- PIPERAZINE DERIVATIVES AS MAGL INHIBITORS
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The invention provides new heterocyclic compounds having general Formula (I), or a pharmaceutically acceptable salt thereof, wherein R1, R2, X, Y1 and Y2 are as described herein, compositions including the compounds, processes of manufacturing the compounds and methods of using the compounds.
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Page/Page column 218; 219
(2019/05/02)
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- Mtb PKNA/PKNB Dual Inhibition Provides Selectivity Advantages for Inhibitor Design to Minimize Host Kinase Interactions
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Drug resistant tuberculosis (TB) infections are on the rise and antibiotics that inhibit Mycobacterium tuberculosis through a novel mechanism could be an important component of evolving TB therapy. Protein kinase A (PknA) and protein kinase B (PknB) are both essential serine-threonine kinases in M. tuberculosis. Given the extensive knowledge base in kinase inhibition, these enzymes present an interesting opportunity for antimycobacterial drug discovery. This study focused on targeting both PknA and PknB while improving the selectivity window over related mammalian kinases. Compounds achieved potent inhibition (Ki ≈ 5 nM) of both PknA and PknB. A binding pocket unique to mycobacterial kinases was identified. Substitutions that filled this pocket resulted in a 100-fold differential against a broad selection of mammalian kinases. Reducing lipophilicity improved antimycobacterial activity with the most potent compounds achieving minimum inhibitory concentrations ranging from 3 to 5 μM (1-2 μg/mL) against the H37Ra isolate of M. tuberculosis.
- Wang, Tiansheng,Bemis, Guy,Hanzelka, Brian,Zuccola, Harmon,Wynn, Michael,Moody, Cameron Stuver,Green, Jeremy,Locher, Christopher,Liu, Aixiang,Gao, Hongwu,Xu, Yuzhou,Wang, Shaohui,Wang, Jie,Bennani, Youssef L.,Thomson, John A.,Müh, Ute
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supporting information
p. 1224 - 1229
(2017/12/26)
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- SUBSTITUTED QUINAZOLINE COMPOUNDS AND PREPARATION AND USES THEREOF
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The present invention relates quinazolinone compounds of Formula (I), as well as their preparation and uses, and further relates pharmaceutical compositions comprising these compounds and their uses; wherein the compounds or pharmaceutical compositions disclosed herein can be used for antagonizing the orexin receptor. The present invention also relates to uses of the compounds or pharmaceutical compositions in treating or preventing neurological and psychiatric disorders and diseases of the central nervous system in mammals, especially in humans.
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Page/Page column 52; 53; 58
(2017/03/08)
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- Octahydropyrrole[3, 4-c]pyrrole derivative and using method and application thereof
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The invention relates to an ctahydropyrrole[3, 4-c]pyrrole derivative and a using method and application thereof. A compound and a drug composition containing the same are used for resisting orexin receptors. The invention further relates to methods of pr
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Paragraph 0190; 0253; 0263; 0264
(2018/02/04)
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- Substituted piperazine compounds, application method and applications thereof
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The invention discloses substituted piperazine compounds, an application method and applications thereof. Specifically, the invention relates to piperazine compounds and pharmaceutical compositions thereof for inhibiting reuptake of 5-hydroxytryptamine and/or stimulation of 5-HT1A acceptor. The invention also relates to a preparation method of the compounds and pharmaceutical compositions thereof, and an application of the compounds and pharmaceutical compositions thereof in the treatment of central nervous system dysfunction.
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Paragraph 0311; 0312; 0313; 0314; 0352; 0353; 0354; 0355
(2016/10/09)
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- Discovery of alogliptin: A potent, selective, bioavailable, and efficacious inhibitor of dipeptidyl peptidase IV
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Alogliptin is a potent, selective inhibitor of the serine protease dipeptidyl peptidase IV (DPP-4). Herein, we describe the structure-based design and optimization of alogliptin and related quinazolinone-based DPP-4 inhibitors. Following an oral dose, these noncovalent inhibitors provide sustained reduction of plasma DPP-4 activity and a lowering of blood glucose in animal models of diabetes. Alogliptin is currently undergoing phase 111 trials in patients with type 2 diabetes.
- Feng, Jun,Zhang, Zhiyuan,Wallace, Michael B.,Stafford, Jeffrey A.,Kaldor, Stephen W.,Kassel, Daniel B.,Navre, Marc,Shi, Lihong,Skene, Robert J.,Asakawa, Tomoko,Takeuchi, Koji,Xu, Rongda,Webb, David R.,Gwaltney II, Stephen L.
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p. 2297 - 2300
(2008/02/05)
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- Synthesis and antihyperglycemic activity of suitably functionalized 3H-quinazolin-4-ones
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A series of 2-sec-amino-3H-quinazolin-4-ones (4a-p) and 4-sec-amino-2-chloroquinazolines (5a-b) have been synthesized by nucleophilic substitution reaction of 2-chloro-4(3H)-quinazolones (3) and 2,4-dichloroquinazolines (2) with amines, respectively. Most of the synthesized compounds were evaluated for antihyperglycemic activity but only 4a,b,d,j,o displayed significant reduction in blood glucose level in streptozotocin and sucrose loaded rat models.
- Ram, Vishnu Ji,Farhanullah,Tripathi, Brajendra K.,Srivastava, Arvind K.
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p. 2439 - 2444
(2007/10/03)
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- Substituted phenylamine- and phenyloxy-quinazolines as herbicides
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The invention concerns novel compounds of the formula I STR1 The compounds are herbicides and in further embodiments the invention provides: processes for the preparation of compounds of formula I; intermediates useful in the preparation of compounds of formula I; compositions containing as active ingredient compounds of formula I; and processes for severely damaging or killing unwanted plants by applying to the plants or to the growth medium of the plants an effective amount of a compound of formula I.
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