Heterocyclic Building Blocks-Pyridazine

Matsumoto, Kiyoshi published the artcileSelectivity in consecutive SNAr-dequaternization reactions of chlorodiazines with tertiary amines, Safety of 6-Chloro-N,N-dimethylpyridazin-3-amine, the main research area is dequaternization reaction chloropyrimidine tertiary amine; chloropyrimidine amination tertiary amine; dealkylation tertiary amine amination chlorodiazine; alkylmethylaminodiazine; diazine alkylmethylamino.

Consecutive SNAr-dealkylation reactions of chlorodiazines, such as, 2-chloropyrimidine (I) and 3,6-dichloropyridazine, with tertiary amines took place in a highly selective fashion. Thus, I was treated with Me2N(CH2)7Me in THF at 100° under 8 kbar pressure to give 97% 2-(methyloctylamino)pyrimidine (II) and 2% 2-(dimethylamino)pyrimidine (III).

Synthetic Communications published new progress about Amination. 7145-60-0 belongs to class pyridazine, name is 6-Chloro-N,N-dimethylpyridazin-3-amine, and the molecular formula is C6H8ClN3, Safety of 6-Chloro-N,N-dimethylpyridazin-3-amine.

Referemce:
Pyridazine – Wikipedia,
Pyridazine | C4H4N2 – PubChem

Crossland, Ingolf published the artcileDimethylamination of chloropyridazines, Product Details of C6H8ClN3, the main research area is PYRIDAZINES CHLORO AMINATION.

3,6-Dichloropyridazine, 4-methyl-3,6-dichloropyridazine, the 2 trichloropyridazines, and tetrachloropyridazine are treated with aqueous Me2NH in EtOH at reflux temperature In no case is more than 1 dimethylamino group introduced, the 4- (or 5-) position being substituted in the tri- and tetra-chlorinated pyridazines. The reaction products are reductively dehalogenated and subsequently identified by N.M.R. anal. The Cl atoms ortho to the dimethylamino group are preferentially eliminated by hydrogenolysis.

Acta Chemica Scandinavica (1947-1973) published new progress about Amination. 7145-60-0 belongs to class pyridazine, name is 6-Chloro-N,N-dimethylpyridazin-3-amine, and the molecular formula is C6H8ClN3, Product Details of C6H8ClN3.

Referemce:
Pyridazine – Wikipedia,
Pyridazine | C4H4N2 – PubChem

Cookson, R. F. published the artcileBasicities of pyridazine derivatives, Formula: C6H8ClN3, the main research area is Hammett basicity pyridazine; pyridazone oxygen protonation Hammett; protonation pyridazine mechanism.

The Hammett free-energy relation was used to correlate the differences in basicity of six 3-(dimethylamino)pyridazines, five 3-chloropyridazines, and seven 3-pyridazones with substituent constants; protonation occurred meta to the Me2N group of the (dimethylamino)-pyridazines, ortho to the Cl of the chloropyridazines, and on the exocyclic O of the pyridazones.

Journal of the Chemical Society, Perkin Transactions 10: Physical Organic Chemistry published new progress about Ionization. 7145-60-0 belongs to class pyridazine, name is 6-Chloro-N,N-dimethylpyridazin-3-amine, and the molecular formula is C6H8ClN3, Formula: C6H8ClN3.

Referemce:
Pyridazine – Wikipedia,
Pyridazine | C4H4N2 – PubChem

Matulenko, Mark A. published the artcile4-Amino-5-aryl-6-arylethynylpyrimidines: Structure-activity relationships of non-nucleoside adenosine kinase inhibitors, Synthetic Route of 17259-32-4, the main research area is aminoarylarylethynylpyrimidine derivative preparation structure adenosine kinase inhibitor analgesic pain.

