- INHIBITORS OF BRUTON'S TYROSINE KINASE AND METHODS OF THEIR USE
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The present disclosure is directed to compounds of Formula (I) and methods of their use and preparation, as well as compositions comprising compounds of Formula (I).
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Page/Page column 102; 121
(2018/06/30)
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- INHIBITORS OF BRUTON'S TYROSINE KINASE AND METHODS OF THEIR USE
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Compounds of formula (I') and methods of their use and preparation, as well as compositions comprising compounds of formula (I').
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Page/Page column 149
(2018/06/30)
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- POLYCYCLIC COMPOUNDS AS INHIBITORS OF BRUTON'S TYROSINE KINASE
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The present disclosure is directed to compounds of Formula (I) as Bruton's kinase inhibitors and their preparation, as well as compositions comprising compounds of Formula (I).
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Page/Page column 103; 122
(2017/07/06)
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- INHIBITORS OF BRUTON'S TYROSINE KINASE AND METHODS OF THEIR USE
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The present disclosure is directed to compounds of formula I and methods of their use and preparation, as well as compositions comprising compounds of formula I.
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Page/Page column 149
(2017/09/02)
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- Radiochemical 18F-fluoroarylation of unsaturated α-, β- and γ-amino acids, application to a radiolabelled analogue of baclofen
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Unsaturated α-, β- and γ-amino acids have been investigated as substrates for the reductive Meerwein arylation. Radical reactions of this type have been shown to be a valuable tool for the fast and efficient introduction of the 4-[18F]fluorophenyl group into precursor molecules allowing short-time syntheses of potential PET radiotracers, which would be more difficult to access by other methods.
- H?fling, Sarah B.,Hultsch, Christina,Wester, Hans-Jürgen,Heinrich, Markus R.
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experimental part
p. 11846 - 11851
(2009/04/06)
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- Functionalized heterocycles as modulators of chemokine receptor function and methods of use therefor
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Disclosed are novel compounds having the formula or a physiologically acceptable salt, amide, ester or prodrug thereof. The compounds can be used to modulate (antagonize, agonize) chemokine receptor function. Also disclosed is a method for treating a patient having an inflammatory disease and/or viral infection comprising administering an effective amount of a compound of Formula I. In particular embodiments, the invention is a method for treating a patient infected with HIV.
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- Structure-Activity Relationships for Inhibition of Papain by Peptide Michael Acceptors
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Two series of peptidyl Michael acceptors, N-Ac-L-Phe-NHCH2CH=CH-E with different electron withdrawing groups (E = CO2CH3, 1a; SO2CH3, 1b; CO2H, 1c; CN, 1d; CONH2, 1e; and C6H4-p-NO2, 1f) and R-NHCH2CH=CHCOOCH3 with different recognition and binding groups (R = N-Ac-D-Phe, 2a; N-Ac-L-Leu, 3a; N-Ac-L-Met, 4a; PhCH2CH2CO, 5a; PhCO, 6a), were synthesized and evaluated as inactivators against papain.It was found that the inhibition of papain by peptidyl Michael acceptors is a general phenomenon and that the intrinsic chemical reactivity of the E group in the Michael acceptors has a direct effect on the kinetics of the inactivation process as reflected in k2/Ki.At pH 6.2, the reactivity of papain toward the Michael acceptors is about 283 000-fold higher than the reactivity of the model thiol 3-mercaptopropionate.This large increase in reactivity is attributable to at least 2 factors; one is the low apparent pKa of Cys-25 of papain, and the other is the recruitment of catalytic power by specific enzyme-substrate interactions.The unexpectedly high reactivity of 1c (E = COOH) was rationalized by proposing a direct interaction of the acid group with His-159 in the active site of papain.The unexpected inactivity of 1f (E = C6H4-p-NO2) as a Michael acceptor and its very powerful competitive inhibition of papain were rationalized by molecular graphics which showed the nitrophenyl moiety rotated out of conjugation with the olefin and interacting instead with the hydrophobic S1' region of papain.A plot of log (k2/Ki) for 1a-6a vs log (kcat/Km) for analogous R-Gly-p-NA substrates was linear (r = 0.98) with slope 0.83, suggesting that the binding energy from specific enzyme-ligand interactions can be used to drive the self-inactivation reaction to almost the same extent as it is used to drive catalysis.
- Liu, Siming,Hanzlik, Robert P.
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p. 1067 - 1075
(2007/10/02)
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- Unsaturated diphenylazomethine derivatives, their preparation and pharmaceutical compositions containing them
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Diphenylazomethine derivatives of formula (I) STR1 wherein R1 is hydrogen or methyl and R2 is an --OH,--OM (M=alkaline metal or alkaline earth metal), --NH2 or --O(C1-4 alkyl) group, and which are in the form of
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- Convenient synthesis of (RS)-4-amino-3-hydroxybutyric acid.
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A new three-step synthesis of 4-amino-3-hydroxybutyric acid from an inexpensive starting material and under mild reaction conditions is described. Crotonic acid was brominated by the Wohl-Ziegler reaction to 4-bromocrotonic acid, which, in turn, was converted with ammonium hydroxide into 4-aminocrotonic acid. This compound, refluxed in water in the presence of a strong acid resin, afforded 4 amino-3-hydroxybutyric acid in good yields.
- Pinza,Pifferi
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p. 120 - 121
(2007/10/05)
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