- Controlled meta-Selective C-H Mono- And Di-Olefination of Mandelic Acid Derivatives
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Mandelic acids represent a key structural motif present in many drug molecules. Herein, we report the controlled meta-selective mono- and diolefination of mandelic acids by the careful design of the substrate and oxidant. Furthermore, free meta-functional
- Muthuraja, Perumal,Usman, Rahamdil,Sajeev, Revathy,Gopinath, Purushothaman
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supporting information
p. 6014 - 6018
(2021/08/03)
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- Expedited Kilolab Development of AZD7624 Using Kulinkovich-de Meijere Cyclopropanation
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AZD7624 is a small molecule compound developed for the treatment of chronic obstructive pulmonary disease. This study describes the lab development and kilolab manufacture of the drug substance. A small number of route options were evaluated using lab pro
- Ashok, Mithun,Ashwini, D. j.,Leuser, Helena,Malapati, Ajaya K.,Parker, Jeremy S.,Rowley, Naomi A.,Steven, Alan,Timms, Lee,Tyler, Simon N. G.,Whitmarsh, Samuel
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p. 2351 - 2366
(2021/10/21)
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- Probing the Existence of a Metastable Binding Site at the β2-Adrenergic Receptor with Homobivalent Bitopic Ligands
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Herein, we report the development of bitopic ligands aimed at targeting the orthosteric binding site (OBS) and a metastable binding site (MBS) within the same receptor unit. Previous molecular dynamics studies on ligand binding to the β2-adrenergic receptor (β2AR) suggested that ligands pause at transient, less-conserved MBSs. We envisioned that MBSs can be regarded as allosteric binding sites and targeted by homobivalent bitopic ligands linking two identical pharmacophores. Such ligands were designed based on docking of the antagonist (S)-alprenolol into the OBS and an MBS and synthesized. Pharmacological characterization revealed ligands with similar potency and affinity, slightly increased β2/β1AR-selectivity, and/or substantially slower β2AR off-rates compared to (S)-alprenolol. Truncated bitopic ligands suggested the major contribution of the metastable pharmacophore to be a hydrophobic interaction with the β2AR, while the linkers alone decreased the potency of the orthosteric fragment. Altogether, the study underlines the potential of targeting MBSs for improving the pharmacological profiles of ligands.
- Gaiser, Birgit I.,Danielsen, Mia,Marcher-R?rsted, Emil,R?pke J?rgensen, Kira,Wróbel, Tomasz M.,Frykman, Mikael,Johansson, Henrik,Br?uner-Osborne, Hans,Gloriam, David E.,Mathiesen, Jesper Mosolff,Sejer Pedersen, Daniel
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p. 7806 - 7839
(2019/09/07)
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- 4-(aminomethyl)chromane-3-ol preparation method
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The invention relates to a 4-(aminomethyl)chromane-3-ol preparation method. A purpose of the present invention is mainly to solve the technical problem that no suitable industrial synthesis method exists in the prior art. According to the present inventio
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Paragraph 0007
(2019/12/25)
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- Novel organic compounds derivatives and organic light-emitting diode therewith
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The present invention relates to an organic compound represented by the chemical formula (A) or (B) and to an organic light-emitting device comprising the same. In the chemical formulas (A) and (B), R_1 to R_14, L1, L2, Ar1 to Ar3, n and m are as described in detailed description of the invention. The first object of the present invention is to provide the organic compound having a specific structure capable of having high efficiency, low voltage and long life characteristics by using the compound in an electron transporting layer or a hole transporting layer in the organic light emitting device.COPYRIGHT KIPO 2018
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Paragraph 0550-0556
(2018/05/03)
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- NOVEL HETEROCYCLIC COMPOUNDS AND ORGANIC LIGHT-EMITTING DIODE INCLUDING THE SAME
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Disclosed are an organic heterocyclic compound represented by Chemical Formula A and an organic light-emitting diode comprising the same.
