Pyridazine Ring System Research Articles

Synthesis of Furo[2,3-c]pyridazines via Tandem Transition-Metal Catalysis.

A general and efficient catalytic approach to synthesis of the furo[2,3-c]pyridazine ring system is reported. Building on the easily accessible 2-bromo-3-aminopyridizinone skeleton, a tandem Sonogashira coupling-cycloisomerization provides ready access to functionalized furopyridazines. A wide functional group tolerance was observed in the tandem reaction, which proceeds in high yield in 1-3 h. The structure of the heterocyclic ring system was confirmed through single-crystal X-ray crystallography.

Tandem mass spectrometric study of annelation isomers of the novel thieno[3′,2′:4,5]pyrido[2,3-d]pyridazine ring system

In the present communication, we describe tandem combinations of Suzuki – condensation ring closure reactions to obtain a novel thieno[3 �,2 �:4,5]pyrido[2,3-d]pyridazine ring system. These compounds were studied by tandem mass spectrometry in detail and characteristic fragmentations were observed, which can be useful to confirm the presence of N-substituted pyridazine ring in synthesized compounds.

6-Chloro-3-(3-methylphenyl)-1,2,4-triazolo[4,3-b]pyridazine

The title compound, C12H9ClN4, was prepared from dichloro­pyridazine and tolyl­tetra­zole in a nucleophilic biaryl coupling followed by thermal ring transformation. The mol­ecule is essentially planar (r.m.s. deviation for all non-H atoms = 0.036 Å) and an intra­molecular C—H⋯N hydrogen bond occurs. In the crystal, the mol­ecules form dimers connected via π–π inter­actions [centroid–centroid distance = 3.699 (2) Å], which are further connected to neighbouring mol­ecules via C—H—N bonds. The bond lengths in the pyridazine ring system indicate a strong localization of the double bonds and there is a weak C—Cl bond [1.732 (3) Å].

Nucleosides with self-complementary hydrogen-bonding motifs: Synthesis and base-pairing studies of two nucleosides containing the imidazo[4,5- d]pyridazine ring system

Synthesis and base-pairing studies of two 2′-deoxyribonucleosides, containing a common heterocyclic base, 7(4)-amino-5(6) H-imidazo[4,5- d]pyridazin-4(7)one ( 1 and 2), have been reported. The synthesis was accomplished by base-promoted deoxyribosylation of ethyl 5(4)-cyanoimidazole-4(5)-carboxylate ( 6), followed by ring-closure with hydrazine hydrate. The 1H NMR-based base-pair studies were conducted using DMF- d 7 as a solvent by measuring changes in chemical shifts of the amino, hydrazide, imidazole H-2, and the sugar H-1′ protons of the nucleosides with variations in concentrations and temperatures. Large downfield chemical shifts were observed for the NH, NH 2, and to a lesser extent for the H-1′ protons when the temperature was lowered from 25 to 0 °C, and then further down to −50 °C in 10 degree intervals. The observed experimental data are consistent with the results of molecular modeling studies. Nucleoside 2 exhibited low level antiviral activity against HIV-1 in CEM-SS cells with an IC 50 of 89.2 μM. No cellular toxicity was observed at the highest concentration of the compound tested.

Novel ortho- and peri-fused pyridazine ring systems

By utilizing nucleophilic and electrophilic substitution reactions of 3(2 H)-pyridazinones, and application of various types of ring forming reactions, some novel polycyclic fused compounds containing pyrrolo[ b]-, pyrido[ b]-, pyrrolooxazino[ b]- or pyrrolopyrazino[ b]pyridazine skeletons were synthesized. From mechanistic point of view, structure–reactivity relationships were analyzed. In most cases, the cyclization reaction was strongly dependent on the substituents of the pyridazine ring.

