- Alkyl Radical Addition to Aliphatic and Aromatic N-Acylhydrazones Using an Organic Photoredox Catalyst
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Increased versatility of intermolecular radical addition to imino acceptors via photoredox catalysis is reported. Primary and secondary radicals, generated via visible-light photocatalysis from alkyl biscatecholatosilicates with organocatalyst 4CzIPN, add
- Cullen, Stephen T. J.,Friestad, Gregory K.
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- Catalytic asymmetric oxidative carbonylation-induced kinetic resolution of sterically hindered benzylamines to chiral isoindolinones
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A highly enantioselective kinetic resolution of sterically hindered benzylamines has been achieved for the first time through transition-metal-catalyzed oxidative carbonylation, in which the new KR strategy offered a new approach to afford chiral isoindolinones (er up to 97?:?3) and the origin of chemoselectivity and stereoselectivity was confirmed by density functional theory (DFT) calculations.
- Mu, Qiu-Qi,Nie, Yi-Xue,Li, Hang,Bai, Xing-Feng,Liu, Xue-Wei,Xu, Zheng,Xu, Li-Wen
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supporting information
p. 1778 - 1781
(2021/02/27)
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- Method for synthesizing chiral amine compound
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The present invention provides a method for synthesizing a chiral amine compound. The method comprises the following steps: (1) reacting a compound of formula I with t-butylsulfonamide in the presenceof a catalyst to obtain a compound having a structure represented by formula II; 2) reacting the compound of the formula II in a hydrogen atmosphere in the presence of an iridium catalyst and a ligand to obtain a compound of formula III; and (3) carrying out a t-butylsulfonyl group removal reaction on the compound of the formula III to obtain the chiral amine compound. The method constructs the structure of sulfonamide by a keto carbonylgroup, and synthesizes the chiral amine compound with the aralkylamine structure by an asymmetric catalytic hydrogenation reaction of the sulfonamide structure, the ee value is generally 80% or above, the highest ee value is 99% or above, the yield of each step reaction can reach 90% or above, and the total yield is high.
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Paragraph 0064; 0071-0073; 0129-0131
(2019/10/01)
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- Method for synthesizing dextral alpha-cyclohexylbenzylamine
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The invention discloses a method for synthesizing dextral alpha-cyclohexylbenzylamine. The method comprises synthesizing racemic alpha-cyclohexylbenzylamine through catalytic reduction of cyclohexyl phenyl ketone in the presence of a reduction catalyst, and carrying out dynamic kinetic resolution on alpha-cyclohexylbenzylamine under combined action of lipase and a racemization catalyst to obtain alpha-cyclohexylbenzylamine. The method has the characteristics of simple operation, wide raw material source, good product yield and high optical purity of the resolution product.
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Paragraph 0006; 0009
(2017/07/01)
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- PROCESS FOR THE PREPARATION OF CHIRAL AMINES FROM PROCHIRAL KETONES
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There is provided a method for the preparation of an enantiomerically enriched amine from a prochiral ketone.
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Page/Page column 5; 6
(2015/12/11)
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- APPLICATIONS OF N6-SUBSTITUTED ADENOSINE DERIVATIVE AND N6-SUBSTITUTED ADENINE DERIVATIVE TO CALMING, HYPNOSES, CONVULSION RESISTANCE, EPILEPTIC RESISTANCE, PARKINSON DISEASE RESISTANCE, AND DEMENTIA PREVENTION AND TREATMENT
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PROBLEM TO BE SOLVED: To prepare analgesics, hypnotic agents, anticonvulsant agents, antiepileptics, antiparkinson drugs, dementia prophylactics, and health care food. SOLUTION: The present invention relates to an N6-substituted adenosine derivative and an N6-substituted adenine derivative selected from the group consisting of specific compounds. The present invention also relates to a pharmaceutical composition at least comprising a therapeutically effective amount of the compounds and a pharmaceutically acceptable carrier. The invention further relates to the compounds used in preparation of analgesics, hypnotic agents, anticonvulsant agents, antiepileptics, antiparkinson drugs, dementia prophylactics, and health care food. COPYRIGHT: (C)2016,JPO&INPIT
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- Discovery of inhibitors of the mitotic kinase TTK based on N-(3-(3-sulfamoylphenyl)-1H-indazol-5-yl)-acetamides and carboxamides
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TTK kinase was identified by in-house siRNA screen and pursued as a tractable, novel target for cancer treatment. A screening campaign and systematic optimization, supported by computer modeling led to an indazole core with key sulfamoylphenyl and acetamido moieties at positions 3 and 5, respectively, establishing a novel chemical class culminating in identification of 72 (CFI-400936). This potent inhibitor of TTK (IC50 = 3.6 nM) demonstrated good activity in cell based assay and selectivity against a panel of human kinases. A co-complex TTK X-ray crystal structure and results of a xenograft study with TTK inhibitors from this class are described.
