- Synthesis of: N -methylated amines from acyl azides using methanol
-
The transformation of acyl azide derivatives into N-methylamines was developed using methanol as the C1 source via the one-pot Curtius rearrangement and borrowing hydrogen methodology. Following this protocol, various functionalised N-methylated amines were synthesized using the (NNN)Ru(ii) complex from carboxylic acids via an acyl azide intermediate. Several kinetic studies and DFT calculations were carried out to support the mechanism and also to determine the role of the Ru(ii) complex and base in this transformation.
- Chakrabarti, Kaushik,Dutta, Kuheli,Kundu, Sabuj
-
supporting information
p. 5891 - 5896
(2020/08/21)
-
- Assaying RNA solvent accessibility in living cells with LASER
-
RNA molecules perform a wide variety of functions to control many cellular pathways. Critical to these roles is the ability of an RNA to fold into complex three-dimensional structures. As part of this folding, unique elements of RNA structure become more exposed or hidden to solvent and these properties are important to understand an RNAs final fold. Characterizing solvent accessibility can enable researchers to better understand the overall fold of an RNA and how it interacts with trans acting factors, such as proteins. Herein we describe the methods toward using light activated structural evaluation of RNA, or LASER, which measures purine nucleobase solvent accessibility. To date, LASER has been used inside and outside of cells to measure RNA solvent accessibility and RNA interactions with proteins.
- Feng, Chao,Spitale, Robert C.
-
p. 401 - 411
(2020/06/23)
-
- Deoxygenative Amination of Azine-N-oxides with Acyl Azides via [3 + 2] Cycloaddition
-
A transition-metal-free deoxygenative C-H amination reaction of azine-N-oxides with acyl azides is described. The initial formation of an isocyanate from the starting acyl azide via a Curtius rearrangement can trigger a [3 + 2] dipolar cycloaddition of polar N-oxide fragments to generate the aminated azine derivative. The applicability of this method is highlighted by the late-stage and sequential amination reactions of complex bioactive compounds, including quinidine and fasudil. Moreover, the direct transformation of aminated azines into various bioactive N-heterocycles illustrates the significance of this newly developed protocol.
- Ghosh, Prithwish,Han, Sang Hoon,Han, Sangil,Kim, Dongeun,Kim, In Su,Kim, Saegun,Kwon, Na Yeon,Mishra, Neeraj Kumar
-
p. 2476 - 2485
(2020/03/13)
-
- Spectroscopic Characterization of Nicotinoyl and Isonicotinoyl Nitrenes and the Photointerconversion of 4-Pyridylnitrene with Diazacycloheptatetraene
-
Recently, nicotinoyl nitrene (2) has been generated from the photodecomposition of nicotinoyl azide (1) and used as the key intermediate in probing nucleobase solvent accessibility inside cells. Following the 266 nm laser photolysis of nicotinoyl azide (1) and isonicotinoyl azide (5) in solid N2 matrices at 15 K, nicotinoyl nitrene (2) and isonicotinoyl nitrene (6) have now been identified by matrix-isolation infrared (IR) spectroscopy. Both aroyl nitrenes 2 and 6 adopt closed-shell singlet ground states stabilized by significant Nnitrene···O interactions, which is consistent with the spectroscopic analysis and calculations at the CBS-QB3 level of theory. Upon subsequent visible light irradiations, 2 (400 ± 20 nm) and 6 (532 nm) undergo rearrangement to pyridyl isocyanates 3 and 7. Further dissociation of 3 and 7 under 193 nm laser irradiation results in CO elimination and formation of ketenimines 12 and 13 via the ring opening of elusive pyridyl nitrenes 4 and 8, respectively. In addition to the IR spectroscopic identification of 8 in the triplet ground state, its reversible photointerconversion with ring expansion to diazacycloheptatetraene 9 has been observed directly. The spectroscopic identification of the nitrene intermediates was aided by calculations at the B3LYP/6-311++G(3df,3pd) level, and the mechanism for their generation in stepwise decompositions of the azides is discussed in the light of CBS-QB3 calculations.
