research communications
Crystal structures of two 4H-chromene derivatives: 2-amino-3-cyano-4-(3,4-dichlorophenyl)-7-hydroxy-4H-benzo[1,2-b]pyran 1,4-dioxane monosolvate and 2-amino-3-cyano-4-(2,6-dichlorophenyl)-7-hydroxy-4H-benzo[1,2-b]pyran
aDepartment of Chemistry, Jamal Mohamed College, Tiruchirappalli 620 020, India, and bDepartment of Physics, K. Ramakrishnan College of Engineering, Samayapuram, Tiruchirappalli 621 115, India
*Correspondence e-mail: ssilambu2012@gmail.com
In the title compounds, C16H9Cl2N2O2·C4H8O2 and C16H9Cl2N2O2, the bicyclic 4H-chromene cores are nearly planar with maximum deviations of 0.081 (2) and 0.087 (2) Å. In both structures, the chromene derivative molecules are linked into centrosymmetric dimers by pairs of N—H⋯O hydrogen bonds, forming R22(16) motifs. These dimers are further linked in the 3,4-dichlorophenyl derivative by N—H⋯N hydrogen bonds into double layers parallel to (100) and in the 2,6-dichlorophenyl derivative by O—H⋯N hydrogen bonds into ribbons along the [10] direction. In the 3,4-dichlorophenyl derivative, the 1,4-dioxane solvent molecules are connected to the chromene molecules via O—H⋯O hydrogen bonds.
Keywords: crystal structure; 4H-chromene; π-conjugation; hydrogen bond; solvate.
1. Chemical context
Many compounds containing the heterocyclic pyran moiety exhibit diverse pharmacological activities. The pyran ring is a core unit found in benzopyrans, chromones, ), antimicrobial (Khafagy et al., 2002), mutagenicity (Hiramoto et al., 1997), sex pheromone (Bianchi & Tava, 1987), antitumor (Mohr et al., 1975), cancer therapy (Anderson et al., 2005), central nervous system activity (Eiden & Denk, 1991), antifungal (Schiller et al., 2010), antiproliferative (Osman et al., 2011), antidiabetic (Bisht et al., 2011), anti-inflammatory (Wang et al., 1996; Wang et al., 2005) and calcium channel antagonist activity (Shahrisa et al., 2011).
and flavanoids. Numerous naturally occurring compounds containing a pyran ring show therapeutic activities such as antiviral (Martínez-Grau & Marco, 19972-Amino-4H-benzo[1,2-b]pyrans (2-amino-4H-chromenes) act as synthetic building blocks for the design of various pyran-containing bio-active molecules (Kale et al., 2013; Sabry et al., 2011; Kidwai et al., 2010); among them are cytotoxic and anti-HIV preparations (Patil et al., 1993; Emmadi et al., 2012) and anticancer (Wu et al., 2003; Perrella et al., 1994), antimicrobial (Mungra et al., 2011) and anticoagulant agents (Cingolani et al., 1969).
Against this background we carried out the crystallographic studies of the title 4H-chromenes 2-amino-3-cyano-4-(3,4-dichlorophenyl)-7-hydroxy-4H-benzo[1,2-b]pyran 1,4-dioxane mono solvate (I) and 2-amino-3-cyano-4-(2,6-dichlorophenyl)-7-hydroxy-4H-benzo[1,2-b]pyran (II).
2. Structural commentary
The asymmetric units of the title compounds are illustrated in Figs. 1 and 2. The molecules of the two 4H-chromene derivatives differ only in the positions of the chlorine atoms attached to the phenyl ring, and the key bond dimensions in (I) and (II) essentially coincide. The bicyclic chromene cores in the two structures are nearly planar, with the largest deviation from the mean plane being observed for the sp3-hybridized C7 atom in both cases [0.081 (2) and 0.087 (2) Å in (I) and (II), respectively]. The interatomic distances in the pyran rings indicate a strong π-conjugation of the electron-donating atoms O2 and N2 with the cyano acceptor groups. As a result of this conjugation, the C8=C9 bonds [1.349 (3) Å in (I) and 1.354 (2) Å in (II)] are longer than the typical double bonds (Allen et al., 1987), whereas the C9—N2 bonds are shortened [1.335 (3) and 1.342 (2) Å for (I) and (II), respectively], thus the amino groups in the studied structures were assumed to be planar and treated with the AFIX 43 instruction. Besides this, the O—C distances in the pyran rings are asymmetric [1.393 (2) and 1.393 (2) Å for O2—C10 vs. 1.357 (3) and 1.353 (2) Å for O2—C9 in (I) and (II), respectively]. The observed planarity of the bicyclic chromene units is also a consequence of π-conjugation. The dihedral angle between the mean planes of the 4H-chromene ring system and the phenyl ring attached to C7 is 80.82 (9)° in (I) and 85.36 (8)° in (II). In (II), the o-chlorine atom Cl1 forms short intramolecular contacts with atoms C8 and C9 of the pyran ring of 3.111 (2) and 3.193 (2) Å, respectively.
3. Supramolecular features
As shown in Figs. 3 and 4, in both of the title structures the 4H-chromene derivative molecules are linked by pairs of N—H⋯O hydrogen bonds (Tables 1 and 2) into centrosymmetric dimers, thus forming R22(16) motifs. In (I), these dimers are further connected by N—H⋯N hydrogen bonds into double layers parallel to the (100) plane (Fig. 5). In (II), the dimers are linked by O—H⋯N hydrogen bonds into ribbons along the [10] direction. In (I), the 1,4-dioxane solvent molecules are linked to the chromene molecules via O—H⋯O hydrogen bonds. In this compound, the C—H⋯Cl contacts (Table 2) also contribute to the stability of crystal structure.