Synthesis and Some Biochemical Properties of a Novel 5,6,7,8‐Tetrahydropyrimido[4,5‐c]pyridazine Nucleoside

AbstractA novel nucleoside analogue is described based on the pyridazine ring system. The nucleoside was successfully incorporated into DNA via both its phosphoramidite and 5′‐triphosphate derivatives. Enzymatically, the analogue behaves essentially as thymidine: it is a good substrate for the DNA polymerases Taq and exonuclease‐free Klenow fragment, leading to full‐length products when present in either the primer or template strands. In hybridisation studies, the nucleoside displays ambiguous base‐pairing properties, including universal base properties.

Synthesis and Diels–Alder reactions of the benzo[4,5]thieno [2,3- c]pyrrole ring system

The first synthesis of the parent compound of the benzo[4,5]thieno[2,3- c]pyrrole ring system and its derivatives, as well as their Diels–Alder reactions with DMAD and N-phenylmaleimide are reported. A new synthesis of the benzo[4,5]thieno[2,3- d]pyridazine ring system is also described.

Characterization of imidazo[4,5-d]pyridazine nucleosides as modulators of unwinding reaction mediated by West Nile virus nucleoside triphosphatase/helicase: evidence for activity on the level of substrate and/or enzyme.

Compounds that interact with DNA or RNA generally act as inhibitors of enzymes that unwind DNA or RNA. In the present study we describe the synthesis and properties of some nucleoside analogues that interact with double-stranded DNA but that, in contrast, facilitate the unwinding reaction mediated by West Nile (WN) virus nucleoside triphosphatase (NTPase)/helicase. The nucleoside analogues described, 1-(2'-O-methyl-beta-D-ribofuranosyl)imidazo[4,5-d]pyridazine-4,7(5H,6H)-dione (HMC-HO4), 1-(beta-D-ribofuranosyl)imidazo[4,5-d]pyridazine-4,7(5H,6H)-dione, and 1-(2'-deoxy-alpha-D-ribofuranosyl)imidazo[4,5-d]pyridazine-4,7(5H,6H)dione, all contain the imidazo[4,5-d]pyridazine ring system. The extent of the enhancing effect on helicase activity was found to be dependent on the time of exposure of the DNA substrate to the compounds and their concentrations. The nucleoside analogues were nevertheless found to be capable of uncoupling the ATPase and helicase activities of the enzyme by a mechanism operating on the level of the enzyme. Thus, in the case of HMC-HO4, the direct interaction with the enzyme caused inhibition of its helicase activity, with a half-maximal inhibitory concentration of 30 microM. The similar potency of the compound against replication of WN virus in cell culture suggests that inhibition of the helicase activity of the viral enzyme is responsible for the observed antiviral activity of HMC-HO4 and may indeed represent an important mode of action of antiviral drugs in general. Comparative studies performed with the related NTPase/helicase from hepatitis C virus revealed that the extent of the effects mediated by imidazo[4,5-d]pyridazine nucleosides is enzyme specific. The substances described may represent a starting point for the development of a new class of helicase-specific antivirals.

Synthetic Potential Inherent in D-Isoascorbic Acid as a Precursor for Pyridazine and Furo[3,2-c]pyridazine Ring Systems with Two Asymmetric Centers

Reaction of D-erythro-2,3-hexodiulosono-1,4-lactone-2,3-bis(phenylhydrazone) (2) with an iodine, triphenylphosphine and imidazole mixture afforded the furo[3,2-c]pyridazine derivative 11. Condensation of 6-bromo-6-deoxy-D-erythro-2,3-hexodiulosono-1,4-lactone with phenylhydrazine gave the bishydrazones 6, and 8 or the furo[3,2-c]pyridazine (11) depending on the reaction conditions. The lactone ring in 11 could be opened by treatment with alkali to give the pyridazine derivative 9. Lactonization of the later with simultaneous acetylation by acetic anhydride afforded the lactone derivative 14. Alkali treatment of 6 gave the pyrazolindione derivative 13 that gave upon reation with HBr/AcO H the dibromide 15. The assigned structures were based on spectral analysis. The activity of compounds 11 and 14 against hepatitis B virus has been studied.