- Liu, Qian,Qin, Yuanyuan,Lu, Yan,Wentrup, Curt,Zeng, Xiaoqing
-
p. 3793 - 3801
(2019/05/10)
-
- Visible Light-Induced Regioselective Cycloaddition of Benzoyl Azides and Alkenes to Yield Oxazolines
-
Visible light catalysis allows the regioselective synthesis of oxazolines in high yields. The mild photosensitized manifold leverages the intermolecular formation of oxazolines with a wide functional group tolerance on both benzoyl azides and alkenes part
- Bellotti, Peter,Brocus, Julien,El Orf, Fatima,Selkti, Mohamed,K?nig, Burkhard,Belmont, Philippe,Brachet, Etienne
-
supporting information
p. 6278 - 6285
(2019/05/24)
-
- Ligand Isomerism in Coordination Cages
-
Complexation reactions of palladium(II) nitrate with a set of 3-pyridyl appended nonchelating bidentate ligands possessing regioisomeric phenylene-diurea functionalities as spacers were carried out. The ligands utilized in this study are 1,1′-(1,2-phenylene)bis(3-(pyridin-3-yl)urea), L1; 1,1′-(1,3-phenylene)bis(3-(pyridin-3-yl)urea), L2; and 1,1′-(1,4-phenylene)bis(3-(pyridin-3-yl)urea), L3. The complexation reactions of the ligands (L1, L2, and L3) with palladium(II) produced single discrete isomeric cages (1, 2, and 3) of Pd2L4 formulation in each case and thereby illustrated ligand-isomerism in coordination cages. All 16 hydrogen atoms of eight urea moieties present in four ligand strands are delineated completely endohedrally in cage 1 and completely exohedrally in cage 3, whereas cage 2 exhibited half of the urea hydrogens in exohedral locations and the remaining half in endohedral locations. In addition to the variable number of solvent molecules, the cavities of cages 1 and 2 lodged four and two nitrate ions, respectively, using the endohedral (H)urea atoms (i.e., NH groups) as binding sites, whereas the cavity of 3 remained anion free. The abilities of the complexes 1-3 for adsorption of CO2 gas are demonstrated, and their behaviors are compared.
- Dasary, Hareesha,Jagan, Rajamony,Chand, Dillip Kumar
-
p. 12222 - 12231
(2018/10/02)
-
- Titanium-Promoted Cross-Coupling for the Selective Synthesis of Polysubstituted, Conjugated Amides
-
α,β-Unsaturated amides are important building blocks and are key structural elements in a number of biologically active natural products. Despite their importance and prevalence, few methods exist to prepare conjugated amides directly and modularly. To address this gap, a titanium-promoted coupling of alkynes and isocyanates has been developed. The method is highly stereoselective, producing only the E isomer with good chemoselectivity and regioselectivity (>95/5), for unsymmetrical internal alkynes that contain a steric bias. The reactive titanacyclopentene intermediate formed from the coupling of the alkyne and isocyanate was additionally reacted with various electrophiles to access tetrasubstituted enamides.
- Chenniappan, Vinoth Kumar,Rahaim, Ronald J.
-
supporting information
p. 5090 - 5093
(2016/10/14)
-
- Synthesis and biological evaluation of novel hydrogen sulfide releasing nicotinic acid derivatives
-
Twelve novel hybrids of slowly releasing hydrogen sulfide donor ADT-OH combined with nicotinic acid were synthesized. All of their structures had been confirmed by1H NMR,13C NMR and MS spectra. The target compounds were evaluated for their neuroprotective effects on hippocampal neuron HT22 cells against glutamate-induced injury at the concentrations of 1–100?μM with MTT assay, and their toxicity on HT22 cells untreated by glutamine at the concentration of 100?μM. The active compound was further investigated for its effect on ischemic infarct volume by intraperitoneal injection at 3?h after ischemia in mice models of permanent middle cerebral artery occlusion (pMCAO). The results showed that all the compounds significantly protected HT22 cells from glutamate-induced damage at most of the experimental concentrations, and had no or little neurotoxicity on normal HT22 cells at the high concentration. More importantly, compound A6 significantly reduced infarct volume in the pMCAO model. These results suggested that compound A6 may be promising for further evaluation for the intervention of cerebral ischemic injury.
