- One-pot three-component synthesis of novel pyrazolo[3,4-b]pyridines as potent antileukemic agents
-
In the current study, we report on the development of novel series of pyrazolo[3,4-b]pyridine derivatives (8a-u, 11a-n, and 14a,b) as potential anticancer agents. The prepared pyrazolo[3,4-b]pyridines have been screened for their antitumor activity in vitro at NCI-DTP. Thereafter, compound 8a was qualified by NCI for full panel five-dose assay to assess its GI50, TGI and LC50 values. Compound 8a showed broad-spectrum anti-proliferative activities over the whole NCI panel, with outstanding growth inhibition full panel GI50 (MG-MID) value equals 2.16 μM and subpanel GI50 (MG-MID) range: 1.92–2.86 μM. Furthermore, pyrazolo[3,4-b]pyridines 8a, 8e-h, 8o, 8u, 11a, 11e, 11h, 11l and 14a-b were assayed for their antiproliferative effect against a panel of leukemia cell lines (K562, MV4-11, CEM, RS4;11, ML-2 and KOPN-8) where they possessed moderate to excellent anti-leukemic activity. Moreover, pyrazolo[3,4-b]pyridines 8o, 8u, 14a and 14b were further explored for their effect on cell cycle on RS4;11 cells, in which they dose-dependently increased populations of cells in G2/M phases. Finally we analyzed the changes of selected proteins (HOXA9, MEIS1, PARP, BcL-2 and McL-1) related to cell death and viability in RS4;11 cells via Western blotting. Collectively, the obtained results suggested pyrazolo[3,4-b]pyridines 8o, 8u, 14a and 14b as promising lead molecules for further optimization to develop more potent and efficient anticancer candidates.
- Barghash, Reham F.,Eldehna, Wagdy M.,Kovalová, Markéta,Vojá?ková, Veronika,Kry?tof, Vladimír,Abdel-Aziz, Hatem A.
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- Modular synthesis and antiproliferative activity of new dihydro-1H-pyrazolo[1,3-b]pyridine embelin derivatives
-
A set of new dihydro-1H-pyrazolo[1,3-b]pyridine and pyrazolo[1,3-b]pyridine embelin derivatives was synthesized through a multicomponent reaction from natural embelin, 3-substituted-5-aminopyrazoles and aldehydes. The synthesized compounds were evaluated against three hematologic tumor cell lines, HEL (acute erythroid leukemia), K-562 (chronic myeloid leukemia) and HL-60 (acute myeloid leukemia), and five breast cancer cell lines (SKBR3, MCF-7, MDA-MB-231, BT-549, HS-578T). The primate non-malignant kidney Vero cell line was used as the control of cytotoxicity. From the obtained results, some structure–activity relationships were out-lined. Furthermore, in silico prediction of physicochemical properties and ADME parameters were determined for the derivatives with the best antiproliferative values.
- Amesty, ángel,Estévez-Braun, Ana,Fernández-Pérez, Leandro,Guerra, Borja,Guerra-Rodríguez, Miguel,Martín-Acosta, Pedro
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-
- Deadly KCN and pricey metal free track for accessing β-ketonitriles employing mild reaction conditions
-
A one pot synthesis of β-ketonitriles from readily accessible 3-chloropropenals using economically benign iodine, aqueous ammonia and sodium hydroxide solution, employing mild reaction conditions have been described. This report presents a convenient, inexpensive, highly toxic-matter-free and eco-friendly approach for β-ketonitriles.
- Sharma, Pawan K.,Kumar, Rajiv,Ram, Sita,Chandak, Navneet
-
supporting information
p. 1847 - 1856
(2021/04/26)
-
- Selective Synthesis of β-Ketonitriles via Catalytic Carbopalladation of Dinitriles
-
A practical, convenient, and highly selective method of synthesizing β-ketonitriles from the Pd-catalyzed addition of organoboron reagents to dinitriles has been developed. This method provides excellent functional-group tolerance, a broad scope of substrates, and the convenience of using commercially available substrates. The method is expected to show further utility in future synthetic procedures.