- Laufer, Radoslaw,Ng, Grace,Liu, Yong,Patel, Narendra Kumar B.,Edwards, Louise G.,Lang, Yunhui,Li, Sze-Wan,Feher, Miklos,Awrey, Don E.,Leung, Genie,Beletskaya, Irina,Plotnikova, Olga,Mason, Jacqueline M.,Hodgson, Richard,Wei, Xin,Mao, Guodong,Luo, Xunyi,Huang, Ping,Green, Erin,Kiarash, Reza,Lin, Dan Chi-Chia,Harris-Brandts, Marees,Ban, Fuqiang,Nadeem, Vincent,Mak, Tak W.,Pan, Guohua J.,Qiu, Wei,Chirgadze, Nickolay Y.,Pauls, Henry W.
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p. 4968 - 4997
(2014/10/16)
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- INDAZOLE COMPOUNDS AS KINASE INHIBITORS AND METHOD OF TREATING CANCER WITH SAME
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The present teaching provide indazole compounds represented by Structural Formulae (I) or (I') or a pharmaceutically acceptable salt thereof. Also described are pharmaceutical compositions and methods of use thereof as protein kinase inhibitors, such as T
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Page/Page column 69; 75; 123
(2013/04/25)
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- A versatile Ru catalyst for the asymmetric transfer hydrogenation of both aromatic and aliphatic sulfinylimines
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A highly efficient Ru catalyst based on an achiral, very simple, and inexpensive amino alcohol ligand (2-amino-2-methylpropan-1-ol) has been developed for the asymmetric transfer hydrogenation (ATH) of chiral N-(tert-butylsulfinyl)imines. This complex is able to catalyze the ATH of both aromatic and the most challenging aliphatic sulfinylimines by using isopropyl alcohol as the hydrogen source. The diastereoselective reduction of aromatic, heteroaromatic, and aliphatic sulfinylketimines, including sterically congested cases, over short reaction times (1-4 h), followed by desulfinylation of the nitrogen atom, affords the corresponding highly enantiomerically enriched (ee up to >99%) α-branched primary amines in excellent yields. The same ligand was equally effective for the synthesis of both (R)- and (S)-amines by using the appropriate absolute configuration in the iminic substrate. DFT mechanistic studies show that the hydrogen-transfer process is stepwise. Moreover, the origin of the diastereoselectivity has been rationalized.
- Pablo, Oscar,Guijarro, David,Kovacs, Gabor,Lledos, Agusti,Ujaque, Gregori,Yus, Miguel
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p. 1969 - 1983
(2012/03/26)
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- KINASE INHIBITORS AND METHOD OF TREATING CANCER WITH SAME
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The present teachings provide a compound represented by Structural Formula (I): or a pharmaceutically acceptable salt thereof. Also described are a pharmaceutical composition and method of use thereof.
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Page/Page column 100
(2011/10/31)
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- Synthesis of highly enantiomerically enriched amines by the diastereoselective addition of triorganozincates to N-(tert-butanesulfinyl)imines
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The reaction of triorganozincates with (R)-N-(tert-butanesulfinyl) imines gives the expected α-branched sulfinamides in good to excellent yields with diastereomeric ratios of up to 98:2. The N-sulfinyl group of the products can be easily removed by acidic treatment, affording the corresponding chiral primary amines in enantiomeric excesses of up to 96%. The reactivity and the selectivity shown by the triorganozincates are different from the ones observed with the corresponding Grignard reagents, which allows, in several cases, the preparation of both enantiomers of an amine from the same imine substrate. When mixed triorganozincates are used, one can take advantage of the slow transfer rate of the methyl group to use it as a non-transferable one. Both aromatic and aliphatic aldimines, as well as activated ketimines, are good substrates for these addition reactions.