- Sun, Yinxing,Zhang, Yusuo,Li, Yuyao,Cheng, Jian,Chen, Shiyu,Xiao, Yunqi,Ao, Guizhen
-
p. 5368 - 5373
(2016/10/24)
-
- The challenge of palladium-catalyzed aromatic azidocarbonylation: From mechanistic and catalyst deactivation studies to a highly efficient process
-
Azidocarbonylation of iodoarenes with CO and NaN3, a novel Heck-type carbonylation reaction, readily occurs in an organic solvent-H 2O biphasic system to furnish aroyl azides at room temperature and 1 atm. The reaction is catalyzed by Xantphos-Pd and exhibits high functional group tolerance. The catalyst deactivation product, [(Xantphos)PdI2], can be reduced in situ with PMHS to Pd(0) to regain catalytic activity. In this way, the catalyst loading has been lowered to 0.2% without any losses in selectivity at nearly 100% conversion to synthesize a series of aroyl azides in 80-90% isolated yield on a gram scale. Alternatively, the ArCON3 product can be used without isolation for further transformations in situ, e.g., to isocyanates, ureas, benzamides, and iminophosphoranes. A detailed experimental and computational study has identified two main reaction pathways for the reaction. For both routes, Ar-I oxidative addition to Pd(0) is the rate-determining step. In the presence of CO in excess, the Ar-I bond is activated by the less electron-rich Pd center of a mixed carbonyl phosphine complex. Under CO-deficient conditions, a slightly lower energy barrier pathway is followed that involves Ar-I oxidative addition to a more reactive carbonyl-free (Xantphos)Pd0 species. Mass transfer in the triphasic liquid-liquid-gas system employed for the reaction plays an important role in the competition between these two reaction channels, uniformly leading to a common aroyl azido intermediate that undergoes exceedingly facile ArCO-N 3 reductive elimination. Safety aspects of the method have been investigated.
- Miloserdov, Fedor M.,McMullin, Claire L.,Belmonte, Marta Martinez,Benet-Buchholz, Jordi,Bakhmutov, Vladimir I.,Macgregor, Stuart A.,Grushin, Vladimir V.
-
supporting information
p. 736 - 752
(2014/03/21)
-
- Photolysis and thermolysis of pyridyl carbonyl azide monolayers on single-crystal platinum
-
The photochemical and thermal reactivity of a number of acyl azide-substituted pyridine compounds, namely nicotinyl azide, isonicotinyl azide, picolinyl azide and dinicotinyl azide with investigated as saturated monolayers on a single-crystal Pt(111) surface in an ultrahigh vacuum chamber. Multilayers of the substrates exhibited a maximum rate of desorption at 270 K, above which, stable saturated monolayers formed as characterized by reflection-absorption infrared spectroscopy by observation of C=O and N 3 bands at 1700 cm-1, and 2100 and 1300 cm-1 respectively. The monolayers were stable up to 400 K. Photolysis of the monolayer (or heating above 400 K) results in the formation of the respective isocyanate intermediate after loss of nitrogen as evidenced by the appearance of a new infrared band at 2260 cm-1 with concomitant loss of the azide bands. The resulting isocyanate saturated monolayer is stable in absence of nucleophiles, but can be quenched with appropriate nucleophiles. Saturated monolayers of a number of acyl azide-substituted pyridine compounds, namely nicotinyl azide, isonicotinyl azide, picolinyl azide and dinicotinyl azide, were formed on single-crystal Pt(111) surfaces in a UHV chamber. These monolayers were characterized by RAIR and thermal programmed desorption. Photolysis or thermolysis of these saturated monolayers leads to the corresponding isocyanate via a Curtius rearrangement.
- Adkinson, Dana K.,Magri, David C.,Pitters, Jason L.,Griffiths, Keith,Norton, Peter R.,Workentin, Mark S.