- Zeng, Ge,Liu, Jichao,Shao, Yinlin,Zhang, Fangjun,Chen, Zhongyan,Lv, Ningning,Chen, Jiuxi,Li, Renhao
-
p. 861 - 867
(2021/01/09)
-
- Method for synthesizing beta-ketonitrile and derivatives thereof
-
The invention discloses a method for synthesizing beta-ketonitrile and derivatives thereof. The beta-ketonitrile is prepared by a reaction of malononitrile and derivatives thereof with arylboronic acid. According to the invention, reactants are wide in source and low in cost; the reaction is carried out in a solvent, and the solvent is a mixture of toluene and water; in the process of the reaction, a palladium catalyst, an acid additive and a ligand are also added into the solvent; the acidic additive is any one selected from benzenesulfonic acid, p-toluenesulfonic acid, p-nitrobenzenesulfonic acid, trifluoromethanesulfonic acid and trifluoroformic acid; and the ligand is any one selected from 4,4'-dimethyl-2,2'-bipyridyl, 6,6'-dimethyl-2,2'-bipyridyl and 5,5'-dimethyl-2,2'-bipyridyl. The method in the invention can directly synthesize the target product in one step, does not need to separate an intermediate product, can obtain the target product only by a stirring reaction under normal pressure, has the highest yield of 98%, is especially suitable for synthesis of beta-ketonitrile derivatives sensitive to alkaline conditions, and provides better guarantee for development of organic compounds related to beta-ketonitrile derivatives.
- -
-
Paragraph 0056-0060
(2021/04/21)
-
- Asymmetric Hydroacylation Involving Alkene Isomerization for the Construction of C3-Chirogenic Center
-
A new transformation pattern for enantioselective intramolecular hydroacylation has been developed involving an alkene isomerization strategy. Proceeding through a five-membered rhodacycle intermediate, 3-enals were converted to C3- or C3,C5-chirogenic cyclopentanones with satisfactory yields, diastereoselectivities, and enantioselectivities. A catalytic cycle has been theoretically calculated and the origin of the stereoselection is rationally explained.
- Liu, Chong,Yuan, Jing,Zhang, Zhenfeng,Gridnev, Ilya D.,Zhang, Wanbin
-
supporting information
p. 8997 - 9002
(2021/03/16)
-
- Hydrogen Bond Directed Photocatalytic Hydrodefluorination and Methods of Use Thereof
-
Methods of synthesizing compounds comprising fluorinated aryl groups are disclosed, wherein said methods utilize hydrogen bond directed photocatalytic hydrodefluorination.
- -
-
-
- Synthesis and Structure-Activity Relationship of Dual-Stage Antimalarial Pyrazolo[3,4- b]pyridines
-
Malaria remains one of the most deadly infectious diseases, causing hundreds of thousands of deaths each year, primarily in young children and pregnant mothers. Here, we report the discovery and derivatization of a series of pyrazolo[3,4-b]pyridines targeting Plasmodium falciparum, the deadliest species of the malaria parasite. Hit compounds in this series display sub-micromolar in vitro activity against the intraerythrocytic stage of the parasite as well as little to no toxicity against the human fibroblast BJ and liver HepG2 cell lines. In addition, our hit compounds show good activity against the liver stage of the parasite but little activity against the gametocyte stage. Parasitological profiles, including rate of killing, docking, and molecular dynamics studies, suggest that our compounds may target the Qo binding site of cytochrome bc1.