4. Database survey
A search in the Cambridge Structural Database (CSD version 5.40, last update August 2019; Groom et al., 2016), revealed 107 structures of 4H-chromene derivatives, among them 25 containing the 2-amino-3-cyano-4H-chromene moiety. Of these, two structures, viz. 2-amino-7-hydroxy-4-(4-hydroxyphenyl)-4H-chromene-3-carbonitrile (HUPCEC; Horton et al., 2015) and 2-amino-4-(4-bromophenyl)-7-hydroxy-4H-chromene-3-carbonitrile (UFEKOI; Bi et al., 2017) are closely related to compounds (I) and (II). In the structures of both HUPCEC and UFEKOI, the molecules adopt the same conformation as in (I) and (II) and also form centrosymmetric dimers by pairs of N—H⋯O hydrogen bonds as in the title structures.
5. Synthesis and crystallization
Both studied compounds were prepared by the same procedure. Mixtures of 3,4-chlorobenzaldehyde (8.75 g, 0.05 mol) [for (I)] or 2,4-dichlorobenzaldehyde (8.75 g, 0.05 mol) [for (II)], malononitrile (3.3 ml, 0.05 mol) and resorcinol (5.5 g, 0.05 mol) in 150 ml of water were refluxed for about 10-20 minutes in 250 ml round-bottom flasks. The progress of the reaction was monitored by thin layer or acetonitrile (II). The melting points are 518-523 K for (I) and 513-515 K for (II).
using silica gel-G plates. After the product had formed, the reaction mixtures were kept in the refrigerator overnight. The solid mass that settled was filtered using a suction pump, washed well with a mixture of methanol and water and dried in air. The crude products were recrystallized from methanol giving white powders. Single crystals were grown by slow evaporation of solutions in 1,4-dioxane (I)6. Refinement
Crystal data, diffraction data and structure and (II) are summarized in Table 3. All hydrogen atoms bound to C and N were located from the difference-Fourier maps and refined isotropically using a riding model, with Uiso(H) = 1.2Ueq(C,N) and C—H = 0.98 Å for methine, 0.97 Å for methylene and 0.93 Å for aromatic C atoms, and N—H = 0.86 Å. In (I), the hydroxy H atom was constrained with AFIX 147, but its Uiso value was allowed to refine freely. In (II), the OH hydrogen atom was freely refined.
details for (I)
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Supporting information
https://doi.org/10.1107/S2056989019013197/yk2126sup1.cif
contains datablocks I, II, global. DOI:Structure factors: contains datablock I. DOI: https://doi.org/10.1107/S2056989019013197/yk2126Isup2.hkl
Structure factors: contains datablock II. DOI: https://doi.org/10.1107/S2056989019013197/yk2126IIsup3.hkl
Supporting information file. DOI: https://doi.org/10.1107/S2056989019013197/yk2126Isup4.cml
Supporting information file. DOI: https://doi.org/10.1107/S2056989019013197/yk2126IIsup5.cml
For both structures, data collection: APEX3 (Bruker, 2018); cell
APEX3 and SAINT (Bruker, 2018); data reduction: SAINT and XPREP (Bruker, 2018); program(s) used to solve structure: SHELXT2014/5 (Sheldrick, 2015a); program(s) used to refine structure: SHELXL2014/6 (Sheldrick, 2015b); molecular graphics: DIAMOND (Brandenburg, 2007) and Mercury (Macrae et al., 2008); software used to prepare material for publication: PLATON (Spek, 2009).C16H9Cl2N2O2·C4H8O2 | Dx = 1.401 Mg m−3 |
Mr = 420.25 | Melting point: 520 K |
Monoclinic, P21/c | Mo Kα radiation, λ = 0.71073 Å |
a = 12.753 (9) Å | Cell parameters from 9965 reflections |