A series of nonnucleoside adenosine kinase (AK) inhibitors is reported. These inhibitors originated from the modification of 5-(3-bromophenyl)-7-(6-morpholin-4-ylpyridin-3-yl)pyrido[2,3-d]pyrimidin-4-ylamine (ABT-702). The identification of a linker that would approx. the spatial arrangement found between the pyrimidine ring and the aryl group at C(7) in ABT-702 was a key element in this modification. A search of potential linkers led to the discovery of an acetylene moiety as a suitable scaffold. It was hypothesized that the aryl acetylenes, ABT-702, and adenosine bound to the active site of AK (closed form) in a similar manner with respect to the orientation of the heterocyclic base. Although potent acetylene analogs were discovered based on this assumption, an x-ray crystal structure of 5-(4-dimethylaminophenyl)-6-(6-morpholin-4-ylpyridin-3-ylethynyl)pyrimidin-4-ylamine (I) revealed a binding orientation contrary to adenosine. In addition, this compound bound tightly to a unique open conformation of AK. The structure-activity relationships and unique ligand orientation and protein conformation are discussed.

Bioorganic & Medicinal Chemistry published new progress about Analgesics. 17259-32-4 belongs to class pyridazine, name is 4-(6-Chloropyridazin-3-yl)morpholine, and the molecular formula is C8H10ClN3O, Synthetic Route of 17259-32-4.

Referemce:
Pyridazine – Wikipedia,
Pyridazine | C4H4N2 – PubChem

Gokce, Mehtap published the artcileSynthesis and antinociceptive activity of 6-substituted 3-pyridazinone derivatives, Formula: C8H10ClN3O, the main research area is pyridazinone morpholino arylpiperidino arylpiperazino preparation antinociceptive activity; antinociceptive activity morpholinopyridazinone arylpiperidinopyridazinone arylpiperazinopyridazinone.

Title compounds I (X = O, CH-benzyl, N-benzyl, N-aryl) were prepared and evaluated for antinociceptive activity. In the modified Koster test in mice, I (X = NC6H4F-4) was the most active compound All the compounds except I (X = NPh) were more active than aspirin in the antinociceptive activity test.

Farmaco published new progress about Analgesics. 17259-32-4 belongs to class pyridazine, name is 4-(6-Chloropyridazin-3-yl)morpholine, and the molecular formula is C8H10ClN3O, Formula: C8H10ClN3O.

Referemce:
Pyridazine – Wikipedia,
Pyridazine | C4H4N2 – PubChem

Landquist, Justus K. published the artcilePyridazines. II. Reaction of polychloropyridazines with trimethylamine, Category: pyridazine, the main research area is chloropyridazine amination; pyridazines chloro amination; triazine chloro amination; pyrimidines chloro amination; cyanuric chloride amination; trimethylamine amination pyridazines; ammoniums pyridazines.

3,6-Dichloro-, 3,4,6-trichloro-, 3,4,5-trichloro-, and 3,4,5,6-tetrachloropyridazine reacted with Me3N to give trimethylpyridazinylammonium chlorides, which, with the exception of (5,6-dichloro-3-pyridazinyl)ammonium chloride, underwent demethylation in the reaction mixture at room temperature to give (dimethylamino)pyridazines. The position of substitution was governed by steric requirements. 4,6-Dichloropyrimidine, 4,5,6-trichloropyrimidine, cyanuric chloride, and 4-butoxy-3,6-dichloropyridazine were also dimethylaminated by Me3N.

Journal of the Chemical Society [Section] C: Organic published new progress about Demethylation. 7145-60-0 belongs to class pyridazine, name is 6-Chloro-N,N-dimethylpyridazin-3-amine, and the molecular formula is C6H8ClN3, Category: pyridazine.

Referemce:
Pyridazine – Wikipedia,
Pyridazine | C4H4N2 – PubChem

Alagoz, Mehmet Abdullah published the artcileDevelopment of a Novel Class of Pyridazinone Derivatives as Selective MAO-B Inhibitors, HPLC of Formula: 17259-32-4, the main research area is pyridazinone derivative development MAOB inhibitor; PAMPA; docking; kinetics; monoamine oxidase-B; pyridazinones; reversibility.