- Eagon, Scott,Hammill, Jared T.,Sigal, Martina,Ahn, Kevin J.,Tryhorn, Julia E.,Koch, Grant,Belanger, Briana,Chaplan, Cory A.,Loop, Lauren,Kashtanova, Anna S.,Yniguez, Kenya,Lazaro, Horacio,Wilkinson, Steven P.,Rice, Amy L.,Falade, Mofolusho O.,Takahashi, Rei,Kim, Katie,Cheung, Ashley,Dibernardo, Celine,Kimball, Joshua J.,Winzeler, Elizabeth A.,Eribez, Korina,Mittal, Nimisha,Gamo, Francisco-Javier,Crespo, Benigno,Churchyard, Alisje,García-Barbazán, Irene,Baum, Jake,Anderson, Marc O.,Laleu, Beno?t,Guy, R. Kiplin
-
p. 11902 - 11919
(2020/11/26)
-
- Structure guided design of potent indole-based ATX inhibitors bearing hydrazone moiety with tumor suppression effects
-
ATX was capable of catalyzing the hydrolysis of LPC to the lipid mediator LPA which attracted considerable attention on the development of potent ATX inhibitors. Herein, driven by the HTS product indole-based lead 1, a hybridization strategy was utilized to construct the trifluoroacetyl hydrazone moiety through assembling the phenyl thiazole fragment to the indole skeleton of lead 1. After a systematic structure guided optimization, by cycling the phenyl thiazole to the compacted benzothiazole or decreasing the lipophilicity, two promising ATX inhibitors (9j and 25a) were identified with IC50 values of 2.1 nM and 19.0 nM, respectively. All compounds were tested a panel of cancer cell lines and a preliminary affinity on breast cancer cell lines (SI > 16.5) were observed which shed a light on their potential application of breast cancer relevant cases. Through a dedicated docking study, the intramolecular pseudo-ring within the trifluoroacetylhydrazone moiety played a significant role in constraining the binding poses of 9j and 25a. Finally, a binding free energy calculation was conducted to examine the contribution of different interactions in binding affinity.
- Guo, Ming,Jia, Fang,Jiang, Nan,Lei, Hongrui,Li, Changtao,Yang, Yu,Zhai, Xin,Zhu, Minglin
-
-
- Synthesis and refining method of 4-fluorobenzoyl acetonitrile
-
The invention relates to a synthesis and refining method of 4-fluorobenzoyl acetonitrile, which comprises the following steps: dissolving malononitrile in a solvent, and adding fluorobenzene and trifluoromethanesulfonic acid to react, thereby obtaining a 4-fluorobenzoyl acetonitrile crude product; adding an alcohol and a small molecular alkane into the 4-fluorobenzoyl acetonitrile crude product for recrystallizationso as to obtain 4-fluorobenzoyl acetonitrile. The method has the advantages of short synthesis steps, safety and simplicity in operation, high conversion rate and low cost, anda basis is provided for development and application of 4-fluorobenzoyl acetonitrile.
- -
-
Paragraph 0025; 0026
(2020/06/20)
-
- METHOD OF PRODUCING BLONANSERIN
-
PROBLEM TO BE SOLVED: To provide a method of producing blonanserin. SOLUTION: The invention relates to an improved method of producing high-purity 2-(4-ethyl-1-piperazinyl)-4-(4-fluorophenyl)-5,6,7,8,9,10-hexahydrocycloocta[b]pyridine (INN name blonanserin). The method is implemented through four successive steps starting from C1-4-alkyl 4-fluorobenzoate. The invention also relates to a method of producing 3-(4-fluorophenyl)-3-oxopropanenitrile (BLON1) being an intermediate. SELECTED DRAWING: None COPYRIGHT: (C)2018,JPOandINPIT
- -
-
Paragraph 0129
(2018/05/03)
-
- One-pot dichlorinative deamidation of primary β-ketoamides
-
An approach to the dichlorinative deamidation of primary β-ketoamides through ketonic cleavage is described, and a series of α,α-dichloroketones were furnished mostly in the presence of TEMPO. Based on control experiments, a mechanism involving tandem dichlorination and deamidation is proposed to interpret the observed reactivity.
- Zheng, Congke,Zhang, Xiaohui,Ijaz Hussain, Muhammad,Huang, Mingming,Liu, Qing,Xiong, Yan,Zhu, Xiangming
-
supporting information
p. 574 - 577
(2017/01/16)
-
- Blonanserin intermediate 4-fluorobenzoylacetonitrile synthesis method
-
The invention provides a Blonanserin intermediate 4-fluorobenzoylacetonitrile synthesis method. The method comprises the following steps: (1) mixing acetonitrile, t-butanol, p-fluorobenzonitrile and organic solvent A into mixed solution; (2) adding potassium tert-butoxide and the organic solvent A to a reactor, then adding the mixed solution obtained in the step (1), and stirring for reaction to obtain 3-amino-3-p-fluorophenyl acrylonitrile; (3) hydrolyzing the 3-amino-3-p-fluorophenyl acrylonitrile with hydrochloric acid solution to obtain the 4-fluorobenzoylacetonitrile, wherein the organic solvent A is isopropyl ether and/or tetrahydrofuran. According to the method, the potassium tert-butoxide is used as a condensing agent, which greatly improves the safety of the process. The potassium t-butoxide is mild in nature, has hygroscopicity but is nonflammable, and can be used in wider temperature and humidity ranges, and is more conducive to industrial production. And meanwhile, the method is stable in yield and high in obtained product purity.
