- Selective Chemical Functionalization at N6-Methyladenosine Residues in DNA Enabled by Visible-Light-Mediated Photoredox Catalysis
-
Selective chemistry that modifies the structure of DNA and RNA is essential to understanding the role of epigenetic modifications. We report a visible-light-activated photocatalytic process that introduces a covalent modification at a C(sp3)-H bond in the methyl group of N6-methyl deoxyadenosine and N6-methyl adenosine, epigenetic modifications of emerging importance. A carefully orchestrated reaction combines reduction of a nitropyridine to form a nitrosopyridine spin-trapping reagent and an exquisitely selective tertiary amine-mediated hydrogen-atom abstraction at the N6-methyl group to form an α-amino radical. Cross-coupling of the putative α-amino radical with nitrosopyridine leads to a stable conjugate, installing a label at N6-methyl-adenosine. We show that N6-methyl deoxyadenosine-containing oligonucleotides can be enriched from complex mixtures, paving the way for applications to identify this modification in genomic DNA and RNA.
- Nappi, Manuel,Hofer, Alexandre,Balasubramanian, Shankar,Gaunt, Matthew J.
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supporting information
p. 21484 - 21492
(2021/01/11)
-
- Suzuki-Miyaura Cross-Couplings under Acidic Conditions
-
Suzuki-Miyaura reactions with Pd(PPh 3) 4 have been carried out using lithium N -phenylsydnone-4-carboxylate as additive, which gave best yields at pH 5.7 in a mixture of acetic acid, water, and sodium carbonate. Reaction parameters such as the Pd source, the solvent, reaction time and temperature, acid, base and carboxylate have been varied and some representative examples of the Suzuki-Miyaura reaction have been examined.
- Freese, Tyll,Kahnert, Sean-Ray,Lücke, Ana-Luiza,Mummel, Sebastian,Pruschinski, Lucas,Schmidt, Andreas
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p. 882 - 892
(2020/03/13)
-
- Transition-Metal-Free Decarboxylative Arylation of 2-Picolinic Acids with Arenes under Air Conditions
-
A facile, transition-metal-free, and direct decarboxylative arylation of 2-picolinic acids with simple arenes is described. The oxidative decarboxylative arylation of 2-picolinic acids with arenes proceeds readily via N-chloro carbene intermediates to afford 2-arylpyridines in satisfactory to good yields under transition-metal-free conditions. This new type of decarboxylative arylation is operationally simple and scalable and exhibits high functional-group tolerance. Various synthetically useful functional groups, such as halogen atoms, methoxycarbonyl, and nitro, remain intact during the decarboxylative arylation of 2-picolinic acids.
- Zhang, Xitao,Feng, Xiujuan,Zhou, Chuancheng,Yu, Xiaoqiang,Yamamoto, Yoshinori,Bao, Ming
-
supporting information
p. 7095 - 7099
(2018/11/23)
-
- METHODS OF USING INDAZOLE-3-CARBOXAMIDES AND THEIR USE AS WNT/B-CATENIN SIGNALING PATHWAY INHIBITORS
-
This disclosure features the use of one or more indazole-3-carboxamide compounds or salts or analogs thereof, in the treatment of one or more diseases or conditions independently selected from the group consisting of a tendinopathy, dermatitis, psoriasis, morphea, ichthyosis, Raynaud's syndrome, and Darier's disease; and/or for promoting wound healing. The methods include administering to a subject (e.g., a subject in need thereof) a therapeutically effective amount of one or more indazole-3-carboxamide compounds or salts or analogs thereof as described anywhere herein.
- -
-
Paragraph 0326; 0327
(2018/05/16)
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- Synthesis, Characterization, and Rapid Cycloadditions of 5-Nitro-1,2,3-triazine
-
The synthesis, characterization, and a study of the cycloaddition reactions of 5-nitro-1,2,3-triazine (3) are reported. The electron-deficient nature of 3 permits rapid cycloaddition with a variety of electron-rich dienophiles, including amidines, enamines, enol ethers, ynamines, and ketene acetals in high to moderate yields. 1H NMR studies of a representative cycloaddition reaction between 3 and an amidine revealed a remarkable reaction rate and efficiency (1 mM, 3CN, 23 °C, >95%).