b = 6.665 (4) Å | θ = 3.2–26.7° |
c = 24.050 (14) Å | µ = 0.36 mm−1 |
β = 102.95 (3)° | T = 294 K |
V = 1992 (2) Å3 | Block, colourless |
Z = 4 | 0.15 × 0.15 × 0.10 mm |
F(000) = 868 |
Bruker Kappa APEX3 CMOS diffractometer | 3492 independent reflections |
Radiation source: fine-focus sealed tube | 2885 reflections with I > 2σ(I) |
Graphite monochromator | Rint = 0.033 |
ω and φ scan | θmax = 25.0°, θmin = 3.2° |
Absorption correction: multi-scan (SADABS; Bruker, 2018) | h = −15→15 |
Tmin = 0.704, Tmax = 0.745 | k = −7→7 |
34682 measured reflections | l = −28→26 |
Refinement on F2 | Secondary atom site location: difference Fourier map |
Least-squares matrix: full | Hydrogen site location: difference Fourier map |
R[F2 > 2σ(F2)] = 0.044 | H atoms treated by a mixture of independent and constrained refinement |
wR(F2) = 0.121 | w = 1/[σ2(Fo2) + (0.0541P)2 + 1.1852P] where P = (Fo2 + 2Fc2)/3 |
S = 1.11 | (Δ/σ)max < 0.001 |
3492 reflections | Δρmax = 0.26 e Å−3 |
256 parameters | Δρmin = −0.24 e Å−3 |
0 restraints | Extinction correction: SHELXL, Fc*=kFc[1+0.001xFc2λ3/sin(2θ)]-1/4 |
Primary atom site location: structure-invariant direct methods | Extinction coefficient: 0.0174 (18) |
Geometry. All esds (except the esd in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell esds are taken into account individually in the estimation of esds in distances, angles and torsion angles; correlations between esds in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell esds is used for estimating esds involving l.s. planes. |
Refinement. Refinement of F2 against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F2, conventional R-factors R are based on F, with F set to zero for negative F2. The threshold expression of F2 > 2sigma(F2) is used only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F2 are statistically about twice as large as those based on F, and R- factors based on ALL data will be even larger. |
x | y | z | Uiso*/Ueq | ||
Cl1 | 0.60648 (5) | 0.18411 (11) | 0.42962 (4) | 0.0702 (3) | |
Cl2 | 0.52933 (5) | 0.63066 (11) | 0.40894 (4) | 0.0679 (3) | |
O1 | 0.12386 (15) | 0.8018 (3) | 0.63654 (6) | 0.0519 (5) | |
HO1 | 0.1545 | 0.7386 | 0.6648 | 0.074 (10)* | |
O2 | 0.07140 (12) | 0.8197 (2) | 0.43851 (6) | 0.0379 (4) | |
N2 | 0.01565 (18) | 0.8571 (3) | 0.34552 (8) | 0.0530 (6) | |
HNA | 0.0051 | 0.8207 | 0.3104 | 0.064* | |
HNB | −0.0032 | 0.9750 | 0.3540 | 0.064* | |
N1 | 0.0608 (2) | 0.3924 (4) | 0.28098 (9) | 0.0748 (8) | |
C3 | 0.47549 (17) | 0.2502 (4) | 0.42953 (10) | 0.0424 (6) | |
C4 | 0.40418 (19) | 0.1065 (4) | 0.43879 (12) | 0.0512 (6) | |
H4 | 0.4266 | −0.0260 | 0.4452 | 0.061* | |
C5 | 0.29931 (18) | 0.1579 (3) | 0.43861 (11) | 0.0439 (6) | |
H5 | 0.2516 | 0.0592 | 0.4448 | 0.053* | |
C6 | 0.26401 (16) | 0.3532 (3) | 0.42946 (8) | 0.0303 (5) | |
C7 | 0.14837 (15) | 0.4087 (3) | 0.43059 (8) | 0.0305 (5) | |
H7 | 0.1068 | 0.2841 | 0.4279 | 0.037* | |
C11 | 0.14231 (15) | 0.5105 (3) | 0.48595 (8) | 0.0292 (4) | |
C12 | 0.17291 (16) | 0.4127 (3) | 0.53832 (9) | 0.0358 (5) | |
H12 | 0.1980 | 0.2815 | 0.5391 | 0.043* | |
C13 | 0.16731 (17) | 0.5037 (4) | 0.58889 (9) | 0.0382 (5) | |
H13 | 0.1868 | 0.4337 | 0.6231 | 0.046* | |
C14 | 0.13242 (16) | 0.7003 (3) | 0.58846 (8) | 0.0354 (5) | |
C10 | 0.10667 (15) | 0.7052 (3) | 0.48756 (8) | 0.0291 (4) | |
C15 | 0.10195 (16) | 0.8023 (3) | 0.53756 (8) | 0.0337 (5) | |
