- TYK2 INHIBITORS AND USES THEREOF
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The present invention provides compounds, compositions thereof, and methods of using the same for the inhibition of TYK2, and the treatment of TYK2-mediated disorders.
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Paragraph 1343; 1344; 1345
(2019/02/13)
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- α,β-Dehydrogenation of esters with free O–H and N–H functionalities via allyl-palladium catalysis
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A direct and selective method for the α,β-dehydrogenation of esters using palladium catalysis in the presence of free O–H and N–H functionalities is reported herein. Allyl-palladium catalysis allows for preservation of readily oxidizable functionalities s
- Szewczyk, Suzanne M.,Zhao, Yizhou,Sakai, Holt A.,Dube, Pascal,Newhouse, Timothy R.
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p. 3293 - 3300
(2018/03/21)
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- Synthesis and evaluation of chirally defined side chain variants of 7-chloro-4-aminoquinoline to overcome drug resistance in malaria chemotherapy
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A novel 4-aminoquinoline derivative [(S)-7-chloro-N-(4-methyl-1-(4-methyl-piperazin-1-yl)pentan-2-yl)-quinolin-4-amine triphosphate] exhibiting curative activity against chloroquine-resistant malaria parasites has been identified for preclinical development as a blood schizonticidal agent. The lead molecule selected after detailed structure-activity relationship (SAR) studies has good solid-state properties and promising activity against in vitro and in vivo experimental malaria models. The in vitro absorption, distribution, metabolism, and excretion (ADME) parameters indicate a favorable drug-like profile.
- Dola, Vasantha Rao,Soni, Awakash,Agarwal, Pooja,Ahmad, Hafsa,Raju, Kanumuri Siva Rama,Rashid, Mamunur,Wahajuddin, Muhammad,Srivastava, Kumkum,Haq,Dwivedi,Puri,Katti
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- Synthesis of new C-glycosyl aza-β3-amino acids building blocks
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New C-glycosylated Nβ-protected aza-β3- amino acid building blocks have been prepared from C-glycosyl aldehydes of gluco and galacto configuration by reductive amination and subsequent N-alkylation. These moieties were elaborated to
- Andreini, Manuel,Felten, Anne-Sophie,Thien, Hoang-Trang Tran,Taillefumier, Claude,Pellegrini-Mo?se, Nadia,Chapleur, Yves
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scheme or table
p. 2702 - 2705
(2012/07/27)
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- Photostable, amino reactive and water-soluble fluorescent labels based on sulfonated rhodamine with a rigidized xanthene fragment
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Highly water soluble fluorescent dyes were synthesized and transformed into new amino reactive fluorescent labels for biological microscopy. To this end, rhodamine 8 (prepared from 7-hydroxy-1,2,3,4-tetrahydroquinoline (7) and phthalic anhydride in 85% aq. H3PO4) was sulfonated with 30% SO3 in H2SO4 and afforded the water soluble disulfonic acid 3 a (64%). Amidation of the carboxy group in 3 a with 2-(methylamino)ethanol in the presence of O-(7-azabenzotriazol-1-yl)-N,N,N, N′-tetramethyluronium·PF6- (HATU) led to alcohol 3b (66%), which was transformed into the amino reactive mixed carbonate 3d with di(N-succinimidyl)carbonate and Et3N, Reaction of the carboxy group in 3a with MeNH(CH2)2CO2Me and N,N,N′,N′-tetramethyl-O-(N-succinimidyl)-uronium-BF4 - (TSTU) yielded methyl ester 13. After saponification of the aliphatic carboxy group in 13, the compound was converted into NHS-ester 3e (using HATU and Et3N). Heating of 7 with trimellitic anhydride in H3PO4 gave a mixture of dicarboxylic acids 14 and 15 (1:1). Regioisomer 15 was isolated, sulfonated with 30% SO3 in H 2SO4, and disulfonic acid 3f was used for the synthesis of the mono NHS-ester 3g, in which the sterically unhindered carboxy group was selectively activated (with n-hydroxysuccinimide, HATU, and Et3N). The sulfonated rhodamines 3 b, c and f are soluble in water (up to 0.1 M), have excellent photostabilities and large fluorescence quantum yields. Subdiffraction resolution images of tubulin filaments of mammalian cells stained with these dyes illustrate their applicability as labels for stimulated emission depletion microscopy and other fluorescence techniques.