- Glinkerman, Christopher M.,Boger, Dale L.
-
supporting information
p. 2628 - 2631
(2018/05/17)
-
- A Zwitterionic Palladium(II) Complex as a Precatalyst for Neat-Water-Mediated Cross-Coupling Reactions of Heteroaryl, Benzyl, and Aryl Acid Chlorides with Organoboron Reagents
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The Suzuki–Miyaura cross-coupling (SMC) reactions of several heteroaryl chlorides, benzyl chlorides, and aryl acid chlorides with (hetero)arylboron reagents have been investigated in the presence of [Pd(HL1)(PPh3)Cl2] (I) [HL1 = 3-[(2,6-diisopropylphenyl)-1-imidazolio]-2-quinoxalinide] as catalyst and K2CO3 as base in neat water. The synthesis of the heterocycle-containing biaryls required the addition of 2 mol-% of a phosphine ligand (PPh3 or X-Phos). A combination of more than 115 substrates were screened and it was found that I is a versatile catalyst that can produce heterocycle-containing biaryls, diarylmethanes, and benzophenones in moderate-to-excellent yields.
- Ramakrishna, Visannagari,Rani, Morla Jhansi,Reddy, Nareddula Dastagiri
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p. 7238 - 7255
(2018/01/01)
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- Newly-generated Al(OH)3-supported Pd nanoparticles-catalyzed Stille and Kumada coupling reactions of diazonium salts, (Het)aryl chlorides
-
A ligand-free Pd/Al(OH)3 nano-catalyst which is prepared by one-pot three-component method using Pd(PPh3)4, tetra (ethylene glycol), and aluminum tri-sec-butoxide exhibits excellent catalytic activity in Stille cross-couplings of (Het)aryl chlorides, arenediazonium tetrafluoroborate salts with phenyltributylstannane, respectively, and Kumada couplings of (Het)aryl chlorides with various Grignard reagents. More importantly, these two processes show excellent functional group compatibility with moderate to good yields and they are also versatile with respect to not only (Het)aryl chlorides, but also diazonium salts, and heteroaryl Grignard reagents. The nano-catalyst could also be recycled and reused 5 times without loss of activity and decrease of yield.
- Li, Xing,Zhu, Tingting,Shao, Zhongqi,Li, Yingjun,Chang, Honghong,Gao, Wenchao,Zhang, Yongli,Wei, Wenlong
-
supporting information
p. 69 - 75
(2015/12/23)
-
- 5-SUBSTITUTED INDAZOLE-3-CARBOXAMIDES AND PREPARATION AND USE THEREOF
-
Indazole compounds for treating various diseases and pathologies are disclosed. More particularly, the present disclosure concerns the use of an indazole compound or analogs thereof, in the treatment of disorders characterized by the activation of Wnt pathway signaling (e.g., cancer, abnormal cellular proliferation, angiogenesis, Alzheimer's disease, lung disease, fibrotic disorders, cartilage (chondral) defects, and osteoarthritis), the modulation of cellular events mediated by Wnt pathway signaling, and neurological conditions/disorders/diseases linked to overexpression of DYRK1A.
- -
-
Paragraph 1314; 1315
(2015/11/09)
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- Complete Switch of Selectivity in the C-H Alkenylation and Hydroarylation Catalyzed by Iridium: The Role of Directing Groups
-
A complete switch in the CpIr(III)-catalyzed paths between C-H olefination and hydroarylation was found to be crucially dependent on the type of directing groups. This dichotomy in product distribution was correlated to the efficiency in attaining syn-coplanarity of olefin-inserted 7-membered iridacycles. Theoretical studies support our hypothesis that the degree of flexibility of this key intermediate modulates the β-H elimination, which ultimately affords the observed chemoselectivity.