H15 | 0.0786 | 0.9346 | 0.5369 | 0.040* | |
C9 | 0.06130 (16) | 0.7304 (3) | 0.38688 (8) | 0.0342 (5) | |
C8 | 0.09544 (16) | 0.5416 (3) | 0.38111 (8) | 0.0347 (5) | |
C22 | 0.07678 (19) | 0.4596 (4) | 0.32560 (10) | 0.0459 (6) | |
C1 | 0.33627 (17) | 0.4972 (3) | 0.42043 (9) | 0.0361 (5) | |
H1 | 0.3140 | 0.6298 | 0.4143 | 0.043* | |
C2 | 0.44144 (17) | 0.4463 (3) | 0.42042 (9) | 0.0380 (5) | |
O16 | 0.24114 (17) | 0.6481 (4) | 0.73252 (9) | 0.0769 (6) | |
C17 | 0.2288 (3) | 0.5035 (7) | 0.77295 (16) | 0.0937 (12) | |
H171 | 0.1565 | 0.4491 | 0.7630 | 0.112* | |
H172 | 0.2389 | 0.5659 | 0.8102 | 0.112* | |
C18 | 0.3066 (3) | 0.3413 (7) | 0.7754 (2) | 0.1008 (13) | |
H181 | 0.2976 | 0.2450 | 0.8042 | 0.121* | |
H182 | 0.2930 | 0.2727 | 0.7389 | 0.121* | |
O19 | 0.4122 (2) | 0.4128 (5) | 0.78824 (13) | 0.1129 (10) | |
C20 | 0.4249 (4) | 0.5602 (9) | 0.7484 (3) | 0.140 (2) | |
H201 | 0.4159 | 0.4986 | 0.7111 | 0.169* | |
H202 | 0.4974 | 0.6137 | 0.7590 | 0.169* | |
C21 | 0.3484 (3) | 0.7239 (7) | 0.7450 (2) | 0.1147 (16) | |
H211 | 0.3622 | 0.7957 | 0.7810 | 0.138* | |
H212 | 0.3573 | 0.8171 | 0.7154 | 0.138* |
U11 | U22 | U33 | U12 | U13 | U23 | |
Cl1 | 0.0349 (3) | 0.0613 (5) | 0.1189 (7) | 0.0130 (3) | 0.0268 (4) | 0.0064 (4) |
Cl2 | 0.0449 (4) | 0.0492 (4) | 0.1188 (7) | −0.0051 (3) | 0.0379 (4) | 0.0059 (4) |
O1 | 0.0682 (12) | 0.0615 (11) | 0.0250 (8) | 0.0233 (9) | 0.0080 (8) | −0.0009 (8) |
O2 | 0.0528 (9) | 0.0356 (8) | 0.0245 (7) | 0.0081 (7) | 0.0070 (6) | 0.0006 (6) |
N2 | 0.0766 (15) | 0.0540 (13) | 0.0266 (10) | 0.0236 (11) | 0.0079 (9) | 0.0035 (9) |
N1 | 0.100 (2) | 0.0820 (18) | 0.0351 (13) | 0.0287 (16) | −0.0006 (12) | −0.0151 (12) |
C3 | 0.0294 (11) | 0.0424 (13) | 0.0557 (14) | 0.0061 (10) | 0.0105 (10) | −0.0031 (11) |
C4 | 0.0408 (13) | 0.0324 (12) | 0.0819 (18) | 0.0077 (10) | 0.0171 (12) | 0.0016 (12) |
C5 | 0.0362 (12) | 0.0333 (12) | 0.0634 (15) | −0.0015 (10) | 0.0138 (11) | −0.0009 (11) |
C6 | 0.0300 (10) | 0.0334 (11) | 0.0273 (10) | 0.0020 (9) | 0.0059 (8) | −0.0045 (9) |
C7 | 0.0258 (10) | 0.0325 (11) | 0.0328 (11) | −0.0011 (8) | 0.0062 (8) | −0.0046 (9) |
C11 | 0.0220 (9) | 0.0354 (11) | 0.0305 (10) | −0.0020 (8) | 0.0062 (8) | −0.0008 (9) |
C12 | 0.0333 (11) | 0.0346 (12) | 0.0394 (12) | 0.0048 (9) | 0.0082 (9) | 0.0041 (9) |
C13 | 0.0374 (12) | 0.0481 (14) | 0.0285 (11) | 0.0053 (10) | 0.0060 (9) | 0.0080 (10) |
C14 | 0.0305 (11) | 0.0481 (13) | 0.0275 (11) | 0.0035 (9) | 0.0065 (8) | −0.0018 (9) |
C10 | 0.0244 (9) | 0.0370 (11) | 0.0253 (10) | −0.0007 (8) | 0.0042 (8) | 0.0035 (9) |
C15 | 0.0323 (11) | 0.0377 (12) | 0.0306 (11) | 0.0046 (9) | 0.0061 (8) | −0.0010 (9) |
C9 | 0.0317 (11) | 0.0455 (13) | 0.0261 (10) | 0.0020 (9) | 0.0079 (8) | 0.0005 (9) |
C8 | 0.0284 (10) | 0.0474 (13) | 0.0274 (10) | 0.0041 (9) | 0.0043 (8) | −0.0054 (9) |
C22 | 0.0459 (13) | 0.0541 (15) | 0.0347 (13) | 0.0145 (11) | 0.0028 (10) | −0.0041 (11) |
C1 | 0.0344 (11) | 0.0306 (11) | 0.0450 (12) | 0.0042 (9) | 0.0126 (9) | −0.0021 (9) |
C2 | 0.0320 (11) | 0.0395 (12) | 0.0439 (12) | −0.0026 (9) | 0.0115 (9) | −0.0032 (10) |
O16 | 0.0632 (13) | 0.0935 (16) | 0.0644 (13) | 0.0044 (12) | −0.0062 (10) | 0.0279 (12) |
C17 | 0.067 (2) | 0.126 (3) | 0.091 (2) | 0.018 (2) | 0.0234 (18) | 0.049 (2) |
C18 | 0.082 (3) | 0.096 (3) | 0.126 (3) | 0.008 (2) | 0.027 (2) | 0.042 (2) |
