S.;Elkins, Jonathan M.;Ward, Simon E.. And the article was included in Journal of Medicinal Chemistry in 2021.Synthetic Route of C5H6N2O This article mentions the following:

Dual-specificity tyrosine-regulated kinase 1A (DYRK1A) regulates the proliferation and differentiation of neuronal progenitor cells during brain development. Consequently, DYRK1A has attracted interest as a target for the treatment of neurodegenerative diseases, including Alzheimer’s disease (AD) and Down’s syndrome. Recently, the inhibition of DYRK1A has been investigated as a potential treatment for diabetes, while DYRK1A’s role as a mediator in the cell cycle has garnered interest in oncol. indications. Structure-activity relationship (SAR) anal. in combination with high-resolution X-ray crystallog. leads to a series of pyrazolo[1,5-b]pyridazine inhibitors with excellent ligand efficiencies, good physicochem. properties, and a high degree of selectivity over the kinome. Compound 11 (I) exhibited good permeability and cellular activity without P-glycoprotein liability, extending the utility of 11 in an in vivo setting. These pyrazolo[1,5-b]pyridazines are a viable lead series in the discovery of new therapies for the treatment of diseases linked to DYRK1A function. In the experiment, the researchers used many compounds, for example, 3-Methoxypyridazine (cas: 19064-65-4Synthetic Route of C5H6N2O).

3-Methoxypyridazine (cas: 19064-65-4) belongs to pyridazine derivatives. The pyridazine structure is a popular pharmacophore which is found within a number of herbicides such as credazine, pyridafol and pyridate. In the past decade, X-ray data were reported with regard to the characterization and structural elucidation of a number of pyridazine-metal complexes, including pyridazine ligands with zinc, nickel, copper, cadmium and ruthenium.Synthetic Route of C5H6N2O

Referemce:
Pyridazine – Wikipedia,
Pyridazine | C4H4N2 – PubChem

Pyridazines. IX. Proton(nuclear)magnetic resonance studies of pyridazine, pyrazine, and substituted pyridazines was written by Tori, Kazuo;Ogata, Masaru. And the article was included in Chemical & Pharmaceutical Bulletin in 1964.Application In Synthesis of 3-Methoxypyridazine This article mentions the following:

CA 59, 5962b. Pyridazine (I) gives an A₂X₂ spectrum, τ₃ = τ₆ = 0.76, τ₄ = τ₅ = 2.46, J₃₄ = 4.9 cycles/sec., J₃₅ = 2.0, J₃₆ = 3.5, J₄₆ = 2.0, J₄₅ = 8.4, and J₅₆ = 4.9. 4Me-I and 3Me-I give ABX spectra. Pyrazine (II) gives a singlet τ = 1.37, J₂₅ = 1.8, J₂₆ = 0.5, J₃₅ = 0.5, J₃₆ = 1.8, and J₅₆ = 1.8 (calculated from C₁₃ satellites). The values of τ and J and the chem. shift of the protons in I due to substitution are comparable with other heteroaromatic systems. π electron ds. calculated from the ring proton chem. shift compared with C₆H₆ and compared with those calculated by the Hueckel M.O. method show large discrepancies in the case of I and II compared with pyrimidine (III). This effect is owed to the anisotropy of the N lone pair, which is mutually cancelled in III. In the experiment, the researchers used many compounds, for example, 3-Methoxypyridazine (cas: 19064-65-4Application In Synthesis of 3-Methoxypyridazine).

3-Methoxypyridazine (cas: 19064-65-4) belongs to pyridazine derivatives. Pyridazines is a six-membered nitrogen-containing significant heterocycle. It has received considerable interest because of its useful applications as natural products, pharmaceuticals, and various bioactive molecules. The unsubstituted pyridazines are more resistant to eletrophilic substitution due to the nature of withdrawal of electron density from the ring by two heteroatoms, while the related electron deficiency of the ring makes pyridazine more easily attacked by nucleophiles.Application In Synthesis of 3-Methoxypyridazine

Referemce:
Pyridazine – Wikipedia,
Pyridazine | C4H4N2 – PubChem

Cephalosporins. III. 7-(o-Aminomethylphenylacetamido)cephalosporanic acids with bicyclic heteroaromatics in the C-3 side chain was written by Naito, Takayuki;Okumura, Jun;Kamachi, Hajime;Hoshi, Hideaki;Kawaguchi, Hiroshi. And the article was included in Journal of Antibiotics in 1977.Electric Literature of C5H3ClN4O This article mentions the following:

Cephalosporins I (R = bicyclic N heterocycle) (10 compounds) were prepared Thus, 7-aminocephalosporanic acid was treated with 6-tetrazolo[1,5-b]pyridazinethiol, followed by 2-Me₃CO₂CNHCH₂C₆H₄CH₂CO₂C₆H₃(NO₂)₂-2,4 and deblocked to give 74% I (R = 6-tetrazolo[1,5-b]pyridazinyl). This compound had min. inhibitory concentrations against Staphylococcus aureus Smith 0.1 and Escherichia coli NIHJ 0.4 μg/mL. In the experiment, the researchers used many compounds, for example, 6-Chloro-[1,2,4]triazolo[4,3-b]pyridazin-3(2H)-one (cas: 33050-32-7Electric Literature of C5H3ClN4O).

6-Chloro-[1,2,4]triazolo[4,3-b]pyridazin-3(2H)-one (cas: 33050-32-7) belongs to pyridazine derivatives. Pyridazines are rare in nature, possibly reflecting the scarcity of naturally occurring hydrazines, common building blocks for the synthesis of these heterocycles. Pyridazine can act as a hydrogen bond acceptor to improve the physicochemical properties of drug molecules by increasing their water solubility, and has a high affinity for complexing with targets due to its dipole moment.Electric Literature of C5H3ClN4O

Referemce:
Pyridazine – Wikipedia,
Pyridazine | C4H4N2 – PubChem