- Kim, Jiyu,Park, Sung-Woo,Baik, Mu-Hyun,Chang, Sukbok
-
supporting information
p. 13448 - 13451
(2015/11/09)
-
- Organo functionalized graphene with Pd nanoparticles and its excellent catalytic activity for Suzuki coupling reaction
-
Synthesis of well distributed palladium nanoparticles (3-7 nm) on organo di-amine functionalized graphene is reported, which demonstrated excellent catalytic activity for Suzuki coupling reaction. Organo functionalized graphene support acted as an excellent host which helped in avoiding "Ostwald ripening" i.e., preventing palladium nanoparticle sintering and because of which the catalyst as a whole showed excellent catalytic activity for Suzuki coupling reaction. The catalytic material was characterized by X-ray diffraction (XRD), Fourier-transfer infrared spectroscopy (FTIR), Raman spectra, X-ray photoelectron spectra (XPS), and Scanning electron microscope (SEM), Transmittance electron microscopy (TEM) analysis. FT-IR revealed that the organic amine functional group was successfully grafted onto the graphene oxide surface. The formation of palladium nanoparticles was confirmed by XPS techniques. The catalytic activity in the coupling reaction using idobenzene was superb with 100% conversion and 98% yield and also activity remained almost unaltered up to six cycles. Typically, an extremely high turnover frequency of 185,078 h-1 or 3,084.64 min-1 is observed in the C-C Suzuki coupling reaction using organo di-amine functionalized graphene as catalyst. Experiments were also conducted under identical conditions to prove heterogeneity of the catalyst.
- Rana, Surjyakanta,Maddila, Suresh,Yalagala, Kotaiah,Jonnalagadda, Sreekantha B.
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p. 539 - 547
(2015/10/28)
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- Cross-coupling study of iodo/chloropyridines and 2-chloroquinoline with atom-economic triarylbismuth reagents under Pd-catalysis
-
This study describes the palladium-catalyzed couplings of iodopyridines, chloropyridines, and chloroquinoline with atom-economic BiAr3 reagents in sub-stoichiometric loadings. Mono-arylations of iodo and chloropyridines produced arylpyridines i
- Rao, Maddali L.N.,Dhanorkar, Ritesh J.
-
p. 338 - 349
(2015/03/04)
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- Recyclable palladium catalyst on grapheme oxide for the C-C/C-N cross-coupling reactions of heteroaromatic sulfonates
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Abstract A well-defined heterogeneous palladium catalyst, graphene oxide grafted with PdCl2, was prepared and found to be an effective catalyst for the C-C, C-N coupling of hetero aryl sulfonates with aryl boronic acids, terminal alkynes, amines, respectively, leading to the desired coupling products in moderate to excellent yields. The catalyst was characterized by XRD, IR, SEM, TEM, XPS and ICP. It is worthy noting that this catalyst offers a number of advantages such as high stability and negligible metal leaching. It also retains good activity for at least five successive runs without any additional activation treatment, showing a better performance than the well-known commercial Pd/C catalysts. This approach would be very useful from a practical viewpoint.
- Yang, Quanlu,Quan, Zhengjun,Wu, Shang,Du, Baoxin,Wang, Mingming,Li, Peidong,Zhang, Yinpan,Wang, Xicun
-
supporting information
p. 6124 - 6134
(2015/08/03)
-
- Triarylbismuthanes as threefold aryl-transfer reagents in regioselective cross-coupling reactions with bromopyridines and quinolines
-
Cross-coupling studies using bromopyridines and bromoquinolines with triarylbismuths as threefold coupling reagents in substoichiometric amounts under Pd-catalysed conditions are disclosed. The reactivity was high with both mono- and dibromopyridyl substrates, and mono- and bis-couplings were carried out regioselectively. A library of monoaryl and diaryl pyridines was formed in high yields. A one-pot strategy provided a simple and straightforward synthesis of both symmetrical and unsymmetrical diarylpyridines. Arylations of 2-bromo- and 3-bromoquinolines were achieved with triarylbismuth reagents. This study demonstrates that triarylbismuths may be used as threefold arylating reagents for the synthesis of aryl pyridines and quinolines through couplings with bromopyridines and bromoquinolines under Pd-catalysed conditions. Copyright
- Rao, Maddali L.N.,Dhanorkar, Ritesh J.
