- Microwave-Assisted Ruthenium- and Rhodium-Catalyzed Couplings of α-Amino Acid Ester-Derived Phosphinamides with Alkynes
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Two different types of new phosphinamide α-amino ester derivatives have been prepared in moderate to high yields via ruthenium(II) and rhodium(III)-catalyzed ortho-C?H functionalization under microwave irradiation. Specifically, the ortho-alkenylated phosphinamides were produced through coupling of phosphinamides containing an α-substituted or α,α-disubstituted α-amino ester with internal alkynes under ruthenium catalysis. In contrast, Ru and the more effective Rh-catalyzed coupling of the α-unsubstituted glycine ester phosphinamide with alkynes resulted in formation of oxidative annulation products, phosphaisoquinolin-1-ones. The developed methods feature the use of easily accessible starting materials, short reaction time, exclusive E-stereoselectivity (for ortho-alkenylation) and good functional group tolerance. The alkenylation reaction was readily scaled up to gram scale. Furthermore, the obtained alkenylated phosphinamide could be transformed into P-containing dipeptides through hydrolysis of the ester group in the catalysis product and subsequent condensation with an α-amino ester.
- Li, Xue-Hong,Gong, Jun-Fang,Song, Mao-Ping
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supporting information
(2021/12/23)
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- Carboxamide derivatives, intermediate, preparation method, pharmaceutical composition and application
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The invention discloses a formamide derivative, an intermediate, a preparation method, a pharmaceutical composition and an application. The invention provides a formamide derivative shown in a formula 1 as well as pharmaceutically acceptable salt or solvates of the derivative. The formamide derivative disclosed by the invention is an inhibitor of 11 beta-hydroxysteroid dehydrogenase in a type I, can be used for preparing medicines for treating various diseases which are related to expression or activity of 11beta-HSD1, and has a good market development prospect.
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Paragraph 0235; 0236; 0237
(2017/08/26)
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- INHIBITORS OF HEPATITIS C VIRUS POLYMERASE
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The present invention provides, among other things, compounds represented by the general Formula I: (I) and pharmaceutically acceptable salts thereof, wherein L and A (and further substituents) are as defined in classes and subclasses herein and compositions (e.g., pharmaceutical compositions) comprising such compounds, which compounds are useful as inhibitors of hepatitis C virus polymerase, and thus are useful, for example, as medicaments for the treatment of HCV infection.
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Paragraph 409; 410; 413
(2016/10/11)
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- Synthesis of the First Representatives of Spiro-1λ6-isothiazolidine-1,1,4-triones
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A strategy for the construction of spiro[cycloalkane-1,3′-1′λ6-isothiazolidine]-1′,1′,4′-triones through the sulfonylation of 1-aminocyclopropane- and 1-aminocyclobutanecarboxylates with methanesulfonyl chloride followed by alkylation with methyl iodide and subsequent cyclization in the presence of potassium tert-butoxide in N,N-dimethylformamide is reported. An efficient synthesis of starting 1-aminocyclopropane- and 1-aminocyclobutanecarboxylic acids was developed. The reaction of spiro[cycloalkane-1,3′-1′λ6-isothiazolidine]-1′,1′,4′-triones with N,N-dimethylformamide dimethyl acetal (DMF-DMA) gives 5′-[(Z)-(dimethylamino)methylene]spiro[cycloalkane-1,3′-1′λ6-isothiazolidine]-1′,1′,4′-triones, the structure of which was confirmed by X-ray diffraction study.
- Dobrydnev, Alexey V.,Popova, Maria V.,Saffon-Merceron, Nathalie,Listunov, Dymytrii,Volovenko, Yulian M.
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p. 2523 - 2528
(2015/09/01)
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- A COMPOUND FOR INHIBITING 11B-HYDROXY STEROID DEHYDROGENASE 1, AND A PHARMACEUTICAL COMPOSITION COMPRISING THE SAME
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Disclosed are a novel compound or a pharmaceutically acceptable salt thereof, and a pharmaceutical composition including the same for inhibiting human 11-β-hydroxy steroid dehydrogenase type 1 (11β-HSD1). The disclosed compound and the pharmaceutical composition including the same for inhibiting human 11-β-hydroxy steroid dehydrogenase type 1 (11β-HSD1) are excellent in activity and solubility, and is more efficient in formulation and transfer.
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Paragraph 0349-0350
(2014/08/06)
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- SUBSTITUTED SULFONAMIDE COMPOUNDS
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The invention is concerned with the compounds of formula (I), and salts thereof, wherein X, Y, Z, R1, R2, R3, R3, R4, R5 and R6 are defined in the detailed description and claims. In addition, the present invention relates to methods of manufacturing and using the compounds of Formula (I) as well as pharmaceutical compositions containing such compounds. The compounds may be useful in treating diseases and conditions mediated by TRPA1, such as pain.
