Structure–Activity Relationship Study of Selective Excitatory Amino Acid Transporter Subtype 1 (EAAT1) Inhibitor 2-Amino-4-(4-methoxyphenyl)-7-(naphthalen-1-yl)-5-oxo-5,6,7,8-tetrahydro-4H-chromene-3-carbonitrile (UCPH-101) and Absolute Configurational Assignment Using Infrared and Vibrational Circular Dichroism Spectroscopy in Combination with ab Initio Hartree–Fock Calculations

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Structure-activity relationship study of selective excitatory amino acid transporter subtype 1 (EAAT1) inhibitor 2-amino-4-(4-methoxyphenyl)-7-(naphthalen-1-yl)-5-oxo-5,6,7,8-tetrahydro-4H-chromene-3-carbonitrile (UCPH-101) and absolute configurational assignment using infrared and vibrational circular dichroism spectroscopy in combination with ab initio Hartree-Fock calculations.

The excitatory amino acid transporters (EAATs) play essential roles in regulating the synaptic concentration of the neurotransmitter glutamate in the mammalian central nervous system. To date, five subtypes have been identified, named EAAT1-5 in humans, and GLAST, GLT-1, EAAC1, EAAT4, and EAAT5 in rodents, respectively. In this paper, we present the design, synthesis, and pharmacological evalua...

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2-amino-4-(4-chlorophenyl)-7,7-dimethyl-5-oxo-5,6,7,8-tetrahydro-4H-chromene-3-carbonitrile.

The supramolecular structure of the title compound, C(18)H(17)ClN(2)O(2), is determined by the intersection of two chains formed by N-H...O and N-H...N hydrogen bonds, forming a two-dimensional sheet.

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2-Amino-6-(naphthalen-1-yl)-4-phenyl­pyridine-3-carbonitrile

In the title compound, C(22)H(15)N(3), the naphthyl ring system makes dihedral angles of 67.40 (2) and 59.80 (3)° with the pyridyl and phenyl rings, respectively. In the crystal, the mol-ecules are connected via inter-molecular N-H⋯N hydrogen bonds, forming a three-dimensional network.

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2-Amino-4-(4-methyl­phen­yl)-5-oxo-5,6,7,8-tetra­hydro-4H-chromene-3-carbonitrile

The 4H-pyran ring of the title compound, C(17)H(16)N(2)O(2), is nearly planar [maximum deviation = 0.077 (2) Å] and the cyclo-hexene ring adopts a flattened chair conformation [puckering parameters: Q(T) = 0.435 (2) Å, θ = 122.0 (3)° and ϕ = 53.5 (3)°]. The 4H-pyran ring is almost perpendicular to the benzene ring [dihedral angle = 87.23 (8)°] and is almost coplanar with the mean plane of the c...

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2-Amino-4-[4-(dimethyl­amino)­phen­yl]-5-oxo-5,6,7,8-tetra­hydro-4H-chromene-3-carbonitrile

In the title mol-ecule, C(18)H(19)N(3)O(2), the fused cyclo-hexenone and pyran rings adopt sofa conformations. Inter-molecular N-H⋯N and N-H⋯O hydrogen bonds link mol-ecules into corrugated layers parallel to the bc plane.

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ژورنال

عنوان ژورنال: Journal of Medicinal Chemistry

سال: 2012

ISSN: 0022-2623,1520-4804

DOI: 10.1021/jm300345z