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p. 1020 - 1028
(2013/09/24)
-
- Consequence of presence and absence of π-clouds at strategic locations of designed binuclear Pd(II) complexes on packing: Self-assembly of self-assembly by intermolecular locking and packing
-
Self-assembled binuclear coordination cages of general formula [Pd 2(N-N)2(L)2](X)4, 1a/b-4a/b are prepared by the combination of N,N′-bis(m-pyridyl)urea, L, with a variety of cis-protected palladium(II) components, Pd(N-N)(X)2. The cis-protecting units "N-N" employed for the synthesis of 1-4 are ethylenediamine (en), tetramethylethylenediamine (tmeda), 2,2′-bipyridine (bpy), and 1,10-phenanthroline (phen), respectively. The term "X" stands for nitrate and perchlorate for a and b, respectively. The assemblies are characterized by NMR and electrospray ionization mass spectrometry (ESI-MS) techniques, and in some cases (i.e., 1a, 2b, 3b, 4a, and 4b) the structures are confirmed by single crystal X-ray diffraction. The conformations of bound L in the crystal structures of all the Pd(II) complexes are found to be syn-syn. The influence of the presence and absence of π cloud at the cis-protecting units on the crystal packing has been studied in detail. In the packing of [Pd 2(phen)2L2](NO3)4, 4a, one unit of [Pd2(phen)2L2]4+ is associated with two other units by π-π stacking interactions thus giving a one-dimensional growth as envisioned on the basis of a design principle. In the case of [Pd2(en)2(L)2](NO3) 4, 1a, and [Pd2(tmeda)2(L)2] (ClO4)4, 2b, such packing is not observed due to the absence of π-cloud at the strategic locations, instead notable H-bonding interactions are seen. However, [Pd2(bpy)2(L) 2](ClO4)4, 3b, displays a π-π interactions using only two units of [Pd2(bpy)2(L) 2]4+(ClO4)-.
- Naranthatta, Mili C.,Das, Deepika,Tripathy, Debakanta,Sahoo, Himansu S.,Ramkumar, Venkatachalam,Chand, Dillip K.
-
p. 6012 - 6022
(2013/03/13)
-
- Palladium-catalyzed aromatic azidocarbonylation
-
Aryl iodides smoothly react with NaN3 and CO in the presence of a Pd/Xantphos catalyst to give aroyl azides (ArCON3) in 75-92 % yield. The reaction occurs under mild reaction conditions (1 atm, 20-50 °C) and exhibits high functional-group tolerance. (Xantphos=9,9-dimethyl-4,5- bis(diphenylphosphino)xanthene)
- Miloserdov, Fedor M.,Grushin, Vladimir V.
-
supporting information; experimental part
p. 3668 - 3672
(2012/05/20)
-
- Application of 2-(1H-benzotriazol-1-yl)-1,1,3,3-tetramethyluronium tetrafluoroborate (TBTU) for the synthesis of acid azides
-
Conversion of acids to acyl azides using peptide coupling agent TBTU has been demonstrated. The procedure is simple and applicable to a range of carboxylic acids under mild reaction conditions. The protocol is extended to the synthesis of urethane protect
- Naik, Shankar A.,Lalithamba,Sureshbabu, Vommina V.
-
scheme or table
p. 103 - 109
(2011/04/15)
-
- New and simple synthesis of acid azides, ureas and carbamates from carboxylic acids: Application of peptide coupling agents EDC and HBTU
-
Conversion of carboxylic acids into acid azides using peptide coupling agents, EDC and HBTU is described. The procedure is efficient, practical and applicable to a diverse range of carboxylic acids including N-protected amino acids. Using the same reagents, one-pot synthesis of ureas, dipeptidyl urea esters and carbamates from acids has also been achieved. The Royal Society of Chemistry 2010.
- Sureshbabu, Vommina V.,Lalithamba,Narendra,Hemantha
-
experimental part
p. 835 - 840
(2010/06/20)
-
- T3P (propylphosphonic anhydride) mediated conversion of carboxylic acids into acid azides and one-pot synthesis of ureidopeptides
-
A general, mild, efficient, and environmentally benign protocol, which makes use of T3P as an acid activating agent for the direct synthesis of acid azides from carboxylic acids is described. Further, the protocol is employed for the one-pot synthesis of α-ureidopeptides starting from N-protected α-amino acids.
- Basavaprabhu,Narendra,Lamani, Ravi S.,Sureshbabu, Vommina V.
-
experimental part
p. 3002 - 3005
(2010/07/10)
-
- UREA COMPOUND OR SALT THEREOF
-
[Object] To provide a compound which can be used for the treatment of a disease associated with fatty acid amide hydrolase (FAAH), particularly urinary frequency, urinary incontinence and/or overactive bladder. [Means for solution] It is confirmed that a urea compound chemical-structurally characterized by having a piperidine or piperazine ring or a salt thereof has an excellent FAAH-inhibitory activity, and thus the present invention is completed. The urea compound or its pharmaceutically acceptable salt of the present invention can increase the effective bladder capacity and ameliorate the state of urinary frequency, and is therefore useful as an agent for treating urinary frequency, urinary incontinence and/or overactive bladder.