- Boyarskiy, Vadim P.,Belov, Vladimir N.,Medda, Rebecca,Hein, Birka,Bossi, Mariano,Hell, Stefan W.
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experimental part
p. 1784 - 1792
(2009/04/07)
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- Iron-catalyzed four-component reaction for the synthesis of protected primary amines
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The first catalytic four-component reaction (4CR) of carbonyl compounds with alkyl chloroformate, HMDS and Et3SiH has been developed to produce protected primary amines by a novel tandem nitrogen protection/direct reductive amination of carbonyl compounds. In the presence of 5 mol-% of an iron(II) salt, a wide variety of aldehydes and ketones were transformed into their corresponding protected primary amines in good to excellent yields under "pure" multicomponent reaction (MCR) conditions. This chemistry was further extended to masked carbonyl compounds such as acetals, ketals, and vinyl ethers. When compared with previous methods to prepare protected primary amines from a large excess of ammonia or ammonium salts, this 4CR not only saved at least one step of synthetic manipulation, but also utilized nearly stoichiometric nitrogen and hydrogen sources and avoided the formation of (protected) secondary amines. Additional advantages of this protocol include broader substrate scope, the use of an inexpensive and environmentally friendly catalyst, and mild reaction conditions. Wiley-VCH Verlag GmbH & Co. KGaA, 2007.
- Yang, Bai-Ling,Tian, Shi-Kai
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p. 4646 - 4650
(2008/03/12)
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- Preparation of both enantiomers of β2-(3,4-dihydroxybenzyl) -β-alanine, higher homologues of Dopa
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β2-(3,4-Dihydroxybenzyl)-β-alanine [β2-Homo-Dopa, 1] is a novel β-amino acid homologue of Dopa, the most successful therapeutic agent in the treatment of Parkinson's disease. Enantioenriched (R)-1 and (S)-1 were obtained via the diastereoselective alkylation of enantiopure pyrimidinone (R)- and (S)-3, chiral derivatives of β-alanine, with veratryl iodide. The major diastereomeric products (2S,5R)-4 and (2R,5S)-4 were hydrolyzed with 57% HBr, and the desired β-amino acids were purified by silica gel chromatography. Alternatively, enantioenriched (R)- and (S)-1 were prepared by means of the highly diastereoselective alkylation (3,4-dimethoxybenzyl iodide) of open-chain β-aminopropionic acid derivatives (R,R,S)-8 and (S,S,R)-8 containing the chiral auxiliary α-phenylethylamine. Finally, nearly enantiopure (R)- and (S)-1 were obtained by resolution of racemic N-benzyloxycarbonyl-2-(3,4- dibenzyloxybenzyl)-3-aminopropionic acid, rac-12, with (R)- or (S)-α-phenylethylamine, followed by catalytic hydrogenolysis.
- Avila-Ortiz, Claudia G.,Reyes-Rangel, Gloria,Juaristi, Eusebio
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p. 8372 - 8381
(2007/10/03)
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- Acyclic compounds promote release of growth hormone
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The present invention is directed to certain compounds of the general structural formula: STR1 wherein R1, R1a, R2a, R3, R3a, R4, R5, R6, A, W, and n are as defined herein. These compounds promote the release of growth hormone in humans and animals. This property can be utilized to promote the growth of food animals to render the production of edible meat products more efficient, and in humans, to treat physiological or medical conditions characterized by a deficiency in growth hormone secretion, such as short stature in growth hormone deficient children, and to treat medical conditions which are improved by the anabolic effects of growth hormone. Growth hormone releasing compositions containing such compounds as the active ingredient thereof are also disclosed.
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- Nitrosourea derivatives
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Nitrosourea derivatives are provided which possess a high level of inhibitory activity against leukemia and tumors and which are therefore useful for pharmaceutical purposes. The compounds have the structure represented by formulae (I), (II) and (III): ST
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