- Structures, Phase Behavior, and Fluorescent Properties of 3-Phenyl-1-(pyridin-2-yl)-1 H-pyrazol-5-amine and Its ZnCl2 Complex
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The synthesis of the asymmetric ligand 3-phenyl-1-(pyridin-2-yl)-1H-pyrazol-5-amine (L1) and its single-crystal X-ray structure are reported. L1 displays crystallographic symmetry (orthorhombic, Pccn) higher than its molecular symmetry (point group C1) and also displays supercooling, with a difference in the melting and solidification points of over 100 °C. Upon complexation with ZnCl2, L1 engages in both primary cation and secondary anion coordination via hydrogen bonding, and the complex exhibits a room-to-low-temperature single crystal-to-crystal phase transition. The ZnCl2 complex becomes a birefringent fluid mixed with crystalline domains at high temperatures, as detected by polarized optical microscopy. Examination of the photoluminescence properties showed that the emission intensity increased and a pronounced bathochromic shift was observed in the emission maximum upon going from solution to the solid state, for both the ligand and complex, consistent with aggregation-induced emission behavior.
- Hiscock, Lana K.,Joekar, Delara,Balonova, Barbora,Tomas Piqueras, Marta,Schroeder, Zachary W.,Jarvis, Victoria,Maly, Kenneth E.,Blight, Barry A.,Dawe, Louise N.
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- Substituent effects of N-(1,3-diphenyl-1H-pyrazol-5-yl)benzamides on positive allosteric modulation of the metabotropic glutamate-5 receptor in rat cortical astrocytes
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CDPPB [3-cyano-N-(1,3-diphenyl-1H-pyrazol-5-yl)benzamide] was recently described as the first centrally active, positive allosteric modulator of rat and human metabotropic glutamate receptor (mGluR) mGluR5 subtype. We explored the structural requirements for potentiation of glutamate-induced calcium release in naturally expressed mGluR5 in cultured rat astrocytes and increasing affinity for the allosteric antagonist binding site by evaluating 50 analogues of CDPPB. In the fluorometric calcium assay, CDPPB exhibited an EC50 value of 77 ± 15 nM in potentiating mGluR 5-mediated responses in cortical astrocytes and a Ki value of 3760 ± 430 nM in displacing [3H]methoxyPEPy binding in membranes of cultured HEK-293 cells expressing rat mGluR5. The structure-activity relationships showed that electronegative aromatic substituents in the para-position of the benzamide moiety of CDPPB increase potency. Both binding and functional activities were further increased with a halogen atom in the ortho-position of the 1-phenyl ring. These effects of substitution do not match those of either aromatic ring of MPEP [2-methyl-6-(phenylethynyl)-pyridine] for the antagonist allosteric binding site. Combination of the optimal substituents and aromatic positions resulted in 4-nitro-N-(1-(2-fluorophenyl)-3-phenyl-1H-pyrazol-5-yl)benzamide (VU-1545) showing Ki = 156 ± 29 nM and EC50 = 9.6 ± 1.9 nM in the binding and functional assays, respectively.
- De Paulis, Tomas,Hemstapat, Kamondanai,Chen, Yelin,Zhang, Yongqin,Saleh, Samir,Alagille, David,Baldwin, Ronald M.,Tamagnan, Gilles D.,Conn, P. Jeffrey
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p. 3332 - 3344
(2007/10/03)
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- Heterocycles of Biological Importance. Part 2. Novel Synthesis and Pharmacological Evaluation of 5-Amino-3-alkyl-1-(2-pyridyl)pyrazoles and 5-Amino-3-phenyl-1-(2-pyridyl)pyrazole from Allenic or Acetylenic Nitriles and 2-Hydrazinopyridine
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2-Hydrazinopyridine reacts with allenic and acetylenic nitriles to give 5-amino-3-alkyl-1-(2-pyridyl)pyrazoles 6 in excellent yields.One of these compounds, 6e has been shown to possess anticonvulsant and anti-electroshock properties.Phenyl propynenitrile
- Fomum, Tanee Z.,Ifeadike, Ngozi P.
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p. 1611 - 1614
(2007/10/02)
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