The title compound consists of a substituted 2-[(E)-2-arylethenyl]-3-arylquinazolin-4(3H)-one skeleton. The substituents at the ethylene fragment are located in trans positions. In the crystal, molecules are connected via O—H⋯O hydrogen bonds forming a 21 helix propagating along the a-axis direction.
Keywords: crystal structure; 2,3-disubstituted quinazolin-4(3H)-one; styrylquinazolinone conjugation system; hydrogen bonding
Abstract
The title compound, C22H16N2O2 {systematic name: 3-(4-hydroxyphenyl)-2-[(E)-2-phenylethenyl]quinazolin-4(3H)-one}, consists of a substituted 2-[(E)-2-arylethenyl]-3-arylquinazolin-4(3H)-one skeleton. The substituents at the ethylene fragment are located in trans positions. The phenyl ring is inclined to the quinazolone ring by 26.44 (19)°, while the 4-hydroxyphenyl ring is inclined to the quinazolone ring by 81.25 (8)°. The phenyl ring and the 4-hydroxyphenyl ring are inclined to one another by 78.28 (2)°. In the crystal, molecules are connected via O—H⋯O hydrogen bonds, forming a helix along the a-axis direction. The helices are linked by C—H⋯π interactions, forming slabs parallel to (001).
Chemical context
Compounds containing the 2-[(E)-2-arylethenyl]-3-arylquinazolin-4(3H)-one core are well known for their broad biological activities. These compounds demonstrate antibiotic effect in vivo against methicillin-resistant Staphylococcus aureus (Bouley et al., 2015 ▸; Chang et al., 2014 ▸) and antileishmanial activity (Birhan et al., 2014 ▸). 2-Styryl functionalized quinazolinones are applicable as anticancer agents against human cell lines (Kamal et al., 2013 ▸; 2012 ▸; 2010a ▸,b
▸) and anticonvulsants (Das et al., 2014 ▸). Analogues of the title compound are Hsp90 inhibitors with in vitro anti-tumor activity (Park et al., 2007 ▸), as well as suppressants of the ubiquitin ligase activity of a human polypeptide (Erez & Nakache, 2011 ▸), GluN2D-containing NMDA receptors (Hansen & Traynelis, 2011 ▸) and c-KIT expression (Wang et al., 2013 ▸). Compounds with such a structure are good modulators of both γ-secretase (Fischer et al., 2011 ▸) and Rho C activity (Sun et al., 2003 ▸), as well as AMPA receptor antagonists (Chenard et al., 2001 ▸; 1999 ▸; Welch & DeVries, 1998 ▸). Piriqualone (the 2-hetarylvinyl analogue of the above mentioned compounds) has been used as a sedative–hypnotic drug (Kumar et al., 2015 ▸).
Structural commentary
The title compound 1, Fig. 1 ▸, consists of a substituted 2-[(E)-2-arylethenyl]-3-arylquinazolin-4(3H)-one skeleton. The substituents at the ethylene fragment are located in trans-positions. Unlike the structure reported by Nosova et al. (2012 ▸), where the conjugation system of styrylquinazolinone is practically planar, in compound 1 the 2-phenyleth-(E)-enyl substituent is twisted with respect to the plane of the quinazolone ring. The phenyl (C21–C26) and the 4-hydroxyphenyl (C12–C17) rings are inclined to one another by 78.2 (2)°, and to the quinazolone ring (N1/N2/C2/C4–C10) by 26.44 (19) and 81.25 (8)°, respectively. A similar styrylquinazolinone conjugation system geometry has been found in structures reported previously (Trashakhova et al., 2011 ▸; Ovchinnikova et al., 2014 ▸).
Figure 1.
The molecular structure of compound 1, showing the atom labelling. Displacement ellipsoids are drawn at the 50% probability level.
Supramolecular features
In the crystal of 1, molecules are connected via O—H⋯O hydrogen bonds forming a 21 helix, with graph set C(3), propagating along the a-axis direction (Table 1 ▸ and Fig. 2 ▸). This is similar to the crystal packing reported for the structure of diltiazem acetylsalicilate hydrate (Stepanovs et al., 2016 ▸). In 1, the helices are linked via C—H⋯π interactions, forming slabs lying parallel to the ab plane (Table 1 ▸ and Fig. 3 ▸).
Table 1. Hydrogen-bond geometry (Å, °).
Cg3 and Cg4 are the centroids of the C12–C17 and C21–C26 rings, respectively.
| D—H⋯A | D—H | H⋯A | D⋯A | D—H⋯A |
|---|---|---|---|---|
| O18—H18⋯O11i | 0.82 | 1.84 | 2.654 (5) | 172 |
| C4—H4⋯Cg4ii | 0.94 | 2.96 | 3.829 (5) | 157 |
| C16—H16⋯Cg3i | 0.94 | 2.95 | 3.646 (5) | 133 |
Symmetry codes: (i) 
; (ii) 
.
