Solid-state characterization of an NR2B selective N-methyl d-aspartate (NMDA) antagonist polymorphs.
(-)-6-[2-[4-(3-Fluorophenyl)-4-hydroxy-piperidin-1-yl]-1-hydroxyethyl]-3,4-dihydro-quinolin-2(1H)-one (compound A) is an NR2B selective N-methyl d-aspartate (NMDA) antagonist that has shown at least two polymorphs, forms I and II. In this report, we prepared two polymorphs, forms I and II and their crystal forms were identified and characterized by single crystal X-ray diffractometry, differential scanning calorimetry (DSC) and variable temperature powder X-ray diffractometry (VT-PXRD). The results of DSC and VT-PXRD suggested that compound A has at least three polymorphic forms: I, II and a new form III, and that forms II and III showed an enantiotropic relationship. We also performed single crystal X-ray analyses of specific conditions based on the results of VT-PXRD. The unit cell dimensions in crystallographic parameter and molecular arrangements of form I were quite different from forms II and III. Whereas, the crystal structures of forms II and III were similar with the exception of the C58-C59-C61-C62 torsion angle.
Kojima
Takashi
T
Pfizer Global Research and Development, Nagoya Laboratories, Pfizer Japan Inc., 5-2 Taketoyo, Aichi 470-2393, Japan. tak_kojimajpn@yahoo.co.jp
Sato
Morimichi
M
Omura
Atsushi
A
Kawai
Makoto
M
Sakai
Mio
M
Matsuoka
Yoko
Y
Murata
Yoshinori
Y
Hattori
Kazunari
K
Sakemi
Shinichi
S
Bordner
Jon
J
Samardjiev
Ivan
I
Mano
Takashi
T
D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D007536:Isomerism; D008855:Microscopy, Electron, Scanning; D008958:Models, Molecular; D008968:Molecular Conformation; D010880:Piperidines / Q000737:chemistry / Q000494:pharmacology*; D015363:Quinolones / Q000737:chemistry / Q000494:pharmacology*; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*; D014961:X-Ray Diffraction
C524665:6-(2-(4-(3-fluorophenyl)-4-hydroxy-1-piperidinyl)-1-hydroxyethyl)-3,4-dihydro-2(1H)-quinolinone; D018691:Excitatory Amino Acid Antagonists; C121001:NR2B NMDA receptor; D010880:Piperidines; D015363:Quinolones; D016194:Receptors, N-Methyl-D-Aspartate