- Reaction of 1,3-Bis(het)arylmonothio-1,3-diketones with Sodium Azide: Regioselective Synthesis of 3,5-Bis(het)arylisoxazoles via Intramolecular N-O Bond Formation
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An efficient new synthesis of 3,5-bis(het)arylisoxazoles, involving the reaction of 1,3-bis(het)arylmonothio-1,3-diketones with sodium azide in the presence of IBX catalyst, has been reported. The reaction proceeds at room temperature in high yields and is applicable to a broad range of substrates including the synthesis of 5-methyl-3-arylisoxazoles, a key subunit present in several β-lactamase-resistant antibiotics. A probable mechanism for the formation of isoxazoles has been suggested. A few of the 5-styryl/arylbutadienyl-3-(het)arylisoxazoles have also been synthesized by reacting the corresponding 1-(het)aryl-1-(methylthio)-4-(het)arylidene-but-1-en-3-ones with sodium azide at higher temperatures. The reaction of β-ketodithioesters with sodium azide is shown to furnish β-ketonitriles in good yields.
- Antony P, Mary,Balaji, Gantala L.,Iniyavan, Pethaperumal,Ila, Hiriyakkanavar
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p. 15422 - 15436
(2020/11/30)
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- Synthesis and biological evaluation of 7-(aminoalkyl)pyrazolo[1,5-a]pyrimidine derivatives as cathepsin K inhibitors
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A series of novel 7-aminoalkyl substituted pyrazolo[1,5-a]pyrimidine derivatives were synthesized and tested for inhibition of cathepsin K. The synthetic methodology comprises cyclization of 5-aminopyrazoles with N-Boc-α-amino acid-derived ynones followed by transformation of the ester and the Boc-amino functions. It allows for easy diversification of the pyrazolo[1,5-a]pyrimidine scaffold at various positions. Molecular docking studies with pyrazolo[1,5-a]pyrimidine derivatives were also performed to elucidate the binding mode in the active site of cathepsin K. The synthesized compounds exhibited moderate inhibition activity (Ki ≥ 77 μM).
- Petek, Nejc,?tefane, Bogdan,Novinec, Marko,Svete, Jurij
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p. 226 - 238
(2018/12/04)
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- One-pot synthesis of benzoylacetonitriles through sequential Pd-catalyzed carbonylation and decarboxylation
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Benzoylacetonitrile were prepared through sequential carbonylation and decarboxylation. The palladium-catalyzed carbonylation of aryl iodides and methyl cyanoacetate using Mo(CO)6 as a carbon monoxide source afforded beta-keto cyanoesters, and then the subsequent reaction with Li/H2O produced the desired benzoylacetonitriles.
- Lee, Sunwoo,Kim, Han-Sung,Min, Hongkeun,Pyo, Ayoung
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p. 239 - 242
(2015/12/31)
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- Pyrazolotriazines as inhibitors of nucleases
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The invention provides compounds represented by the structural formula (1): wherein R1, R2, R3 and R4 are as defined in the claims. The compounds are inhibitors of nucleases, and are useful in particular in a method of treatment and/or prevention of proliferative diseases, neurodegenerative diseases, and other genomic instability associated diseases.
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Paragraph 0060; 0061; 0062; 0063; 0064; 0090-0096
(2016/01/12)
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- Cascade synthesis of 3-aza-bicyclo[3.1.0]hex-2-ene derivatives from N-allyl enamines
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An efficient iodine-mediated cascade synthesis of 3-aza-bicyclo[3.1.0]hex-2-ene derivatives from easily prepared N-allyl enamines has been developed. The advantages of the reaction include facilitative preparation of substrates 3a-t, good functional group tolerance and transition-metal-free conditions.