- -
-
Paragraph 0039; 0042
(2017/09/02)
-
- Synthetic method for Blonanserin
-
The invention discloses a synthetic method for Blonanserin. The synthetic method comprises the following steps: 1) methyl fluorobenzoate is taken as a raw material and subjected to condensation with acetonitrile, and a compound 3 is obtained; 2) polyphosphoric acid is heated, then the compound 3 and a cyclooctanone and an ionic liquid are added, and a compound 4 is obtained through a one-step reaction; 3) the compound 4 is subjected to chlorination through a phenylphosphonic dichloride compound, and a compound 5 is obtained; 4) the compound 5 is mixed with potassium iodide and 1-ethylpiperazine, the ionic liquid is added, heating and nucleophilic substitution are performed, and Blonanserin is obtained, wherein the ionic liquid in the step 2) and the step 3) is 1-ethyl-3-methylimidazolium tetrafluoroborate, the adding quantity of the ionic liquid in the step 2) is 30% of the mass of the compound 3, and the adding quantity of the ionic liquid in the step 3) is 30% of the mass of the compound 5. Compared with the conventional synthetic method for Blonanserin, the synthetic method has the advantages that the reaction time is shortened greatly, the yield is increased, the production cost is reduced, and the method is applicable to industrial production.
- -
-
Paragraph 0018; 0028; 0029; 0030; 0031
(2017/01/12)
-
- Palladium-Catalyzed Carbonylative α-Arylation of tert -Butyl Cyanoacetate with (Hetero)aryl Bromides
-
A three-component coupling protocol has been developed for the generation of 3-oxo-3-(hetero)arylpropanenitriles via a carbonylative palladium-catalyzed α-arylation of tert-butyl 2-cyanoacetates with (hetero)aryl bromides followed by an acid-mediated decarboxylation step. Through the combination of only a stoichiometric loading of carbon monoxide and mild basic reaction conditions such as MgCl2 and dicyclohexylmethylamine for the deprotonation step, an excellent functional group tolerance was ensured for the methodology. Through the use of 13C-labeled carbon monoxide generated from 13COgen, the corresponding 13C-isotopically labeled β-ketonitriles were obtained, and these products could subsequently be converted into cyanoalkynes and 3-cyanobenzofurans with site specific 13C-isotope labeling. (Chemical Equation Presented).
- Jensen, Mikkel T.,Juhl, Martin,Nielsen, Dennis U.,Jacobsen, Mikkel F.,Lindhardt, Anders T.,Skrydstrup, Troels
-
p. 1358 - 1366
(2016/03/01)
-
- One-pot synthesis of benzoylacetonitriles through sequential Pd-catalyzed carbonylation and decarboxylation
-
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
-
p. 239 - 242
(2015/12/31)
-
- Chemoselective efficient synthesis of functionalized β-oxonitriles through cyanomethylation of Weinreb amides
-
A synthesis of β-oxonitriles is reported via the generation of R1R2CLiCN species followed by the trapping with variously decorated Weinreb amides. The optimization study revealed that lithiation of acetonitriles is best accomplished by deprotonation with MeLi-LiBr at low temperature. The protocol can be conveniently adapted to the synthesis of α-mono or α,α-disubstituted cyanoketones. 15N- and 17O-NMR data are reported for selected compounds. This journal is
- Mamuye, Ashenafi Damtew,Castoldi, Laura,Azzena, Ugo,Holzer, Wolfgang,Pace, Vittorio
-
supporting information
p. 1969 - 1973
(2015/03/05)
-
- Umpolung Strategy for Synthesis of β-Ketonitriles through Hypervalent Iodine-Promoted Cyanation of Silyl Enol Ethers
-
An efficient method to synthesize β-ketonitriles from silyl enol ethers by an umploung hypervalent iodine(III)-CN species generated in situ from PhIO/BF3·Et2O/TMSCN has been developed for the first time. This method can be applied to structurally diverse aromatic and aliphatic substrates and further extended to preparation of bioactive compounds like 5-aminopyrazole and 5-aminoisoxazole.