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Paragraph 0285; 0286; 0287; 0288; 0289
(2018/01/05)
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- Novel heterocyclic compounds and organic light-emitting diode including the same
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The present invention relates to a novel heterocyclic compound having long lifespan properties, low voltage driving properties, and excellent light emitting efficiency, and an organic light emitting device comprising the same and, more specifically, to an organic light emitting compound represented by any one selected from chemical formula A and chemical formula B, and an organic light emitting device comprising the same. In chemical formulas, each substituent of A1 to A4, Randprime;, Randprime;andprime;, X, Y, and Z, and n are the same as defined in the detailed description of the invention.COPYRIGHT KIPO 2016
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Paragraph 0455-0461
(2016/10/10)
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- Palladium-catalyzed three-component coupling reactions of 2-(cyanomethyl)phenol, aryl halides, and carbon monoxide
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Three-component coupling reactions of 2-(cyanomethyl)phenol, aryl halides, and carbon monoxide (CO) in orthogonal-tandem catalysis were investigated. In the reactions, 2-(cyanomethyl)phenyl esters, which are produced through Pd(PPh3)4-catalyzed alkoxycarbonylation of aryl halides with 2-(cyanomethyl)phenol, undergo cycloisomerization in situ catalyzed by Pd(PCy3)2 as a co-catalyst to give 3-acyl-2-aminobenzofurans. Palladium species with homoleptic tertiary phosphines, such as Pd(PPh3)4 and Pd(PCy3)2, can catalyze the mechanistically distinct reactions in an orthogonal-tandem manner without interference. By switching the base used in this reaction, 3-acyl-2-(N-acylamino)benzofurans were obtained as major products instead of 3-acyl-2-aminobenzofurans. Given that 2-(cyanomethyl)phenols can be synthesized from commercially available salicylic acid derivatives in two steps, the present method thus provides facile access to synthetically useful 3-acyl-2-aminobenzofurans.
- Murai, Masahito,Okamoto, Kazuhiro,Miki, Koji,Ohe, Kouichi
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p. 4432 - 4437
(2015/06/08)
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- Ionic liquid-induced conversion of methoxymethyl-protected alcohols into nitriles and iodides using [Hmim][NO3]
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This Letter reports a one-pot efficient conversion of methoxymethyl-ethers into their corresponding nitriles and iodides using the ionic liquid, 1-methyl-3H-imidazolium nitrate ([Hmim][NO3]) under microwave irradiation. A variety of products were prepared in high yields using this method.
- Noei, Jalil,Mirjafari, Arsalan
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supporting information
p. 4424 - 4426
(2014/08/05)
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- Ipso-hydroxylation of arylboronic acids and boronate esters by using sodium chlorite as an oxidant in water
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A facile and efficient procedure for the ipso-hydroxylation of arylboronic acids to phenols in water was developed. A series of electron-rich and electron-deficient arylboronic acids were smoothly ipso-hydroxylated with this protocol to afford products in excellent yields. Moreover, the protocol is amenable to boronate esters. In most cases, the phenolic products were obtained in pure form without any chromatographic purification. An efficient procedure for the ipso-hydroxylation of arylboronic acids to phenols in water is reported. A wide range of electronically varied boronic acids are smoothly ipso-hydroxylated with this protocol, which is amenable to boronate esters. The reaction strategy is facile and clean, and the products are obtained in pure form and do not require chromatographic purification. Copyright
- Gogoi, Pranjal,Bezboruah, Pranjal,Gogoi, Junali,Boruah, Romesh C.
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supporting information
p. 7291 - 7294
(2013/11/19)
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- Copper-assisted/copper-free synthesis of functionalized dibenzo[b,f]oxepins and their analogs via a one-pot tandem reaction
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A simple, convenient, and efficient method for the formation of functionalized dibenzo[b,f]oxepins and their analogs bearing both electron-donating and electron-withdrawing groups has been developed via a one-pot cascade reaction. Most starting materials are commercially available 2-(2-hydroxyphenyl)acetonitriles and 2-haloarylaldehydes. The procedure makes use of Cs2CO3 as the base, and DMF as solvent under copper-assisted/copper-free conditions. The reaction has a comprehensive group tolerance for substrates. Most of the reactions were complete within 1 h in good-to-excellent yields, and the reaction temperatures were relatively low. The protocol could be scaled up to grams without lowering the yield. A reaction mechanism was also proposed. Copyright
- Wang, Yuqin,Chen, Yanhong,He, Qian,Xie, Yuyuan,Yang, Chunhao
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p. 296 - 308
(2013/03/28)
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- New synthetic method for benzofurans from 2-(cyanomethyl)phenyl derivatives
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A convenient and mild synthetic method of synthesizing benzofuran from various 2-(cyanomethyl)phenyl carbonyl compounds under reduced oxygen conditions is reported. Nine C-2 substituted benzofurans were synthesized at 52-89%.