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Page/Page column 113
(2014/04/17)
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- A COMPOUND FOR INHIBITING 11BETA-HYDROXY STEROID DEHYDROGENASE 1, AND A PHARMACEUTICAL COMPOSITION COMPRISING THE SAME
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Disclosed are a novel compound or a pharmaceutically acceptable salt thereof, and a pharmaceutical composition including the same for inhibiting human 11-beta-hydroxy steroid dehydrogenase type 1 (11beta-HSD1). The disclosed compound and the pharmaceutical composition including the same for inhibiting human 11-beta-hydroxy steroid dehydrogenase type 1 (11beta-HSD1) are excellent in activity and solubility, and is more efficient in formulation and transfer.
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Paragraph 635-637
(2013/03/26)
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- Discovery of a novel sulfonamide-pyrazolopiperidine series as potent and efficacious γ-secretase inhibitors (Part II)
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Significant improvement in metabolic stability on the pyrazolopiperidine scaffold over the original series were achieved and this stability improvement translated in an improved in vivo efficacy.
- Ye, Xiaocong M.,Konradi, Andrei W.,Smith, Jenifer,Aubele, Danielle L.,Garofalo, Albert W.,Marugg, Jennifer,Neitzel, Marty L.,Semko, Chris M.,Sham, Hing L.,Sun, Minghua,Truong, Anh P.,Wu, Jing,Zhang, Hongbin,Goldbach, Erich,Sauer, John-Michael,Brigham, Elizabeth F.,Bova, Michael,Basi, Guriqbal S.
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scheme or table
p. 3502 - 3506
(2010/08/07)
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- CYCLYLAMINE DERIVATIVES AS CALCIUM CHANNEL BLOCKERS
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Methods and compounds effective in ameliorating conditions characterized by unwanted calcium channel activity, particularly unwanted N-type and/or T-type calcium channel activity are disclosed. Specifically, a series of compounds of substituted or unsubstituted cyclylamine derivatives as shown in formulas (1).
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Page/Page column 13
(2009/10/31)
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- NOVEL MICROBIOCIDES
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Compounds of formula (I), in which the substituents are as defined in claim 1, are suitable for use as microbiocides.
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Page/Page column 29
(2009/12/02)
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- LACTAM COMPOUNDS AND THEIR USE AS PHARMACEUTICALS
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The present invention relates to inhibitors of 11-β hydroxyl steroid dehydrogenase type 1, antagonists of the mineralocorticoid receptor (MR), and pharmaceutical compositions thereof. The compounds of the invention can be useful in the treatment of various diseases associated with expression or activity of 11-β hydroxyl steroid dehydrogenase type 1and/or diseases associated with aldosterone excess.
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Page/Page column 49
(2008/06/13)
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- Hepatitis C virus inhibitors
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The present invention relates to tripeptide compounds, compositions and methods for the treatment of hepatitis C virus (HCV) infection. In particular, the present invention provides novel tripeptide analogs, pharmaceutical compositions containing such analogs and methods for using these analogs in the treatment of HCV infection.
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- Hydrogen-bonded tapes based on symmetrically substituted diketopiperazines: A robust structural motif for the engineering of molecular solids
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A series of eight symmetrically substituted diketopiperazines (DKPs) derived from 1-amino-1-carboxycycloalkanes (n = 3-7; 3,3,5,5-tetramethylcyclohexane; 4,4-dimethylcyclohexane; 2-indan) were synthesized and their crystal structures determined. In the solid state, all eight compounds form two pairs of hydrogen bonds with two adjacent molecules to form a one-dimensional structure that we refer to as 'tapes'. These molecules represent a range of volumes and shapes that contain a common molecular fragment (DKP ring). We examined this series of compounds with three objectives in mind: (i) to establish the ability of the hydrogen-bonded 'tape' motif to persist through these differences in volume and shape; (ii) to provide a series of structurally related compounds to use to test computational methods of predicting crystal structure from molecular structure; (iii) to search for qualitative correlations between molecular structure and crystal packing. All compounds form tapes and with one exception, all tapes pack with their long axes parallel. When viewed down their long axis, two types of tapes emerge: planar and nonplanar. The type of tape that forms reflects the conformation adapted by the DKP ring-planar or boat. Planar tapes form when the angle (α) between the two planes defined by the cis-amides in the DKP ring is 180°; nonplanar tapes form when α 180°. Five of the eight compounds studied form planar tapes, the remaining three compounds form nonplanar tapes. Despite the variability in volume and shape represented by this series of molecules, the persistence of the tape motif in their crystalline solids suggests that the hydrogen-bonding interactions between parallel alignment of tapes that pack in a manner that permits the interdigitation of substituents on adjacent tapes.