- Shen, Hang,Li, Jiaqiang,Liu, Qing,Pan, Jing,Huang, Ruofeng,Xiong, Yan
-
p. 7212 - 7218
(2015/07/28)
-
- Specific 1,2-Hydride Shift in the Boron Trifluoride Catalyzed Reactions of Aromatic Aldehydes with Diazoacetonitrile: Simple Synthesis of β-Ketonitriles
-
A series of β-ketonitriles was synthesized within 30 min under mild conditions through the BF3 ·OEt2-catalyzed addition reactions of diazoacetonitrile to aromatic aldehydes and subsequent 1,2-hydride shift. This method is advantageous in that it is operationally simple, mild and metal-free conditions are used, the substrate scope is wide, and the products are obtained in moderate to high yields (up to 81 %). Additionally, γ,δ-unsaturated β-ketonitriles are also accessible by this method by using cinnamaldehydes.
- Yang, Zhanhui,Son, Kwon-Il,Li, Siqi,Zhou, Bingnan,Xu, Jiaxi
-
supporting information
p. 6380 - 6384
(2016/02/18)
-
- Copper-catalyzed Aerobic Oxidative coupling of Aromatic Alcohols and Acetonitrile to β-Ketonitriles
-
A practical, convenient, and cheap coppercatalyzed aerobic oxidative coupling of aromatic alcohols and acetonitrile to β-ketonitriles has been developed. The green C-C bond formation involving the loss of two hydrogen atoms from the corresponding two carbons, respectively, unlocks opportunities for markedly different synthetic strategies.
- Shen, Jiaxuan,Yang, Dejun,Liu, Yuxiao,Qin, Shuangshuang,Zhang, Jingwu,Sun, Jiangkai,Liu, Chunhui,Liu, Chaoyang,Zhao, Xiaomei,Chu, Changhu,Liu, Renhua
-
supporting information
p. 350 - 353
(2014/04/03)
-
- Substituted pyrazoloquinazolinones and pyrroloquinazolinones as allosteric modulators of group II metabotropic glutamate receptors
-
The present invention relates to the pyrazoloquinazolinone and pyrroloquinazolinone derivatives of the general formula (I), as well as pharmaceutical compositions containing them, and their use in the treatment and/or prophylaxis of conditions associated with altered glutamatergic signalling and/or functions, and/or conditions which can be affected by alteration of glutamate level or signalling in mammals, in particular their use in the treatment and/or prophylaxis of acute and chronic neurological and/or psychiatric disorders.
- -
-
Paragraph 0324
(2014/01/07)
-
- SUBSTITUTED PYRAZOLOQUINAZOLINONES AND PYRROLOQUINAZOLINONES AS ALLOSTERIC MODULATORS OF GROUP II METABOTROPIC GLUTAMATE RECEPTORS
-
The present invention relates to the pyrazoloquinazolinone and pyrroloquinazolinone derivatives of the general formula (I), as well as pharmaceutical compositions containing them, and their use in the treatment and/or prophylaxis of conditions associated with altered glutamatergic signalling and/or functions, and/or conditions which can be affected by alteration of glutamate level or signalling in mammals, in particular their use in the treatment and/or prophylaxis of acute and chronic neurological and/or psychiatric disorders.
- -
-
Page/Page column 94; 116
(2014/01/07)
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- Palladium-catalyzed carbonylation with Mo(CO)for the synthesis of benzoylacetonitriles
-
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
-
supporting information
p. 2885 - 2888
(2012/10/29)
-
- Synthesis of benzoylacetonitriles from Pd-catalyzed carbonylation of aryl iodides and trimethylsilylacetonitrile
-
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
-
supporting information; experimental part
p. 1118 - 1121
(2012/03/27)
-
- Phase transfer catalyst in grindstone synthesis of 3-oxopropanenitrile: One pot synthesis of polysubstituted amino thiophenes
-
The chemoselective SN2 reaction of ω-bromoacetophenone with sodium cyanide or potassium cyanide in DMF-water or in biphasic solvent toluene-water using tetrabutylammonium bromide (TBAB) as phase-transfer catalyst, performed by grinding, furnished 3-oxopropanenitriles 2 as the sole product in 70-80% yield, while in ethanolwater, mixture of compound 2 and oxirane 3 were obtained. The obtained 3-oxopropanenitriles 2 were used for one pot synthesis of 2-amino-3-carbonitrile thiophenes.
