- Towards new neuroprotective agents: Design and synthesis of 4H-thieno[2,3-c] isoquinolin-5-one derivatives as potent PARP-1 inhibitors
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An excessive activation of poly(ADP-ribose) polymerase-1 (PARP-1), a nuclear enzyme able to catalyze the transfer of ADP-ribose from NAD to acceptor proteins, is involved in the progression of neuronal damage after brain insult. Potent and selective PARP-
- Pellicciari, Roberto,Camaioni, Emidio,Costantino, Gabriele,Marinozzi, Maura,Macchiarulo, Antonio,Moroni, Flavio,Natalini, Benedetto
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- Continuous flow synthesis of thieno[2,3-c ]isoquinolin-5(4 H)-one scaffold: A valuable source of PARP-1 inhibitors
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An efficient multistep method for the continuous flow synthesis of thieno[2,3-c]isoquinolin-5(4H)-one-A (TIQ-A), an important pharmacological tool and building block for PARP-1 inhibitors, has been developed. The synthesis involves a Suzuki coupling reaction to generate 3-phenylthiophene-2-carboxylic acid which is transformed into the corresponding acyl azide and readily cyclized by a thermal Curtius rearrangement. A statistical design of experiments (DoE) was employed as a valuable support for decision-making of further experiments enabling the development of a robust and reliable protocol for large-scale preparation. As a result, the reactions are facile, safe, and easy to scale-up. The large-scale applicability of this improved flow method was tested by conducting the reactions on multigram scale to produce the desired product in high yield and quality for biopharmacological appraisals.
- Filipponi, Paolo,Ostacolo, Carmine,Novellino, Ettore,Pellicciari, Roberto,Gioiello, Antimo
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- Visible-Light-Induced Arene C(sp 2)-H Lactonization Promoted by DDQ and tert -Butyl Nitrite
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A visible-light photocatalytic aerobic oxidative lactonization of arene C(sp 2)-H bonds proceeds in the presence of 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) and tert -butyl nitrite (TBN). Under the optimized conditions, a range of 2-arylbenzoic acids is converted into the corresponding benzocoumarin derivatives in moderate to excellent yields. This method is characterized by its atom economy, mild reaction conditions, the use of a green oxidant and metal-free catalysis.
- Chen, Bajin,Hu, Baoxiang,Hu, Xinquan,Jin, Liqun,Li, Meichao,Shen, Zhenlu,Sun, Nan,Wang, Shengpeng,Wang, Yiqing
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p. 261 - 266
(2020/02/18)
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- Ruthenium-Catalyzed C-H Arylation of Diverse Aryl Carboxylic Acids with Aryl and Heteroaryl Halides
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Ruthenium ligated to tricyclohexylphosphine or di-tert-butylbipyridine catalyzes the arylation of carboxylic acids with diverse aryl halides (iodide, bromide, and triflate; aryl and heteroaryl). In addition, arylations with 2-iodophenol formed benzochromenones, carboxylate was shown to be a stronger donor than an amide, and the arylation of a pyridine carboxylate was demonstrated. Stoichiometric studies demonstrated that the added ligand is required for reaction with the electrophile but not the C-H bond.
- Huang, Liangbin,Weix, Daniel J.
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supporting information
p. 5432 - 5435
(2016/11/04)
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- Silver-Catalyzed C(sp2)-H Functionalization/C-O Cyclization Reaction at Room Temperature
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Silver-catalyzed C(sp2)-H functionalization/C-O cyclization has been developed. The scalable reaction proceeds at room temperature in an open flask. The present method exhibits good functional-group compatibility because of the mild reaction conditions. Using a AgNO3 catalyst and a (NH4)2S2O8 oxidant in CH2Cl2/H2O solvent, various lactones are obtained in good to excellent yields. A kinetic isotope effect (KIE) study indicates that the reaction may occur via a radical process.
- Dai, Jian-Jun,Xu, Wen-Tao,Wu, Ya-Dong,Zhang, Wen-Man,Gong, Ying,He, Xia-Ping,Zhang, Xin-Qing,Xu, Hua-Jian
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p. 911 - 919
(2015/01/30)
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- New non-annulated thiophenylamides
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The invention provides novel compounds having the general formula (I) wherein R1, R2, R3, R4, R5, R6, R7, A, E and n are as described herein, compositions including the compounds and methods of using the compounds.
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Paragraph 0305; 0306
(2015/07/15)
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- NON-ANNULATED THIOPHENYLAMIDES AS INHIBITORS OF FATTY ACID BINDING PROTEINI(FABP) 4 AND/OR 5
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The invention provides novel compounds having the general formula (I), wherein R1, R2, R3, R4, R5, R6 , R7, A, E and n are as described herein, compositions including the compounds and methods of using the compounds.
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Page/Page column 81
(2014/04/03)
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- Novel quinuclidinyl heteroarylcarbamate derivatives as muscarinic receptor antagonists
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Herein, we describe the synthesis and pharmacological profiles of novel quinuclidinyl heteroarylcarbamate derivatives. Among them, the quinuclidin-4-yl thiazolylcarbamate derivative ASP9133 was identified as a promising long-acting muscarinic antagonist (LAMA) showing more selective inhibition of bronchoconstriction against salivation and more rapid onset of action in a rat model than tiotropium bromide.
- Nagashima, Shinya,Matsushima, Yuji,Hamaguchi, Hisao,Nagata, Hiroshi,Kontani, Toru,Moritomo, Ayako,Koshika, Tadatsura,Takeuchi, Makoto
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p. 3478 - 3487
(2014/06/23)
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- Thieno[2,3-c]iosquinolines for use as inhibitors of parp
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Heterocyclic derivatives, including derivatives of thieno[2,3-c]isoquinolin-3-one and their use in therapy as inhibitors of poly(ADP-ribose) polymers (PARP), for use in the prevention and treatment of tissue damage due to ischaemia and reperfusion, degene
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