- Zhai, Sheng-Xian,Dong, Hong-Ru,Chen, Zi-Bao,Hu, Yi-Ming,Dong, Heng-Shan
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p. 8405 - 8412
(2015/03/04)
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- Discovery of a novel alpha-7 nicotinic acetylcholine receptor agonist series and characterization of the potent, selective, and orally efficacious agonist 5-(4-acetyl[1,4]diazepan-1-yl)pentanoic acid [5-(4-methoxyphenyl)-1H- pyrazol-3-yl] amide (SEN15924, WAY-361789)
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Alpha-7 nicotinic acetylcholine receptors (α7 nAChR) are implicated in the modulation of many cognitive functions such as attention, working memory, and episodic memory. For this reason, α7 nAChR agonists represent promising therapeutic candidates for the treatment of cognitive impairment associated with Alzheimer's disease (AD) and schizophrenia. A medicinal chemistry effort, around our previously reported chemical series, permitted the discovery of a novel class of α7 nAChR agonists with improved selectivity, in particular against the α3 receptor subtype and better ADME profile. The exploration of this series led to the identification of 5-(4-acetyl[1,4] diazepan-1-yl)pentanoic acid [5-(4-methoxyphenyl)-1H-pyrazol-3-yl] amide (25, SEN15924, WAY-361789), a novel, full agonist of the α7 nAChR that was evaluated in vitro and in vivo. Compound 25 proved to be potent and selective, and it demonstrated a fair pharmacokinetic profile accompanied by efficacy in rodent behavioral cognition models (novel object recognition and auditory sensory gating).
- Zanaletti, Riccardo,Bettinetti, Laura,Castaldo, Cristiana,Cocconcelli, Giuseppe,Comery, Thomas,Dunlop, John,Gaviraghi, Giovanni,Ghiron, Chiara,Haydar, Simon N.,Jow, Flora,MacCari, Laura,Micco, Iolanda,Nencini, Arianna,Scali, Carla,Turlizzi, Elisa,Valacchi, Michela
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experimental part
p. 4806 - 4823
(2012/07/28)
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- Palladium-catalyzed carbonylation with Mo(CO)for the synthesis of benzoylacetonitriles
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Benzoylacetonitriles were synthesized by the palladium-catalyzed carbonylation of aryl iodides and trimethylsilylacetonitrile using Mo(CO)as a carbon monoxide source. Pd(PPhCland CuFwere employed as the catalyst and activator, respectively. A variety of aryl iodides bearing alkyl, alkoxy, fluoro, chloro, bromo, nitrile, ester, and ketone groups afforded the corresponding benzoylacetonitriles in moderate to good yields. Georg Thieme Verlag Stuttgart ? New York.
- Pyo, Ayoung,Park, Ahbyeol,Jung, Hyunmin,Lee, Sunwoo
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supporting information
p. 2885 - 2888
(2012/10/29)
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- Synthesis of benzoylacetonitriles from Pd-catalyzed carbonylation of aryl iodides and trimethylsilylacetonitrile
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Palladium-catalyzed carbonylation of aryl iodides and trimethylsilylacetonitrile to produce benzoylacetonitrile derivatives through a one-pot, three-component reaction is described. This preparation method provides good yields of the carbonylated products without any additional ligands. It has a broad substrate scope with a high tolerance for a variety of functional groups.
- Park, Ahbyeol,Lee, Sunwoo
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supporting information; experimental part
p. 1118 - 1121
(2012/03/27)
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- Iridium diamine catalyst for the asymmetric transfer hydrogenation of ketones
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A simple and very efficient chiral aqua iridium(III) diamine complex leads to excellent enantioselectivities in the asymmetric transfer hydrogenation of various α-cyano and α-nitro ketones. The catalyst provides the ortho-substituted aromatic alcohols with especially high ee values. The diamine ligands can be used directly as chiral ligands; conversion into the corresponding sulfamide is not necessary.
- Vazquez-Villa, Henar,Reber, Stefan,Ariger, Martin A.,Carreira, Erick M.