Figure 2.
A fragment of the crystal structure of compound 1, showing the helix-like hydrogen-bonded chain propagating along the a-axis direction.
Figure 3.
A view along the a axis of the crystal packing of compound 1. The hydrogen bonds are shown as dashed lines and the C—H⋯π interactions (see Table 1 ▸) are represented as thin black lines.
Database survey
A search of the Cambridge Structural Database (Version 5.37; Groom & Allen, 2014 ▸) for substructure S1 (Fig. 4 ▸) gave 137 hits, while a search for substructure S2 (2-arylvinyl 3-aryl quinazolin-4(3H)-one skeleton, Fig. 4 ▸) gave only three hits: Nosova et al. (2012 ▸); Trashakhova et al. (2011 ▸); Ovchinnikova et al. (2014 ▸). However, none of the characterized single crystals contains a hydrogen-bond donor/acceptor in the aryl substituent at position 3 of the quinazolinone unit and information on intermolecular interactions of such structures is still missing. The only example containing a carboxylic functionality at the 3-aryl substituent of quinazolin-4(3H)-one was analysed as a complex with Staphylococcus aureus at the PBP2a binding site (Bouley et al., 2015 ▸).
Figure 4.
Substructures used for the Database survey.
Synthesis and crystallization
The title compound 1 was synthesized applying two pathways starting from 2-methyl (2) or 2-styryl (3) benzoxazin-4-one (methods A and B, respectively, Fig. 5 ▸).
Figure 5.
Synthesis of the title compound, 1.
Method A
2-Methyl benzoxazin-4-one (2) (0.263 g, 1.6 mmol) and 4-aminophenol (4) (0.175 g, 1.6 mmol) in glacial acetic acid (2 ml) were refluxed for 7 h, then poured into crushed ice (50 ml) and filtered. Compound 5 was obtained as a greyish solid. Its spectroscopic data corresponded to those in the literature (Marinho & Proença, 2015 ▸). The crude product 5, without further purification, was subjected to condensation with benzaldehyde analogously to a known method (Krastina et al., 2014 ▸): 3-(4-hydroxyphenyl)-2-methylquinazolin-4(3H)-one (5) (0.276 g, 1.1 mmol), benzaldehyde (0.27 g, 2.53 mol) and acetanhydride (0.5 ml) in acetic acid (4 ml) were refluxed for 8 h, poured into crushed ice (50 ml), filtered and air-dried. The mixture containing compounds 1 and 6 (0.25 g) was refluxed for 7 h in NaOH/methanol (5%, 5 ml), poured into crushed ice (50 ml), acidified with conc. hydrochloric acid and filtered. The target compound 1 was obtained as a white solid with 53% (0.197 g) yield over two steps.
Method B
The title compound 1 was obtained as a by-product during the synthesis of 2-cinnamamido-N-(4-hydroxyphenyl)benzamide: benzoxazin-4-one 3 (1.00 g, 4 mmol) and 4-aminophenol (4) (0.44 g, 4 mmol) were refluxed in toluene (5 ml) for 3 h, then the mixture was filtered. The title compound was isolated by crystallization from ethanol.
Single crystals suitable for X-ray analysis were obtained by slow evaporation from ethanol at room temperature (m.p. > 523 K).
Spectroscopic data: IR (KBr), ν, cm−1: 3300 (OH), 1655 (CON), 1150, 1515, 1470, 1450, 1340, 1225, 970, 775, 965. 1H NMR (300 MHz, DMSO-d 6), δ (p.p.m.): 9.91 (1H, s, OH), 8.12 (1H, d, J = 7.8 Hz, H-5), 7.91–7.83 (2H, m, H-b, H-6/7), 7.76 (1H, d, J = 7.8 Hz, H-8), 7.52 (1H, t, J = 7.8 Hz, H-6/7), 7.41–7.33 (5H, m, Ph), 7.23 (2H, d, J = 8.6 Hz, H-1′), 6.94 (2H, d, J = 8.6 Hz, H-2′), 6.42 (1H, d, J = 15.4 Hz, H-a). 13C NMR (75 MHz, DMSO-d 6), δ (p.p.m.): 161.5, 157.8, 152.0, 147.4, 138.6, 134.9, 134.7, 129.9, 129.8, 129.1, 127.9, 127.4, 127.1, 126.52, 126.47, 120.6, 120.2, 116.1. HRMS. Calculated [M+H]+, m/z: 341.1285. C22H16N2O2. Found, m/z: 341.1282.
Refinement
Crystal data, data collection and structure refinement details are summarized in Table 2 ▸. The C-bound H atoms were positioned geometrically and refined as riding on their parent atoms: C—H = 0.93 − 0.98 Å with U iso(H) = 1.5U eq(C) for methyl H atoms and 1.2U eq(C) for other H atoms. The H atom of the hydroxyl group was included in the position identified from a difference Fourier map and was then refined as riding: O—H = 0.82 Å with U iso(H) = 1.5U eq(O).
