2469-99-0Relevant articles and documents
Kinetic Evidence for the Intermediacy of 1-Azirines in the Gas-Phase Thermal Isomerization of 3H-Isoxazoles to α-Carbonylacetonitrile Derivatives
Perez, Jorge D.,Yranzo, Gloria I.,Wunderlin, Daniel A.
, p. 982 - 984 (1982)
Thermal isomerization of 5-methylisoxazole and 5-amino-4-methylisoxazole to acetylacetonitrile and 2-cyanopropionamide, respectively, was studied in a flow system.The activation parameters are reported.According to the experimental results, a concerted 1,3 sigmatropic shift to 1-azirines is proposed as the rate-limiting step in these reactions.A general reaction mechanism for the isomerization of isoxazoles into 1-azirines, oxazoles, and α-carbonylacetonitrile derivatives is discussed.
Synthesis of some novel pyrazolo[3,4-b]pyridine and pyrazolo[3,4-d]pyrimidine derivatives bearing 5,6-diphenyl-1,2,4-triazine moiety as potential antimicrobial agents
El-Sayed Ali, Tarik
, p. 4385 - 4392 (2009)
The reaction of 5,6-diphenyl-3-hydrazino-1,2,4-triazine (1) with bis(methylthio)methylene]malononitrile (2) afforded 5-amino-1-(5,6-diphenyl-1,2,4-triazin-3-yl)-3-(methylthio)-1H-pyrazole-4-carbonitrile (3). Compound 3 reacted with thiourea to give 3,4-di
Design, synthesis, and in vitro anticancer screening of novel pyrazolinyl-pyrazole/1, 2, 3-triazole hybrids
Ismail, Magda M. F.,Abdulwahab, Hanan G.,Elnagdi, Mohamed H.
, p. 3584 - 3596 (2020)
Novel hybrids, pyrazolinylpyrazoles, and pyrazolinyltriazoles were designed, synthesized, and screened for their anticancer activity. Eleven compounds were selected by the National Cancer Institute (NCI)/USA for anticancer screening at single high dose (10?5 M) in full NCI 60 cell panels. Two compounds: 4-aminopyrazole-5-carbonitrile, 5c (NSC-747630/1) and ethyl 4-aminopyrazole-5- carboxylate, 7d (NSC-747634/1) were the most active candidates of the series and were selected for further evaluation at five dose screening as they displayed significant growth inhibition with full panel median growth inhibition (GI50) 5.47 and 2.24 μM, respectively. Both 5c and 7d hybrids exhibited broad spectrum antitumor activity; however 7d showed moderate selectivity (selectivity ratio 3.6) toward leukemia.
Synthesis of Novel 3-Acetyl-2-aminothiophenes and Investigation of their Behaviour in the Reaction with Vilsmeier-Haack Reagent
Abdelwahab, Ahmed B.,Hanna, Atef G.,Kirsch, Gilbert
, p. 2881 - 2888 (2016)
Through an investigation into the behaviour of 3-acetyl-2-aminothiophene in the reaction with Vilsmeier-Haack reagent, an efficient method for the synthesis of 4-chlorothieno[2,3-b]pyridine derivatives has been established. Gewald's classical synthesis starting from cyanoacetone, ketones and elemental sulphur has been applied to produce the starting materials.
AMIDITE COMPOUND AND METHOD FOR PRODUCING POLYNUCLEOTIDE USING SAID COMPOUND
-
Paragraph 0173-0174, (2021/08/06)
The present invention provides an amidite compound represented by formula (1) which enables a synthesis of RNA with high purity, and the method for preparing a polynucleotide by using the same compound. (In the formula (1), wherein R represents the following formula (wherein Ra and Rb are identical to or different from each other and each represents a methyl group, an ethyl group, or a hydrogen atom, with the proviso that Ra and Rb does not represent a hydrogen atom, n is an integer of 1 to 5), and Ba represents a group containing optionally protected nucleobase structure, and G1 and G2 are identical to or different from each other and each represents a protecting group for a hydroxy group, and G3 are identical to or different from each other and each represents an alkyl group.
Identification of diphenylalkylisoxazol-5-amine scaffold as novel activator of cardiac myosin
Boggu, Pulla Reddy,Venkateswararao, Eeda,Manickam, Manoj,Sharma, Niti,Kang, Jong Seong,Jung, Sang-Hun
, (2020/09/16)
To identify novel potent cardiac myosin activator, a series of diphenylalkylisoxazol-5-amine compounds 4–7 have been synthesized and evaluated for cardiac myosin ATPase activation. Among the 37 compounds, 4a (CMA at 10 μM = 81.6%), 4w (CMA at 10 μM = 71.2%) and 6b (CMA at 10 μM = 67.4%) showed potent cardiac myosin activation at a single concentration of 10 μM. These results suggested that the introduction of the amino-isoxazole ring as a bioisostere for urea group is acceptable for the cardiac myosin activation. Additional structure–activity relationship (SAR) studies were conducted. Para substitution (-Cl, –OCH3, -SO2N(CH3)2) to the phenyl rings or replacement of a phenyl ring with a heterocycle (pyridine, piperidine and tetrahydropyran) appeared to attenuate cardiac myosin activation at 10 μM. Additional hydrogen bonding acceptor next to the amino group of the isoxazoles did not enhance the activity. The potent isoxazole compounds showed selectivity for cardiac myosin activation over skeletal and smooth muscle myosin, and therefore these potent and selective isoxazole compounds could be considered as a new series of cardiac myosin ATPase activators for the treatment of systolic heart failure.
