- Catalyst-Free Deaminative Functionalizations of Primary Amines by Photoinduced Single-Electron Transfer
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The use of pyridinium-activated primary amines as photoactive functional groups for deaminative generation of alkyl radicals under catalyst-free conditions is described. By taking advantage of the visible light absorptivity of electron donor–acceptor complexes between Katritzky pyridinium salts and either Hantzsch ester or Et3N, photoinduced single-electron transfer could be initiated in the absence of a photocatalyst. This general reactivity platform has been applied to deaminative alkylation (Giese), allylation, vinylation, alkynylation, thioetherification, and hydrodeamination reactions. The mild conditions are amenable to a diverse range of primary and secondary alkyl pyridiniums and demonstrate broad functional group tolerance.
- Wu, Jingjing,Grant, Phillip S.,Li, Xiabing,Noble, Adam,Aggarwal, Varinder K.
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supporting information
p. 5697 - 5701
(2019/03/21)
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- N-ARYL AND N-HETEROARYL PIPERIDINE DERIVATIVES AS LIVER X RECEPTOR β AGONISTS, COMPOSITIONS, AND THEIR USE
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Provided herein are certain substituted N-aryl and N-heteroaryl piperidine compounds of the formula (I) and pharmaceutically acceptable salts thereof, wherein R1, R2, R3, L, R4, L1, Q, R5 and R 6 are as defined. The said novel compounds, and pharmaceutically acceptable compositions comprising a compound thereof, may be useful as Liver X-β receptor(LXRβ) agonists, and may be useful for treating or preventing pathologies related thereto. Such pathologies include, but are not limited to, inflammatory disease and diseases characterized by defects in cholesterol and lipid metabolism, such as Alzheimer's disease.
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Page/Page column 55
(2018/04/27)
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- NOVEL BENZODIOXANE-PIPERIDINE DERIVATIVES AND THEIR THERAPEUTIC APPLICATIONS FOR TREATING NEUROPSYCHIATRIC DISORDERS
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The present invention concerns benzodioxane-piperidine with general formula I: wherein notably: R1 represents one or more identical or different substituent(s) on the benzene ring, each independently representing a hydrogen or halogen atom, or a C1-4 alkyl group, or a C1-4 alkoxy group or a C1-4 hydroxyalkyl group or a C1-4 alkylcarbonyl or an alkoxycarbonyl group or an OH group or an SO2R group with R alkyl, or a CN group, or a CF3 group, or an OCF 3 group; n=1, 2 or 3;m=0 or 1, andR2 represents one or more identical or different substituent(s) on the oxazolidinone or morpholinone ring, each independently representing: a hydrogen atom, a C1-4 alkyl group, or a C1-4 alkoxy group, or a C1-4 hydroxyalkyl group, or an alkylcarbonyl group, or an alkoxycarbonyl group, or an alkoxyphenyl group.
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Paragraph 1429-1430
(2015/12/05)
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- Synthesis and in vitro evaluation of tetrahydroisoquinolines with pendent aromatics as sigma-2 (σ2) selective ligands
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5-Bromo-N-[4-(6,7-dimethoxy-3,4-dihydro-1H-isoquinolin-2-yl)-butyl)]-2, 3-dimethoxybenzamide 1 is a potent and selective σ2 receptor ligand suitable for further development. A series of new analogues, incorporating a variety of isoquinoline and carboxylic acid moieties, linked together with either a linear or cyclic amine spacer have been synthesised and assessed for their σ1/σ2 binding affinity and selectivity. Compounds with a rigid piperidine spacer gave Ki values for the σ2 receptor between 8.7-845 nM. Changing the configuration of the methoxy groups on the isoquinoline moiety resulted in molecules with σ2Ki values of 4.4-133 nM whereas varying the length and flexibility of the carbon spaces gave σ2Ki values 0.88-15.0 nM, some of the most active, selective σ2 ligands to date. Thus, the flexibility and length of the carbon linker and the carboxylic acid moiety are confirmed to be key to the exceptional binding affinity and selectivity for this active series. Additionally, the incorporation of a halogen on selected carboxylic acid moieties provided a convenient strategy for the introduction of a radiohalogen for applications in pharmacological and imaging studies.