Table 2. Experimental details.
| Crystal data | |
| Chemical formula | C22H16N2O2 |
| M r | 340.37 |
| Crystal system, space group | Orthorhombic, P21 n b |
| Temperature (K) | 173 |
| a, b, c (Å) | 5.3469 (2), 16.5139 (6), 19.8885 (10) |
| V (Å3) | 1756.12 (13) |
| Z | 4 |
| Radiation type | Mo Kα |
| μ (mm−1) | 0.08 |
| Crystal size (mm) | 0.22 × 0.18 × 0.09 |
| Data collection | |
| Diffractometer | Nonius KappaCCD |
| No. of measured, independent and observed [I > 2σ(I)] reflections | 3862, 3862, 2236 |
| (sin θ/λ)max (Å−1) | 0.649 |
| Refinement | |
| R[F 2 > 2σ(F 2)], wR(F 2), S | 0.068, 0.139, 1.03 |
| No. of reflections | 3862 |
| No. of parameters | 236 |
| No. of restraints | 1 |
| H-atom treatment | H-atom parameters constrained |
| Δρmax, Δρmin (e Å−3) | 0.17, −0.19 |
Computer programs: KappaCCD Server Software (Nonius, 1997 ▸), DENZO and SCALEPACK (Otwinowski & Minor, 1997 ▸), SIR2011 (Burla et al., 2012 ▸), ORTEP-3 for Windows (Farrugia, 2012 ▸), Mercury (Macrae et al., 2008 ▸), SHELXL2015 (Sheldrick, 2015 ▸), PLATON (Spek, 2009 ▸) and publCIF (Westrip, 2010 ▸).
Supplementary Material
Crystal structure: contains datablock(s) I. DOI: 10.1107/S2056989016004473/su5288sup1.cif
Structure factors: contains datablock(s) I. DOI: 10.1107/S2056989016004473/su5288Isup2.hkl
Supporting information file. DOI: 10.1107/S2056989016004473/su5288Isup3.cml
CCDC reference: 1468806
Additional supporting information: crystallographic information; 3D view; checkCIF report
Acknowledgments
The authors thank the Latvian–Lithuanian–Taiwanese co-project W1935//LV-LT-TW/2015/2 for financial support. JK is grateful for an ERASMUS+ mobility grant for the opportunity of a traineeship at RTU.
supplementary crystallographic information
Crystal data
| C22H16N2O2 | Dx = 1.287 Mg m−3 |
| Mr = 340.37 | Mo Kα radiation, λ = 0.71073 Å |
| Orthorhombic, P21nb | Cell parameters from 6856 reflections |
| a = 5.3469 (2) Å | θ = 1.0–27.5° |
| b = 16.5139 (6) Å | µ = 0.08 mm−1 |
| c = 19.8885 (10) Å | T = 173 K |
| V = 1756.12 (13) Å3 | Plate, colorless |
| Z = 4 | 0.22 × 0.18 × 0.09 mm |
| F(000) = 712 |
Data collection
| Nonius KappaCCD diffractometer | 2236 reflections with I > 2σ(I) |
| Radiation source: fine-focus sealed tube | θmax = 27.5°, θmin = 3.2° |
| φ and ω scan | h = −6→6 |
| 3862 measured reflections | k = −21→21 |
| 3862 independent reflections | l = −25→25 |
Refinement
| Refinement on F2 | Secondary atom site location: difference Fourier map |
| Least-squares matrix: full | Hydrogen site location: inferred from neighbouring sites |
| R[F2 > 2σ(F2)] = 0.068 | H-atom parameters constrained |
| wR(F2) = 0.139 | w = 1/[σ2(Fo2) + (0.0478P)2 + 0.3939P] where P = (Fo2 + 2Fc2)/3 |
| S = 1.03 | (Δ/σ)max < 0.001 |
