Tag: 148.9781

Pharmacological Evaluation of Novel Bioisosteres of an Adamantanyl Benzamide P2X₇ Receptor Antagonist was written by Wilkinson, Shane M.;Barron, Melissa L.;O’Brien-Brown, James;Janssen, Bieneke;Stokes, Leanne;Werry, Eryn L.;Chishty, Mansoor;Skarratt, Kristen K.;Ong, Jennifer A.;Hibbs, David E.;Vugts, Danielle J.;Fuller, Stephen;Windhorst, Albert D.;Kassiou, Michael. And the article was included in ACS Chemical Neuroscience in 2017.COA of Formula: C4H2Cl2N2 This article mentions the following:

Adamantanyl benzamide 1 was identified as a potent P2X₇R antagonist but failed to progress further due to poor metabolic stability. We describe the synthesis and SAR of a series of bioisosteres of benzamide 1 to explore improvements in the pharmacol. properties of this lead. Initial efforts investigated a series of heteroaromatic bioisosteres, which demonstrated improved physicochem. properties but reduced P2X₇R antagonism. Installation of bioisosteric fluorine on the adamantane bridgeheads was well tolerated and led to a series of bioisosteres with improved physicochem. properties and metabolic stability. Trifluorinated benzamide 34 demonstrated optimal physicochem. parameters, superior metabolic stability (ten times longer than lead benzamide 1), and an improved physicokinetic profile and proved effective in the presence of several known P2X₇R polymorphisms. In the experiment, the researchers used many compounds, for example, 3,6-Dichloropyridazine (cas: 141-30-0COA of Formula: C4H2Cl2N2).

3,6-Dichloropyridazine (cas: 141-30-0) belongs to pyridazine derivatives. Pyridazine and phthalazine have quite different spectroscopic properties compared with their isomers, pyrazine and quinoxaline. 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.COA of Formula: C4H2Cl2N2

Referemce:
Pyridazine – Wikipedia,
Pyridazine | C4H4N2 – PubChem

LipE guided discovery of isopropylphenyl pyridazines as pantothenate kinase modulators was written by Sharma, Lalit Kumar;Yun, Mi Kyung;Subramanian, Chitra;Tangallapally, Rajendra;Jackowski, Suzanne;Rock, Charles O.;White, Stephen W.;Lee, Richard E.. And the article was included in Bioorganic & Medicinal Chemistry in 2021.Recommanded Product: 3,6-Dichloropyridazine This article mentions the following:

Pantothenate kinase (PANK) is the critical regulator of intracellular levels of CoA and has emerged as an attractive target for treating neurol. and metabolic disorders. This report describes the optimization, synthesis, and full structure-activity relationships of a new chem. series of pantothenate competitive PANK inhibitors. Potent drug-like mols. were obtained by optimizing a high throughput screening hit, using lipophilic ligand efficiency (LipE) derived from human PANK3 IC₅₀ values to guide ligand development. X-ray crystal structures of PANK3 with index inhibitors from the optimization were determined to rationalize the emerging structure activity relationships. The anal. revealed a key bidentate hydrogen bonding interaction between pyridazine and R306鈥?as a major contributor to the LipE gain observed in the optimization. A tractable series of PANK3 modulators with nanomolar potency, excellent LipE values, desirable physicochem. properties, and a well-defined structural binding mode was produced from this study. In the experiment, the researchers used many compounds, for example, 3,6-Dichloropyridazine (cas: 141-30-0Recommanded Product: 3,6-Dichloropyridazine).

