- Sc(OTf)3-catalyzed bicyclization of o-alkynylanilines with aldehydes: Ring-fused 1, 2-dihydroquinolines
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A Sc(OTf)3-catalyzed cascade Prins-type cyclization reaction of o-alkynylanilines, bearing a hydroxy or amine functionality, with aldehydes affords 1, 2-dihydroquinoline derivatives having an extra fused ring efficiently under mild reaction con
- Zhu, Can,Ma, Shengming
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- Discovery and Optimization of Orally Bioavailable Phthalazone and Cinnolone Carboxylic Acid Derivatives as S1P2 Antagonists against Fibrotic Diseases
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Idiopathic pulmonary fibrosis (IPF) is a chronic and progressive lung disease. Current treatments only slow down disease progression, making new therapeutic strategies compelling. Increasing evidence suggests that S1P2 antagonists could be effective agents against fibrotic diseases. Our compound collection was mined for molecules possessing substructure features associated with S1P2 activity. The weakly potent indole hit 6 evolved into a potent phthalazone series, bearing a carboxylic acid, with the aid of a homology model. Suboptimal pharmacokinetics of a benzimidazole subseries were improved by modifications targeting potential interactions with transporters, based on concepts deriving from the extended clearance classification system (ECCS). Scaffold hopping, as a part of a chemical enablement strategy, permitted the rapid exploration of the position adjacent to the carboxylic acid. Compound 38, with good pharmacokinetics and in vitro potency, was efficacious at 10 mg/kg BID in three different in vivo mouse models of fibrotic diseases in a therapeutic setting.
- Allart, Brigitte,Auberval, Marielle,Blanc, Javier,Borgonovi, Monica,Brys, Reginald,Bucher, Denis,Christophe, Thierry,Coornaert, Beatrice,De Wachter, Maxim,Duys, Inge,El Bkassiny, Sandy,Heckmann, Bertrand,Houvenaghel, Nicolas,Jagerschmidt, Catherine,Jans, Mia,Jansen, Koen,Jaunet, Alex,Lecru, Lola,Letfus, Vatroslav,Mammoliti, Oscar,Marsais, Florence,Menet, Christel,Oste, Line,Palisse, Adeline,Poljak, Tanja,Pujuguet, Philippe,Rupcic, Renata,Saniere, Laurent,Smehil, Mario,Sonck, Kathleen,Triballeau, Nicolas,Tricarico, Giovanni,Waeckel, Ludovic,Wakselman, Emanuelle
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p. 14557 - 14586
(2021/10/20)
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- Silver-catalyzed tandem 5- And 6-endo-cyclizationsviaconcomitant yne-ol-imine activation: selective entry to 2-aryldihydrofuroquinolines
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A silver(i) catalyzed domino imination-intramolecular biheterocyclization-aromatization cascade has been developed to construct 2-aryl/-heteroaryl dihydrofuroquinolines in moderate to good yield using an aldehyde and unprotected 4-(2-aminophenyl)but-3-yn-1-ol as precursors. Sequential Ag-(i)-induced 5-endo-digcyclization of the yne-ol part and 6-endo-trigcyclization of a proposed Ag-bound imine, followed by aromatization, furnish the furoquinoline derivatives.
- Das, Prasanta,Karmakar, Swastik,Kundu, Sandip
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supporting information
p. 16112 - 16118
(2021/09/22)
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- Dibrominative Spirocyclization of 2-Butynolyl Anilides: Synthesis of gem-Dibromospirocyclic Benzo[ d][1,3]oxazines and Their Application in the Synthesis of 4 H-Furo[3,2- b]indoles
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The combination of catalytic aqueous hydrochloric acid (HCl) and N-bromosuccinimide (NBS) generated electrophilic bromine monochloride (BrCl), which readily induced spiroannulation of 2-alkynolyl anilides (n = 1-3) to form gem-dibromospirocyclic benzo[d][
- Chaisan, Nattawadee,Ruengsangtongkul, Sureeporn,Tummatorn, Jumreang,Ruchirawat, Somsak,Chainok, Kittipong,Thongsornkleeb, Charnsak
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p. 4671 - 4698
(2021/04/06)
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- NOVEL COMPOUNDS AND PHARMACEUTICAL COMPOSITIONS THEREOF FOR THE TREATMENT OF FIBROSIS
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The present invention discloses compounds according to Formula (I) Wherein R1, R2, L, A1, A2, A3, Cy and the subscript n are as defined herein. The present invention relates to antagonists compounds of sphingosine 1-phosphate (SIP) receptor, methods for their production, pharmaceutical compositions comprising the same, and methods of treatment using the same, for the prophylaxis and/or treatment of diseases involving fibrotic diseases, inflammatory diseases, respiratory diseases, autoimmune diseases, metabolic diseases, cardiovascular diseases, and/or proliferative diseases by administering the compound of the invention.