O19 | 0.0663 (16) | 0.131 (3) | 0.137 (2) | 0.0268 (17) | 0.0141 (15) | 0.043 (2) |
C20 | 0.075 (3) | 0.139 (4) | 0.219 (6) | 0.007 (3) | 0.056 (3) | 0.052 (5) |
C21 | 0.079 (3) | 0.108 (3) | 0.141 (4) | −0.018 (3) | −0.008 (2) | 0.034 (3) |
Cl1—C3 | 1.727 (2) | C12—H12 | 0.9300 |
Cl2—C2 | 1.727 (2) | C13—C14 | 1.383 (3) |
O1—C14 | 1.365 (3) | C13—H13 | 0.9300 |
O1—HO1 | 0.8200 | C14—C15 | 1.378 (3) |
O2—C9 | 1.357 (3) | C10—C15 | 1.379 (3) |
O2—C10 | 1.393 (2) | C15—H15 | 0.9300 |
N2—C9 | 1.335 (3) | C9—C8 | 1.349 (3) |
N2—HNA | 0.8600 | C8—C22 | 1.413 (3) |
N2—HNB | 0.8600 | C1—C2 | 1.384 (3) |
N1—C22 | 1.138 (3) | C1—H1 | 0.9300 |
C3—C4 | 1.373 (3) | O16—C17 | 1.403 (4) |
C3—C2 | 1.379 (3) | O16—C21 | 1.426 (5) |
C4—C5 | 1.380 (3) | C17—C18 | 1.459 (5) |
C4—H4 | 0.9300 | C17—H171 | 0.9700 |
C5—C6 | 1.379 (3) | C17—H172 | 0.9700 |
C5—H5 | 0.9300 | C18—O19 | 1.396 (5) |
C6—C1 | 1.381 (3) | C18—H181 | 0.9700 |
C6—C7 | 1.527 (3) | C18—H182 | 0.9700 |
C7—C11 | 1.512 (3) | O19—C20 | 1.406 (5) |
C7—C8 | 1.515 (3) | C20—C21 | 1.453 (7) |
C7—H7 | 0.9800 | C20—H201 | 0.9700 |
C11—C10 | 1.378 (3) | C20—H202 | 0.9700 |
C11—C12 | 1.394 (3) | C21—H211 | 0.9700 |
C12—C13 | 1.375 (3) | C21—H212 | 0.9700 |
C14—O1—HO1 | 109.5 | C10—C15—H15 | 120.5 |
C9—O2—C10 | 118.75 (17) | N2—C9—C8 | 127.6 (2) |
C9—N2—HNA | 120.0 | N2—C9—O2 | 109.9 (2) |
C9—N2—HNB | 120.0 | C8—C9—O2 | 122.48 (19) |
HNA—N2—HNB | 120.0 | C9—C8—C22 | 117.9 (2) |
C4—C3—C2 | 119.4 (2) | C9—C8—C7 | 124.17 (18) |
C4—C3—Cl1 | 119.81 (19) | C22—C8—C7 | 117.8 (2) |
C2—C3—Cl1 | 120.80 (18) | N1—C22—C8 | 179.3 (3) |
C3—C4—C5 | 120.2 (2) | C6—C1—C2 | 120.7 (2) |
C3—C4—H4 | 119.9 | C6—C1—H1 | 119.6 |
C5—C4—H4 | 119.9 | C2—C1—H1 | 119.6 |
C6—C5—C4 | 121.1 (2) | C3—C2—C1 | 120.2 (2) |
C6—C5—H5 | 119.4 | C3—C2—Cl2 | 120.48 (17) |
C4—C5—H5 | 119.4 | C1—C2—Cl2 | 119.31 (18) |
C5—C6—C1 | 118.41 (19) | C17—O16—C21 | 110.4 (3) |
C5—C6—C7 | 120.53 (19) | O16—C17—C18 | 110.9 (3) |
C1—C6—C7 | 121.05 (19) | O16—C17—H171 | 109.5 |
C11—C7—C8 | 109.13 (17) | C18—C17—H171 | 109.5 |
C11—C7—C6 | 111.39 (16) | O16—C17—H172 | 109.5 |
C8—C7—C6 | 112.94 (16) | C18—C17—H172 | 109.5 |
C11—C7—H7 | 107.7 | H171—C17—H172 | 108.1 |
C8—C7—H7 | 107.7 | O19—C18—C17 | 111.6 (4) |
C6—C7—H7 | 107.7 | O19—C18—H181 | 109.3 |
C10—C11—C12 | 116.24 (18) | C17—C18—H181 | 109.3 |
C10—C11—C7 | 121.97 (18) | O19—C18—H182 | 109.3 |
C12—C11—C7 | 121.79 (19) | C17—C18—H182 | 109.3 |
C13—C12—C11 | 122.2 (2) | H181—C18—H182 | 108.0 |
C13—C12—H12 | 118.9 | C18—O19—C20 | 109.9 (3) |
C11—C12—H12 | 118.9 | O19—C20—C21 | 112.6 (4) |
C12—C13—C14 | 119.5 (2) | O19—C20—H201 | 109.1 |
C12—C13—H13 | 120.3 | C21—C20—H201 | 109.1 |
C14—C13—H13 | 120.3 | O19—C20—H202 | 109.1 |
O1—C14—C15 | 116.6 (2) | C21—C20—H202 | 109.1 |
O1—C14—C13 | 123.34 (19) | H201—C20—H202 | 107.8 |
C15—C14—C13 | 120.01 (19) | O16—C21—C20 | 110.2 (4) |
C11—C10—C15 | 123.07 (18) | O16—C21—H211 | 109.6 |
C11—C10—O2 | 122.57 (17) | C20—C21—H211 | 109.6 |
C15—C10—O2 | 114.36 (18) | O16—C21—H212 | 109.6 |
C14—C15—C10 | 119.0 (2) | C20—C21—H212 | 109.6 |
C14—C15—H15 | 120.5 | H211—C21—H212 | 108.1 |
C2—C3—C4—C5 | 0.4 (4) | C11—C10—C15—C14 | −1.1 (3) |
Cl1—C3—C4—C5 | −179.8 (2) | O2—C10—C15—C14 | 178.35 (18) |
C3—C4—C5—C6 | −0.3 (4) | C10—O2—C9—N2 | 173.17 (18) |
C4—C5—C6—C1 | 0.0 (3) | C10—O2—C9—C8 | −7.7 (3) |
C4—C5—C6—C7 | −178.7 (2) | N2—C9—C8—C22 | −3.7 (3) |
C5—C6—C7—C11 | 102.8 (2) | O2—C9—C8—C22 | 177.2 (2) |