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supporting information; experimental part
p. 8979 - 8981
(2011/11/30)
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- Design, synthesis, and evaluation of 2-aryl-7-(3′,4′-dialkoxyphenyl)-pyrazolo[1,5-a]pyrimidines as novel PDE-4 inhibitors
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Described herein is design, synthesis, and biological evaluation of novel series of 2-aryl-7-(3′,4′-dialkoxyphenyl)-pyrazolo[1,5-a]pyrimidines acting as inhibitors of type 4 phosphodiesterase (PDE4) which is known as a good target for the treatment of asthma and COPD. For this purpose, structure optimization was conducted with the aid of structure-based drug design using the known X-ray crystallography. Also, biological effects of these compounds on the target enzyme were evaluated by using in vitro assays, leading to the potent and selective PDE-4 inhibitor (IC50 10 nM).
- Kim, Ikyon,Song, Jong Hwan,Park, Chang Min,Jeong, Joon Won,Kim, Hyung Rae,Ha, Jin Ryul,No, Zaesung,Hyun, Young-Lan,Cho, Young Sik,Sook Kang, Nam,Jeon, Dong Ju
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scheme or table
p. 922 - 926
(2010/06/22)
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- Bromophilic substitution/carbophilic substitution cascade reactions of α,α-dibromo-2-methoxyacetophenone with C-, N- and O-nucleophiles
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α,α-Dibromo-2-methoxyacetophenone reacts, under mild reaction conditions, with C-, N- and O-nucleophiles via a bromophilic substitution/protonation/carbophilic substitution cascade process to afford α-monosubstituted-2-methoxyacetophenones in moderate to good yield. The only exception from this reaction pathway is the reaction with the anion derived from malononitrile in which 2-aroyl-1,1,3,3-tetracyanopropene is obtained.
- Tatar, Jovana,Markovi?, Rade,Stojanovi?, Milovan,Baranac-Stojanovi?, Marija
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scheme or table
p. 4851 - 4855
(2010/10/02)
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- Reactions of ortho-substituted α,α-dibromoacetophenones with nucleophiles: first examples of combined carbophilic and bromophilic attack on C-Br bonds
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An efficient method for the formation of α-carbonyl-monosubstituted acetophenones from ortho-methoxy- and ortho-hydroxy-α,α-dibromoacetophenones and a range of selected nucleophiles, occurring via a carbophilic substitution/bromophilic substitution/protonation cascade process, is described. In turn, the preparation of α,α-dibromoacetophenones, isolated in high yields, relies on the neighboring group participation of the ortho-substituents in the starting ortho-substituted acetophenones.
- Tatar, Jovana,Baranac-Stojanovi?, Marija,Stojanovi?, Milovan,Markovi?, Rade
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experimental part
p. 700 - 703
(2011/02/27)
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- 3-Substituted-(5-arylfuran-2-ylcarbonyl)guanidines as NHE-1 inhibitors
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The C-3 substituents effect on NHE-1 inhibitory activity of (5-arylfuran-2-ylcarbonyl)guanidines, previously identified as potent NHE-1 inhibitors, was investigated. The introduction of amine or alkyl groups at the 3-position of the furan ring, next to the acylguanidine moiety, remarkably improves NHE-1 inhibitory potency. Especially the important finding is that 5-(2,5-dichloro)phenyl and 5-(2-methoxy-5-chloro)phenyl derivatives exhibit high NHE-1 inhibitory activities (IC50 0.02 μM) that match those of 3-unsubstituted derivatives.
- Lee, Sunkyung,Kim, Taemi,Lee, Byung Ho,Yoo, Sung-eun,Lee, Kyunghee,Yi, Kyu Yang
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p. 1291 - 1295
(2008/02/02)
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- Novel potent neuropeptide Y Y5 receptor antagonists: Synthesis and structure-activity relationships of phenylpiperazine derivatives
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A series of phenylpiperazine derivatives were synthesized and evaluated for their neuropeptide Y (NPY) Y5 receptor antagonistic activities. The benzindane portion of 2 was replaced by 1-phenylpiperazine, resulting in novel urea derivative 3f. Subsequent optimization of the phenylpiperazine template by substitution of the phenyl moiety resulted in a series of (2-methanesulfonamidephenyl)piperazine derivatives that showed potent binding affinity and antagonistic activity for the Y5 receptor.
