- Discovery of a potent dual inhibitor of wild-type and mutant respiratory syncytial virus fusion proteins through the modulation of atropisomer interconversion properties
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The development of effective respiratory syncytial virus (RSV) fusion glycoprotein (F protein) inhibitors against both wild-type and the D486N-mutant F protein is urgently required. We recently reported a 15-membered macrocyclic pyrazolo[1,5-a]pyrimidine derivative 4 that exhibited potent anti-RSV activities against not only wild-type, but also D486N-mutant F protein. However, NMR studies revealed that the 15-membered derivative 4 existed as a mixture of atropisomers. An optimization study of the linker moiety between the 2-position of the benzoyl moiety and the 7-position of the pyrazolo[1,5-a]pyrimidine scaffold identified a 16-membered derivative 42c with an amide linker that showed a rapid interconversion of atropisomers. Subsequent optimization of the 5-position of the pyrazolo[1,5-a]pyrimidine scaffold and the 5-position of the benzoyl moiety resulted in the discovery of a potent clinical candidate 60b for the treatment of RSV infections.
- Yamaguchi-Sasaki, Toru,Kawaguchi, Takanori,Okada, Atsushi,Tokura, Seiken,Tanaka-Yamamoto, Nozomi,Takeuchi, Tomoki,Ogata, Yuya,Takahashi, Ryo,Kurimoto-Tsuruta, Risa,Tamaoki, Tomokazu,Sugaya, Yutaka,Abe-Kumasaka, Tomoko,Arikawa, Kaho,Yoshida, Ippei,Sugiyama, Hiroyuki,Kanuma, Kosuke,Yoshinaga, Mitsukane
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- HISTONE ACETYLTRANSFERASE (HAT) INHIBITOR AND USE THEREOF
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The present invention relates to a histone acetyltransferase (HAT) inhibitor. Provided are a compound represented by general formula I, a pharmaceutically acceptable salt, a stereoisomer, an enantiomer, a diastereomer, an atropisomer, a racemate, a polymorph, a solvate or an isotope-labeled compound (including deuterium substitution) thereof, a preparation method therefor, a pharmaceutical composition comprising the same, and use thereof in the treatment of various HAT-related diseases or conditions.
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Paragraph 0465; 0468
(2021/02/25)
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- 2,4,6,7-TETRAHYDRO-PYRAZOLO[4,3-D]PYRIMIDIN-5-ONE DERIVATIVES AND RELATED COMPOUNDS AS C5A RECEPTOR MODULATORS FOR TREATING VASCULITIS AND INFLAMMATORY DISEASES
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The present invention relates to derivatives of formula (I) wherein Ring A, X, Y, Z, RA, R1, R2, R3 and R4 are The present invention discloses derivatives of formula (I), wherein Ring A, X, Y, Z, RA, R1, R2, R3 and R4 are as described in the description, and in particular e.g. 2,4,6,7-tetrahydro-pyrazolo[4,3- d]pyrimidin-5-one derivatives and related compounds, their preparation, pharmaceutically acceptable salts thereof, their use as pharmaceuticals, pharmaceutical compositions containing one or more compounds of formula (I), and especially their use as C5a receptor modulators for treating e.g. vasculitis and inflammatory diseases.
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Page/Page column 97; 98
(2019/08/20)
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- FUSED MORPHOLINOPYRIMIDINES AND METHODS OF USE THEREOF
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The present disclosure relates to Fused Morpholinopyrimidines, pharmaceutical compositions comprising an effective amount of a Fused Morpholinopyrimidine and methods for using a Fused Morpholinopyrimidine in the treatment of a neurodegenerative disease, comprising administering to a subject in need thereof an effective amount of a Fused Morpholinopyrimidine.
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Paragraph 1095
(2017/05/14)
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- FUSED MORPHOLINOPYRIMIDINES AND METHODS OF USE THEREOF
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The present disclosure relates to Fused Morpholinopyrimidines, pharmaceutical compositions comprising an effective amount of a Fused Morpholinopyrimidine and methods for using a Fused Morpholinopyrimidine in the treatment of a neurodegenerative disease, comprising administering to a subject in need thereof an effective amount of a Fused Morpholinopyrimidine.
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Paragraph 0799
(2015/08/03)
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- 2, N6 -disubstituted adenosines, tri-O-ester derivatives and their pharmaceutical compositions to treat ischemias
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A compound of formula (I), or a pharmaceutically acceptable salt thereof: STR1 wherein X is halogen, trifluoromethyl, cyano, C 1-6 -alkoxy, C 1-6 -alkylthio, C 1-6 -alkylamino or C 1-6 -dialkylamino;R 1 and R 4 are H or straight or branched C 1-6 -alkyl o
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- New Synthetic Pathways to 3,3,3-Trifluoroalanine, 2-Deutero-3,3,3-trifluoroalanine and their Derivatives
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New synthetic pathways to 3,3,3-trifluoroalanine, 2-deutero-3,3,3-trifluoroalanine, their esters, amides, and thioamides are described, starting from hexafluoroacetone, and trifluoropyruvates, respectively.
- Burger, Klaus,Hoess, Eva,Gaa, Karl,Sewald, Norbert,Schierlinger, Christian
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p. 361 - 384
(2007/10/02)
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