C1—C6—C7—C11 | −75.9 (2) | N2—C9—C8—C7 | 178.9 (2) |
C5—C6—C7—C8 | −134.0 (2) | O2—C9—C8—C7 | −0.1 (3) |
C1—C6—C7—C8 | 47.3 (3) | C11—C7—C8—C9 | 7.6 (3) |
C8—C7—C11—C10 | −8.1 (2) | C6—C7—C8—C9 | −116.9 (2) |
C6—C7—C11—C10 | 117.2 (2) | C11—C7—C8—C22 | −169.73 (19) |
C8—C7—C11—C12 | 172.12 (18) | C6—C7—C8—C22 | 65.8 (2) |
C6—C7—C11—C12 | −62.5 (2) | C5—C6—C1—C2 | 0.2 (3) |
C10—C11—C12—C13 | 0.5 (3) | C7—C6—C1—C2 | 178.92 (19) |
C7—C11—C12—C13 | −179.75 (19) | C4—C3—C2—C1 | −0.2 (4) |
C11—C12—C13—C14 | −1.4 (3) | Cl1—C3—C2—C1 | 179.98 (18) |
C12—C13—C14—O1 | 179.6 (2) | C4—C3—C2—Cl2 | 179.7 (2) |
C12—C13—C14—C15 | 1.1 (3) | Cl1—C3—C2—Cl2 | −0.1 (3) |
C12—C11—C10—C15 | 0.8 (3) | C6—C1—C2—C3 | −0.1 (3) |
C7—C11—C10—C15 | −178.98 (18) | C6—C1—C2—Cl2 | 179.97 (16) |
C12—C11—C10—O2 | −178.63 (18) | C21—O16—C17—C18 | −56.6 (5) |
C7—C11—C10—O2 | 1.6 (3) | O16—C17—C18—O19 | 57.7 (5) |
C9—O2—C10—C11 | 6.9 (3) | C17—C18—O19—C20 | −56.0 (5) |
C9—O2—C10—C15 | −172.56 (18) | C18—O19—C20—C21 | 55.8 (6) |
O1—C14—C15—C10 | −178.52 (19) | C17—O16—C21—C20 | 55.5 (5) |
C13—C14—C15—C10 | 0.1 (3) | O19—C20—C21—O16 | −55.7 (6) |
D—H···A | D—H | H···A | D···A | D—H···A |
O1—HO1···O16 | 0.82 | 1.85 | 2.658 (3) | 167 |
N2—HNB···O1i | 0.86 | 2.19 | 2.978 (3) | 153 |
N2—HNA···N1ii | 0.86 | 2.22 | 2.989 (3) | 149 |
C4—H4···Cl2iii | 0.93 | 2.87 | 3.692 (3) | 148 |
Symmetry codes: (i) −x, −y+2, −z+1; (ii) −x, y+1/2, −z+1/2; (iii) x, y−1, z. |
C16H9Cl2N2O2 | F(000) = 338 |
Mr = 332.15 | Dx = 1.548 Mg m−3 |
Triclinic, P1 | Melting point: 514 K |
a = 6.271 (3) Å | Mo Kα radiation, λ = 0.71073 Å |
b = 8.697 (5) Å | Cell parameters from 8750 reflections |
c = 13.794 (7) Å | θ = 3.1–30.4° |
α = 107.06 (2)° | µ = 0.46 mm−1 |
β = 94.269 (17)° | T = 294 K |
γ = 95.00 (3)° | Block, colourless |
V = 712.5 (7) Å3 | 0.15 × 0.15 × 0.10 mm |
Z = 2 |
Bruker Kappa APEX3 CMOS diffractometer | 2499 independent reflections |
Radiation source: fine-focus sealed tube | 2239 reflections with I > 2σ(I) |
Graphite monochromator | Rint = 0.023 |
ω and φ scan | θmax = 25.0°, θmin = 3.9° |
Absorption correction: multi-scan (SADABS; Bruker, 2018) | h = −7→7 |
Tmin = 0.704, Tmax = 0.746 | k = −10→10 |
22289 measured reflections | l = −16→16 |
Refinement on F2 | Secondary atom site location: difference Fourier map |
Least-squares matrix: full | Hydrogen site location: mixed |
R[F2 > 2σ(F2)] = 0.033 | H atoms treated by a mixture of independent and constrained refinement |
wR(F2) = 0.081 | w = 1/[σ2(Fo2) + (0.0263P)2 + 0.4717P] where P = (Fo2 + 2Fc2)/3 |
S = 1.11 | (Δ/σ)max < 0.001 |
2499 reflections | Δρmax = 0.23 e Å−3 |
204 parameters | Δρmin = −0.25 e Å−3 |
0 restraints | Extinction correction: SHELXL, Fc*=kFc[1+0.001xFc2λ3/sin(2θ)]-1/4 |
Primary atom site location: structure-invariant direct methods | Extinction coefficient: 0.080 (10) |
Geometry. All esds (except the esd in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell esds are taken into account individually in the estimation of esds in distances, angles and torsion angles; correlations between esds in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell esds is used for estimating esds involving l.s. planes. |