| 3862 reflections | Δρmax = 0.17 e Å−3 |
| 236 parameters | Δρmin = −0.19 e Å−3 |
| 1 restraint |
Special details
| Geometry. All e.s.d.'s (except the e.s.d. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell e.s.d.'s are taken into account individually in the estimation of e.s.d.'s in distances, angles and torsion angles; correlations between e.s.d.'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell e.s.d.'s is used for estimating e.s.d.'s involving l.s. planes. |
Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å2)
| x | y | z | Uiso*/Ueq | ||
| N1 | 0.6956 (7) | 0.7742 (2) | 0.45545 (18) | 0.0333 (9) | |
| C2 | 0.8449 (8) | 0.7044 (3) | 0.4584 (2) | 0.0317 (10) | |
| N3 | 0.8479 (7) | 0.6500 (2) | 0.41192 (18) | 0.0372 (9) | |
| C4 | 0.6912 (9) | 0.6013 (3) | 0.3061 (2) | 0.0436 (12) | |
| H4 | 0.7956 | 0.5564 | 0.3096 | 0.052* | |
| C5 | 0.5358 (9) | 0.6089 (3) | 0.2518 (2) | 0.0476 (13) | |
| H5 | 0.5349 | 0.5690 | 0.2188 | 0.057* | |
| C6 | 0.3791 (11) | 0.6756 (3) | 0.2457 (3) | 0.0564 (15) | |
| H6 | 0.2738 | 0.6801 | 0.2086 | 0.068* | |
| C7 | 0.3795 (12) | 0.7346 (3) | 0.2939 (3) | 0.0588 (15) | |
| H7 | 0.2750 | 0.7793 | 0.2895 | 0.071* | |
| C8 | 0.5362 (10) | 0.7885 (3) | 0.4018 (3) | 0.0435 (12) | |
| C9 | 0.6946 (8) | 0.6604 (3) | 0.3564 (2) | 0.0337 (11) | |
| C10 | 0.5376 (9) | 0.7278 (3) | 0.3501 (2) | 0.0372 (11) | |
| O11 | 0.4054 (7) | 0.8506 (2) | 0.40120 (19) | 0.0653 (12) | |
| C12 | 0.7042 (8) | 0.8360 (3) | 0.5076 (2) | 0.0315 (10) | |
| C13 | 0.5181 (8) | 0.8382 (3) | 0.5557 (2) | 0.0354 (11) | |
| H13 | 0.3953 | 0.7983 | 0.5563 | 0.042* | |
| C14 | 0.5143 (9) | 0.8993 (3) | 0.6027 (2) | 0.0372 (11) | |
| H14 | 0.3905 | 0.9002 | 0.6356 | 0.045* | |
| C15 | 0.6941 (8) | 0.9595 (3) | 0.6013 (2) | 0.0309 (10) | |
| C16 | 0.8821 (8) | 0.9566 (3) | 0.5533 (2) | 0.0344 (11) | |
| H16 | 1.0059 | 0.9962 | 0.5528 | 0.041* | |
| C17 | 0.8859 (8) | 0.8951 (3) | 0.5064 (2) | 0.0339 (11) | |
| H17 | 1.0110 | 0.8936 | 0.4739 | 0.041* | |
| O18 | 0.6763 (7) | 1.01968 (18) | 0.64797 (15) | 0.0426 (8) | |
| H18 | 0.7583 | 1.0589 | 0.6356 | 0.064* | |
| C19 | 0.9961 (7) | 0.6928 (3) | 0.5188 (2) | 0.0338 (11) | |
| H19 | 0.9602 | 0.7230 | 0.5570 | 0.041* | |
| C20 | 1.1845 (8) | 0.6398 (3) | 0.5204 (2) | 0.0341 (10) | |
| H20 | 1.2220 | 0.6133 | 0.4804 | 0.041* | |
| C21 | 1.3390 (9) | 0.6191 (3) | 0.5794 (2) | 0.0361 (11) | |
| C22 | 1.2883 (9) | 0.6474 (3) | 0.6437 (2) | 0.0435 (12) | |
| H22 | 1.1527 | 0.6816 | 0.6508 | 0.052* | |
| C23 | 1.4371 (8) | 0.6252 (3) | 0.6973 (3) | 0.0498 (15) | |
| H23 | 1.4006 | 0.6441 | 0.7402 | 0.060* | |
| C24 | 1.6404 (9) | 0.5748 (3) | 0.6875 (3) | 0.0512 (14) | |
| H24 | 1.7421 | 0.5605 | 0.7235 | 0.061* | |
