- Macrocyclic compounds and methods for their production
-
There is provided inter alia compounds of formula (I): for use in treatment of viral infection or as an immunosuppressant.
- -
-
Page/Page column 43
(2015/11/10)
-
- Antibacterial inhibitors of gram-positive thymidylate kinase: Structure-activity relationships and chiral preference of a new hydrophobic binding region
-
Thymidylate kinase (TMK), an essential enzyme in bacterial DNA biosynthesis, is an attractive therapeutic target for the development of novel antibacterial agents, and we continue to explore TMK inhibitors with improved potency, protein binding, and pharmacokinetic potential. A structure-guided design approach was employed to exploit a previously unexplored region in Staphylococcus aureus TMK via novel interactions. These efforts produced compound 39, with 3 nM IC50 against S. aureus TMK and 2 μg/mL MIC against methicillin-resistant S. aureus (MRSA). This compound exhibits a striking inverted chiral preference for binding relative to earlier compounds and also has improved physical properties and pharmacokinetics over previously published compounds. An example of this new series was efficacious in a murine S. aureus infection model, suggesting that compounds like 39 are options for further work toward a new Gram-positive antibiotic by maintaining a balance of microbiological potency, low clearance, and low protein binding that can result in lower efficacious doses.
- Kawatkar, Sameer P.,Keating, Thomas A.,Olivier, Nelson B.,Breen, John N.,Green, Oluyinka M.,Guler, Satenig Y.,Hentemann, Martin F.,Loch, James T.,McKenzie, Andrew R.,Newman, Joseph V.,Otterson, Linda G.,Martínez-Botella, Gabriel
-
p. 4584 - 4597
(2014/07/07)
-
- Sanglifehrin Derivatives and Methods for Their Production
-
There are provided inter alia compounds of formula (I) and (II) and their use in therapy, particularly for the treatment of viral infection.
- -
-
Paragraph 0167; 0168
(2014/04/03)
-
- Novel Dosage Form
-
There is provided inter alia a pharmaceutical dosage form for oral administration comprising a sanglifehrin as active ingredient in which the sanglifehrin active ingredient is protected from acid degradation in the stomach environment following oral admin
- -
-
Paragraph 0272; 0273
(2014/09/03)
-
- NOVEL DOSAGE FORM
-
There is provided inter alia apharmaceutical dosage form fororal administration comprising a sanglifehrin as active ingredient in which the sanglifehrin active ingredient is protected from acid degradation in the stomach environment following oral adminis
- -
-
Page/Page column 65
(2013/05/21)
-
- HETEROARYL COMPOUNDS, COMPOSITIONS THEREOF, AND USE THEREOF AS PROTEIN KINASE INHIBITORS
-
Provided herein are Heteroaryl Compounds having the following structure: (I) wherein R1, R2, L, X, Y, Z, Q, A and B are as defined herein, compositions comprising an effective amount of a Heteroaryl Compound and methods for treating or preventing cancer, inflammatory conditions, immunological conditions, metabolic conditions and conditions treatable or preventable by inhibition of a kinase pathway comprising administering an effective amount of a Heteroaryl Compound to a patient in need thereof.
- -
-
Page/Page column 115
(2008/12/05)
-
- NOVEL COMPOUNDS
-
Novel inhibitors of Rho-kinases are disclosed.
- -
-
Page/Page column 70
(2008/06/13)
-
- A convenient route to new fluorinated photodynamic therapeutic photosensitizers based on meso-tetra(hydroxyphenyl)porphyrins
-
A general synthetic route was developed for the synthesis of new fluorinated tetra(hydroxyphenyl) porphyrins [5,10,15,20-tetrakis(2-fluoro-3-hydroxyphenyl)porphyrin 10, 5,10,15,20-tetrakis(2,4-difluoro-3-hydroxyphenyl)porphyrin 11, and 5,10,15,20-tetrakis(3,5-difluoro-4-hydroxyphenyl)porphyrin 12], analogues of sensitisers 1-3 which are known to be active in vivo in cancer photodynamic therapy.
- Songca, Sandile P.,Bonnett, Raymond,Maes, Catherine M.
-
-
- Desilylation of tert-Butyldimethylsilyl Ethers of Phenols
-
Treatment of tert-butyldimethylsilyl ethers of phenols and diphenols with potassium fluoride in the presence of catalytic amounts of hydrobromic acid in dimethylformamide generates the corresponding phenols or diphenols in high yields.
- Sinhababu, Achintya K.,Kawase, Masami,Borchardt, Ronald T.
-
p. 710 - 712
(2007/10/02)
-
- Synthesis and Adrenergic Activity of Ring-Fluorinated Phenylephrines
-
2-Fluoro-, 4-fluoro-, and 6-fluorophenylephrine (6-FPE) were synthesized from the corresponding fluorinated 3-hydroxybenzaldehydes.New routes to 2-fluoro- and 6-fluoro-3-hydroxybenzaldehydes were developed based on regioselective lithiation of 2- and 4-fluorobenzene ortho to fluorine.As with norepinephrine and isoproterenol analogues, the adrenergic properties of phenylephrine were markedly altered by ring fluorination.The order of potency of the fluoro analogues as α1-adrenergic agonists in the stimulation of contraction of aorticstrips and of phosphatidylinositol turnover and potentiation of cyclic AMP accumulation in guinea pig synaptoneurosomes was 6-FPE > PE > 4-FPE > 2-FPE.The same pattern was observed for the displacement of radioligands specific for α1- and α2-adrenergic receptors on brain membranes.The order of potency for the displacement of 3H>dihydroalprenolol, a β-specific adrenergic ligand from brain membranes, was 2-FPE > 4-FPE = PE >> 6-FPE. 6-FPE was much more selective for α-adrenergic receptors compared to β-receptors than was phenylephrine.A rationale for the observed fluorine-induced alterations in potency and selectivity of the FPEs for α- and β-adrenergic systems is presented based on fluorine-induced conformations due to electrostatic repulsion of fluorine and the benzyl hydroxyl group.
- Kirk, Kenneth L.,Olubajo, Olarangbe,Buchhold, Konstantin,Lewandowski, Gail A.,Gusovsky, Fabian,et al.
-
p. 1982 - 1988
(2007/10/02)
-