- Patil, Shivaraj P.,Kanawade, Shrikant B.,Shinde, Madhukar P.,Toche, Raghunath B.
-
-
- Iridium diamine catalyst for the asymmetric transfer hydrogenation of ketones
-
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.
-
supporting information; experimental part
p. 8979 - 8981
(2011/11/30)
-
- Biocatalytic strategy toward asymmetric β-hydroxy nitriles and γ-amino alcohols
-
A library of 20 bakers' yeast reductases, that are overexpressed in Escherichia coli, were screened against a variety of β-keto nitriles. Enzymes from the aldose reductase and the short chain dehydrogenase family displayed activity toward these substrates. All of the seven substrates were reduced with high enantioselectivities and in some cases both antipodes could be synthesized in high ees. These whole-cell reactions afforded gram quantities of asymmetric compounds that could ultimately lead to scaleable and simple synthesis to new drug analogs of serotonin reuptake inhibitors and β-adrenergic blocking agents.
- Nowill, Randall W.,Patel, Trisha J.,Beasley, David L.,Alvarez, Jose A.,Jackson III, Elizah,Hizer, Todd J.,Ghiviriga, Ion,Mateer, Scott C.,Feske, Brent D.
-
supporting information; experimental part
p. 2440 - 2442
(2011/05/16)
-
- Transfer hydrogenation in water: Enantioselective, catalytic reduction of α-cyano and α-nitro substituted acetophenones
-
Catalytic reduction of α-substituted acetophenones under conditions involving asymmetric transfer hydrogenation in water is described. The reaction is conducted in water and open to air, and formic acid is used as reductant.
- Soltani, Omid,Ariger, Martin A.,Vazquez-Villa, Henar,Carreira, Erick M.
-
supporting information; experimental part
p. 2893 - 2895
(2010/09/09)
-
- GAMMA SECRETASE MODULATORS
-
In its many embodiments, the present invention provides a novel class of heterocyclic compounds of the formula: as modulators of gamma secretase, methods of preparing such compounds, pharmaceutical compositions containing one or more such compounds, methods of preparing pharmaceutical formulations comprising one or more such compounds, and methods of treatment, prevention, inhibition, or amelioration of one or more diseases associated with the central nervous system using such compounds or pharmaceutical compositions.
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Page/Page column 350
(2010/06/15)
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- Unexpected stereorecognition in nitrilase-catalyzed hydrolysis of β-hydroxy nitriles
-
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
-
p. 4429 - 4431
(2007/10/03)
-
- THIENO-PYRIDINE DERIVATIVES AS GABA-B ALLOSTERIC ENHANCERS
-
The present invention relates to compounds of formula (I), Wherein R1 to R5 are as defined in the specification which compounds are active on the GABABreceptor and can be used for the manufacture of medicaments useful for treating CNS disorders.
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Page/Page column 30
(2008/06/13)
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- Reactions of 1,3-diaryl-2-chloropropane-1,3-diones with nucleophiles - Cyanide-induced retro-Claisen-Claisen condensation
-
Treatment of some 1,3-diaryl-2-chloropropane-1,3-diones, acyclic chloro-substituted enaminones and β-oxo esters with nucleophiles was shown to proceed easily with the formation, at least in the first stage, of formal nucleophilic substitution products. Treatment of enaminones and β-oxo esters with azide and cyanide ions proceeds with the preservation of the skeleton, whereas chloro-substituted diaroylmethanes undergo retro-Claisen-Claisen condensation reactions in the course of the reaction with cyanide. Dibenzoylchloromethane reacts with azide and cyanide ions with fragmentation of the molecule and subsequent reassembly, resulting in benzoylated benzaldehyde cyanohydrin and a 1,3-oxathiol derivative, respectively. Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004.
- Roshchupkina, Galina I.,Gatilov, Yury V.,Rybalova, Tatyana V.,Reznikov, Vladimir A.