Refinement. Refinement of F2 against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F2, conventional R-factors R are based on F, with F set to zero for negative F2. The threshold expression of F2 > 2sigma(F2) is used only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F2 are statistically about twice as large as those based on F, and R- factors based on ALL data will be even larger. |
x | y | z | Uiso*/Ueq | ||
Cl1 | 0.84692 (8) | 0.84534 (6) | 0.32241 (4) | 0.04703 (19) | |
Cl2 | 0.10752 (8) | 0.50064 (7) | 0.36100 (4) | 0.0536 (2) | |
O1 | 1.0482 (2) | 0.15972 (18) | 0.09764 (12) | 0.0484 (4) | |
HO1 | 1.058 (5) | 0.092 (4) | 0.130 (2) | 0.084 (10)* | |
O2 | 0.7394 (2) | 0.62001 (14) | 0.07971 (9) | 0.0331 (3) | |
N1 | 0.1786 (3) | 0.9314 (2) | 0.18547 (15) | 0.0538 (5) | |
N2 | 0.6119 (3) | 0.83118 (18) | 0.04811 (12) | 0.0372 (4) | |
HNB | 0.7128 | 0.8266 | 0.0087 | 0.045* | |
HNA | 0.5262 | 0.9046 | 0.0540 | 0.045* | |
C14 | 0.8930 (3) | 0.2578 (2) | 0.12922 (13) | 0.0314 (4) | |
C13 | 0.7476 (3) | 0.2339 (2) | 0.19616 (13) | 0.0327 (4) | |
H13 | 0.7498 | 0.1452 | 0.2207 | 0.039* | |
C12 | 0.6001 (3) | 0.3428 (2) | 0.22588 (13) | 0.0303 (4) | |
H12 | 0.5033 | 0.3258 | 0.2706 | 0.036* | |
C11 | 0.5912 (3) | 0.47743 (19) | 0.19116 (12) | 0.0252 (4) | |
C7 | 0.4337 (3) | 0.59914 (19) | 0.22777 (12) | 0.0244 (3) | |
H7 | 0.2892 | 0.5394 | 0.2131 | 0.029* | |
C6 | 0.4733 (3) | 0.67923 (19) | 0.34378 (12) | 0.0256 (4) | |
C1 | 0.3324 (3) | 0.6415 (2) | 0.40945 (13) | 0.0340 (4) | |
C2 | 0.3630 (4) | 0.7086 (3) | 0.51432 (15) | 0.0489 (5) | |
H2 | 0.2637 | 0.6808 | 0.5549 | 0.059* | |
C3 | 0.5406 (4) | 0.8159 (3) | 0.55754 (15) | 0.0545 (6) | |
H3 | 0.5623 | 0.8621 | 0.6280 | 0.065* | |
C8 | 0.4401 (3) | 0.7173 (2) | 0.16603 (12) | 0.0272 (4) | |
C22 | 0.2927 (3) | 0.8338 (2) | 0.17803 (13) | 0.0333 (4) | |
C9 | 0.5883 (3) | 0.72374 (19) | 0.10034 (12) | 0.0270 (4) | |
C10 | 0.7341 (3) | 0.49354 (19) | 0.12257 (12) | 0.0258 (4) | |
C15 | 0.8841 (3) | 0.3873 (2) | 0.09093 (13) | 0.0306 (4) | |
H15 | 0.9778 | 0.4028 | 0.0446 | 0.037* | |
C4 | 0.6873 (4) | 0.8561 (3) | 0.49742 (15) | 0.0482 (5) | |
H4 | 0.8094 | 0.9282 | 0.5269 | 0.058* | |
C5 | 0.6524 (3) | 0.7886 (2) | 0.39261 (13) | 0.0333 (4) |
U11 | U22 | U33 | U12 | U13 | U23 | |
Cl1 | 0.0390 (3) | 0.0566 (3) | 0.0404 (3) | −0.0157 (2) | 0.0042 (2) | 0.0129 (2) |
Cl2 | 0.0435 (3) | 0.0712 (4) | 0.0448 (3) | −0.0174 (2) | 0.0084 (2) | 0.0216 (3) |
O1 | 0.0615 (10) | 0.0440 (8) | 0.0580 (9) | 0.0319 (7) | 0.0295 (7) | 0.0303 (7) |
O2 | 0.0421 (7) | 0.0305 (6) | 0.0376 (7) | 0.0150 (5) | 0.0189 (5) | 0.0204 (5) |
N1 | 0.0546 (11) | 0.0603 (12) | 0.0685 (12) | 0.0324 (10) | 0.0294 (9) | 0.0405 (10) |
N2 | 0.0469 (9) | 0.0356 (8) | 0.0409 (9) | 0.0166 (7) | 0.0178 (7) | 0.0231 (7) |
C14 | 0.0388 (10) | 0.0269 (8) | 0.0303 (9) | 0.0110 (7) | 0.0057 (7) | 0.0088 (7) |
C13 | 0.0433 (10) | 0.0254 (8) | 0.0340 (9) | 0.0057 (7) | 0.0052 (8) | 0.0154 (7) |
C12 | 0.0362 (9) | 0.0298 (9) | 0.0276 (8) | 0.0013 (7) | 0.0063 (7) | 0.0128 (7) |
C11 | 0.0289 (8) | 0.0243 (8) | 0.0222 (8) | 0.0023 (6) | 0.0012 (6) | 0.0071 (6) |
C7 | 0.0235 (8) | 0.0264 (8) | 0.0242 (8) | 0.0026 (6) | 0.0033 (6) | 0.0090 (6) |
C6 | 0.0285 (8) | 0.0259 (8) | 0.0247 (8) | 0.0063 (7) | 0.0043 (6) | 0.0098 (7) |
C1 | 0.0354 (10) | 0.0376 (10) | 0.0314 (9) | 0.0017 (8) | 0.0065 (7) | 0.0139 (8) |
C2 | 0.0648 (14) | 0.0541 (12) | 0.0293 (10) | −0.0009 (11) | 0.0165 (9) | 0.0143 (9) |
C3 | 0.0846 (17) | 0.0510 (13) | 0.0232 (9) | −0.0059 (12) | 0.0054 (10) | 0.0076 (9) |