- Ashford, Mark E.,Nguyen, Vu H.,Greguric, Ivan,Pham, Tien Q.,Keller, Paul A.,Katsifis, Andrew
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p. 783 - 794
(2014/01/23)
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- COMPOUNDS AND COMPOSITIONS AS MODULATORS OF GPR119 ACTIVITY
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The invention provides compounds, pharmaceutical compositions comprising such compounds and methods of using such compounds to treat or prevent diseases or disorders associated with the activity of GPR119.
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Page/Page column 92
(2008/12/08)
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- [4-(Benzo[B]Thiophen-2-Yl) Pyrimidin-2-Yl]-Amine Derivatives As Ikk-Beta Inhibitors For The Treatment Of Cancer And Inflammatory Diseases
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The present invention provides compounds of Formula I: useful in the treatment of cancer and inflammatory diseases.
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Page/Page column 5-6
(2009/01/20)
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- AZAINDOLES USEFUL AS INHIBITORS OF ROCK AND OTHER PROTEIN KINASES
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The present invention relates to compounds useful as inhibitors of protein kinases. The invention also provides pharmaceutically acceptable compositions comprising said compounds and methods of using the compositions in the treatment of various disease, conditions, or disorders.
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Page/Page column 174
(2008/06/13)
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- COMPOSITIONS USEFUL AS INHIBITORS OF ROCK AND OTHER PROTEIN KINASES
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The present invention relates to compounds useful as inhibitors of protein kinases. The invention also provides pharmaceutically acceptable compositions comprising said compounds and methods of using the compositions in the treatment of various disease, conditions, or disorders.
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Page/Page column 72
(2008/06/13)
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- COMPOSITIONS USEFUL AS INHIBITORS OF ROCK AND OTHER PROTEIN KINASES
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The present invention relates to substitute thiazole and thiophene derivatives useful as inhibitors of rock and other protein kinaeses. The invention also provides pharmaceutically acceptable compositions comprising said compounds and methods of using the compositions in the treatment of various disease, conditions, or disorders, including proliferative, cardiac and neurodegenerative diseases.
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Page 118-119
(2010/02/07)
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- Synthesis of cyclic prodrugs of Aggrastat and its analogue with a modified phenylpropionic acid linker
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(formula presented) 1a, n=2; 1b, n=1 The objective of this work was to synthesize cyclic prodrugs 1a and 1b from Aggrastat 2a and its analogue 2b, respectively, to improve their membrane permeation. Cyclic prodrugs 1a and 1b were formed using an ester bond between the -COOH group of Aggrastat or its analogue and the phenylpropionic acid linker 3 and an amide bond between the piperidinylamine and the -COOH group of the linker 3, respectively, as outlined in Scheme 4.
- Song, Xiaoping,He, Henry T.,Siahaan, Teruna J.
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p. 549 - 552
(2007/10/03)
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- Structure - Activity relationships of non-imidazole H3 receptor ligands. Part 1
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SAR studies for novel non-imidazole containing H3 receptor antagonists with high potency and selectivity for rat H3 receptors are described. A high throughput screening lead, A-923, was further elaborated in a systematic manner to clarify a pharmacophore for this class of aryloxyalkyl piperazine based compounds.
- Faghih, Ramin,Dwight, Wesley,Gentles, Robert,Phelan, Kathleen,Esbenshade, Timothy A,Ireland, Lynne,Miller, Thomas R,Kang, Chae-Hee,Fox, Gerard B,Gopalakrishnan, Sujatha M,Hancock, Arthur A,Bennani, Youssef L
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p. 2031 - 2034
(2007/10/03)
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- Farnesyl protein transferase inhibitors
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Disclosed are compounds of the formula: wherein R8represents a cyclic moiety to which is bound an imodazolylalkyl group; R9represents a carbamate, urea, amide or sulfonamide group; and the remaining substituents are as defined herein. Also disclosed is a method of treating cancer and a method of inhibiting farnesyl protein transferase using the disclosed compounds.
