57260-67-0Relevant academic research and scientific papers
MONOACYLGLYCEROL LIPASE INHIBITORS
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Paragraph 0111-0112; 0141; 0153-0154; 0208-0209, (2021/09/09)
Provided are compounds of formula (I), or a pharmaceutically acceptable salt or solvate thereof: Also provided are compositions comprising compounds of formula (I). The compounds and compositions are also provided for use as medicaments, for example as medicaments useful in the treatment of a condition modulated by monoacylglycerol lipase (MAGL). Also provided are the use of compounds and compositions for the inhibition of monoacylglycerol lipase (MAGL).
Optimization of 5-substituted thiazolyl ureas and 6-substituted imidazopyridines as potential HIV-1 latency reversing agents
Blackmore, Timothy R.,Jacobson, Jonathan,Jarman, Kate E.,Lewin, Sharon R.,Nguyen, William,Purcell, Damian F.,Sabroux, Helene Jousset,Sleebs, Brad E.
, (2020/04/08)
A persistent latent reservoir of virus in CD4+ T cells is a major barrier to cure HIV. Activating viral transcription in latently infected cells using small molecules is one strategy being explored to eliminate latency. We previously described the use of a FlpIn.FM HEK293 cellular assay to identify and then optimize the 2-acylaminothiazole class to exhibit modest activation of HIV gene expression. Here, we implement two strategies to further improve the activation of viral gene expression and physicochemical properties of this class. Firstly, we explored rigidification of the central oxy-carbon linker with a variety of saturated heterocycles, and secondly, investigated bioisosteric replacement of the 2-acylaminothiazole moiety. The optimization process afforded lead compounds (74 and 91) from the 2-piperazinyl thiazolyl urea and the imidazopyridine class. The lead compounds from each class demonstrate potent activation of HIV gene expression in the FlpIn.FM HEK293 cellular assay (both with LTR EC50s of 80 nM) and in the Jurkat Latency 10.6 cell model (LTR EC50 220 and 320 nM respectively), but consequently activate gene expression non-specifically in the FlpIn.FM HEK293 cellular assay (CMV EC50 70 and 270 nM respectively) manifesting in cellular cytotoxicity. The lead compounds have potential for further development as novel latency reversing agents.
Discovery of imidazole carboxamides as potent and selective CCK1R agonists
Zhu, Cheng,Hansen, Alexa R.,Bateman, Thomas,Chen, Zhesheng,Holt, Tom G.,Hubert, James A.,Karanam, Bindhu V.,Lee, Susan J.,Pan, Jie,Qian, Su,Reddy, Vijay B.G.,Reitman, Marc L.,Strack, Alison M.,Tong, Vincent,Weingarth, Drew T.,Wolff, Michael S.,MacNeil, Doug J.,Weber, Ann E.,Duffy, Joseph L.,Edmondson, Scott D.
scheme or table, p. 4393 - 4396 (2009/04/06)
High-throughput screening revealed diaryl pyrazole 3 as a selective albeit modest cholecystokinin 1 receptor (CCK1R) agonist. SAR studies led to the discovery and optimization of a novel class of 1,2-diaryl imidazole carboxamides. Compound 44, which was profiled extensively, showed good in vivo mouse gallbladder emptying (mGBE) and lean mouse overnight food intake (ONFI) reduction activities.
Gram-scale synthesis of N-aryl- and N-aryl-N′-methylpiperazines on a novel, water-swellable, oxethane-linked poly(ethylene glycol) high-loading resin
Rudbeck, Hans Christian,Johannsen, Ib,Nielsen, Ole,Ruhland, Thomas,Sommer, Michael Bech,Tanner, David,Dancer, Robert
, p. 3456 - 3462 (2007/10/03)
A new methodology for the synthesis of N-arylpiperazines was developed using a poly(ethylene glycol)-derived solid support. The reactions proceeded in up to 60% overall yield over four steps. The scope and limitations of the method are discussed, as well as the utility of 13C gel-phase NMR spectroscopy for reaction monitoring. Georg Thieme Verlag Stuttgart.
Tetracyclic benzimidazole derivatives and combinatorial libraries thereof
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, (2008/06/13)
The present invention relates to novel tetracyclic benzimidazole derivative compounds of the following formula: wherein R1to R10have the meanings described in here. The invention further relates to combinatorial libraries containing two or more such compounds, as well as methods of preparing tetracyclic benzimidazole derivative compounds.
