- RET INHIBITORS, PHARMACEUTICAL COMPOSITIONS AND USES THEREOF
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Provided herein are a RET inhibitor, a pharmaceutical composition thereof and uses thereof. In particular, provided is a compound having Formula (I) or a stereoisomer, a geometric isomer, a tautomer, an N-oxide, a solvate, a metabolite, a pharmaceutically acceptable salt or a prodrug thereof. Provided is a pharmaceutical composition comprising the compound, and uses of the compound and pharmaceutical composition thereof for the preparation of a medicament, in particular for treatment and prevention of RET-related diseases and conditions, including cancer, irritable bowel syndrome, and/or pain associated with irritable bowel syndrome.
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Paragraph 00392; 00446
(2020/07/06)
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- RET INHIBITORS, PHARMACEUTICAL COMPOSITIONS AND USES THEREOF
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Provided herein are a RET inhibitor, a pharmaceutical composition thereof and uses thereof. In particular, provided is a compound having Formula (I) or a stereoisomer, a geometric isomer, a tautomer, an N-oxide, a solvate, a metabolite, a pharmaceutically acceptable salt or a prodrug thereof. Provided is a pharmaceutical composition comprising the compound, and uses of the compound and pharmaceutical composition thereof for the preparation of a medicament, in particular for treatment and prevention of RET-related diseases and conditions, including cancer, irritable bowel syndrome, and/or pain associated with irritable bowel syndrome.
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Paragraph 00230; 00627
(2020/07/05)
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- Chemoselective Hydrogenation of Alkynes to (Z) -Alkenes Using an Air-Stable Base Metal Catalyst
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A highly selective hydrogenation of alkynes using an air-stable and readily available manganese catalyst has been achieved. The reaction proceeds under mild reaction conditions and tolerates various functional groups, resulting in (Z)-alkenes and allylic alcohols in high yields. Mechanistic experiments suggest that the reaction proceeds via a bifunctional activation involving metal-ligand cooperativity.
- Zubar, Viktoriia,Sklyaruk, Jan,Brzozowska, Aleksandra,Rueping, Magnus
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supporting information
p. 5423 - 5428
(2020/07/24)
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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 0057-0059
(2018/04/18)
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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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- The insulin secretory action of novel polycyclic guanidines: Discovery through open innovation phenotypic screening, and exploration of structure-activity relationships
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We report the discovery of the glucose-dependent insulin secretogogue activity of a novel class of polycyclic guanidines through phenotypic screening as part of the Lilly Open Innovation Drug Discovery platform. Three compounds from the University of California, Irvine, 1-3, having the 3- arylhexahydropyrrolo[1,2-c]pyrimidin-1-amine scaffold acted as insulin secretagogues under high, but not low, glucose conditions. Exploration of the structure-activity relationship around the scaffold demonstrated the key role of the guanidine moiety, as well as the importance of two lipophilic regions, and led to the identification of 9h, which stimulated insulin secretion in isolated rat pancreatic islets in a glucose-dependent manner.
- Shaghafi, Michael B.,Barrett, David G.,Willard, Francis S.,Overman, Larry E.
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supporting information
p. 1031 - 1036
(2014/03/21)
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- Photochemical synthesis and properties of axially chiral naphthylpyridines
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Five alkynyl pyridines were prepared and cyclized to naphthylpyridines as the main products in the course of a Photo-Dehydro-Diels-Alder reaction. Four of the final products are axially chiral and the determination of the rotational barrier by DFT calculations, dynamic NMR and HPLC experiments is demonstrated.
- Wessig, Pablo,Pick, Charlotte
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scheme or table
p. 263 - 265
(2012/07/13)
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- Palladium-catalyzed coupling reaction of haloheteroaromatic compounds in water
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Palladium-catalyzed coupling reaction of π-deficient heteroaromatic halide in water was accomplished with excellent to good yields without any side reactions such as hydrolysis.
- Inoue, Naoki,Sugimoto, Osamu,Tanji, Ken-ichi
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p. 665 - 671
(2008/03/13)
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- Sonogashira cross-coupling reactions with heteroaryl halides in the presence of a tetraphosphine-palladium catalyst
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Heteroaryl halides undergoes cross-couplings with alkynes in good yields in the presence of [PdCl(C3H5)]2/cis,cis,cis-1,2, 3,4-tetrakis(diphenylphosphinomethyl)cyclopentane as catalyst. A variety of heteroaryl halides such as pyridines, quinolines, a pyrimidine, an indole, a thiophene, or a thiazole have been used successfully. The reaction also tolerates several alkynes such as phenylacetylene and a range of alk-1-ynols. Furthermore, this catalyst can be used at low loading with some substrates.
- Feuerstein, Marie,Doucet, Henri,Santelli, Maurice
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p. 1717 - 1720
(2007/10/03)
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