| C25 | 1.6909 (10) | 0.5460 (3) | 0.6243 (3) | 0.0496 (13) | |
| H25 | 1.8265 | 0.5117 | 0.6176 | 0.060* | |
| C26 | 1.5421 (9) | 0.5676 (3) | 0.5706 (2) | 0.0399 (12) | |
| H26 | 1.5779 | 0.5475 | 0.5280 | 0.048* |
Atomic displacement parameters (Å2)
| U11 | U22 | U33 | U12 | U13 | U23 | |
| N1 | 0.0351 (19) | 0.030 (2) | 0.035 (2) | 0.0014 (17) | −0.0054 (19) | −0.0034 (17) |
| C2 | 0.031 (2) | 0.027 (2) | 0.037 (3) | 0.003 (2) | −0.004 (2) | −0.002 (2) |
| N3 | 0.041 (2) | 0.033 (2) | 0.037 (2) | 0.0064 (18) | −0.0066 (19) | −0.0067 (19) |
| C4 | 0.050 (3) | 0.038 (3) | 0.042 (3) | 0.003 (2) | −0.001 (3) | −0.007 (2) |
| C5 | 0.052 (3) | 0.051 (4) | 0.040 (3) | −0.011 (3) | −0.001 (3) | −0.013 (3) |
| C6 | 0.066 (3) | 0.065 (4) | 0.038 (3) | −0.002 (3) | −0.017 (3) | −0.007 (3) |
| C7 | 0.067 (3) | 0.059 (4) | 0.050 (3) | 0.012 (3) | −0.021 (3) | −0.003 (3) |
| C8 | 0.045 (3) | 0.041 (3) | 0.043 (3) | 0.004 (3) | −0.012 (3) | −0.001 (2) |
| C9 | 0.036 (2) | 0.034 (3) | 0.031 (3) | −0.001 (2) | −0.004 (2) | −0.002 (2) |
| C10 | 0.044 (2) | 0.038 (3) | 0.030 (3) | 0.004 (2) | −0.006 (2) | −0.001 (2) |
| O11 | 0.081 (3) | 0.055 (3) | 0.060 (3) | 0.029 (2) | −0.030 (2) | −0.010 (2) |
| C12 | 0.031 (2) | 0.031 (3) | 0.032 (3) | 0.003 (2) | −0.003 (2) | −0.003 (2) |
| C13 | 0.036 (2) | 0.029 (3) | 0.041 (3) | −0.009 (2) | −0.001 (2) | 0.004 (2) |
| C14 | 0.039 (2) | 0.037 (3) | 0.036 (3) | −0.002 (2) | 0.006 (2) | 0.003 (2) |
| C15 | 0.040 (2) | 0.027 (3) | 0.026 (2) | −0.003 (2) | −0.003 (2) | 0.001 (2) |
| C16 | 0.034 (2) | 0.033 (3) | 0.036 (3) | −0.007 (2) | 0.001 (2) | 0.000 (2) |
| C17 | 0.032 (2) | 0.036 (3) | 0.034 (3) | −0.001 (2) | 0.004 (2) | 0.001 (2) |
| O18 | 0.062 (2) | 0.0355 (19) | 0.0304 (17) | −0.0100 (17) | 0.0041 (16) | −0.0058 (16) |
| C19 | 0.038 (2) | 0.029 (3) | 0.034 (3) | −0.002 (2) | −0.006 (2) | −0.002 (2) |
| C20 | 0.040 (2) | 0.027 (2) | 0.035 (3) | −0.002 (2) | −0.005 (2) | 0.000 (2) |
| C21 | 0.037 (2) | 0.030 (3) | 0.041 (3) | −0.007 (2) | −0.012 (2) | 0.001 (2) |
| C22 | 0.041 (3) | 0.045 (3) | 0.044 (3) | −0.003 (2) | −0.008 (2) | −0.004 (3) |
| C23 | 0.054 (3) | 0.060 (4) | 0.036 (3) | −0.010 (3) | −0.009 (2) | 0.002 (3) |
| C24 | 0.047 (3) | 0.060 (4) | 0.047 (4) | −0.009 (3) | −0.018 (2) | 0.011 (3) |
| C25 | 0.038 (3) | 0.051 (3) | 0.059 (4) | 0.001 (2) | −0.007 (3) | 0.016 (3) |
| C26 | 0.039 (2) | 0.040 (3) | 0.041 (3) | −0.001 (2) | −0.003 (2) | 0.003 (2) |
Geometric parameters (Å, º)
| N1—C8 | 1.385 (6) | C14—H14 | 0.9300 |
| N1—C2 | 1.404 (5) | C15—O18 | 1.364 (5) |
| N1—C12 | 1.455 (5) | C15—C16 | 1.387 (6) |
| C2—N3 | 1.289 (5) | C16—C17 | 1.379 (6) |
| C2—C19 | 1.459 (6) | C16—H16 | 0.9300 |
| N3—C9 | 1.385 (5) | C17—H17 | 0.9300 |
| C4—C5 | 1.368 (7) | O18—H18 | 0.8200 |