Modulators of dopamine neurotransmission
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, (2008/06/13)
New substituted 4-phenyl N-alkyl)-piperazine and 4-phenyl-N-alkyl)-piperidine compounds of Formula (1) wherein X is N, CH, or C, however X may only be C when the compound comprises a double bind at the dotted line; R1 is CF3, OSO2CF3, OSO2CH3, SOR7, SO2R7, COR7, CN, OR3, NO2, CONHR3, 3-thiophene, 2-thiophene, 3-furane, 2-furane, F, Cl, Br, or I; R2 is F, Cl, Br, I, CN, CF3, CH3, OCH3, OH, and NH2; R3 and R4 are independently H or a C1-C4 alkyl; R5 is a C1-C4 alkyl, an allyl, CH2SCH3, CH2CH2OCH3, CH2CH2CH2F, CH2CF3, 3,3,3-trifluoropropyl, 4,4,4-trifluorobutyl, or —(CH2)—R6; R6 is a C3-C6 cycloalkyl, 2-tetrahydrofurane, or 3-tetrahydrofurane; R7 is a C1-C3 alkyl, CF3, or N(R4)2, and pharmaceutically acceptable salts thereof are disclosed. Also pharmaceutical compositions comprising the above compounds and methods wherein the above compounds are used for treatment of disorders in the central nervous system are disclosed.
Pharmaceutically active pyrrolidine derivatives
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, (2008/06/13)
The present invention is related to pyrrolidine derivatives of formula (I). Said compounds are preferably for use as pharmaceutically active compounds. Specifically, pyrrolidine derivatives of formula (I) are useful in the treatment and/or prevention of premature labor, premature birth and dysmenorrhea. In particular, the present invention is related to pyrrolidine derivatives displaying a substantial modulatory, notably an antagonist activity of the oxytocin receptor. More preferably, said compounds are useful in the treatment and/or prevention of disease states mediated by oxytocin, including premature labor, premature birth and dysmenorrhea. The present invention is furthermore related to novel pyrrolidine derivatives as well as to methods of their preparation, wherein X is selected from the group consisting of CR6R7, NOR6, NNR6R7; A is selected from the group consisting of —(C═O)—, —(C═O)—O—, —C(═NH)—, —(C═O)—NH—, —(C═S)—NH, —SO22—, —SO2NH—, —CH2—,B is either a group —(C═O)—NR8R9 or represents a heterocyclic residue having the formula (a) wherein Q is NR10, O or S; n is an integer selected of 0, 1 or 2; Y, Z and E form together with the 2 carbons to which they are attached a 5-6 membered aryl or heteroaryl ring.
Pharmaceutically active pyrrolidine derivatives as bax inhibitors
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, (2008/06/13)
The present invention is related to new substituted pyrrolidine derivatives of formula (I). Said compounds are preferably for use as pharmaceutically active compounds. Specifically, pyrrolidine derivatives of formula (I) are useful in the treatment and/or prevention of neurodegenerative disorders, diseases associated with polygultamine tracts, epilepsy, ischemia, infertility, cardiovascular disorders renal hypoxia, hepatitis and AIDS. Said pyrrolidine derivatives display a modulatory and most notably a down-regulating-up to an inhibitory-activity with respect to the cellular death agonist Bax and/or the activation pathways leading to Bax and allows therefore to block the release of cytochrome (c). The present invention is furthermore related to novel pharmaceutically activity substituted pyrrolidine derivatives as well as to methods of their preparation, wherein X is selected from the group consisting of O, S, CRR, NOR, NNRR; A is selected from the group consisting of —(C═O)—, —(C═O)—O—, —C(═NH)—, —(C═O)—NH—, —(C═S)—NH, —SO2-, —SO2NH—; —CH2-; B is either a group —(C═O)—NRR or represents a heterocyclic residue having the formula (II) wherein Q is NR, O or S; n is an integer selected of 0, 1 or 2; Y, Z and E form together with the 2 carbons to which they are attached a 5-6 membered aryl or heteroaryl ring.
Fused heterocyclic compounds and pharmaceutical applications thereof
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, (2008/06/13)
The present invention relates to a fused heterocyclic compound of the formula (I) wherein each symbol is as defined in the specification, an optical isomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutical composition containing a compound of the formula (I), an optical isomer thereof or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable additive, and a medicament containing a compound of the formula (I), an optical isomer thereof or a pharmaceutically acceptable salt thereof. The compound of the present invention is a useful antipsychotic agent effective not only for positive symptoms centering on hallucination and delusion characteristic of the acute stage of schizophrenia, but also negative symptoms of apathy, abulia and autism. The inventive compound is expected to make a highly safe antipsychotic agent associated with less side effects, such as extrapyramidal symptoms and endocrine disturbance, which are observed when a conventional antipsychotic agent having a D2receptor blocking action is administered. Therefore, the inventive compound can be used as a therapeutic agent for the diseases such as schizophrenia.
Series of 5-[-(4-aryl-1-piperazinyl)alkyl]-2-oxazolidinone derivatives useful in the treatment of allergic conditions
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, (2008/06/13)
A method of treating allergic disorders and pharmaceutical compositions therefore are disclosed for a series of 5-[(4-aryl-1-piperazinyl)alkyl]-2-oxazolidinone derivatives of Formula I. These compounds are useful in inhibiting Type I allergic STR1 responses in a living animal and thus can be used to treat allergic phenomena such as asthma, rhinitis, atopic dermatitis, chronic hives, allergic conjunctivitis and the like.