One-Pot Four-Component Coupling Approach to Polyheterocycles: 6 H-Furo[3,2- f]pyrrolo[1,2- d][1,4]diazepine
Yoon, Seok Hyun,Kim, Sung June,Kim, Ikyon
, p. 15082 - 15091 (2020/12/02)
A novel polyheterocyclic chemical space, 6H-furo[3,2-f]pyrrolo[1,2-d][1,4]diazepine, was generated by a one-pot four-component coupling reaction where multiple bonds (three C-C, one C-O, and one C-N) were formed through a domino sequence. Two heterocyclic rings (furan and diazepine) were sequentially constructed from the monocyclic pyrrole derivative under environment-friendly reaction conditions to furnish the tricyclic fused scaffold.
Discovery, synthesis and characterization of a series of (1-alkyl-3-methyl-1H-pyrazol-5-yl)-2-(5-aryl-2H-tetrazol-2-yl)acetamides as novel GIRK1/2 potassium channel activators
Sharma, Swagat,Kozek, Krystian A.,Abney, Kristopher K.,Kumar, Sushil,Gautam, Nagsen,Alnouti, Yazen,David Weaver,Hopkins, Corey R.
, p. 791 - 796 (2019/02/06)
The present study describes the discovery and characterization of a series of 5-aryl-2H-tetrazol-3-ylacetamides as G protein-gated inwardly-rectifying potassium (GIRK) channels activators. Working from an initial hit discovered during a high-throughput screening campaign, we identified a tetrazole scaffold that shifts away from the previously reported urea-based scaffolds while remaining effective GIRK1/2 channel activators. In addition, we evaluated the compounds in Tier 1 DMPK assays and have identified a (3-methyl-1H-pyrazol-1-yl)tetrahydrothiophene-1,1-dioxide head group that imparts interesting and unexpected microsomal stability compared to previously-reported pyrazole head groups.
Benzimidazolyl-pyrazolo[3,4- b]pyridinones, Selective Inhibitors of MOLT-4 Leukemia Cell Growth and Sea Urchin Embryo Spiculogenesis: Target Quest
Lichitsky, Boris V.,Komogortsev, Andrey N.,Dudinov, Arkady A.,Krayushkin, Mikhail M.,Khodot, Evgenii N.,Samet, Alexander V.,Silyanova, Eugenia A.,Konyushkin, Leonid D.,Karpov, Alexei S.,Gorses, Delphine,Radimerski, Thomas,Semenova, Marina N.,Kiselyov, Alex S.,Semenov, Victor V.
supporting information, p. 805 - 816 (2019/12/02)
1,3-Substituted pyrazolo[3,4-b]pyridinones 11-18 were synthesized by a three-component condensation of Meldrum's acid with aryl aldehydes and 1,3-substituted 5-aminopyrazoles. Their biological activity was evaluated using the in vivo phenotypic sea urchin embryo assay and the in vitro cytotoxicity screen against human cancer cell lines. In the sea urchin embryo model, 1-benzimidazolyl-pyrazolo[3,4-b]pyridinones 11 caused inhibition of hatching and spiculogenesis at sub-micromolar concentrations. These compounds also selectively and potently inhibited growth of the MOLT-4 leukemia cell line. Subsequent structure-activity relationship studies determined the benzimidazolyl fragment as an essential pharmacophore for both effects. We applied numerous techniques for target identification. A preliminary QSAR target identification search did not result in tangible leads. Attempts to prepare a relevant photoaffinity probe that retained potency in both assays were not successful. Compounds 11 were further characterized for their activity in a wild-type versus Notch-mutant leukemia cell lines, and in in vitro panels of kinases and matrix metalloproteinases. Using a series of diverse modulators of spiculogenesis as standards, we excluded multiple signaling networks including Notch, Wnt/β-catenin, receptor tyrosine kinases (VEGF/VEGFR, FGF/FGFR), PI3K, and Raf-MEK-ERK as possible targets of 11. On the other hand, matrix metalloproteinase-9/hatching enzyme was identified as one potential target.
Preparation method for 3-amino-5-methylisoxazole
-
Paragraph 0025; 0033; 0041, (2018/04/03)
The invention discloses a preparation method for 3-amino-5-methylisooxazole, belonging to the technical field of organic chemistry. The preparation method is completed through three steps: with an easily-available raw material namely ethyl acetate as a starting material, carrying out a reaction with acetonitrile in the presence of an alkali metal so as to form acetyl acetonitrile, then carrying out a reaction with p-toluenesulfonhydrazide so as to form hydrazone, and carrying out a ring closing reaction with hydroxylamine under an alkaline condition so as to obtain the 3-amino-5-methylisoxazole. According to the invention, raw materials in the reactions are common; chloroform or carbon tetrachloride in a traditional method are avoided; and analogous isomers of the 3-amino-5-methylisoxazoleare not detected in the reaction process.