The synthesis and biological evaluation of 4- p-nitrobenzylthio- v-triazolo [4,5- d]pyridazine and imidazo[4,5- d]pyridazine ribosides as potential nucleoside transport inhibitors

The synthesis of S 4-substituted nucleosides possessing the imidazo- and v-triazolo[4,5- d]pyridazine ring systems was undertaken and the compounds prepared were evaluated as inhibitors of nucleoside transport into human erythrocytes. 1-(2,3,5-Tri-O- acetyl-β- d-ribofuranosyl) -v- triazolo[4,5-d ]pyridazine-4(5H)- thione and 1-(2,3,5-tri-O- acetyl-β- d-ribofuranosyl)imidazo[ 4,5-d ]pyridazine-4(5H)- thione were each synthesized by two different routes and served as precursors for the title analogues. The nitrobenzylmercaptopurine riboside (NBMPR) analogues, 4-(p- nitrobenzylthio)-1-(β- d-ribofuranosyl)imidazo[ 4,5-d ]pyridazine and 4-(p- nitrobenzylthio)-1-(β- d-ribofuranosyl) -v- triazolo[4,5-d ]pyridazine , inhibited the transport of adenosine, but were approximately 4- and 28-fold less active, respectively, than NBMPR and nitrobenzylthioformycin, known potent and specific inhibitors of carrier-mediated transport.

Structure-property relationships in PMR-15-type polyimide resins: IIH. New polyimides incorporating triazoles, quinoxalines, pyridopyrazines and pyrazinopyridazines

Polyimide oligomers (prepolymers) and resins of the PMR-15 type have been prepared from 5-norbomene-2,3-dicarboxylic half acid ester (NE), 3,3',4,4'-benzophenone tetracarboxylic diester (BTDE) and a series of diamines incorporating 1,2,3-triazole, quinoxaline, pyrido[2,3-b]pyrazine, pyrido[3,4-b]pyrazine, benzo[g]quinoxaline, pyrazino-[2,3]-d]pyridazine and bis(pyrido[3,4-b]pyrazino)benzene ring systems. Two tetraamines in the bis(pyrazino[2,3-d]pyridazino)benzene ring system were also employed. Selected diamine monomers from the above ring systems provde PMR-15-analogue resins of higher thermal and thermooxidative stability than PMR-15 itself. The physical behaviour during oligomerization and curing of PMR systems has been studied by dynamic mechanical thermal analysis (DMTA). Traces akin to that from PMR-15 are obtained using certain diamine monomers (e.g. triazole and pyrido[3,4-b]pyrazine containing) but a featureless thermogram is observed using tetraamines in the bis(pyrazino[2,3-dj]pyridazino) benzene system.

Polycyclic pyridazines. II [3]. Synthesis of pyrazolo[4′,3′:5,6]pyrido[2,3‐d]pyrid‐azine derivatives from dimethyl pyrazolo[3,4‐d]pyrid‐azine‐5,6‐dicarboxylates as the key intermediates

AbstractThe synthesis of the novel pyrazolo[4′,3′:5,6]pyrido[2,3‐d]pyridazine ring system and some of its derivatives has been accomplished such as 4‐amino‐1‐phenyl‐5,8‐dioxo‐, 4‐amino‐5,8‐dioxo‐, 1‐phenyl‐5,8‐dioxo‐, 5,8‐dioxo‐, 5,8‐dichloro‐1‐phenyl‐, 5‐ethoxy‐1‐phenyl‐ and 8‐ethoxy‐1‐phenylpyrazolo[4′,3′:5,6]pyrido[2,3‐d]pyrid‐azines.

ChemInform Abstract: A New Route for the Synthesis of Tetrahydro‐ and Dihydro‐3H‐pyrazolo(3,4‐c)pyridazino(4,3‐e)pyridazine Ring Systems.