- Almansa, Raquel,Guijarro, David,Yus, Miguel
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experimental part
p. 2484 - 2491
(2009/04/11)
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- Tetrahydro-indazole cannabinoid modulators
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This invention is directed to a tetrahydro-indazole cannabinoid modulator compound of formula I: and a method for use in treating, ameliorating or preventing a cannabinoid receptor mediated syndrome, disorder or disease.
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Page/Page column 118-119
(2008/06/13)
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- Chemoselective reductive alkylation of ammonia with carbonyl compounds: Synthesis of primary and symmetrical secondary amines
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An efficient, general procedure for highly chemoselective reductive mono-alkylation of ammonia with ketones is reported. Treatment of ketones with ammonia in ethanol and titanium(IV) isopropoxide, followed by in situ sodium borohydride reduction, and a straightforward workup afforded primary amines in good to excellent yields. Reductive alkylation of ammonia with aldehydes, on the other hand, afforded the corresponding symmetrical secondary amines selectively.
- Miriyala, Bruhaspathy,Bhattacharyya, Sukanta,Williamson, John S.
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p. 1463 - 1471
(2007/10/03)
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- 3,4-DI-SUBSTITUTED CYCLOBUTENE-1, 2-DIONES AS CXC-CHEMOKINE RECEPTOR LIGANDS
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Disclosed are novel compounds of the formula (I)or a pharmaceutically acceptable salt or solvate thereof. Also disclosed is the treatment of chemokine-mediated diseases using compounds of the formula (II)
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- Influence of bulky substituents on histamine H3 receptor agonist/antagonist properties
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Novel derivatives of 3-(1H-imidazol-4-yl)propanol were designed on the basis of lead compounds belonging to the carbamate or ether series possessing (partial) agonist properties on screening assays of the histamine H3 receptor. One pair of enantiomers in the series of α-methyl-branched chiral carbamates was stereoselectively prepared in high optical yields. Enantiomeric purity was checked by Mosher amide derivatives of precursors and capillary electrophoresis of the final compounds with trimethyl-β-cyclodextrin as chiral selector, and was determined to be ≥95%. The novel compounds were investigated in various histamine H3 receptor assays in vitro and in vivo. Some compounds displayed partial agonist activity on synaptosomes of rat brain cortex, whereas others exhibited antagonist properties only. Selected compounds were investigated in [125I]iodoproxyfan binding studies on the human histamine H3 receptor and showed high affinity in the nanomolar concentration range. Under in vivo conditions after oral administration to mice, some of the compounds exhibited partial or full agonist activity in the brain at low dosages. The (S)-enantiomer of one pair of chiral carbamates (9) proved to be the eutomer; thus, the (S)-enantiomer was selected for further pharmacological studies. In a peripheral in vivo test model in rats, measuring the level of inhibition of capsaicin-induced plasma extravasation, (S)-9 again proved its high oral agonist potency with full intrinsic activity (ED50 values of 0.07-0.1 mg/kg depending on tissue).