-
p. 1765 - 1773
(2007/10/03)
-
- MONOCYCLIC AROYLPYRIDINONES AS ANTIINFLAMMATORY AGENTS
-
The present invention relates to monocyclic aroylpyridinones, processes for their preparation, and their use in medicaments, especially for the treatment of COPD: (formula I).
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Page/Page column 64
(2010/02/07)
-
- Synthesis and biological effects of a new series of 2-amino-3-benzoylthiophenes as allosteric enhancers of A1-adenosine receptor
-
New derivatives of PD 81,723, an allosteric enhancer of agonist binding to the A1-adenosine receptor, have been synthesized and evaluated in an intact cell assay. Compounds 3a, 3o and 3p appeared to be more potent than PD 81,723 and at a concentration of 0.1 μM caused significant reductions of cAMP content of CHO cells expressing the human A1-adenosine receptor. Compounds 4e and 4o appeared to be allosteric enhancers at a low concentration and antagonists at a higher concentration, whereas compounds 3c, 3g, 3s and 4l appeared to be weak antagonists that are also allosteric enhancers at the higher concentration of 10 μM. (C) 2000 Elsevier Science Ltd.
- Baraldi, Pier Giovanni,Zaid, Abdel Naser,Lampronti, Ilaria,Fruttarolo, Francesca,Pavani, Maria Giovanna,Tabrizi, Mojgan Aghazadhe,Shryock, John C.,Leung, Edward,Romagnoli, Romeo
-
p. 1953 - 1957
(2007/10/03)
-
- Tyrphostins. 2. Heterocyclic and α-Substituted Benzylidenemalonitrile Tyrphostins as Potent Inhibitors of EGF Receptor and ErbB2/neu Tyrosine Kinases
-
We have previously described a novel series of low molecular weight protein tyrosine kinase inhibitors which we named tyrphostins.The characteristic active pharmacophore of these compounds was the hydroxy-cis-benzylidenemalonitrile moiety.In this article we describe three novel groups of tyrphostins: (i) one group has the phenolic moiety of the cis-benzylidenemalononitrile replaced either with other substituted benzenes or with heteroaromatic rings, (ii) another is a series of conformationally constrained derivatives of hydroxy-cis-benzylidenemalononitriles in which the malononitrile moiety is fixed relative to the aromatic ring, and (iii) two groups of compounds in which the position trans to the benzenemalononitrile has been substituted by ketones and amides.Among the novel tyrphostins examined we found inhibitors which discriminate between the highly homologous EGF receptor kinase (HER1) and ErbB2/neu kinase (HER2).These findings may lead to selective tyrosine kinase blockers for the treatment of diseases in which ErbB2/neu is involved.
- Gazit, Aviv,Osherov, Nir,Posner, Israel,Yaish, Pnina,Poradosu, Enrique,et al.
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p. 1896 - 1907
(2007/10/02)
-
- Heteroaryl 3-oxo-propanenitrile derivatives, pharmaceutical compositions and use
-
The invention relates to compounds having the general formula (I) STR1 and the pharmaceutically acceptable salts thereof, which possess immunomodulating activity and are useful e.g. in the treatment of neoplastic diseases and acute and chronic infections of both bacterial and viral origin in mammals.
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-
-
- 1-Benzoyl-3-(isoxazolyl or benzisoxazolyl)-ureas and insecticidal use thereof
-
The present invention is directed to 1-(benzoyl)-3-(isoxazolyl or benzisoxazolyl)urea or thiourea compounds useful as insecticides.
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- STABLE 2H-PYRAN DERIVATIVES ACCESSIBLE BY CYCLOCONDENSATION OF p-SUBSTITUTED BENZOYLACETONITRILES
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The 2H-pyrans IIa-f can be prepared by thermal cyclocondensation of the ketonitriles Ia-f.The alternative structure III of the compounds obtained has been excluded unambiguously on the basis of spectral data.The compounds VII to XI have been isolated as byproducts of the said cyclocondensation of the compound Ia in acetic acid with catalysis of ammonium acetate.Probable course of the reaction investigated is discussed.
- Kuthan, Josef,Palecek, Jaroslav,Valihrach, Jiri
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p. 748 - 758
(2007/10/02)
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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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