Sixteen compounds (TR1-TR16) were synthesized and evaluated for their inhibitory activities against monoamine oxidase A and B (MAOs). Most of the derivatives showed potent and highly selective MAO-B inhibition. Compound TR16 was the most potent inhibitor against MAO-B with an IC50 value of 0.17 μM, followed by TR2 (IC50 = 0.27 μM). TR2 and TR16 selectivity index (SI) values for MAO-B vs. MAO-A were 84.96 and higher than 235.29, resp. Compared to the basic structures, the para-chloro substituent in TR2 and TR16 increased the inhibitory activity of MAO-B. TR2 and TR16 were reversible MAO-B inhibitors that were competitive, with Ki values of 0.230 ± 0.004 and 0.149 ± 0.016 μM, resp. The PAMPA method indicated that compounds TR2 and TR16 had the tendency to traverse the blood-brain barrier. Docking investigations revealed that lead compounds were beneficial for MAO-B inhibition via association with key as well as selective E84 or Y326 residues, but not for MAO-A inhibition via interaction primarily driven by hydrophobic contacts. In conclusion, TR2 and TR16 are therapeutic prospects for the management of multiple neurodegenerative diseases.

Molecules published new progress about Bioavailability. 17259-32-4 belongs to class pyridazine, name is 4-(6-Chloropyridazin-3-yl)morpholine, and the molecular formula is C8H10ClN3O, HPLC of Formula: 17259-32-4.

Referemce:
Pyridazine – Wikipedia,
Pyridazine | C4H4N2 – PubChem

Hallot, Andre published the artcileSynthesis and activity of 6-aryl-3-(hydroxypolymethyleneamino)pyridazines in animal models of epilepsy, Quality Control of 58059-33-9, the main research area is hydroxypolymethyleneamino pyridazine preparation anticonvulsant; piperidinopyridazine chlorophenylhydroxy preparation anticonvulsant.

Title pyridazines, e.g. I (R = ClC6H4, Cl2C6H3, thienyl, pyridyl), were synthesized and evaluated for anticonvulsant activity. The compounds were screened in mice for their ability to antagonize maximal electroshock- and bicuculline-induced seizures; neurotoxicity was evaluated in the rotorod test. The anticonvulsant activity of the most potent compounds was examined in kindled amygdaloid rats and in photoepileptic Papio papio baboons. Structure-activity relationships were examined by either varying the aryl ring in the 6-position of the pyridazine ring or by modifying the 3-amino side chain. Only the compounds with a Ph ring in the 6-position of the pyridazine ring exhibited appreciable anticonvulsant activity, and a 4-hydroxypiperidine side chain in the 3-position of the pyridazine ring appeared essential for anticonvulsant activity. Substituting the Ph ring with a Cl in the 2-position led to a substantial increase of activity and disubstituting the Ph ring with a Cl in the 2- and 4-positions yielded the most potent compounds, some of which were as potent as, or more potent than, phenobarbital. 6-(2-Chlorophenyl)-3-(4-hydroxypiperidino)pyridazine and 6-(2,4-dichlorophenyl-3-(4-hydroxypiperidino)pyridazine were selected for further studies.

Journal of Medicinal Chemistry published new progress about Anticonvulsants. 58059-33-9 belongs to class pyridazine, name is 3-Chloro-6-(3-nitrophenyl)pyridazine, and the molecular formula is C10H6ClN3O2, Quality Control of 58059-33-9.