- Sasse, Astrid,Ligneau, Xavier,Rouleau, Agnès,Elz, Sigurd,Ganellin, C. Robin,Arrang, Jean-Michel,Schwartz, Jean-Charles,Schunack, Walter,Stark, Holger
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p. 4000 - 4010
(2007/10/03)
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- Synthesis and structure-activity relationships of potential anticonvulsants based on 2-piperidinecarboxylic acid and related pharmacophores
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Using N-(2,6-dimethyl)phenyl-2-piperidinecarboxamide (1) and N-(α-methylbenzyl)-2-piperidinecarboxamide (2) as structural leads, a variety of analogues were synthesised and evaluated for anticonvulsant activity in the MES test in mice. In the N-benzyl series, introduction of 3-Cl, 4-Cl, 3,4-Cl2, or 3-CF3 groups on the aromatic ring led to an increase in MES activity. Replacement of the α-methyl group by either i-Pr or benzyl groups enhanced MES activity with no increase in neurotoxicity. Substitution on the piperidine ring nitrogen led to a decrease in MES activity and neurotoxicity, while reduction of the amide carbonyl led to a complete loss of activity. Movement of the carboxamide group to either the 3- or 4-positions of the piperidine ring decreased MES activity and neurotoxicity. Incorporation of the piperidine ring into a tetrahydroisoquinoline or diazahydrinone nucleus led to increased neurotoxicity. In the N-(2,6-dimethyl)phenyl series, opening of the piperidine ring between the 1- and 6-positions gave the active norleucine derivative 75 (ED50 = 5.8 mg kg-1, TD50 = 36.4 mg kg-1, PI = 6.3). Replacement of the piperidine ring of 1 by cycloalkane (cyclohexane, cyclopentane, and cyclobutane) resulted in compounds with decreased MES activity and neurotoxicity, whereas replacement of the piperidine ring by a 4-pyridyl group led to a retention of MES activity with a comparable PI. Simplification of the 2-piperidinecarboxamide nucleus of 1 into a glycinecarboxamide nucleus led to about a six-fold decrease in MES activity. The 2,6-dimethylanilides were the most potent compounds in the MES test in each group of compounds evaluated, and compounds 50 and 75 should be useful leads in the development of agents for the treatment of tonic-clonic and partial seizures in man.
- Ho, Bin,Michael Crider,Stables, James P
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p. 265 - 286
(2007/10/03)
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- ASYMETRIC SYNTHESIS X: THE HIGH ENANTIOSELECTIVE SYNTHESIS OF (R)-α-SUBSTITUTED BENZYLIC AMINES VIA THE MODIFIED (+)-CAMPHOR DERIVATIVE AS CHIRAL SYNTHON
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A new chiral synthon-10-substituted (+)-camphor derivative (III) is synthesized.The alkylation of the (III) with a variety of alkylating agents gives the high enantioselectivity ranging from 72-100percent e.e..And the crystal structures of the (III) and (IV) are involved in explaining the results.
- Yaozhong, Jiang,Peng, Guo,Guilan, Liu
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- ASYMMETRIC SYNTHESIS VIII: ENANTIONSELECTIVE SYNTHESIS OF (R) OR (S)-α-SUBSTITUTED BENZYLAMINES VIA CHIRAL PINANONE KETIMINE TEMPLATE
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An excellent asymmetric synthesis of both (R) and (S)-α-substituted benzylamines in optical purity 90.4 - 99.9percent has been achieved by alkylation of a chiral ketimine, prepared from pinanone and benzylamine.Diastereoselectivity in the alkylation is not dependent on the alkyl halides.
- Yuanwei, Chen,Aiqiao, Mi,Xun, Xiao,Yaozhong, Jiang
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p. 1423 - 1430
(2007/10/02)
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- Tandem Alkylation-Reduction of Nitriles. Synthesis of Branched Primary Amines
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Tandem alkylation-reduction of a series of nitriles by alkylating with Grignard reagents followed by reducing with lithium-ammonia afforded the corresponding branched primary amines in reasonable isolated yields.Alkyl and aromating nitriles and a variety of Grignard reagents have been employed in this convenient procedure.A mechanism for the reduction of the imine intermediate is suggested.
- Weiberth, Franz J.,Hall, Stan S.
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p. 5338 - 5341
(2007/10/02)
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- Hypoglycemic α cycloalkylphenylmethyl, furanalkyl, and thiophenealkyl lactamimides
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A series of α cycloalkylphenylmethyl lactamimides and a series of furan and thiophenealkyl lactamimides were prepared for biological evaluation as an extension of earlier findings of hypoglycemic activity in lactamimides. Several compounds produced pronouced hypoglycemia after oral administration to fasted, glucose primed rats.
- Grisar,Claxton,Wiech
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p. 365 - 369
(2007/10/04)
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