3,6-Dichloropyridazine (cas: 141-30-0) 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. 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: 3,6-Dichloropyridazine

Referemce:
Pyridazine – Wikipedia,
Pyridazine | C4H4N2 – PubChem

Amination of chloro-substituted heteroarenes with adamantane-containing amines was written by Abel, A. S.;Grigorova, O. K.;Averin, A. D.;Maloshitskaya, O. A.;Butov, G. M.;Savelyev, E. N.;Orlinson, B. S.;Novakov, I. A.;Beletskaya, I. P.. And the article was included in Russian Chemical Bulletin in 2016.Recommanded Product: 141-30-0 This article mentions the following:

Amination of 3,6-dichloropyridazine, chloropyrazine, 2,3- and 2,6-dichloropyrazines, 2-chloroquinoxaline, 1-chloro and 1,3-dichloroisoquinolines with various adamantane-containing amines characterized by different steric hindrances at the amino group was studied. The yields of the amination products depended on the structure of starting compounds In the reactions of all the dichloroheteroarenes, selective substitution of only one chlorine atom took place, with the best yields being observed for 2,6-dichloropyrazine. In the reaction of 1,3-dichloroisoquinoline, the chlorine atom at position 1 was selectively substituted in up to 90% yield. In the experiment, the researchers used many compounds, for example, 3,6-Dichloropyridazine (cas: 141-30-0Recommanded Product: 141-30-0).

3,6-Dichloropyridazine (cas: 141-30-0) belongs to pyridazine derivatives. Pyridazine-based compounds continued to be a great source of biologically active compounds as evidenced by the number of publications which emerged in 2021. 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.Recommanded Product: 141-30-0

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.Safety of 3,6-Dichloropyridazine 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-Dichloropyridazine (cas: 141-30-0Safety of 3,6-Dichloropyridazine).

3,6-Dichloropyridazine (cas: 141-30-0) belongs to pyridazine derivatives. Pyridazine-based compounds continued to be a great source of biologically active compounds as evidenced by the number of publications which emerged in 2021. Pyridazine and derivatives coordinate readily with transition metals to form complexes and catalysts with synthetic utility.Safety of 3,6-Dichloropyridazine

Referemce:
Pyridazine – Wikipedia,
Pyridazine | C4H4N2 – PubChem

Benzohydrazide incorporated imidazo[1,2-b]pyridazine: synthesis, characterization and in vitro anti-tubercular activity was written by Paidi, K. R.;Tatipamula, V. B.;Kolli, M. K.;Pedakotla, V. T.. And the article was included in International Journal of Chemical Sciences in 2017.Application In Synthesis of 3,6-Dichloropyridazine This article mentions the following:

A novel series of imidazo[1,2-b]pyridazine comprising benzohydrazide derivatives I (R = 4-OMe, 3-NO₂, 4-Cl, etc.) have been synthesized, characterized by using spectral data and screened for anti-tuberculosis activity. The anti-tubercular activity of the synthesized compounds I was determined by microplate alamar blue assay and the outcomes were screened in vitro against Mycobacterium tuberculosis H37Rv strain. All synthesized compounds exhibited good to potent anti-tubercular activity when compared with the standard first line anti-tuberculosis drugs (ciprofloxacin, pyrazinamide and streptomycin). Some of the tested compounds exhibited highest inhibitory activity at 1.6 渭g/mL minimal inhibitory concentration In the experiment, the researchers used many compounds, for example, 3,6-Dichloropyridazine (cas: 141-30-0Application In Synthesis of 3,6-Dichloropyridazine).

3,6-Dichloropyridazine (cas: 141-30-0) 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 In Synthesis of 3,6-Dichloropyridazine

Referemce:
Pyridazine – Wikipedia,
Pyridazine | C4H4N2 – PubChem

Synthesis and characterization of some nitrogen containing heterocyclic derivatives via novel chalcones was written by Tupare, Shrikrishn D.. And the article was included in World Journal of Pharmaceutical Research in 2021.Electric Literature of C4H2Cl2N2 This article mentions the following:

A highly stable five-membered ring structures like 1, 3, 5-triphenyl 1H pyrazoles and its derivatives I [R = H, 2-NO₂, 4-NO₂] was prepared via novel chalcones II synthesized by aromatic ketone and aldehydes in alk. medium having heterocyclic moiety. These compounds were characterized using IR, ¹H-NMR and mass spectra and elemental anal. As per literature, they possess some potent biol. activities. Therefore, antibacterial and antifungal activities were screened for these derivatives most of the compounds were found to be the most active against bacterial and fungal human pathogens. In the experiment, the researchers used many compounds, for example, 3,6-Dichloropyridazine (cas: 141-30-0Electric Literature of C4H2Cl2N2).