-
supporting information
p. 5214 - 5228
(2014/10/15)
-
- INDAZOLE-3-CARBOXAMIDES AND THEIR USE AS WNT/B-CATENIN SIGNALING PATHWAY INHIBITORS
-
lndazole-3-carboxamide compounds for treating various diseases and pathologies are disclosed. More particularly, the present disclosure concerns the use of an indazole-3- carboxamide compound or analogs thereof, in the treatment of disorders characterized by the activation of Wnt pathway signaling (e.g., cancer, abnormal cellular proliferation, angiogenesis and osteoarthritis), the modulation of cellular events mediated by Wnt pathway signaling, as well as genetic diseases and neurological conditions/disorders/diseases due to mutations or dysregulation of the Wnt pathway and/or of one or more of Wnt signaling components. Also provided are methods for treating Wnt-related disease states.
- -
-
Paragraph 00294
(2013/03/28)
-
- NAPHTHALENE DERIVATIVE
-
The present invention provides compounds which can regulate VCP activity. The present invention provides the compound of formula (I) (R is as defined in the description) or oxides, esters, prodrugs, pharmaceutically acceptable salts or solvates thereof. The compounds can regulate VCP activity, and thus are useful for treating VCP-mediated diseases such as neurodegenerative diseases.
- -
-
Paragraph 0178
(2013/06/27)
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- AGENT FOR TREATMENT OF EYE DISEASES
-
The present invention provides agents effective to treat eye diseases, pharmaceutical compositions comprising them, methods for preparing pharmaceuticals for treatment of eye diseases comprising using the agents, use of the agents in manufacture of pharma
- -
-
Paragraph 0079-0080
(2013/08/15)
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- Palladium(II) catalyzed Suzuki/Sonogashira cross-coupling reactions of sulfonates: An efficient approach to C2-functionalized pyrimidines and pyridines
-
Pyrimidin-2-yl sulfonates, as a reaction partner, can be easily prepared from inexpensive commercial materials and are efficiently cross-coupled with arylboronic acids and terminal alkynes by using Pd(OAc)2-catalyzed Suzuki and Sonogashira reactions. A wide array of C2-functionalized pyrimidines have been prepared in good to excellent yields. 2-Arylpyridines and 2-(oct-1-ynyl)pyridine were also synthesized. An efficient means to synthesize expanded pyrimidin-2-yl conjugated systems was developed by using Pd(OAc) 2-catalyzed cross-coupling reaction of pyrimidin/pyridin-2-yl sulfonates with arylboronic acids and terminal alkynes. Compared with 2-chloropyrimidines, pyrimidin-2-yl sulfonates can be easily prepared from inexpensive commercial materials and the reactions are more efficient. Copyright
- Quan, Zheng-Jun,Jing, Fu-Qiang,Zhang, Zhang,Da, Yu-Xia,Wang, Xi-Cun
-
supporting information
p. 7175 - 7183
(2013/11/06)
-
- Palladium-catalyzed cross-coupling reaction of functionalized aryl- and heteroarylbismuthanes with 2-halo(or 2-Triflyl)azines and -diazines
-
The palladium-catalyzed cross-coupling of highly functionalized organobismuthanes with 2-halo(or 2-triflyl)pyridines, -pyrimidines, -pyrazines, and -pyridazines is reported. The reaction tolerates numerous functional groups, including aldehydes. The synthesis of a shelf-stable (formylphenyl)bismuth reagent and its use in a cross-coupling reaction is also described. The palladium-catalyzed cross-coupling of highly functionalized organobismuthanes with 2-halo(or 2-triflyl)pyridines, -pyrimidines, -pyrazines, and -pyridazines is reported. The reaction tolerates numerous functional groups, including aldehydes. The synthesis of a shelf-stable (formylphenyl)bismuth reagent and its use in cross-coupling reactions is also described. Copyright
- Petiot, Pauline,Gagnon, Alexandre
-
supporting information
p. 5282 - 5289
(2013/09/02)
-
- C-H arylation of pyridines: High regioselectivity as a consequence of the electronic character of C-H bonds and heteroarene ring
-
We report a new catalytic protocol for highly selective C-H arylation of pyridines containing common and synthetically versatile electron-withdrawing substituents (NO2, CN, F and Cl). The new protocol expands the scope of catalytic azine functi
- Guo, Pengfei,Joo, Jung Min,Rakshit, Souvik,Sames, Dalibor
-
supporting information; experimental part
p. 16338 - 16341
(2011/11/29)
-
- Structure-based ligand design of novel bacterial RNA polymerase inhibitors
-
Bacterial RNA polymerase (RNAP) is essential for transcription and is an antibacterial target for small molecule inhibitors. The binding region of myxopyronin B (MyxB), a bacterial RNAP inhibitor, offers the possibility of new inhibitor design. The molecular design program SPROUT has been used in conjunction with the X-ray cocrystal structure of Thermus thermophilus RNAP with MyxB to design novel inhibitors based on a substituted pyridyl-benzamide scaffold. A series of molecules, with molecular masses 350 Da, have been prepared using a simple synthetic approach. A number of these compounds inhibited Escherichia coli RNAP.
