186790-11-4Relevant articles and documents
MONOACYLGLYCEROL LIPASE INHIBITORS
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Paragraph 0109-0110; 0141; 0151-0152; 0163-0164, (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).
Design and Synthesis of Fragment Derivatives with a Unique Inhibition Mechanism of the uPAR·uPA Interaction
Bum-Erdene, Khuchtumur,Liu, Degang,Xu, David,Ghozayel, Mona K.,Meroueh, Samy O.
supporting information, p. 60 - 66 (2021/01/12)
There is substantial interest in the development of small molecules that inhibit the tight and highly challenging protein-protein interaction between the glycophosphatidylinositol (GPI)-anchored cell surface receptor uPAR and the serine protease uPA. While preparing derivatives of a fragment-like compound that previously emerged from a computational screen, we identified compound 5 (IPR-3242), which inhibited binding of uPA to uPAR with submicromolar IC50s. The high inhibition potency prompted us to carry out studies to rule out potential aggregation, lack of stability, reactivity, and nonspecific inhibition. We designed and prepared 16 derivatives to further explore the role of each substituent. Interestingly, the compounds only partially inhibited binding of a fluorescently labeled α-helical peptide that binds to uPAR at the uPAR·uPA interface. Collectively, the results suggest that the compounds bind to uPAR outside of the uPAR·uPA interface, trapping the receptor into a conformation that is not able to bind to uPA. Additional studies will have to be carried out to determine whether this unique inhibition mechanism can occur at the cell surface.
DUAL NAV1.2/5HT2A INHIBITORS FOR TREATING CNS DISORDERS
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Paragraph 0294, (2018/03/28)
Compounds of formula I: I are disclosed, as are pharmaceutical compositions containing such compounds. Methods of treating neurological or psychiatric disorders in a patient in need are also disclosed. Such disorders include depression, bipolar disorder, pain, schizophrenia, obsessive compulsive disorder, addiction, social disorder, attention deficit hyperactivity disorder, an anxiety disorder, autism, a cognitive impairment, or a neuropsychiatric symptom such as apathy, depression, anxiety, psychosis, aggression, agitation, impulse control disorders, and sleep disorders in neurological disorders such as Alzheimer's and Parkinson's diseases.
Efficient copper-catalyzed cross-coupling of 1-Boc-piperazine with aryl iodides and its application in the synthesis of trazodone
Yong, Fui-Fong,Teo, Yong-Chua,Tan, Khee-Ngiap
supporting information, p. 5332 - 5334 (2013/09/12)
A convenient and practical strategy is developed for the cross-coupling of N-Boc protected piperazines with aryl iodides using CuBr/1,1′-bi-2- naphthol as the catalyst and K3PO4 as the base. The protocol affords N-arylated piperazine products in moderate to good yields under the optimized conditions. The application of this catalytic system to the synthesis of trazodone is also successfully demonstrated using commercially available substrates.
HETEROCYCLIC COMPOUNDS FOR THE INHIBITION OF PASK
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Page/Page column 53, (2011/04/14)
Disclosed herein are new heterocyclic compounds and compositions and their application as pharmaceuticals for the treatment of disease. Methods of inhibiting PAS Kinase (PASK) activity in a human or animal subject are also provided for the treatment of diseases such as diabetes mellitus.
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.
Parallel synthesis of N-arylpiperazines using polymer-assisted reactions
Duncton, Matthew A. J.,Roffey, Jonathan R. A.,Hamlyn, Richard J.,Adams, David R.
, p. 2549 - 2552 (2007/10/03)
A series of N-arylpiperazines were prepared in a parallel fashion using palladium-catalyzed cross-coupling, or nucleophilic aromatic displacement chemistries, and polymer-assisted sequestration and purification techniques as key steps.
Single-step conversion of N-benzyl, N-trityl and N-diphenylmethyl amines to t-butyl carbamates using polymethylhydrosiloxane
Chandrasekhar,Babu, B. Nagendra,Reddy, Ch. Raji
, p. 2057 - 2059 (2007/10/03)
t-Butyl carbamates were obtained efficiently in high yields from the corresponding N-benzyl, N-trityl and N-diphenylmethyl precursors in a single-step reductive transformation employing polymethylhydrosiloxane and di-t-butyl dicarbonate under Pd(OH)2/C catalysis.
