1201633-72-8Relevant articles and documents
Piperazinyl tetrahydrobenzothiazole oxime ether derivative and application thereof
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, (2020/10/04)
The invention relates to a piperazinyl tetrahydrobenzothiazole oxime ether derivative shown as a general formula (I) and application of the piperazinyl tetrahydrobenzothiazole oxime ether derivative as a bactericide. The compound represents a novel bacter
BICYCLIC HETEROARYL SUBSTITUTED COMPOUNDS
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Page/Page column 543, (2018/03/25)
Disclosed are compounds of Formula (I) to (VIII): (I) (II) (III) (IV) (V) (VI) (VII) (VIII); or a stereoisomer, tautomer, pharmaceutically acceptable salt, solvate or prodrug thereof, wherein R3 is a bicyclic heteroaryl group substituted with zero to 3 R3a; and R1, R2, R3a, R4, and n are defined herein. Also disclosed are methods of using such compounds as PAR4 inhibitors, and pharmaceutical compositions comprising such compounds. These compounds are useful in inhibiting or preventing platelet aggregation, and are useful for the treatment of a thromboembolic disorder or the primary prophylaxis of a thromboembolic disorder.
Dihydrothiazolopyridone derivatives as a novel family of positive allosteric modulators of the metabotropic glutamate 5 (mGlu5) receptor
Bartolomé-Nebreda, José Manuel,Conde-Ceide, Susana,Delgado, Francisca,Iturrino, Laura,Pastor, Joaquín,Pena, Miguel ángel,Trabanco, Andrés A.,Tresadern, Gary,Wassvik, Carola M.,Stauffer, Shaun R.,Jadhav, Satyawan,Gogi, Kiran,Vinson, Paige N.,Noetzel, Meredith J.,Days, Emily,Weaver, C. David,Lindsley, Craig W.,Niswender, Colleen M.,Jones, Carrie K.,Conn, P. Jeffrey,Rombouts, Frederik,Lavreysen, Hilde,Macdonald, Gregor J.,Mackie, Claire,Steckler, Thomas
, p. 7243 - 7259 (2013/10/21)
Starting from a singleton chromanone high throughput screening (HTS) hit, we describe a focused medicinal chemistry optimization effort leading to the identification of a novel series of phenoxymethyl-dihydrothiazolopyridone derivatives as selective positive allosteric modulators (PAMs) of the metabotropic glutamate 5 (mGlu5) receptor. These dihydrothiazolopyridones potentiate receptor responses in recombinant systems. In vitro and in vivo drug metabolism and pharmacokinetic (DMPK) evaluation allowed us to select compound 16a for its assessment in a preclinical animal screen of possible antipsychotic activity. 16a was able to reverse amphetamine-induced hyperlocomotion in rats in a dose-dependent manner without showing any significant motor impairment or overt neurological side effects at comparable doses. Evolution of our medicinal chemistry program, structure activity, and properties relationships (SAR and SPR) analysis as well as a detailed profile for optimized mGlu5 receptor PAM 16a are described.
BICYCLIC THIAZOLES AS ALLOSTERIC MODULATORS OF MGLUR5 RECEPTORS
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Page/Page column 14, (2012/10/08)
The present invention relates to novel bicyclic thiazoles which are positive allosteric modulators of the metabotropic glutamate receptor subtype 5 (“mGluR5”) and which are useful for the treatment or prevention of disorders associated with glutamate dysfunction and diseases in which the mGluR5 subtype of receptors is involved. The invention is also directed to pharmaceutical compositions comprising such compounds, to processes for preparing such compounds and compositions, and to the use of such compounds and compositions for the prevention and treatment of disorders in which mGluR5 is involved.
3-Substituted 3-(4-aryloxyaryl)-propanoic acids as GPR40 agonists
Walsh, Shawn P.,Severino, Alexandra,Zhou, Changyou,He, Jiafang,Liang, Gui-Bai,Tan, Carina P.,Cao, Jin,Eiermann, George J.,Xu, Ling,Salituro, Gino,Howard, Andrew D.,Mills, Sander G.,Yang, Lihu
scheme or table, p. 3390 - 3394 (2011/06/24)
The design, synthesis, and structure-activity relationship (SAR) for a series of β-substituted 3-(4-aryloxyaryl)propanoic acid GPR40 agonists is described. Systematic replacement of the pendant aryloxy group led to identification of potent GPR40 agonists. In order to identify candidates suitable for in vivo validation of the target, serum shifted potency and pharmacokinetic properties were determined for several compounds. Finally, further profiling of compound 7 is presented, including demonstration of enhanced glucose tolerance in an in vivo mouse model.
BICYCLIC THIAZOLES AS ALLOSTERIC MODULATORS OF MGLUR5 RECEPTORS
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Page/Page column 32, (2011/07/07)
The present invention relates to novel bicyclic thiazoles of formula (I) which are positive allosteric modulators of the metabotropic glutamate receptor subtype 5 ("mGluR5") and which are useful for the treatment or prevention of disorders associated with glutamate dysfunction and diseases in which the mGluR5 subtype of receptors is involved. The invention is also directed to pharmaceutical compositions comprising such compounds, to processes for preparing such compounds and compositions, and to the use of such compounds and compositions for the prevention and treatment of disorders in which mGluR5 is involved.
Azole derivatives as histamine H3 receptor antagonists, Part I: Thiazol-2-yl ethers
Walter,Von Coburg,Isensee,Sander,Ligneau,Camelin,Schwartz,Stark
supporting information; experimental part, p. 5879 - 5882 (2010/11/18)
Most human histamine H3 receptor (hH3R) antagonists follow a general structural blueprint, containing a basic moiety linked by a spacer to a substituted core element. In this investigation the acceptance of thiazol-2-yl ether moieties in the core region is proved with some ether derivatives showing hH3R binding affinities in the nanomolar concentration range. A diversity of structural motifs is used as substituents to enhance the in vitro hH3R binding affinity.