- Kim, Hee Jun,Seo, Jai Woong,Lee, Min Hyung,Shin, Dong Seok,Kim, Hyeong Baik,Cho, Hyeongjin,Lee, Byoung Se,Chi, Dae Yoon
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supporting information; experimental part
p. 3942 - 3947
(2012/07/13)
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- Convenient one-pot synthesis of 3-aryl-2H-chromene- 4-carbonitriles via a tandem O-alkylationknoevenagel condensation
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3-Aryl-2H-chromene-4-carbonitriles were synthesized through one-pot tandem reaction of easily available 2-(2-hydroxyphenyl)acetonitrile (1) and 2-bromo-1-arylethanones (2) under the condition of K2CO 3/dioxane. These functionalized chromenes could be useful building-blocks for estrogen receptor ligands and other related heterocycles.
- Chen, Yanhong,Xiang, Haoyue,Xie, Yuyuan,Yang, Chunhao
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experimental part
p. 1355 - 1361
(2011/06/27)
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- Microwave-promoted, one-pot conversion of alkoxymethylated protected alcohols into their corresponding nitriles, bromides, and iodides using [bmim][InCl4] as a green catalyst
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The Lewis acid room temperature ionic liquid, [bmim][InCl4], was found to be an efficient and green catalyst for the highly chemoselective and one-pot conversion of MOM- or EOM-ethers into their corresponding nitriles, bromides, and iodides under microwave irradiation. The procedures are simple, rapid, and high yielding. The catalyst exhibited a remarkable reactivity and is reusable.
- Mirjafari, Arsalan,Mohammadpoor-Baltork, Iraj,Moghadam, Majid,Tangestaninejad, Shahram,Mirkhani, Valiollah,Khosropour, Ahmad Reza
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supporting information; experimental part
p. 3274 - 3276
(2010/07/18)
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- H3PW12O40-[bmim][FeCl4]: A novel and green catalyst-medium system for microwave-promoted selective interconversion of alkoxymethyl ethers into their corresponding nitriles, bromides and iodides
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In the present work, the catalytic activity of 12-tungstophosphoric acid immobilized on [bmim][FeCl4] ionic liquid as a highly efficient and eco-friendly catalytic system for rapid and chemoselective direct conversion of MOM- or EOM-ethers into their corresponding nitriles, bromides and iodides under microwave irradiation is reported. In these reactions, the products are obtained in high yields. The catalyst exhibited remarkable reactivity and was reused several times.
- Mohammadpoor-Baltork, Iraj,Moghadam, Majid,Tangestaninejad, Shahram,Mirkhani, Valiolah,Mirjafari, Arsalan
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experimental part
p. 1468 - 1473
(2011/10/09)
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- NOVEL 1 -BENZYL-4-PIPERIDINAMINES THAT ARE USEFUL IN THE TREATMENT OF COPD AND ASTHMA
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The invention provides 1 -benzyl- 4 -piperidinamines of the general formula (I), processes for their preparation, pharmaceutical compositions containing them and their use in therapy. The compounds are useful in the treatment of respiratory diseses such a
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Page/Page column 86
(2010/11/27)
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- Inhibition of secretory phospholipase A2. 2-Synthesis and structure-activity relationship studies of 4,5-dihydro-3-(4-tetradecyloxybenzyl) -1,2,4-4H-oxadiazol-5-one (PMS1062) derivatives specific for group II enzyme
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We have recently reported the discovery of a series of specific inhibitors of human group IIA phospholipase A2 (hGIIA PLA2) to display promising in vitro and in vivo properties. Here we describe the influence of different structural modifications on the specificity and potency against hGIIA PLA2 versus porcine group IB PLA2. The SAR results, as well as the log P and pKa values of oxadiazolone determined in this work, provide important information towards the comprehension of the mode of action of this kind of compounds.