- Takahashi, Toshiyuki,Sakuraba, Aya,Hirohashi, Tomoko,Shibata, Takunobu,Hirose, Masaaki,Haga, Yuji,Nonoshita, Katsumasa,Kanno, Tetsuya,Ito, Junko,Iwaasa, Hisashi,Kanatani, Akio,Fukami, Takehiro,Sato, Nagaaki
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p. 7501 - 7511
(2007/10/03)
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- Unexpected stereorecognition in nitrilase-catalyzed hydrolysis of β-hydroxy nitriles
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Biocatalytic enantioselective hydrolysis of β-hydroxy nitriles to corresponding (S)-enriched β-hydroxy carboxylic acids has been achieved for the first time by an isolated nitrilase bII6402 from Bradyrhizobium japonicum USDA110. This offers a new "green" approach to optically pure β-hydroxy nitriles and β-hydroxy carboxylic acids. The observed remote stereorecognition is surprising because this nitrilase shows no enantioselectivity for the hydrolysis of α-hydroxy nitriles such as mandelonitrile.
- Kamila, Sukanta,Zhu, Dunming,Biehl, Edward R.,Hua, Ling
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p. 4429 - 4431
(2007/10/03)
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- NOVEL HERBICIDES, USAGE THEREOF, NOVEL THIENOPYRIMIDINE DERIVATIVES, INTERMEDIATES OF THE SAME, AND PROCESS FOR PRODUCTION THEREOF
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A herbicide comprising, as an active ingredient, a substituted thienopyrimidine derivative represented by the formula (I): wherein all symbols are defined in the description, a method of using the same, a novel compound useful as the herbicide and a process for producing the same, and an intermediate thereof.
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Page/Page column 57
(2010/02/12)
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- Steric and electronic control in the addition of hydrazine and phenylhydrazine to α-[(dimethylamino)methylene]-β-oxoarylpropanenitriles
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Reaction of hydrazine with α-[(dimethylamino)methylene]-β-oxoarylpropanenitriles 2 gives a mixture of the 4-aroyl-5-aminopyrazoles 3 and the 5-aryl-4-cyanopyrazoles 4. Similarly reaction of 2 with phenylhydrazine gives rise to the 5-amino-4-aroyl-1-phenylpyrazoles 5 and 5-aryl-4-cyano-1-phenylpyrazoles 6. The regioselectivity of addition has been investigated with respect to the electronic nature and steric requirements of the aromatic substitution. The ratio of products was found to be independent of the electronic nature of the substituent. The outcome of the reaction was however very sensitive to steric factors. Substituents in the para- and meta-positions favoured formation of the pyrazole-nitrile products 4 and 6, whereas sterically demanding ortho-substituents favoured the pyrazole-amino ketones 3 and 5.
- Tupper, David E.,Bray, Mark R.
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p. 337 - 341
(2007/10/03)
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- Potential antiarthritic agents. II. Benzoylacetonitriles and β-aminocinnamonitriles
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Benzoylacetonitrile and β-aminocinnamonitrile are shown to possess potent intiinflammatory activity in the rat adjuvant arthritis model. In a series of phenyl-substituted analogues, only o-, m-, and p-fluorobenzoylacetonitrile and m- and p-fluoro-β-aminocinnamonitrile retained activity. Additionally, β-amino-2- and β-amino-3-thiopheneacrylonitrile and β-oxo-2- and β-oxo-3-thiophenepropionitrile exhibited similar activity. These agents are not believed to be acting via prostaglandin synthetase inhibition. The metabolic profile of benzoylacetonitrile is also described.
- Ridge,Hanifin,Harten,Johnson,Menschik,Nicolau,Sloboda,Watts
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p. 1385 - 1389
(2007/10/09)
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