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Paragraph 0304
(2019/01/21)
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- Tandem cyclization of o-alkynylanilines with isocyanides triggered by intramolecular nucleopalladation: Access to heterocyclic fused 2-aminoquinolines
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Herein, a novel strategy for the synthesis of various heterocyclic fused 2-aminoquinolines via palladium-catalyzed tandem cyclization of o-alkynylanilines with isocyanides has been developed. This process includes trans-oxy/aminopalladation, isocyanide in
- Wu, Wanqing,Li, Meng,Zheng, Jia,Hu, Weigao,Li, Chunsheng,Jiang, Huanfeng
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supporting information
p. 6855 - 6858
(2018/06/26)
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- Ag(I)-Catalyzed Domino Cyclization-Addition Sequence with Simultaneous Carbonyl and Alkyne Activation as a Route to 2,2′-Disubstituted Bisindolylarylmethanes
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An efficient synthesis of symmetrical 3, 3′-bisindolylarylmethanes with various substituents on the indole moiety has been developed by Ag(I)-catalyzed cycloisomerization and an deoxygenative addition sequence on o-alkynylanilines and aryl aldehydes. Ag(I) is proposed to activate alkyne unit and carbonyl moiety simultaneously leading to a domino first 5-endo-dig indole annulation, addition to C=O, second indole annulation, and its dehydroxylative addition.
- Karmakar, Swastik,Das, Prasanta,Ray, Debjyoti,Ghosh, Subhankar,Chattopadhyay, Shital K.
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supporting information
p. 5200 - 5203
(2016/11/02)
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- Gold-catalyzed transformation of 2-alkynyl arylazides: Efficient access to the valuable pseudoindoxyl and indolyl frameworks
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An element of surprise: A series of functionalized 2-alkynyl arylazides has beed converted into 3-substituted indoles or 2,2-disubstituted indolin-3-ones in the presence of a gold(I) complex. Various oxygen or aryl nucleophiles can be used in this process to trap the intermediate α-imino gold carbene. The structural motifs of the products are found in a large variety of biologically active compounds and natural products. Copyright
- Wetzel, Alexander,Gagosz, Fabien
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supporting information; experimental part
p. 7354 - 7358
(2011/09/16)
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- A convenient and efficient protocol for the synthesis of 4(1H)-cinnolones, 1,4-dihydrocinnolines, and cinnolines in aqueous medium: Application for detection of nitrite ions
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3-Aryl/alkyl-4(1H)-cinnolones are obtained in one step from 2-aryl/alkylethynyl aniline by reaction with sodium nitrite and dilute hydrochloric acid via Richter cyclization. The alkyl cinnolones on reduction with Sn/HCl furnish 1,4-dihydro-3-alkylcinnolin
- Dey, Raju,Ranu, Brindaban C.
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body text
p. 8918 - 8924
(2011/11/30)
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- Aryne intermediates and a process for the preparation thereof
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There are provided aryne intermediates of formula I, useful in the manufacture of herbicidal compounds. STR1 Also provided is a method to prepare the formula I intermediates via the palladium catalyzed coupling of an o-halonitrobenzene or o-haloaniline wi
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- Aryne intermediates towards the preparation of herbicidal sulfamoyl urea and a process for their preparation
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There are provided aryne intermediates of formula I, useful in the manufacture of herbicidal compounds. Also provided is a method to prepare the formula I intermediates via the palladium catalyzed coupling of an o-halonitrobenzene or o-haloaniline with 3-
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