| C4—C9 | 1.398 (6) | C19—C20 | 1.335 (6) |
| C4—H4 | 0.9300 | C19—H19 | 0.9300 |
| C5—C6 | 1.390 (7) | C20—C21 | 1.475 (6) |
| C5—H5 | 0.9300 | C20—H20 | 0.9300 |
| C6—C7 | 1.367 (7) | C21—C22 | 1.389 (6) |
| C6—H6 | 0.9300 | C21—C26 | 1.390 (6) |
| C7—C10 | 1.406 (7) | C22—C23 | 1.379 (6) |
| C7—H7 | 0.9300 | C22—H22 | 0.9300 |
| C8—O11 | 1.241 (6) | C23—C24 | 1.382 (7) |
| C8—C10 | 1.436 (6) | C23—H23 | 0.9300 |
| C9—C10 | 1.400 (6) | C24—C25 | 1.370 (7) |
| C12—C17 | 1.378 (6) | C24—H24 | 0.9300 |
| C12—C13 | 1.381 (6) | C25—C26 | 1.378 (7) |
| C13—C14 | 1.377 (6) | C25—H25 | 0.9300 |
| C13—H13 | 0.9300 | C26—H26 | 0.9300 |
| C14—C15 | 1.383 (6) | ||
| C8—N1—C2 | 121.5 (4) | C15—C14—H14 | 119.9 |
| C8—N1—C12 | 116.7 (4) | O18—C15—C14 | 117.4 (4) |
| C2—N1—C12 | 121.8 (3) | O18—C15—C16 | 123.0 (4) |
| N3—C2—N1 | 123.3 (4) | C14—C15—C16 | 119.6 (4) |
| N3—C2—C19 | 119.4 (4) | C17—C16—C15 | 120.1 (4) |
| N1—C2—C19 | 117.3 (4) | C17—C16—H16 | 119.9 |
| C2—N3—C9 | 118.6 (4) | C15—C16—H16 | 119.9 |
| C5—C4—C9 | 120.6 (5) | C12—C17—C16 | 120.0 (4) |
| C5—C4—H4 | 119.7 | C12—C17—H17 | 120.0 |
| C9—C4—H4 | 119.7 | C16—C17—H17 | 120.0 |
| C4—C5—C6 | 120.6 (5) | C15—O18—H18 | 109.5 |
| C4—C5—H5 | 119.7 | C20—C19—C2 | 121.6 (4) |
| C6—C5—H5 | 119.7 | C20—C19—H19 | 119.2 |
| C7—C6—C5 | 120.2 (5) | C2—C19—H19 | 119.2 |
| C7—C6—H6 | 119.9 | C19—C20—C21 | 126.5 (4) |
| C5—C6—H6 | 119.9 | C19—C20—H20 | 116.8 |
| C6—C7—C10 | 120.1 (5) | C21—C20—H20 | 116.8 |
| C6—C7—H7 | 119.9 | C22—C21—C26 | 118.3 (4) |
| C10—C7—H7 | 119.9 | C22—C21—C20 | 123.1 (4) |
| O11—C8—N1 | 119.7 (5) | C26—C21—C20 | 118.7 (4) |
| O11—C8—C10 | 124.9 (5) | C23—C22—C21 | 120.6 (5) |
| N1—C8—C10 | 115.5 (4) | C23—C22—H22 | 119.7 |
| N3—C9—C4 | 119.4 (4) | C21—C22—H22 | 119.7 |
| N3—C9—C10 | 121.7 (4) | C22—C23—C24 | 120.3 (5) |
| C4—C9—C10 | 118.9 (4) | C22—C23—H23 | 119.9 |
| C9—C10—C7 | 119.7 (4) | C24—C23—H23 | 119.9 |
| C9—C10—C8 | 119.5 (4) | C25—C24—C23 | 119.6 (5) |
| C7—C10—C8 | 120.7 (5) | C25—C24—H24 | 120.2 |
| C17—C12—C13 | 120.1 (4) | C23—C24—H24 | 120.2 |
| C17—C12—N1 | 120.4 (4) | C24—C25—C26 | 120.4 (5) |
| C13—C12—N1 | 119.3 (4) | C24—C25—H25 | 119.8 |
| C14—C13—C12 | 120.1 (4) | C26—C25—H25 | 119.8 |
| C14—C13—H13 | 120.0 | C25—C26—C21 | 120.8 (5) |
| C12—C13—H13 | 120.0 | C25—C26—H26 | 119.6 |
| C13—C14—C15 | 120.1 (4) | C21—C26—H26 | 119.6 |
| C13—C14—H14 | 119.9 | ||
| C8—N1—C2—N3 | 1.2 (7) | C8—N1—C12—C17 | −95.4 (5) |
| C12—N1—C2—N3 | −177.5 (4) | C2—N1—C12—C17 | 83.3 (5) |
| C8—N1—C2—C19 | −176.7 (4) | C8—N1—C12—C13 | 80.1 (5) |
| C12—N1—C2—C19 | 4.7 (6) | C2—N1—C12—C13 | −101.2 (5) |
| N1—C2—N3—C9 | −0.6 (6) | C17—C12—C13—C14 | −0.3 (6) |
| C19—C2—N3—C9 | 177.1 (4) | N1—C12—C13—C14 | −175.8 (4) |