ChemInformVolume 21, Issue 12 Heterocyclic Compounds ChemInform Abstract: A New Route for the Synthesis of Tetrahydro- and Dihydro-3H-pyrazolo(3,4-c)pyridazino(4,3-e)pyridazine Ring Systems. G. H. SAYED, G. H. SAYED Chem. Dep., Ain Shams Univ., Cairo, EgyptSearch for more papers by this authorM. EL-MOBAYED, M. EL-MOBAYED Chem. Dep., Ain Shams Univ., Cairo, EgyptSearch for more papers by this authorA. G. EL-SHEKEIL, A. G. EL-SHEKEIL Chem. Dep., Ain Shams Univ., Cairo, EgyptSearch for more papers by this authorE. A. EL-GHANI, E. A. EL-GHANI Chem. Dep., Ain Shams Univ., Cairo, EgyptSearch for more papers by this author G. H. SAYED, G. H. SAYED Chem. Dep., Ain Shams Univ., Cairo, EgyptSearch for more papers by this authorM. EL-MOBAYED, M. EL-MOBAYED Chem. Dep., Ain Shams Univ., Cairo, EgyptSearch for more papers by this authorA. G. EL-SHEKEIL, A. G. EL-SHEKEIL Chem. Dep., Ain Shams Univ., Cairo, EgyptSearch for more papers by this authorE. A. EL-GHANI, E. A. EL-GHANI Chem. Dep., Ain Shams Univ., Cairo, EgyptSearch for more papers by this author First published: March 20, 1990 https://doi.org/10.1002/chin.199012209AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat No abstract is available for this article. Volume21, Issue12March 20, 1990 RelatedInformation

Imidazole Derivatives. Part V. Imidazo[1',2':1,6]pyrdio[2,3-d]pyridazine: Synthesis, Structure, and Preliminary Chemistry of a Novel Heterocyclic Ring System

Reaction of functionalized imidazo[1,2-a]pyridines with hydrazine hydrate to the novel imidazo[1',2' : 1,6]pyrido[2,3-d]pyridazine ring system is described

Imidazo[1,2-b]Pyridazines. VIII. Syntheses and Central Nervous System Activities of Some 6-Benzylamino (and methoxybenzylamino)-3-methoxy-2-phenyl(Substituted phenyl or pyridinyl)imidazo[1,2-b]pyridazines

Syntheses and IC50 values for the displacement of 3H-diazepam from rat brain plasma membrane are reported for a series of 6-benzylamino(and methoxybenzylamino )-3-methoxy-2-phenyl(substituted phenyl and pyridinyl )imidazo[l,2-b]pyridazines (and their 6-anilino and 6-phenethylamino analogues). The results are compared with those reported previously (by us) for the 6-chloro, 6-phenoxy, 6-benzylthio, and 6-benzyloxy compounds. In the imidazo[l,2-b]pyridazine ring system, 6-(o- and m- methoxybenzylamino ) groups were found to be beneficial to binding activity; eight compounds have been prepared with IC50 values less than 2 nM (cf. 3H-diazepam with IC50 of 4.2 nM ).2-(p-Aminopheny1)-3-methoxy- 6-(m- methoxybenzylamino )imidazo[1,2-b]pyridazine exhibited the highest activity with IC50 1.0 nM.

The synthesis of a pyrido[2,3‐c]pyridazine: A cinnoline related to 6‐fluoronalidixic acid

AbstractAn analog of the pyrido[2,3‐c]pyridazine ring system, 1‐ethyl‐6‐fluoro‐1,4‐dihydro‐7‐methyl‐4‐oxopyrido‐[2,3‐c]pyridazine‐3‐carboxylic acid (13), related to both Cinoxacin (1) and nalidixic acid (2), has been synthesized. The reductive ring closure of 2‐chloro‐α‐diazo‐6‐methyl‐5‐nitro‐β‐oxo‐3‐pyridinepropanoic acid, ethyl ester (7), proved to be the key reaction providing entry into the ring system.