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- 2,3-oxidosqualene-lanosterol cyclase inhibitors
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The present invention relates to piperidine derivatives useful for the treatment and/or prophylaxis of diseases which are associated with 2,3-oxidosqualene-lanosterol cyclase such as hypercholesterolemia, hyperlipemia, arteriosclerosis, vascular diseases, mycoses, gallstones, tumors and/or hyperproliferative disorders, and treatment and/or prophylaxis of impaired glucose tolerance and diabetes.
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- Integrin receptor antagonists
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Compounds of the formula (I) are disclosed which are dual fibrinogen receptor and vitronectin receptor antagonists and are useful in the treatment of atherosclerosis, in the prevention of restenosis and in the prevention of tumor metastasis and tumor growth:
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- Fused imidazopyridine derivatives as antihyperlipidemic agents
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A novel compound of the formula: wherein ring Q is an optionally substituted pyridine ring; One of R0, R1and R2is —Y0—Z0, and the other tow groups are a hydrogen, a halogen, an optionally substituted hydroxy group, a hydrocarbon group that may be an optionally substituted hydrocarbon group or an acyl group; Y0is a bond or an optionally substituted bivalent hydrocarbon group; Z0is a basic group which may be bonded via oxygen, nitrogen, —CO—, —CS—, —SO2N(R3)— (where R3is hydrogen or an optionally substituted hydrocarbon group), or S(O)n(wherein n is to 0, 1 or 2); .........is a single bond or a double bond, or a salt thereof, which has an excellent LDL receptor up-regulating, blood-lipids lowering, blood-sugar lowering and diabetic complication-ameliorating activity.
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- Rapid parallel synthesis applied to the optimization of a series of potent nonpeptide neuropeptide Y-1 receptor antagonists
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This study describes the integrated application of parallel synthesis and computational chemistry to the design of potent nonpeptide antagonists for the neuropeptide Y-1 (NPY1) receptor. A lead molecule was modeled in the active site of the NPY1 receptor, and a potentially fruitful region for analog construction was identified. Synthesis of suitable scaffolds followed by solution phase generation of a small library of analogs produced a compound with 5-fold improvement in binding over the already potent lead. This new compound was shown to be an unanticipated side product of the parallel synthesis reaction.
- Siegel, Miles G.,Chaney, Michael O.,Bruns, Robert F.,Clay, Michael P.,Schober, Douglas A.,Van Abbema, Anne M.,Johnson, Douglas W.,Cantrell, Buddy E.,Hahn, Patric J.,Hunden, David C.,Gehlert, Donald R.,Zarrinmayeh, Hamideh,Ornstein, Paul L.,Zimmerman, Dennis M.,Koppel, Gary A.
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p. 11619 - 11639
(2007/10/03)
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- Aromatic compounds containing basic and acidic termini useful as fibrinogen receptor antagonists
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This invention relates to novel compounds containing basic and acidic termini, pharmaceutical compositions containing such compounds, processes for preparing such compounds, and to methods of using these compounds, alone or in combination with other therapeutic agents, for the inhibition of platelet aggregation, as thrombolytics, and/or for the treatment of thromboembolic disorders.
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- Non-Peptide Fibrinogen Receptor Antagonists. 2. Optimization of a Tyrosine Template as a Mimic for Arg-Gly-Asp
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Inhibitors of platelet-fibrinogen binding offer an opportunity to interrupt the final, common pathway for platelet aggregation.Small molecule inhibitors of the platelet fibrinogen receptor GPIIb/IIIa were prepared and evaluated for their ability to prevent platelet aggregation.Compound 23m (L-700, 462/MK-383) inhibited in vitro platelet aggregation with an IC50 of 9 nM and demonstrated a selectivity of >24000-fold between platelet and human umbilical vein endothelial cell fibrinogen receptors.Dose-dependent inhibition of ex vivo platelet aggregation induced by ADP was achieved with iv infusions 0.1-10 μg/kg/min of 23m in anesthetized dogs, with 10 μg/kg/min completely inhibiting platelet aggregation during the entire 6 h infusion protocol.Platelet aggregatability returned rapidly after the termination of the 23m infusions.These features suggest that 23m may be useful in the treatment of arterial occlusive disorders.
- Egbertson, Melissa S.,Chang, Charles T.-C.,Duggan, Mark E.,Gould, Robert J.,Halczenko, Wasyl,et al.
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p. 2537 - 2551
(2007/10/02)
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