| C9—C4—C5—C6 | 0.2 (8) | C12—C13—C14—C15 | 1.1 (7) |
| C4—C5—C6—C7 | 0.2 (9) | C13—C14—C15—O18 | 178.2 (4) |
| C5—C6—C7—C10 | −0.3 (9) | C13—C14—C15—C16 | −1.8 (7) |
| C2—N1—C8—O11 | 179.4 (5) | O18—C15—C16—C17 | −178.4 (4) |
| C12—N1—C8—O11 | −1.9 (7) | C14—C15—C16—C17 | 1.6 (7) |
| C2—N1—C8—C10 | −0.7 (6) | C13—C12—C17—C16 | 0.1 (6) |
| C12—N1—C8—C10 | 178.0 (4) | N1—C12—C17—C16 | 175.5 (4) |
| C2—N3—C9—C4 | −178.7 (4) | C15—C16—C17—C12 | −0.7 (7) |
| C2—N3—C9—C10 | −0.3 (6) | N3—C2—C19—C20 | 17.8 (7) |
| C5—C4—C9—N3 | 178.0 (4) | N1—C2—C19—C20 | −164.3 (4) |
| C5—C4—C9—C10 | −0.5 (7) | C2—C19—C20—C21 | −175.8 (4) |
| N3—C9—C10—C7 | −178.0 (5) | C19—C20—C21—C22 | 6.9 (7) |
| C4—C9—C10—C7 | 0.4 (7) | C19—C20—C21—C26 | −174.5 (4) |
| N3—C9—C10—C8 | 0.7 (7) | C26—C21—C22—C23 | 0.4 (7) |
| C4—C9—C10—C8 | 179.1 (4) | C20—C21—C22—C23 | 179.0 (4) |
| C6—C7—C10—C9 | 0.0 (8) | C21—C22—C23—C24 | 0.5 (7) |
| C6—C7—C10—C8 | −178.7 (5) | C22—C23—C24—C25 | −1.0 (7) |
| O11—C8—C10—C9 | 179.8 (5) | C23—C24—C25—C26 | 0.6 (8) |
| N1—C8—C10—C9 | −0.2 (6) | C24—C25—C26—C21 | 0.3 (7) |
| O11—C8—C10—C7 | −1.6 (8) | C22—C21—C26—C25 | −0.8 (7) |
| N1—C8—C10—C7 | 178.5 (5) | C20—C21—C26—C25 | −179.5 (4) |
Hydrogen-bond geometry (Å, º)
Cg3 and Cg4 are the centroids of the C12–C17 and C21–C26 rings, respectively.
| D—H···A | D—H | H···A | D···A | D—H···A |
| O18—H18···O11i | 0.82 | 1.84 | 2.654 (5) | 172 |
| C4—H4···Cg4ii | 0.94 | 2.96 | 3.829 (5) | 157 |
| C16—H16···Cg3i | 0.94 | 2.95 | 3.646 (5) | 133 |
Symmetry codes: (i) x+1/2, −y+2, −z+1; (ii) x−1/2, −y+1, −z+1.
References
- Birhan, Y. S., Bekhit, A. A. & Hymete, A. (2014). Org. Med. Chem. 4 10.1186/s13588-014-0010-1. [DOI] [PMC free article] [PubMed]
- Bouley, R., Kumarasiri, M., Peng, Z., Otero, L. H., Song, W., Suckow, M. A., Schroeder, V. A., Wolter, W. R., Lastochkin, E., Antunes, N. T., Pi, H., Vakulenko, S., Hermoso, J. A., Chang, M. & Mobashery, S. (2015). J. Am. Chem. Soc. 137, 1738–1741. [DOI] [PMC free article] [PubMed]
- Burla, M. C., Caliandro, R., Camalli, M., Carrozzini, B., Cascarano, G. L., Giacovazzo, C., Mallamo, M., Mazzone, A., Polidori, G. & Spagna, R. (2012). J. Appl. Cryst. 45, 357–361.
- Chang, M., Mobashery, S. & Bouley, R. (2014). Int. Patent Appl. 2014/138302.
- Chenard, B., Menniti, F. S. & Welch, W. K. (1999). Eur. Patent Appl. 0900568.
- Chenard, B. L., Welch, W. M., Blake, J. F., Butler, T. W., Reinhold, A., Ewing, F. E., Menniti, F. S. & Pagnozzi, M. (2001). J. Med. Chem. 44, 1710–1717. [DOI] [PubMed]
- Das, N., Garabadu, D., Banerjee, A. G., Krishnamurthy, S. & Shrivastava, S. K. (2014). Med. Chem. Res. 23, 4167–4176.
- Erez, O. & Nakache, P. (2011). Int. Patent Appl. 2011/064657.
- Farrugia, L. J. (2012). J. Appl. Cryst. 45, 849–854.