- McPhillie, Martin J.,Trowbridge, Rachel,Mariner, Katherine R.,O'Neill, Alex J.,Johnson, A. Peter,Chopra, Ian,Fishwick, Colin W. G.
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supporting information; experimental part
p. 729 - 734
(2011/11/30)
-
- Facile one-pot direct arylation and alkylation of nitropyridine N -oxides with grignard reagents
-
Facile arylation and alkylation of nitropyridine N-oxides were developed through the reactions of Grignard reagents with nitropyridine N-oxides. For the same 4-nitropyridine N-oxide, arylation occurred at the 2- (or 6-) position, whereas alkylation occurred at the 3-position in an adjustably site-selective manner. The cooperative action of the two groups was discovered in the reactions of 3-nitropyridine N-oxides. This protocol can find wide applications in building various pyridine compounds as illustrated in total syntheses of Emoxipin and Caerulomycin A and E.
- Zhang, Fang,Duan, Xin-Fang
-
supporting information; experimental part
p. 6102 - 6105
(2012/01/06)
-
- A general and highly efficient method for the construction of aryl-substituted N-heteroarenes
-
A general, simple and highly efficient method has been developed for the Pd(OAc)2-catalyzed ligand-free and aerobic Suzuki reaction of N-heteroaryl halides, which is strongly dependent on the molecular structure of solvent. A general, simple and highly efficient method has been developed for the Pd(OAc)2-catalyzed ligand-free and aerobic Suzuki reaction of N-heteroaryl halides including 2-pyridyl bromides, 3-pyridyl bromides, 3-quinolyl bromides, 5-pyrimidyl bromides and 2-pyrazyl chloride, which is strongly dependent on the molecular structure of solvent.
- Liu, Chun,Han, Na,Song, Xiaoxiao,Qiu, Jieshan
-
supporting information; experimental part
p. 5548 - 5551
(2011/02/19)
-
- NOVEL PIPERAZINE DERIVATIVES AS INHIBITORS OF STEAROYL-COA DESATURASE
-
The present invention relates to piperazine derivatives that act as inhibitors of stearoyl-CoA desaturase. The invention also relates to methods of preparing the compounds, compositions containing the compounds, and to methods of treatment using the compounds.
- -
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Page/Page column 52
(2010/07/04)
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- Use of polymer-supported phenyltin for the creation of aryl-aryl or aryl-heteroaryl bonds via Stille cross-coupling reactions
-
An insoluble polymer-supported phenyltin reagent was successfully used in Stille cross-coupling reactions with aryl- and heteroaryl-halides. Cross-coupling products were isolated in good to high yields with very low contamination by tin and palladium residues after removal of the residual supported organotin halide. The regeneration and recyclability of the supported phenyltin reagent were also examined and proved to be possible, but required palladium cleaning of the grafted polymer to be efficient along 4 cycles when Pd(PPh3)4 was used as catalyst.
- Kerric, Gaelle,Le Grognec, Erwan,Zammattio, Fran?oise,Paris, Michael,Quintard, Jean-Paul
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experimental part
p. 103 - 110
(2010/09/18)
-
- NOVEL PIPERAZINE DERIVATIVES AS INHIBITORS OF STEAROYL-CoA DESATURASE
-
The present invention relates to piperazine derivatives that act as inhibitors of stearoyl-CoA desaturase. The invention also relates to methods of preparing the compounds, compositions containing the compounds, and to methods of treatment using the compounds.
