- Structural Characterization of Two Polymorphs of 1-(4-Methylpyridin-2-yl)thiourea and Two Derived 2-Aminothiazoles
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Abstract: Two polymorphic forms of 1-(4-methylpyridin-2-yl)thiourea (1) and the crystal and molecular structures of the 2-aminothiazoles N-(4-methylpyridin-2-yl)-4-(pyridin-2-yl)thiazol-2-amine (2) and N-(4-methylpyridin-2-yl)-4-(pyrazin-2-yl)thiazol-2-amine (3), derived from 1 and the respective α-bromoketone via the Hantzsch reaction, are described. Both polymorphic forms 1α (space group P21/c, Z = 4) and 1β (space group P21/n, Z = 8) crystallize in the monoclinic system but exhibit distinctly different intermolecular hydrogen bonding patterns. Compound 2 (orthorhombic, space group Pca21, Z = 8) forms polymeric N–H?N hydrogen-bonded zigzag tapes in the polar crystal structure, with a significant twisting between the thiazole and pyridine rings. In contrast, the crystal structure of 3 (monoclinic, space group P21/c, Z = 4) features nearly planar centrosymmetric N–H?N hydrogen-bonded dimers, which are laterally joined through long C–H?N contacts, affording a π?π stacked layered structure. Graphic Abstract: Two polymorphs of 1-(4-methylpyridin-2-yl)thiourea and the crystal and molecular structures of two 2-aminothiazoles, derived from 1-(4-methylpyridin-2-yl)thiourea and α-bromoketones via Hantzsch reaction, are reported.[Figure not available: see fulltext.]
- B?ck, Denise,Beuchel, Andreas,Goddard, Richard,Imming, Peter,Seidel, Rüdiger W.
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- NOVEL ANTIPRION COMPOUNDS
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Described herein are novel compositions and methods of treatment addressing diseases such as neurodegenerative diseases, including prion diseases and Alzheimer's disease.
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Paragraph 0648; 0649; 0699
(2013/03/28)
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- 2-aminothiazoles as therapeutic leads for prion diseases
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2-Aminothiazoles are a new class of small molecules with antiprion activity in prion-infected neuroblastoma cell lines (J. Virol. 2010, 84, 3408). We report here structure-activity studies undertaken to improve the potency and physiochemical properties of 2-aminothiazoles, with a particular emphasis on achieving and sustaining high drug concentrations in the brain. The results of this effort include the generation of informative structure-activity relationships (SAR) and the identification of lead compounds that are orally absorbed and achieve high brain concentrations in animals. The new aminothiazole analogue (5-methylpyridin-2-yl)-[4-(3-phenylisoxazol-5-yl)-thiazol-2-yl]-amine (27), for example, exhibited an EC50 of 0.94 μM in prion-infected neuroblastoma cells (ScN2a-cl3) and reached a concentration of ～25 μM in the brains of mice following three days of oral administration in a rodent liquid diet. The studies described herein suggest 2-aminothiazoles as promising new leads in the search for effective therapeutics for prion diseases.
- Gallardo-Godoy, Alejandra,Gever, Joel,Fife, Kimberly L.,Silber, B. Michael,Prusiner, Stanley B.,Renslo, Adam R.
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experimental part
p. 1010 - 1021
(2011/04/25)
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- Polycyclic thiazoles as potassium ion channel modulators
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The present invention provides a genus of polycyclic thiazoles that are useful as modulators of potassium ion channels. The modulators of the invention are of use in both therapeutic and diagnostic methods.
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Page/Page column 15-16
(2008/06/13)
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- Heterocyclic inhibitors of kinases
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The present invention provides compounds of formula I and pharmaceutically acceptable salts thereof. The formula I compounds inhibit the tyrosine kinase activity of growth factor receptors such as VEGFR-2, FGFR-1, thereby making them useful as anti-cancer agents. The formula I compounds are also useful for the treatment of other diseases associated with signal transduction pathways operating through growth factor receptors.
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Page/Page column 13
(2008/06/13)
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- Tyrosine kinase inhibitors
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The present invention relates to compounds which inhibit, regulate and/or modulate tyrosine kinase signal transduction, compositions which contain these compounds, and methods of using them to treat tyrosine kinase-dependent diseases and conditions, such as angiogenesis, cancer, tumor growth, atherosclerosis, age related macular degeneration, diabetic retinopathy, inflammatory diseases, and the like in mammals.
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