- -
-
Page/Page column 35
(2009/06/27)
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- 1H-INDOL-1-YL-UREA COMPOUNDS
-
Compounds of formula (I): wherein: R1 and R2, which may be the same or different, represent a hydrogen atom or a linear or branched (C1-C6)alkyl group, R3 represents a hydrogen or halogen atom, a linear or branched (C1-C6)alkyl group, or a linear or branched (C1-C6)alkoxy group, Het represents a pyridyl, pyrimidinyl or piperidyl group, which are optionally substituted by one or more groups selected from halogen, linear or branched (C1-C6)alkyl and linear or branched (C1-C6)alkoxy, —represents a single bond or a double bond, their enantiomers and diastereoisomers, and also addition salts thereof with a pharmaceutically acceptable acid or base. Medicinal products containing the same which are useful in the treatment of depression, anxiety, disorders of memory in the course of aging and/or neurodegenerative diseases, and in the palliative treatment of Parkinson's disease, and for adaptation to stress.
- -
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Page/Page column 2
(2009/07/18)
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- Direct synthesis of acyl azides from carboxylic acids by the combination of trichloroacetonitrile, triphenylphosphine and sodium azide
-
Various carboxylic acids were converted into acyl azides in excellent yields by treating with trichloroacetonitrile, triphenylphosphine and sodium azide at room temperature. The reaction was applicable to the preparation of dipeptide without rearrangement.
- Kim, Joong-Gon,Jang, Doo Ok
-
experimental part
p. 2072 - 2074
(2009/04/07)
-
- Preparation of polyfunctional acyl azides
-
(Chemical Equation Presented) A general synthesis of acyl azides from the corresponding N-acyl benzotriazoles is described. The procedure affords acyl azides in good yields and avoids the use of acid activators and NO+ equivalents typically emp
- Katritzky, Alan R.,Widyan, Khalid,Kirichenko, Kostyantyn
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p. 5802 - 5804
(2008/02/09)
-
- (+)-(2R,5S)-4-[4-cyano-3-(trifluoromethyl)phenyl]-2,5-dimethyl-N-[6- (trifluoromethyl)pyridin-3-yl]piperazine-1-carboxamide (YM580) as an orally potent and peripherally selective nonsteroidal androgen receptor antagonist
-
A novel series of trans-N-aryl-2,5-dimethylpiperazine-1-carboxamide derivatives was synthesized and their androgen receptor (AR) antagonist activities and in vivo antiandrogenic effects were evaluated. Pharmacological assays indicated that compound 33 was a potent AR antagonist, and subsequent optical resolution provided (+)-(2R,5S)4-[4-cyano-3-(trifluoromethyl)phenyl]-2, 5-dimethyl-N-[6(triflouromethyl)pyridin-3-yl]piperazine-1-carboxamide (33a, YM580) which exhibited the most potent antiandrogenic activity. Unlike bicalutamide, compound 33a decreased the weight of rat ventral prostate in a dose-dependent manner (ED50 = 2.2 mg/kg/day), and induced the maximum antiandrogenic effect, comparable to that of surgical castration, without significantly affecting serum testosterone levels. Compound 33a is a promising clinical candidate for prostate cancer monotherapy.