- Dong, Chang-Zhi,Ahamada-Himidi, Azali,Plocki, Stephanie,Aoun, Darina,Touaibia, Mohamed,Meddad-Bel Habich, Nadia,Huet, Jack,Redeuilh, Catherine,Ombetta, Jean-Edouard,Godfroid, Jean-Jacques,Massicot, France,Heymans, Francoise
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p. 1989 - 2007
(2007/10/03)
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- 4H-1,2-benzoxazines with electron-withdrawing substituents on the benzene ring: Synthesis and application as potent intermediates for oxygen-functionalized aromatic compounds
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A new general method for synthesizing functionalized 4H-1,2-benzoxazine derivatives is described. Although 4H-1,2-benzoxazine is one of the fundamental structure of the oxazine group, no general synthetic method for the heterocycle has been established. We found that 3-methoxycarbonyl-4H-1,2-benzoxazine was obtained in good yield when methyl 2-nitro-3-phenylpropionate was treated with an excess amount of trifluoromethanesulfonic acid. This methodology was also applicable for the synthesis of 4H-1,2-benzoxazine rings functionalized with various electron-withdrawing substituents on the benzene ring. Furthermore, we also show that the resulting 4H-1,2-benzoxazines can be used as precursors of functionalized o-quinone methides and multisubstituted phenols. This type of heterocycle can be a potent intermediate to oxygen-fuctionalized aromatic compounds. Copyright
- Nakamura, Satoshi,Uchiyama, Masanobu,Ohwada, Tomohiko
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p. 5282 - 5283
(2007/10/03)
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- A mild anionic method for generating o-quinone methides: Facile preparations of ortho-functionalized phenols
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A low-temperature method for generating o-quinone methides is described which permits facile introduction of assorted R substituents onto the aryl ring system at low temperature. The method is useful for the efficient preparation of ortho-ring-alkylated phenols.
- Jones,Van De Water,Lindsey,Hoarau,Ung,Pettus
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p. 3435 - 3441
(2007/10/03)
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- Alpha-(2-alkoxyphenyl)-alpha-alkyl-1H-1,2,4-triazole-1-propanenitriles and derivatives
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This invention relates to alpha-(2-alkoxyphenyl)-alpha-alkyl-1H-1,2,4-triazole-1-propanenitriles and derivatives, their enantiomorphs, acid addition salts and metal salt complexes. These compounds, enantiomorphs, salts and complexes are highly active broa
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- Process for the manufacture of aromatic cyanides
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The invention provides a process for the preparation of ortho- and para-hydroxybenzyl cyanides. The process of the invention comprises the reaction of an aromatic alcohol selected from ortho- and para-hydroxybenzyl alcohols with a cyanide reagent and an ester capable of esterifying the hydroxyl group of the benzyl alcohol. In a preferred form of the process there is employed a route via the reaction of an ortho- or para-hydroxybenzyl formate with a cyanide reagent preferably selected from sodium and potassium cyanides.
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- Synthesis and hydrolysis kinetics of 4-cyano-4-phenylpiperidine derivatives: A route to morphine analogs
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A description is given of a high-yield synthesis leading to various hydroxy-2 phenylacetonitriles and to various benzodihydro-2,3 furannones-2. The intermediary 12 benzylic mesylates give quantitatively the corresponding 11 chlorides by the action of hydrochlorate of triethylamine; this procedure constitutes a very rewarding and easy method for chlorinating the benzylic alcohols in two stages without isolating the intermediary. A proximate effect has been shown which makes possible the hydrolysis of certain phenylacetonitriles by dilute acetic acid. This hydrolysis becomes very rapid when these nitriles are distributed; the increase of the speed of the hydrolysis illustrates the gem dialkyle effect.
- Gervais,Anker,Chareire,Pacheco
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p. 241 - 248
(2007/10/05)
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- Immonium salts and derivatives thereof
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There are provided: novel aryloxy immonium salts, prepared by the reaction of their corresponding haloformates with amides; and phenolic compositions corresponding to the aryloxy immonium salts. These novel aryloxy immonium salts and their corresponding phenolic compositions have utility as chemical intermediates, antioxidants, stabilizers and antibacterials.
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- Process for the preparation of hydroxyphenylacetonitriles
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Hydroxyphenylacetonitriles, which are known chemical intermediates, are prepared by the reaction of hydroxybenzyl alcohols and hydrogen cyanide. A representative example is the preparation of 3-methoxy-4-hydroxyphenylacetonitrile from 3-methoxy-4-hydroxybenzyl alcohol and hydrogen cyanide.
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- Immonium salts and derivatives thereof
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There are provided: novel aryloxy immonium salts, prepared by the reaction of their corresponding haloformates with amides; and phenolic compositions corresponding to the aryloxy immonium salts. These novel aryloxy immonium salts and their corresponding phenolic compositions have utility as chemical intermediates, antioxidants, stabilizers and antibacterials.
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