- -
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Page/Page column 25
(2009/10/01)
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- Palladium(II) complexes containing a bulky pyridinyl N-heterocyclic carbene ligand: Preparation and reactivity
-
Coordination chemistry of a pyridine imidazole-2-ylidene ligand (pyN ?C) with sterically hindered substituents toward palladium(II) metal ions has been investigated. The palladium carbene complex [(C-pyN ?C)Pd(η3-allyl)Cl] (3) is prepared via the transmetallation from the corresponding silver carbene complexes with [ClPd(η3-allyl)]2. Upon the abstraction of chloride, coordination of pyridinyl-nitrogen becomes feasible to form [C,N-(pyN ?C)Pd(η3-allyl)](BF4) (4). Ligand substitution reaction of 4 with triphenylphosphine results in the formation of [(C-pyN ?C)Pd(PPh3)(η3-allyl)](BF4)], which the pyridinyl-nitrogen donor is substituted by the phosphine. This palladium complex appears to be base sensitive. Treatment of 4 with t-butoxide causes the decomposition to yield the metal nano-particles. Furthermore, de-complexation of 4 takes place under hydrogen atmosphere to generate the carbene precursor, 1-(6-mesityl-2-picolyl)-3-mesitylimidazolium salt. Nevertheless, the palladium complex 4 shows good catalytic activity on the Suzuki-Miyaura and Mizoroki-Heck reactions.
- Wang, Chao-Yu,Liu, Yi-Hong,Peng, Shei-Ming,Chen, Jwu-Ting,Liu, Shiuh-Tzung
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p. 3976 - 3983
(2008/03/12)
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- 1,1,1-TRIFLUORO-4-PHENYL-4-METHYL-2-(1H-PYRROLO
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Compounds of Formula (IA), IB), IC), and (ID) wherein R1, R2, R3, R4, R5, and R6 are as respectively defined herein for Formula (IA), (IB), (IC), and (ID), or a tautomer, prodrug, solvate, or salt thereof; pharmaceutical compositions containing such compounds, and methods of modulating the glucocorticoid receptor function and methods of treating disease-states or conditions mediated by the glucocorticoid receptor function or characterized by inflammatory, allergic, or proliferative processes in a patient using these compounds.
- -
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Page/Page column 171
(2010/02/11)
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- SUBSTITUTED PYRAZOLES
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The invention relates to the compounds of formula (I) and the salts and solvates thereof, wherein X, R1, R2, R3, R4 and R5 are defined as in claim 1. The inventive compounds are suitable as ligands of 5 HT receptors.
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Page/Page column 26
(2008/06/13)
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- Palladium Charcoal-Catalyzed Suzuki-Miyaura Coupling to Obtain Arylpyridines and Arylquinolines
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A phosphine ligand, such as PPh3 or 2-(dicyclohexylphosphino)biphenyl, is essential for the Pd/C-catalyzed Suzuki-Miyaura coupling of halopyridines and haloquinolines, although it has been reported that the reaction of phenyl chlorides can be catalyzed by nonprereduced Pd/C without any additives. In the reactions of bromopyridines, bromoquinolines, 2-chloropyridines, and 2-chloroquinolines, PPh3 was effective enough to provide coupling products in good yields. However, in the reactions of 3-chloropyridine, 4-chloropyridine, and 6-chloroquinoline, sterically hindered 2-(dicyclohexylphosphino)biphenyl was indispensable as a ligand.
