15224-11-0Relevant academic research and scientific papers
Chiral Cyclic Aliphatic Linkers as Building Blocks for Selective Dopamine D2or D3Receptor Agonists
Battiti, Francisco O.,Bonifazi, Alessandro,Katritch, Vsevolod,Newman, Amy Hauck,Zaidi, Saheem A.
supporting information, p. 16088 - 16105 (2021/11/16)
Linkers are emerging as a key component in regulating the pharmacology of bitopic ligands directed toward G-protein coupled receptors (GPCRs). In this study, the role of regio- and stereochemistry in cyclic aliphatic linkers tethering well-characterized primary and secondary pharmacophores targeting dopamine D2 and D3 receptor subtypes (D2R and D3R, respectively) is described. We introduce several potent and selective D2R (rel-trans-16b; D2R Ki = 4.58 nM) and D3R (rel-cis-14a; D3R Ki = 5.72 nM) agonists while modulating subtype selectivity in a stereospecific fashion, transferring D2R selectivity toward D3R via inversion of the stereochemistry around these cyclic aliphatic linkers [e.g., (-)-(1S,2R)-43 and (+)-(1R,2S)-42]. Pharmacological observations were supported with extensive molecular docking studies. Thus, not only is it an innovative approach to modulate the pharmacology of dopaminergic ligands described, but a new class of optically active cyclic linkers are also introduced, which can be used to expand the bitopic drug design approach toward other GPCRs.
Stereoselective Palladium-Catalyzed 1,3-Arylboration of Unconjugated Dienes for Expedient Synthesis of 1,3-Disubstituted Cyclohexanes
Pang, Hailiang,Wu, Dong,Cong, Hengjiang,Yin, Guoyin
, p. 8555 - 8560 (2019/09/12)
As significant pharmacophores, 1,3-disubstituted cyclohexanes are widespread in natural products and synthetic bioactive molecules. In this work, we describe a palladium-catalyzed arylboration of 1,4-cyclohexadienes, which allows expeditious access to an array of functionalized 1,3-disubstituted cyclohexanes from the readily available starting materials. Palladium catalysis enables the arylboration to proceed in a reversed regioselectivity compared with earlier nickel catalysis. The most striking feature of this protocol lies in the 1,3-regioselectivity and exclusive cis-diastereoselectivity. Intriguingly, the success of this three-component reaction does not rely on the application of dative ligands but a cheap ammonium chloride salt instead. The synthetic utility of this method is highlighted by a series of downstream stereospecific transformations and a drug molecule synthesis.
MUSCARINIC ACETYLCHOLINE M1 RECEPTOR ANTAGONISTS
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Paragraph 00329, (2020/01/08)
Provided herein are compounds which are useful as antagonists of the muscarinic acetylcholine receptor M1 (mAChR M1); synthetic methods for making the compounds; pharmaceutical compositions comprising the compounds; and methods of treating neurological and psychiatric disorders associated with muscarinic acetylcholine receptor dysfunction using the compounds and compositions.
SUBSTITUTED INDOLINE DERIVATIVES AS DENGUE VIRAL REPLICATION INHIBITORS
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Page/Page column 34, (2018/12/13)
The present invention concerns substituted indoline derivatives, methods to prevent or treat dengue viral infections by using said compounds and also relates to said compounds for use as a medicine, more preferably for use as a medicine to treat or prevent dengue viral infections. The present invention furthermore relates to pharmaceutical compositions or combination preparations of the compounds, to the compositions or preparations for use as a medicine, more preferably for the prevention or treatment of dengue viral infections. The invention also relates to processes for preparation of the compounds.
Intramolecular cyclopropylmethylation via non-classical carbocations
Skvorcova,Jirgensons
supporting information, p. 6909 - 6912 (2017/09/01)
Cyclopropyl-cyclopropyl rearrangement can be achieved selectively by intramolecular trapping of cyclopropylmethyl carbenium ions with an internal nucleophile. This can be exploited as a useful method for the introduction of a cyclopropyl group into complex molecules using readily accessible disubstituted cyclopropane intermediates.
ANTIBACTERIAL AGENTS
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Page/Page column 75, (2013/12/03)
Antibacterial compounds of formula (I) are provided, as well as stereoisomers and pharmaceutically acceptable salts thereof; pharmaceutical compositions comprising such compounds; methods of treating bacterial infections by the administration of such compounds; and processes for the preparation of such compounds.
INHIBITORS OF DIACYLGLYCEROL ACYLTRANSFERASE
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, (2011/10/04)
The present invention relates to novel heterocyclic compounds as diacylglycerol acyltransferase (“DGAT”) inhibitors, pharmaceutical compositions comprising the heterocyclic compounds and the use of the compounds for treating or preventing a cardiovascular disease, a metabolic disorder, obesity or an obesity-related disorder, diabetes, dyslipidemia, a diabetic complication, impaired glucose tolerance or impaired fasting glucose. An illustrative compound of the invention is shown below: formula (I).
NOVEL CYCLIC BENZIMIDAZOLE DERIVATIVES USEFUL ANTI-DIABETIC AGENTS
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Page/Page column 71; 72, (2011/09/30)
Novel compounds of the structural formula (I) are activators of AMP-protein kinase and are useful in the treatment, prevention and suppression of diseases mediated by the AMPK- activated protein kinase. The compounds of the present invention are useful in
RENIN INHIBITORS
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Page/Page column 33-34, (2008/12/05)
The present invention relates to disubstituted piperidinyl renin inhibitor compounds having the structure (Formula I) and their use in treating cardiovascular events and renal insufficiency.
