- MANUFACTURE OF COMPOUNDS AND COMPOSITIONS FOR INHIBITING ACTIVITY OF SHP2
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Provided herein is a method for the manufacture of a compound of Formula I or a pharmaceutically acceptable salt, acid co-crystal, hydrate or other solvate thereof, said method comprising reacting a compound of the formula II with a compound of the formula III according to the following reaction scheme, wherein LG, A, n, m and p are as defined in the Summary of the Invention, said manufacture including the manufacture and use of a compound of the formula VI, wherein R1 is a secondary amino protecting group and R5 is unsubstituted or substituted alkyl, unsubstituted or substituted cycloalkyl or unsubstituted or substituted aryl.
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- Aryl spiro compound containing formamidine as well as preparation method and application of aryl spiro compound
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The invention belongs to the field of medicinal chemistry, and particularly relates to an aryl spiro compound containing formamidine as well as a preparation method and application of the aryl spiro compound. The invention relates to three aryl spiro compounds as shown in general formulas I-III and pharmaceutically acceptable salts, enantiomers, non-isomers, tautomers, solvates, polymorphic substances or prodrugs thereof. On the basis that SHP099 is used as a lead compound, a brand new compound with guanidyl at the tail end is prepared, and the problems that an existing SHP2 inhibitor is single in structural framework and the like are solved. The aryl spiro compound has the important significance of providing many modification sites and providing a basis for later structural modification. Meanwhile, the embodiment of the invention proves that the compound has an allosteric inhibition effect on SHP2 phosphatase, and a skeleton support is provided for subsequent development of an SHP2 phosphatase inhibitor.
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- MANUFACTURE OF COMPOUNDS AND COMPOSITIONS FOR INHIBITING THE ACTIVITY OF SHP2
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The present invention relates to a method for the manufacture of a compound of Formula I or a pharmaceutically acceptable salt, acid co-crystal, hydrate or other solvate thereof, said method comprising reacting a compound of the formula II with a compound of the formula III according to the following reaction scheme: wherein LG, A, n, m and p are as defined in the Summary of the Invention.
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- PROCESS OF MANUFACTURE OF A COMPOUND FOR INHIBITING THE ACTIVITY OF SHP2
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The invention relates to a method for the manufacture of a compound of Formula I as mentioned above, or a pharmaceutically acceptable salt, acid co-crystal, hydrate or other solvate thereof, said method comprising reacting a compound of the formula II wit
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- Pyrazinothiazole compound and application thereof, and pharmaceutical composition containing pyrazinothiazole compound
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The invention discloses a pyrazinothiazole compound, an application of the pyrazinothiazole compound, and a pharmaceutical composition containing the pyrazinothiazole compound, and provides a pyrazinothiazole compound represented by a formula A or a pharmaceutically acceptable salt of the pyrazinothiazole compound. The pyrazinothiazole compound provided by the invention has relatively good SHP2 inhibitory activity.
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- Novel heterocyclic derivative capable of being used as SHP2 inhibitor
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The invention relates to a novel heterocyclic derivative capable of being used as an SHP2 inhibitor, specifically relates to a compound shown by a formula I or pharmaceutically acceptable salts thereof, further relates to a use of the compound shown by the formula I or the pharmaceutically acceptable salts thereof and a pharmaceutical composition thereof in drug preparation, and particularly relates to a use in preparation of drugs for treatment, inhibition or prevention of diseases or discomforts mediated by SHP2 activity.
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Paragraph 0383-0385
(2019/08/30)
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- FUSED AZAHETEROCYCLIC COMPOUNDS AND THEIR USE AS AMPA RECEPTOR MODULATORS
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Provided herein are compounds of Formula (I), and pharmaceutically acceptable salts, N-oxides, or solvates thereof, Also provided herein are pharmaceutical compositions comprising compounds of Formula (I) and methods of using compounds of Formula (I).
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Paragraph 0251; 0252
(2018/05/03)
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- NOVEL HETEROCYCLIC DERIVATIVES USEFUL AS SHP2 INHIBITORS
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This invention relates to certain novel pyrazine derivatives (Formula I) as SHP2 inhibitors which is shown as formula I, their synthesis and their use for treating a SHP2 mediated disorder. More particularly, this invention is directed to fused heterocyclic group derivatives useful as inhibitors of SHP2, methods for producing such compounds and methods for treating a SHP2-mediated disorder.