- Tagata, Tsuyoshi,Nishida, Mayumi
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p. 9412 - 9415
(2007/10/03)
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- From mutagenic to non-mutagenic nitroarenes: Effect of bulky alkyl substituents on the mutagenic activity of nitroaromatics in Salmonella typhimurium. Part II. Substituents far away from the nitro group
-
Derivatives of 4-nitrobiphenyl, 4-nitrosobiphenyl, 2-phenyl-5-nitropyridine (2-aza-4-nitrobiphenyl) and 2-nitrofluorene, bearing various alkyl substituents far away from the nitro group (4'-position in nitrobiphenyls, 7-position in 2-nitrofluorenes) were synthesised and tested for mutagenic potency in strains TA98 and TA100 of Salmonella typhimurium. In the absence of S9 in both strains, mutagenicity of all compounds decreased with increasing steric demand of the attached alkyl groups as, e.g., for the 4-nitrobiphenyl series in the order 4'-H>4'-Me>4'-Et>4'-nBu>4'-iPr>4'-tBu>4'-Ad (Ad=adamantyl). Changes of the molecular shape from 'planar' to non-planar caused by the bulk of the introduced substituents (without influencing the twisting of the nitro substituent or the phenyl rings in the biphenyl compounds) may be responsible for this effect by interfering with an efficient intercalation into DNA.A comparison between experimental and theoretical values as calculated from recently developed equations (QSAR) confirmed our previous results (see the preceding paper) that mutagenicity of alkyl-substituted nitroaromatics cannot be predicted by hydrophobicity and LUMO-energies alone without including steric parameters. Copyright (C) 2000 Elsevier Science B.V.
- Klein, Markus,Erdinger, Lothar,Boche, Gernot
-
-
- Biarylcarbamoylindolines are novel and selective 5-HT(2C) receptor inverse agonists: Identification of 5-methyl-1-[[2-[(2-methyl-3- pyridyl)oxy]5-pyridyl]carbamoyl]-6-trifluoromethylindoline (SB-243213) as a potential antidepressant/anxiolytic agent
-
The evolution, synthesis, and biological activity of a novel series of 5-HT(2C) receptor inverse agonists are reported. Biarylcarbamoylindolines have been identified with excellent 5-HT(2C) affinity and selectivity over 5- HT(2A) receptors. In addition, (pyridyloxypyridyl)carbamoylindolines have been discovered with additional selectivity over the closely related 5-HT(2B) receptor. Compounds from this series are inverse agonists at the human cloned 5-HT(2C) receptor, completely abolishing basal activity in a functional assay. The new series have reduced P450 inhibitory liability compared to a previously described series of 1-(3-pyridylcarbamoyl)indolines (Bromidge et al. J. Med. Chem. 1998, 41, 1598) from which they evolved. Compounds from this series showed excellent oral activity in a rat mCPP hypolocomotion model and in animal models of anxiety. On the basis of their favorable biological profile, 32 (SB-228357) and 40 (SB-243213) have been selected for further evaluation to determine their therapeutic potential for the treatment of CNS disorders such as depression and anxiety.
- Bromidge, Steven M.,Dabbs, Steven,Davies, David T.,Davies, Susannah,Duckworth, D. Malcolm,Forbes, Ian T.,Gaster, Laramie M.,Ham, Peter,Jones, Graham E.,King, Frank D.,Mulholland, Keith R.,Saunders, Damian V.,Wyman, Paul A.,Blaney, Frank E.,Clarke, Stephen E.,Blackburn, Thomas P.,Holland, Vicky,Kennett, Guy A.,Lightowler, Sean,Middlemiss, Derek N.,Trail, Brenda,Riley, Graham J.,Wood, Martyn D.
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p. 1123 - 1134
(2007/10/03)
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- The palladium catalysed Suzuki coupling of 2- and 4-chloropyridines
-
The Suzuki coupling of 2- and 4-chloropyridines with arylboronic acids is successfully performed under Pd(PPh3)4 catalysis. Moderate to good yields are obtained with 4-chloropyridines while 2-chloropyridines give excellent yields. The corresponding pyridine N-oxides react in the same manner. An easy and cheap access to arylpyridines, a class of compound with medicinal interest, is thus achieved.
- Lohse, Olivier,Thevenin, Philippe,Waldvogel, Erwin
-
-
- Reusable polymer-supported palladium catalysts: An alternative to tetrakis(triphenylphosphine)palladium in the suzuki cross-coupling reaction
-
The Suzuki cross-coupling reaction of a boronic acid and a bromoaromatic requires palldium catalysis. Almost identical yields were obtained in the usual conditions, with 30 mequiv. of Pd(PPh3)4, and with 2 mequiv of a polymer-supported catalyst, which was easily prepared in two steps from Merrified polymer. Recovery and reuse of the catalyst is easy, and only 0.60% of the initial amount of palladium is lost during a reaction.
- Fenger, Isabelle,Le Drian, Claude
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p. 4287 - 4290
(2007/10/03)
-