3,6-Dichloropyridazine (cas: 141-30-0) belongs to pyridazine derivatives. The pyridazine structure is also found within the structure of several drugs such as cefozopran, cadralazine, minaprine, pipofezine, and hydralazine. 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.Electric Literature of C4H2Cl2N2

Referemce:
Pyridazine – Wikipedia,
Pyridazine | C4H4N2 – PubChem

Discovery of VU6028418: A Highly Selective and Orally Bioavailable M₄ Muscarinic Acetylcholine Receptor Antagonist was written by Spock, Matthew;Carter, Trever R.;Bollinger, Katrina A.;Han, Changho;Baker, Logan A.;Rodriguez, Alice L.;Peng, Li;Dickerson, Jonathan W.;Qi, Aidong;Rook, Jerri M.;O’Neill, Jordan C.;Watson, Katherine J.;Chang, Sichen;Bridges, Thomas M.;Engers, Julie L.;Engers, Darren W.;Niswender, Colleen M.;Conn, P. Jeffrey;Lindsley, Craig W.;Bender, Aaron M.. And the article was included in ACS Medicinal Chemistry Letters in 2021.Quality Control of 3,6-Dichloropyridazine This article mentions the following:

Herein, we report the SAR leading to the discovery of VU6028418, a potent M₄ mAChR antagonist with high subtype-selectivity and attractive DMPK properties in vitro and in vivo across multiple species. VU6028418 was subsequently evaluated as a preclin. candidate for the treatment of dystonia and other movement disorders. During the characterization of VU6028418, a novel use of deuterium incorporation as a means to modulate CYP inhibition was also discovered. In the experiment, the researchers used many compounds, for example, 3,6-Dichloropyridazine (cas: 141-30-0Quality Control of 3,6-Dichloropyridazine).

3,6-Dichloropyridazine (cas: 141-30-0) 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 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.Quality Control of 3,6-Dichloropyridazine

Referemce:
Pyridazine – Wikipedia,
Pyridazine | C4H4N2 – PubChem

Pyridazinones containing the (4-methoxyphenyl)piperazine moiety as AChE/BChE inhibitors: design, synthesis, in silico and biological evaluation was written by Merde, Irem B.;Onel, Gulce T.;Turkmenoglu, Burcin;Gursoy, Sule;Dilek, Esra. And the article was included in Medicinal Chemistry Research in 2022.COA of Formula: C4H2Cl2N2 This article mentions the following:

Alzheimer disease is a progressive and fatal neurodegenerative disease affecting the elderly population accompanied by a decrease in cholinergic transmission, impairing cognitive functions. Acetylcholine deficiency is important in the development of disease symptoms. Inhibition of acetylcholinesterase, an important enzyme in acetylcholine hydrolysis, is one of the important drug targets to increase acetylcholine levels. In this study, we aimed to develop acetylcholinesterase inhibitor compounds For this, we synthesized compounds 6(a-e) bearing 3(2H)-pyridazinone and 1,2,4-triazole ring structures. We determined the IC₅₀, Ki and inhibition types of N-substituted-(p-methoxyphenyl)pyridazin-3(2H)-one derivatives that we synthesized and elucidated their structures. The compound with the best AChE activity was compound 6b (Ki = 3.73 ± 0.9 nM) with the p-methylphenyl group it carried and showed competitive inhibition. Kinetic study was also performed for the compounds with the highest BChE 6a (Ki = 0.95 ± 0.16 nM) inhibitory activities. Mol. docking studies have shown that the p-methylphenyl group is indeed active in the hinge region of the AChE crystal structure as a result of exptl. activity. In addition, the best free binding energy (ΔGBind), docking score and Glide score values were determined by examining the interactions with AChE crystal structure for compound 6b and with BChE crystal structure for 6a in silico approaches. Graphical abstract In the experiment, the researchers used many compounds, for example, 3,6-Dichloropyridazine (cas: 141-30-0COA of Formula: C4H2Cl2N2).