- Kinoyama, Isao,Taniguchi, Nobuaki,Toyoshima, Akira,Nozawa, Eisuke,Kamikubo, Takashi,Imamura, Masakazu,Matsuhisa, Akira,Samizu, Kiyohiro,Kawanimani, Eiji,Niimi, Tatsuya,Hamada, Noritaka,Koutoku, Hiroshi,Furutani, Takashi,Kudoh, Masafumi,Okada, Minoru,Ohta, Mitsuaki,Tsukamoto, Shin-Ichi
-
p. 716 - 726
(2007/10/03)
-
- Synthesis and biological studies of a new series of 5- heteroarylcarbamoylaminopyrazolo[4,3-e]1,2,4-triazolo[1,5-c]pyrimidines as human A3 adenosine receptor antagonists. Influence of the heteroaryl substituent on binding affinity and molecular modeling investigations
-
Some pyrazolotriazolopyrimidines bearing different heteroarylcarbamoylamino moieties at the N5-position are described. We previously reported the synthesis of a water soluble compound with high potency and selectivity versus the human A3 adenosine receptor as antagonist, and herein we present an enlarged series of compounds related to the previously mentioned one. These compounds showed A3 adenosine receptor affinity in the nanomolar range and different levels of selectivity evaluated in radioligand binding assays at human A1, A2A, A2B, and A3 adenosine receptors. In particular, the effect of the heteroaryl substituents at the N5 position has been analyzed. This study allows us to recognize that the presence of a pyridinium moiety in this position not only increases water solubility but also improves or retains potency and selectivity at the human A3 adenosine receptors. In contrast, replacement of pyridine with different heterocycles produces loss of affinity and selectivity at the human A3 adenosine receptors. A molecular modeling study has been carried out with the aim to explain these various binding profiles.
- Pastorin, Giorgia,Da Ros, Tatiana,Bolcato, Chiara,Montopoli, Christian,Moro, Stefano,Cacciari, Barbara,Baraldi, Pier Giovanni,Varani, Katia,Borea, Pier Andrea,Spalluto, Giampiero
-
p. 1720 - 1729
(2007/10/03)
-
- DIPHENYL SUBSTITUTED CYCLOALKANES, COMPOSITIONS CONTAINING SUCH COMPOUNDS AND METHODS OF USE
-
The instant invention provides compounds of Formula (I) which are 5-lipoxygenase activating protein inhibitors. Compounds of Formula (I) are useful as anti-atherosclerotic, anti-asthmatic, anti-allergic, anti-inflammatory and cytoprotective agents.
- -
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Page/Page column 54
(2008/06/13)
-
- Pharmacophore based receptor modeling: The case of adenosine A3 receptor antagonists. An approach to the optimization of protein models
-
To design and synthesize new potent and selective antagonists of the human A3 adenosine receptor, pharmacophoric hypotheses were generated with the software Catalyst for a comprehensive set of compounds retrieved from previous literature. Three of these pharmacophores were used to drive the optimization of a molecular model of the receptor built by homology modeling. The alignment of the ligands proposed by Catalyst was then used to manually dock a set of known A3 antagonists into the binding site, and as a result, the model was able to explain the different binding mode of very active compounds with respect to less active ones and to reproduce, with good accuracy, free energies of binding. The docking highlighted that the nonconserved residue Tyr254 could play an important role for A3 selectivity, suggesting that a mutagenesis study on this residue could be of interest in this respect. The reliability of the whole approach was successfully tested by rational design and synthesis of new compounds.
- Tafi, Andrea,Bernardini, Cesare,Botta, Maurizio,Corelli, Federico,Andreini, Matteo,Martinelli, Adriano,Ortore, Gabriella,Baraldi, Pier Giovanni,Fruttarolo, Francesca,Borea, Pier Andrea,Tuccinardi, Tiziano
-
p. 4085 - 4097
(2007/10/03)
-
- Syntheses of ureas
-
The present invention provides intermediates, synthetic methods and novel urea compositions of matter.
- -
-
Page/Page column 21
(2010/02/15)
-
- DIPHENYL SUBSTITUTED CYCLOALKANES, COMPOSITIONS CONTAINING SUCH COMPOUNDS AND METHODS OF USE
-
The instant invention provides compounds of formula: (I) which are 5-lipoxygenase activating protein inhibitors: formula (I). Compounds of formula (I) are useful as anti-atherosclerotic, anti-asthmatic, anti-allergic, anti-inflammatory and cytoprotective
- -
-
-
- Nicotinoyl azide (NCA)-mediated Mitsunobu reaction: An expedient one-pot transformation of alcohols into azides
-
A practical and simple method that allows preparation of azides from alcohols is described. The process involves oxyphosphonium-type activation and it is based upon the use of nicotinoyl azide (NCA), a cheap and easily accessible azide ion source.