- Palacin, Serge,Chin, Donovan N.,Simanek, Eric E.,MacDonald, John C.,Whitesides, George M.,McBride, Mary T.,Palmore, G. Tayhas R.
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p. 11807 - 11816
(2007/10/03)
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- Design and synthesis of 1-aminocycloalkane-1-carboxylic acid-substituted deltorphin analogues: unique delta and mu opioid activity in modified peptides.
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Deltorphin analogues were substituted by a series of achiral C alpha,alpha-dialkyl cyclic alpha-amino acids (1-aminocycloalkane-1-carboxylic acids, Ac chi c, where chi = a hexane, pentane, or propane cycloalkane ring) in position 2, 3, 4, or 2 and 3 in de
- Breveglieri, Angela,Guerrini, Remo,Salvadori, Severo,Bianchi, Clementina,Bryant, Sharon D.,et al.
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p. 773 - 780
(2007/10/03)
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- 1-Aminocyclopropane-1-carboxylic acid derivatives: A new, general synthesis and NMDA receptor complex binding affinity study
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A new synthesis of 1-aminocyclopropane-1-carboxylic acid and of its (E)- and (Z)-2-substituted analogues (R = CH3;i-Pr;C6H5) has been performed by means of the 'diazo-addition' method, starting from N-(diphenylmethylene)-2,3-dehydro-1-amino-1-carboxylate precursors. The (E)- and (Z)-2-phenyl and the (Z)-2-methylcyclopropaneamino acids have been obtained with high diastereospecificity. All the cyclopropaneamino acids prepared were tested for their affinity for some glutamate receptors and resulted inactive, wich the exception of compounds (E)-1b and (Z)-1c which showed a shallow displacement of [H]-glycine binding.
- Spadoni,Balsamini,Bedini,Mugnaini
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p. 1663 - 1674
(2007/10/02)
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- Decarboxylation of 1-Aminocyclopropanecarboxylic Acid and Its Derivatives
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The question of whether the title compounds could be decarboxylated to cyclopropanone derivatives was answered in the affirmative by the following observations. (1) Compound 11a was decarboxylated by 1,2,3-indantrione in acetonitrile, benzene, or methanol.The initially formed intermediate could be trapped by N-phenylmaleimide (to form 3), by diethyl azodicarboxylate (to form an unstable adduct), by ninhydrin itself (to form 5) or by a proton (in methanol, to form 8). (2) Compound 11d was decarboxylated by phenylbis(trifluoroacetato-O)iodine to yield carbinolamine 12d.cis-2,3-Dideuterio-11d yielded cis-2,3-dideuterio-12d under the same conditions. (3) ACC was decarboxylated by phenanthroquinone to yield oxazole 9, probably by way of oxazoline 10.
- Vaidyanathan, Ganesan,Wilson, Joseph W.
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p. 1810 - 1815
(2007/10/02)
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- Peptide Sweeteners. 6. Structural Studies on the C-Terminal Amino Acid of L-Aspartyl Dipeptide Sweeteners
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Stereochemical and structural aspects of the variations in the C-terminal residue of L-aspartyl-L-phenylalanine methyl ester have been investigated.Novel configurational analogues such as L-aspartyl-D-alanine benzyl ester and L-aspartyl-D-α-aminobutyric acid benzyl ester were found to be sweet.In addition, chiral and achiral α,α-dialkylglycine and α-aminocycloalkanecarboxylic acids were incorporated into the dipeptides.The L-aspartic acid based dipeptide derivatives of α-aminoisobutyric acid methyl ester, α-aminocyclopropanecarboxylic acid methyl ester, α-aminocyclobutanecarboxylic acid methyl ester, and α-aminocyclopentanecarboxylic acid methyl ester are sweet.Dipeptides with α-aminocyclohexanecarboxylic acid methyl ester and α-aminocycloheptanecarboxylic acid methyl ester are bitter, whereas the analogues with α-aminocyclooctanecarboxylic acid methyl ester, α,α-diethylglycine methyl ester, and α-aminoisobutyric acid benzyl ester are tasteless.Aspects on chirality and effective volume of the C-terminal residue are discussed and correlated with taste.
- Tsang, Joseph W.,Schmied, Bernhard,Nyfeler, Rolf,Goodman, Murray
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p. 1663 - 1668
(2007/10/02)
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