Referemce:
Pyridazine – Wikipedia,
Pyridazine | C4H4N2 – PubChem

Sengmany, Stephane published the artcileSynthesis and biological evaluation of 3-amino-, 3-alkoxy- and 3-aryloxy-6-(hetero)arylpyridazines as potent antitumor agents, Formula: C6H8ClN3, the main research area is aryl pyridazine preparation antitumor toxicity human; chloropyridazine aryl halide electrochem reductive coupling nickel catalyst; Arylpyridazines; Biological evaluation; Cytotoxic activity; Electrosynthesis; Nickel catalysis.

Various 3-amino-6-arylpyridazines I [R = Me2N, pyrrol-1-yl, morpholino, etc.; Ar = C6H5, 3-MeC6H4, 3-thienyl, etc.] and 3-aryloxy- and alkoxy-6-arylpyridazines II [R1 = Et, C6H5, 4-FC6H4, etc.] were synthesized by an electrochem. reductive cross-coupling between chloropyridazines and aryl or heteroaryl halides. In vitro antiproliferative activity of these products I and II was evaluated against a representative panel of cancer cell lines and oncogenicity prevention of the more efficient derivatives was highlighted on human breast cancer cell line MDA-MB 468-Luc prior establishing their interaction with p44/42 and Akt-dependent signaling pathways. The highest in vitro antiproliferative activity was found for compound I [R = Et2N; Ar = 4-MeO2CC6H4] and also showed a potent ability to inhibit clonogenicity of human breast cancer cell line. The toxicity of the most active compounds I [R = Et2N; Ar = 4-MeO2CC6H4, 4-EtO2CC6H4] was further evaluated in vitro on human hepatocytes and in vivo on zebrafish assays.

Bioorganic & Medicinal Chemistry Letters published new progress about Antitumor agents. 7145-60-0 belongs to class pyridazine, name is 6-Chloro-N,N-dimethylpyridazin-3-amine, and the molecular formula is C6H8ClN3, Formula: C6H8ClN3.

Referemce:
Pyridazine – Wikipedia,
Pyridazine | C4H4N2 – PubChem

Sengmany, Stephane published the artcileSynthesis and biological evaluation of 3-amino-, 3-alkoxy- and 3-aryloxy-6-(hetero)arylpyridazines as potent antitumor agents, Safety of 4-(6-Chloropyridazin-3-yl)morpholine, the main research area is aryl pyridazine preparation antitumor toxicity human; chloropyridazine aryl halide electrochem reductive coupling nickel catalyst; Arylpyridazines; Biological evaluation; Cytotoxic activity; Electrosynthesis; Nickel catalysis.

Various 3-amino-6-arylpyridazines I [R = Me2N, pyrrol-1-yl, morpholino, etc.; Ar = C6H5, 3-MeC6H4, 3-thienyl, etc.] and 3-aryloxy- and alkoxy-6-arylpyridazines II [R1 = Et, C6H5, 4-FC6H4, etc.] were synthesized by an electrochem. reductive cross-coupling between chloropyridazines and aryl or heteroaryl halides. In vitro antiproliferative activity of these products I and II was evaluated against a representative panel of cancer cell lines and oncogenicity prevention of the more efficient derivatives was highlighted on human breast cancer cell line MDA-MB 468-Luc prior establishing their interaction with p44/42 and Akt-dependent signaling pathways. The highest in vitro antiproliferative activity was found for compound I [R = Et2N; Ar = 4-MeO2CC6H4] and also showed a potent ability to inhibit clonogenicity of human breast cancer cell line. The toxicity of the most active compounds I [R = Et2N; Ar = 4-MeO2CC6H4, 4-EtO2CC6H4] was further evaluated in vitro on human hepatocytes and in vivo on zebrafish assays.

Bioorganic & Medicinal Chemistry Letters published new progress about Antitumor agents. 17259-32-4 belongs to class pyridazine, name is 4-(6-Chloropyridazin-3-yl)morpholine, and the molecular formula is C8H10ClN3O, Safety of 4-(6-Chloropyridazin-3-yl)morpholine.

Referemce:
Pyridazine – Wikipedia,
Pyridazine | C4H4N2 – PubChem