- Papeo, Gianluca,Posteri, Helena,Vianello, Paola,Varasi, Mario
-
p. 2886 - 2892
(2007/10/03)
-
- Propane-1,3-dione derivatives
-
Provided is a pharmaceutical composition containing a propane-1,3-dione derivative as the active ingredient, particularly a GnRH receptor antagonist. Also, provided is a propane-1,3-dione derivative having a GnRH antagonistic effect.
- -
-
Page/Page column 26
(2008/06/13)
-
- Iodine(V) reagents in organic synthesis. Dess-Martin periodinane mediated efficient one-pot oxidation of aldehydes to acyl azides
-
A mild, efficient and general method for the one-step preparation of acyl azides from aldehydes using Dess-Martin periodinane and sodium azide is described.
- Bose, D. Subhas,Reddy, A. V. Narsimha
-
p. 3543 - 3545
(2007/10/03)
-
- Potent and selective inhibitors of PDGF receptor phosphorylation. 2. Synthesis, structure activity relationship, improvement of aqueous solubility, and biological effects of 4-[4-(N-substituted (thio)carbamoyl)-1-piperazinyl]-6,7-dimethoxyquinazoline derivatives
-
4-[4-(N-Substituted (thio)carbamoyl)-1-piperazinyl]-6,7-dimethoxyquinazoline derivatives such as KN1022 are potent inhibitors of the phosphorylation of platelet derived growth factor receptor (PDGFR). Structure activity relationships in the (thio)urea moiety, the phenyl ring itself, the linker between these two moieties, and the piperazine moiety were investigated. The role of the linker was found to be quite different, where ureas yielded decreasing activity, while thioureas provided increasing activity. Cyanoguanidine as a bioisostere of thiourea and related dicyanovinyl or nitrovinyl groups were not suitable for potent activity. A hydrogen atom on the (thio)urea moiety was essential for activity. Stereochemistry was also important for inhibition of PDGFR phosphorylation. Through the modification of these moieties, benzylthiourea analogues with a small substituent on the 4-position and the 3,4-methylenedioxy group (KN734/CT52923) were found to be optimal for selective and potent activity. Replacement of the phenyl ring by heterocycles improved aqueous solubility without loss of activity and kinase selectivity. Introduction of a methyl group on 5-position of the piperazine ring and replacement by homopiperazine reduced inhibitory activity. An efficient synthetic method was also developed for 2-pyridylurea-containing analogues, via carbonylation of 2-aminopyridine with N,N′-carbonyldiimidazole. A potent analogue, KN734, inhibited smooth muscle cell proliferation and migration induced by platelet derived growth factor-BB (PDGF-BB) and suppressed neointima formation following balloon injury in rat carotid artery by oral administration. Therefore, 4-[4-(N-substituted (thio)carbamoyl)-1-piperazinyl]-6,7-dimethoxyquinazoline derivatives may be expected to have potential as therapeutic agents for the treatment of restenosis.
- Matsuno, Kenji,Nakajima, Takao,Ichimura, Michio,Giese, Neill A.,Yu, Jin-Chen,Lokker, Nathalie A.,Ushiki, Junko,Ide, Shin-ichi,Oda, Shoji,Nomoto, Yuji
-
p. 4513 - 4523
(2007/10/03)
-
- Synthesis of acyl azides from carboxylic acids using cyanuric chloride
-
A mild, efficient and general method for the preparation of acyl azides from carboxylic acids and sodium azide using cyanuric chloride is described.
- Bandgar,Pandit
-
p. 3413 - 3414
(2007/10/03)
-
- Novel antitumor 2-cyanoaziridine-1-carboxamides
-
A set of 20 2-cyanoaziridine-1-carboxamides was synthesized from 2- cyanoaziridine and appropriate isocyanates. These compounds were active against a variety of solid and hematological tumor cells in culture, including strains resistant to doxorubicin and mitoxantrone. Their potencies in these assays correlated with the lipophilicity of substituents. The N- phenyl derivative was more potent and equally effective to imexon, a cyclized 2-cyanoaziridine-1-carboxamide of clinical interest, against cloned fresh human tumors.
- Iyengar, Bhashyam S.,Dorr, Robert T.,Alberts, David S.,Hersh, Evan M.,Salmon, Sydney E.,Remers, William A.
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p. 510 - 514
(2007/10/03)
-