- 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 39
(2018/04/27)
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- Preparation of monoalkylpiperidines via the mild hydrogenation of monoalkynylpyridines
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Monoalkynylpyridines were prepared via a Sonogashira cross-coupling reaction between monoiodopyridines and alkynes. Mild hydrogenation of the obtained monoalkynylpyridines was then conducted to produce the corresponding monoalkylpiperidines in moderate to excellent yields. The hydrogenation reaction was carried out under H2 (1?atm) in the presence of 10?wt% Pd/C (5?eq) in either AcOH or MeOH at room temperature. The present mild method is therefore useful for the quick and easy preparation of monoalkylpiperidines.
- Usuki, Toyonobu,Komatsu, Akira
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supporting information
p. 2856 - 2858
(2017/06/27)
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- METHOD FOR PRODUCING PIPERIDINE COMPOUND
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PROBLEM TO BE SOLVED: To provide a method for producing a piperidine compound in an industrially convenient manner. SOLUTION: This invention relates to a method for producing a compound represented by general formula (I) or a salt thereof that includes the step of converting a pyridine compound having an alkynylene group in a side chain, by a contact hydrogenation reaction, into the compound represented by general formula (I) or a salt thereof (in the general formula (I), R1 is a hydrogen atom, a hydroxy group, or an optionally substituted alkyl group having carbon atoms of 1 or more and 20 or less). SELECTED DRAWING: None COPYRIGHT: (C)2018,JPOandINPIT
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Paragraph 0057; 0058; 0060
(2018/04/18)
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- 9H-PYRROLO-DIPYRIDINE DERIVATIVES
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The invention relates to 9H-pyrrolo-dipyridine derivatives of formula I, processes for preparing them, pharmaceutical compositions containing them and their use as radiopharmaceuticals in particular as imaging agents for the detection of Tau aggregates.
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Page/Page column 80; 81
(2016/09/22)
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- M2 Subtype preferring dibenzodiazepinone-type muscarinic receptor ligands: Effect of chemical homo-dimerization on orthosteric (and allosteric?) binding
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A series of new dibenzodiazepinone-type muscarinic receptor ligands, including two homo-dimeric compounds, was prepared. Sixteen representative compounds were characterized in equilibrium binding studies with [3H]N-methylscopolamine ([3H]NMS) at the muscarinic receptor subtype M2, and seven selected compounds were additionally investigated at M1, M3, M4 and M5 with respect to receptor subtype selectivity. The side chain of the known M2 preferring muscarinic receptor antagonist DIBA was widely varied with respect to chain length and type of the basic group (amine, imidazole, guanidine and piperazine). Most of the structural changes were well tolerated with respect to muscarinic receptor binding, determined by displacement of [3H]NMS. Compounds investigated at all subtypes shared a similar selectivity profile, which can be summarized as M2 > M1 ≈ M4 > M3 ≈ M5 (46, 50, 57, 62-64) and M2 > M1 ≈ M4 > M3 > M5 (1, 58). The homo-dimeric dibenzodiazepinone derivatives UNSW-MK250 (63) and UNSW-MK262 (64) exhibited the highest M2 receptor affinities (pIC50 = 9.0 and 9.2, respectively). At the M2 receptor a steep curve slope of -2 was found for the dimeric ligand 63, which cannot be described according to the law of mass action, suggesting a more complex mechanism of binding. In addition to equilibrium binding studies, for selected ligands, we determined pEC50,diss, an estimate of affinity to the allosteric site of M2 receptors occupied with [3H]NMS. Compounds 58 and 62-64 were capable of retarding [3H]NMS dissociation by a factor >10 (Emax,diss >92%), with highest potency (pEC50,diss = 5.56) residing in the dimeric compound 64. As the monomeric counterpart of 64 was 100 times less potent (62: pEC50,diss = 3.59), these data suggest that chemical dimerization of dibenzodiazepinone-type M receptor ligands can enhance allosteric binding.
- Keller, Max,Tr?nkle, Christian,She, Xueke,Pegoli, Andrea,Bernhardt, Günther,Buschauer, Armin,Read, Roger W.
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p. 3970 - 3990
(2015/02/19)
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- Synthesis and SAR studies of bicyclic amine series GPR119 agonists
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We disclosed a novel series of G-protein coupled receptor 119 (GPR119) agonists based on a bicyclic amine scaffold. Through the optimization of hit compound 1, we discovered that the basic nitrogen atom of bicyclic amine played an important role in GPR119 agonist activity expression and that an indanone in various bicyclic rings was suitable in this series of compounds. The indanone derivative 2 showed the effect of plasma glucose control in oGTT and scGTT in the rodent model.
- Sakairi, Masao,Kogami, Masakazu,Torii, Masafumi,Kataoka, Hiroyo,Fujieda, Hiroki,Makino, Mitsuhiro,Kataoka, Daisuke,Okamoto, Ryuji,Miyazawa, Toshiyuki,Okabe, Morio,Inoue, Megumi,Takahashi, Naoki,Harada, Satoko,Watanabe, Nobuhide
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scheme or table
p. 5123 - 5128
(2012/08/28)
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- Process for the preparation of substituted pyrimidine derivatives
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The present invention is directed to processes for the preparation of substituted pyrimidine derivatives, useful as intermediates in the synthesis of histamine H4 receptor modulators, and to intermediates in H4 modulator synthesis.
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Page/Page column 14
(2010/02/16)
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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 81-82
(2009/04/25)
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- FUSED BENZENE DERIVATIVE AND USE
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The present invention provides a compound represented by the general formula: [wherein Ring A represents an optionally substituted 5- to 8-membered ring, Ring B represents a further optionally substituted 4- to 10-membered ring, Ring C represents a further optionally substituted benzene ring, X1 represents carbon atom, X2 represents a carbon atom, an oxygen atom, etc., W represents a nitrogen atom, etc., Y11 represents a group represented by the formula CR2R3' (wherein R2 represents a hydrogen atom, a cyano group, a nitro group, etc., and R3' represents a hydrogen atom, a cyano group, a nitro group, etc., respectively), Y21 represents a group represented by the formula CR4R5' (wherein R4 represents a hydrogen atom, a cyano group, a nitro group, etc., and R5' represents a hydrogen atom, a cyano group, a nitro group, etc., respectively), etc., and R1 represents an electron-withdrawing group, respectively. The formula represents a single bond or a double bond] or a salt thereof, which is useful as an androgen receptor modulator.
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Page/Page column 80-81
(2010/02/12)
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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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- 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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- 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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