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Page/Page column 78
(2018/10/19)
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- Synthesis and evaluation of the anticoccidial activity of trifluoropyrido[1,2-a]pyrimidin-2-one derivatives
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Screening of our chemical library to discover new molecules exhibiting in vitro activity against the invasion of host cells by Eimeria tenella revealed a lead compound with an IC50 of 15 μM. Structure-activity relationship studies were conducted with 34 newly synthesized compounds to identify more active molecules and enhance in vitro activity against the parasite. Four compounds were more effective in inhibiting MDBK cell invasion in vitro than the lead compound.
- Silpa, Laurence,Niepceron, Alisson,Laurent, Fabrice,Brossier, Fabien,Pénichon, Mélanie,Enguehard-Gueiffier, Cécile,Abarbri, Mohamed,Silvestre, Anne,Petrignet, Julien
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p. 114 - 120
(2015/12/18)
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- Imidazo[1,2-a]pyridines: Orally active positive allosteric modulators of the metabotropic glutamate 2 receptor
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Advanced leads of an imidazopyridine series of positive allosteric modulators of the metabotropic glutamate 2 (mGlu2) receptor are reported. The optimization of in vitro ADMET and in vivo pharmacokinetic properties led to the identification of 27o. With g
- Trabanco, Andrés A.,Tresadern, Gary,MacDonald, Gregor J.,Vega, Juan Antonio,De Lucas, Ana Isabel,Matesanz, Encarnación,García, Aránzazu,Linares, María Lourdes,Alonso De Diego, Sergio A.,Alonso, José Manuel,Oehlrich, Daniel,Ahnaou, Abdelah,Drinkenburg, Wilhelmus,MacKie, Claire,Andrés, José Ignacio,Lavreysen, Hilde,Cid, José María
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experimental part
p. 2688 - 2701
(2012/06/01)
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- Regiocontrolled microwave assisted bifunctionalization of 7,8-dihalogenated imidazo[1,2-a]pyridines: A one pot double-coupling approach
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The reactivity of the 7-chloro-8-iodo- and 8-chloro-7-iodoimidazo[1,2- a]pyridines 1a-e diversely substituted on the 2 position, towards Suzuki-Miyaura, Sonogashira, and Buchwald-Hartwig cross-coupling reactions as well as cyanation was evaluated. Various methodologies are proposed to introduce aryl, heteroaryl, alkyne, amine or cyano groups in the two positions depending on the nature of the substituent present in position 2. In both series, the substitution of the iodine atom was totally regioselective and the difficulty was to substitute the chlorine atom in a second step. Until now, only hetero(aryl) groups could be introduced though Suzuki-Miyaura cross-coupling. We overcame this problem evaluating both regioisomers in parallel. The double coupling approach was also studied allowing the one pot Suzuki/Suzuki, cyanation/Sonogashira and cyanation/Buchwald reactions leading to polyfunctionnalized imidazo[1,2-a]pyridines.
- Marie, Emilie,Boucle, Sebastien,Enguehard-Gueiffier, Cecile,Gueiffier, Alain
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p. 10683 - 10707,25
(2020/09/09)
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- INDOLE AND BENZOXAZINE DERIVATIVES AS MODULATORS OF METABOTROPIC GLUTAMATE RECEPTORS
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The present invention relates to novel indole and benzoxazine derivatives which are positive allosteric modulators of the metabotropic glutamate receptor subtype 2 ("mGluR2") and which are useful for the treatment or prevention of neurological and psychiatric disorders associated with glutamate dysfunction and diseases in which the mGluR2 subtype of metabotropic receptors is involved. The invention is also directed to pharmaceutical compositions comprising such compounds, to processes to prepare such compounds and compositions, and to the use of such compounds for the prevention or treatment of neurological and psychiatric disorders and diseases in which mGluR2 is involved.
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Page/Page column 32
(2010/06/17)
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- IMIDAZO[1,2-A]PYRIDINE DERIVATIVES AND THEIR USE AS POSITIVE ALLOSTERIC MODULATORS OF MGLUR2 RECEPTORS
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The present invention relates to novel compounds, in particular novel imidazo[1,2-a]piridine derivatives according to Formula (I) wherein all radicals are as defined in the application and claims. The compounds according to the invention are positive allosteric modulators of metabotropic receptors - subtype 2 ("mGluR2") which are useful for the treatment or prevention of neurological and psychiatric disorders associated with glutamate dysfunction and diseases in which the mGluR2 subtype of metabotropic receptors is involved. In particular, such diseases are central nervous system disorders selected from the group of anxiety, schizophrenia, migraine, depression, and epilepsy. The invention is also directed to pharmaceutical compositions and processes to prepare such compounds and compositions, as well as to the use of such compounds for the prevention and treatment of such diseases in which mGluR2 is involved.
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Page/Page column 53
(2009/06/27)
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