Carbon‐13 nuclear magnetic resonance study of a new ring‐chain tautomerism of some pyridazine derivatives

AbstractThe 13C NMR spectra of a number of pyridazine derivatives have been recorded in DMSO‐d6 solution and analysed. Examination of the most diagnostic resonances, with particular emphasis on those arising from the pyridazine ring system, enabled the ready establishment of the presence of a ring‐chain tautomerism in 5‐(o‐aminophenylcarbamoyl)pyridazine‐4‐carboxylic acid, methyl 5‐(o‐aminophenylcarbamoyl)pyridazine‐4‐carboxylate, 5‐(o‐aminophenylcarbamoyl)‐3,6,‐dimethylpyridazine‐4‐carboxylic acid and 5‐(2‐amino‐1,2‐dicyanovinylenecarbamoyl)pyridazine‐4‐carboxylic acid. This gave rise to 3′,4′‐dihydro‐3′‐oxospiro[pyridazine‐5(2H),2′(1H)‐quinoxaline]‐4‐carboxylic acid, methyl 3′,4′‐dihydro‐3′oxospiro[pyridazine‐5(2H),2′(1′H)‐quinoxaline]‐4‐carboxylate, 3′,4′‐dihydro‐3′‐oxo‐3,6‐dimethylspiro[pyridazine‐5(2H), 2′(1′H)‐quinoxaline]‐4‐carboxylic acid and 5‐oxo‐2,3‐dicyano‐1,4,8,9‐tetraazaspiro[5.5]undeca‐2,7,10‐triene‐11‐carboxylic acid, respectively.

Synthesis and biological evaluation of certain 4‐alkylamino and 4‐arylalkylamino derivatives of the imidazo[4,5‐d]pyridazine and v‐triazolo[4,5‐d]pyridazine ring systems

AbstractCertain 4‐alkylamino and 4‐arylalkylamino derivatives of the imidazo‐ and v‐triazolo[4,5‐d]pyridazine ring systems were prepared and evaluated against two human colon carcinomas (DLD‐1 and HCT‐15) and one human lung carcinoma (LX‐1), in vitro. 4‐Methylthioimidazo[4,5‐d]pyridazine (1) and 4‐methylthio‐v‐triazolo‐[4,5‐d]pyridazine (9) served as precursors to the title compounds. Treatment of these heterocycles with the appropriate amine (ammonia, methylamine, dimethylamine, benzylamine and hydrazine) provided the desired derivatives of that ring system. 4‐AIP (2) and 2‐aza‐4‐AIP (10) served as precursors to the 4‐dimethylaminomethyleneamino derivatives 6 and 14, respectively. Likewise, the 4‐hydrazino analogs (7 and 15) served as intermediates in the syntheses of benzaldehyde‐p‐[bis(2‐chloroethyl)amino]amino[4,5‐d]‐pyridazin‐4‐yl‐hydrazone (8) and benzaldehyde‐p‐[bis(2‐chloroethyl)amino]amino‐v‐triazolo[4,5‐d]pyridazin‐4‐yl‐hydrazone (16), respectively.

The synthesis of substituted pyrazino[2,3‐d]‐1,2,4‐triazolo[4,3‐b]pyridazines

AbstractThe synthesis of 1,2,4‐triazolo[4,3‐b]pyridazines and the unknown ring system, pyrazino[2,3‐d]‐1,2,4‐triazolo[4,3‐b]pyridazine, has been achieved. The preparation of the new tricyclic 1,2,4‐triazole was accomplished first by ring closure of the triazole ring followed by formation of the pyrazine ring. Substitution of the pyrazino[2,3‐d]‐1,2,4‐triazolo[4,3‐b]pyridazine ring system was carried out in order to provide information of its reactivity and to provide a variety of interesting compounds for biological testing.

Studies on the imidazo[4,5-d]pyridazine ring system. Course of alkylation of imidazo[4,5-d]pyridazine-4-thione

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTStudies on the imidazo[4,5-d]pyridazine ring system. Course of alkylation of imidazo[4,5-d]pyridazine-4-thioneShih-Fong Chen and Raymond P. PanzicaCite this: J. Org. Chem. 1981, 46, 12, 2467–2473Publication Date (Print):June 1, 1981Publication History Published online1 May 2002Published inissue 1 June 1981https://doi.org/10.1021/jo00325a008RIGHTS & PERMISSIONSArticle Views287Altmetric-Citations18LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InReddit PDF (959 KB) Get e-AlertsSupporting Info (1)»Supporting Information Supporting Information Get e-Alerts