- Fischer, C., Shah, S., Hughes, B. L., Nikov, G. N., Crispino, J. L., Middleton, R. E., Szewczak, A. A., Munoz, B. & Shearman, M. S. (2011). Bioorg. Med. Chem. Lett. 21, 773–776. [DOI] [PubMed]
- Groom, C. R. & Allen, F. H. (2014). Angew. Chem. Int. Ed. 53, 662–671. [DOI] [PubMed]
- Hansen, K. B. & Traynelis, S. F. (2011). J. Neurosci. 31, 3650–3661. [DOI] [PMC free article] [PubMed]
- Kamal, A., Bharathi, E. V., Dastagiri, D., Reddy, J. S. & Viswanath, A. (2010a). Int. Patent Appl. 2010/058416.
- Kamal, A., Sultana, F., Bharathi, E. V., Srikanth, Y. V. V., Viswanath, A. & Swapna, P. (2012). Int. Patent Appl. 2012/111017.
- Kamal, A., Sultana, F., Ramaiah, M. J., Srikanth, Y. V. V., Viswanath, A., Bharathi, E. V., Nayak, R., Pushpavalli, S. N. C. V. L., Srinivas, C. & Pal-Bhadra, M. (2013). Med. Chem. Commun. 4, 575–581.
- Kamal, A., Bharathi, E. V., Ramaiah, M. J., Dastagiri, D., Reddy, J. S., Viswanath, A., Sultana, F., Pushpavalli, S. N. C. V. L., Pal-Bhadra, M., Srivastava, H. K., Sastry, G. N., Juvekar, A., Sen, S. & Zingde, S. (2010b). Bioorg. Med. Chem. 18, 526–542. [DOI] [PubMed]
- Krastina, G., Ravina, I., Mierina, I., Zicane, D., Turks, M., Tetere, Z. & Leonciks, A. (2014). J. Chem. Pharm. Res. 6, 6–14.
- Kumar, D., Jadhavar, P. S., Nautiyal, M., Sharma, H., Meena, P. K., Adane, L., Pancholia, S. & Chakraborti, A. K. (2015). RSC Adv. 5, 30819–30825.
- Macrae, C. F., Bruno, I. J., Chisholm, J. A., Edgington, P. R., McCabe, P., Pidcock, E., Rodriguez-Monge, L., Taylor, R., van de Streek, J. & Wood, P. A. (2008). J. Appl. Cryst. 41, 466–470.
- Marinho, E. & Proença, M. F. (2015). Synthesis, 47, 1623–1632.
- Nonius (1997). KappaCCD Server Software for Windows. Nonius BV, Delft, The Netherlands.
- Nosova, E. V., Stupina, T. V., Lipunova, G. N., Valova, M. S., Slepukhin, P. A. & Charushin, V. N. (2012). Int. J. Org. Chem, 2, 56–63.
- Otwinowski, Z. & Minor, W. (1997). Methods in Enzymology, Vol. 276, Macromolecular Crystallography, Part A, edited by C. W. Carter Jr & R. M. Sweet, pp. 307–326. New York: Academic Press.
- Ovchinnikova, I. G., Kim, G. A., Matochkina, E. G., Kodess, M. I., Barykin, N. V., El’tsov, O. S., Nosova, E. V., Rusinov, G. L. & Charushin, V. N. (2014). Russ. Chem. Bull. 63, 2467–2477.
- Park, H., Kim, Y.-J. & Hahn, J.-S. (2007). Bioorg. Med. Chem. Lett. 17, 6345–6349. [DOI] [PubMed]
- Sheldrick, G. M. (2015). Acta Cryst. C71, 3–8.
- Spek, A. L. (2009). Acta Cryst. D65, 148–155. [DOI] [PMC free article] [PubMed]
- Stepanovs, D., Jure, M., Gosteva, M., Popelis, J., Kiselovs, G. & Mishnev, A. (2016). CrystEngComm, 18, 1235–1241.
- Sun, D., Perkins, E. L. & Tugendreich, S. (2003). Int. Patent Appl. 03/043961.
- Trashakhova, T. V., Nosova, E. V., Valova, M. S., Slepukhin, P. A., Lipunova, G. N. & Charushin, V. N. (2011). Russ. J. Org. Chem. 47, 753–761.
- Wang, X., Zhou, C.-X., Yan, J.-W., Hou, J.-Q., Chen, S.-B., Ou, T.-M., Gu, L.-Q., Huang, Z.-S. & Tan, J. H. (2013). ACS Med. Chem. Lett. 4, 909–914. [DOI] [PMC free article] [PubMed]
- Welch, W. M. & DeVries, K. M. (1998). Int. Patent Appl. 98/38173.
- Westrip, S. P. (2010). J. Appl. Cryst. 43, 920–925.
Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Supplementary Materials
Crystal structure: contains datablock(s) I. DOI: 10.1107/S2056989016004473/su5288sup1.cif
Structure factors: contains datablock(s) I. DOI: 10.1107/S2056989016004473/su5288Isup2.hkl
Supporting information file. DOI: 10.1107/S2056989016004473/su5288Isup3.cml
CCDC reference: 1468806
Additional supporting information: crystallographic information; 3D view; checkCIF report