3,6-Dichloropyridazine (cas: 141-30-0) 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 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.COA of Formula: C4H2Cl2N2

Referemce:
Pyridazine – Wikipedia,
Pyridazine | C4H4N2 – PubChem

Synthesis of New 6-[4-(2-Fluorophenylpiperazin-1-yl)]-3(2H)-Pyridazinone-2-Acetyl-2- (Substituted benzal)Hydrazone Derivatives and Evaluation of Their Cytotoxic Effects in Liver and Colon Cancer Cell Lines was written by Ozdemir, Zeynep;Basak-Turkmen, Nese;Ayhan, Idris;Ciftci, Osman;Uysal, Mehtap. And the article was included in Pharmaceutical Chemistry Journal in 2019.Application of 141-30-0 This article mentions the following:

In this study, seven new 3(2H)-pyridazinone derivatives I (R = H, 2-Cl, 4-NMe₂, 4-Me, 4-Cl, 4-Br, 2-MeO) expected to show cytotoxic activity in liver and colon cancer cell lines were synthesized. Compounds I were tested on HEP3B (liver cancer) and HTC116 (colon cancer) cell lines for cytotoxicity by using MTS [3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium] proliferation assay. Human fibroblast cells were used as a safety control in these tests. Compound I (R = 2-Cl) was the most active agent with respect to HEP3B and HTC116 cell lines. In the experiment, the researchers used many compounds, for example, 3,6-Dichloropyridazine (cas: 141-30-0Application of 141-30-0).

3,6-Dichloropyridazine (cas: 141-30-0) 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. 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 of 141-30-0

Referemce:
Pyridazine – Wikipedia,
Pyridazine | C4H4N2 – PubChem

Pharmacological Evaluation of Novel Bioisosteres of an Adamantanyl Benzamide P2X₇ Receptor Antagonist was written by Wilkinson, Shane M.;Barron, Melissa L.;O’Brien-Brown, James;Janssen, Bieneke;Stokes, Leanne;Werry, Eryn L.;Chishty, Mansoor;Skarratt, Kristen K.;Ong, Jennifer A.;Hibbs, David E.;Vugts, Danielle J.;Fuller, Stephen;Windhorst, Albert D.;Kassiou, Michael. And the article was included in ACS Chemical Neuroscience in 2017.COA of Formula: C4H2Cl2N2 This article mentions the following:

Adamantanyl benzamide 1 was identified as a potent P2X₇R antagonist but failed to progress further due to poor metabolic stability. We describe the synthesis and SAR of a series of bioisosteres of benzamide 1 to explore improvements in the pharmacol. properties of this lead. Initial efforts investigated a series of heteroaromatic bioisosteres, which demonstrated improved physicochem. properties but reduced P2X₇R antagonism. Installation of bioisosteric fluorine on the adamantane bridgeheads was well tolerated and led to a series of bioisosteres with improved physicochem. properties and metabolic stability. Trifluorinated benzamide 34 demonstrated optimal physicochem. parameters, superior metabolic stability (ten times longer than lead benzamide 1), and an improved physicokinetic profile and proved effective in the presence of several known P2X₇R polymorphisms. In the experiment, the researchers used many compounds, for example, 3,6-Dichloropyridazine (cas: 141-30-0COA of Formula: C4H2Cl2N2).

3,6-Dichloropyridazine (cas: 141-30-0) belongs to pyridazine derivatives. Pyridazine and phthalazine have quite different spectroscopic properties compared with their isomers, pyrazine and quinoxaline. 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.COA of Formula: C4H2Cl2N2

Referemce:
Pyridazine – Wikipedia,
Pyridazine | C4H4N2 – PubChem