C8 | 0.0309 (9) | 0.0284 (8) | 0.0249 (8) | 0.0082 (7) | 0.0036 (7) | 0.0107 (7) |
C22 | 0.0358 (9) | 0.0374 (10) | 0.0341 (9) | 0.0099 (8) | 0.0097 (7) | 0.0191 (8) |
C9 | 0.0325 (9) | 0.0252 (8) | 0.0255 (8) | 0.0085 (7) | 0.0032 (7) | 0.0094 (7) |
C10 | 0.0328 (9) | 0.0232 (8) | 0.0248 (8) | 0.0055 (7) | 0.0043 (7) | 0.0113 (6) |
C15 | 0.0362 (9) | 0.0304 (9) | 0.0299 (9) | 0.0092 (7) | 0.0109 (7) | 0.0130 (7) |
C4 | 0.0604 (13) | 0.0444 (11) | 0.0323 (10) | −0.0108 (10) | −0.0050 (9) | 0.0073 (9) |
C5 | 0.0375 (10) | 0.0336 (9) | 0.0298 (9) | 0.0002 (7) | 0.0057 (7) | 0.0118 (7) |
Cl1—C5 | 1.7383 (19) | C11—C7 | 1.515 (2) |
Cl2—C1 | 1.736 (2) | C7—C8 | 1.515 (2) |
O1—C14 | 1.362 (2) | C7—C6 | 1.538 (2) |
O1—HO1 | 0.85 (3) | C7—H7 | 0.9800 |
O2—C9 | 1.353 (2) | C6—C5 | 1.394 (3) |
O2—C10 | 1.392 (2) | C6—C1 | 1.397 (2) |
N1—C22 | 1.144 (2) | C1—C2 | 1.383 (3) |
N2—C9 | 1.342 (2) | C2—C3 | 1.364 (3) |
N2—HNB | 0.8600 | C2—H2 | 0.9300 |
N2—HNA | 0.8600 | C3—C4 | 1.373 (3) |
C14—C15 | 1.381 (2) | C3—H3 | 0.9300 |
C14—C13 | 1.390 (3) | C8—C9 | 1.354 (2) |
C13—C12 | 1.380 (3) | C8—C22 | 1.413 (2) |
C13—H13 | 0.9300 | C10—C15 | 1.380 (2) |
C12—C11 | 1.392 (2) | C15—H15 | 0.9300 |
C12—H12 | 0.9300 | C4—C5 | 1.384 (3) |
C11—C10 | 1.378 (2) | C4—H4 | 0.9300 |
C14—O1—HO1 | 112 (2) | C2—C1—Cl2 | 116.30 (15) |
C9—O2—C10 | 118.64 (13) | C6—C1—Cl2 | 120.20 (14) |
C9—N2—HNB | 120.0 | C3—C2—C1 | 119.25 (19) |
C9—N2—HNA | 120.0 | C3—C2—H2 | 120.4 |
HNB—N2—HNA | 120.0 | C1—C2—H2 | 120.4 |
O1—C14—C15 | 116.39 (16) | C2—C3—C4 | 120.18 (19) |
O1—C14—C13 | 123.88 (16) | C2—C3—H3 | 119.9 |
C15—C14—C13 | 119.73 (16) | C4—C3—H3 | 119.9 |
C12—C13—C14 | 119.48 (15) | C9—C8—C22 | 115.95 (15) |
C12—C13—H13 | 120.3 | C9—C8—C7 | 123.49 (14) |
C14—C13—H13 | 120.3 | C22—C8—C7 | 120.51 (15) |
C13—C12—C11 | 122.22 (16) | N1—C22—C8 | 177.10 (19) |
C13—C12—H12 | 118.9 | N2—C9—O2 | 110.03 (14) |
C11—C12—H12 | 118.9 | N2—C9—C8 | 126.71 (15) |
C10—C11—C12 | 116.26 (15) | O2—C9—C8 | 123.25 (15) |
C10—C11—C7 | 122.30 (14) | C11—C10—C15 | 123.29 (15) |
C12—C11—C7 | 121.44 (15) | C11—C10—O2 | 122.40 (14) |
C11—C7—C8 | 109.10 (13) | C15—C10—O2 | 114.31 (14) |
C11—C7—C6 | 111.28 (13) | C10—C15—C14 | 118.96 (16) |
C8—C7—C6 | 114.32 (14) | C10—C15—H15 | 120.5 |
C11—C7—H7 | 107.3 | C14—C15—H15 | 120.5 |
C8—C7—H7 | 107.3 | C3—C4—C5 | 119.6 (2) |
C6—C7—H7 | 107.3 | C3—C4—H4 | 120.2 |
C5—C6—C1 | 114.50 (15) | C5—C4—H4 | 120.2 |
C5—C6—C7 | 124.05 (14) | C4—C5—C6 | 123.02 (17) |
C1—C6—C7 | 121.41 (15) | C4—C5—Cl1 | 116.49 (15) |
C2—C1—C6 | 123.48 (18) | C6—C5—Cl1 | 120.49 (13) |
O1—C14—C13—C12 | 178.13 (17) | C10—O2—C9—N2 | −176.56 (14) |
C15—C14—C13—C12 | −1.9 (3) | C10—O2—C9—C8 | 4.5 (2) |
C14—C13—C12—C11 | −0.1 (3) | C22—C8—C9—N2 | 1.8 (3) |
C13—C12—C11—C10 | 2.0 (2) | C7—C8—C9—N2 | −175.57 (16) |
C13—C12—C11—C7 | −177.63 (15) | C22—C8—C9—O2 | −179.42 (15) |
C10—C11—C7—C8 | 8.4 (2) | C7—C8—C9—O2 | 3.2 (3) |
C12—C11—C7—C8 | −172.08 (15) | C12—C11—C10—C15 | −2.0 (2) |
C10—C11—C7—C6 | −118.71 (17) | C7—C11—C10—C15 | 177.61 (15) |
C12—C11—C7—C6 | 60.9 (2) | C12—C11—C10—O2 | 178.39 (15) |
C11—C7—C6—C5 | 70.1 (2) | C7—C11—C10—O2 | −2.0 (2) |
C8—C7—C6—C5 | −54.1 (2) | C9—O2—C10—C11 | −5.0 (2) |
C11—C7—C6—C1 | −107.41 (18) | C9—O2—C10—C15 | 175.30 (15) |
C8—C7—C6—C1 | 128.44 (17) | C11—C10—C15—C14 | 0.1 (3) |
C5—C6—C1—C2 | 1.3 (3) | O2—C10—C15—C14 | 179.77 (15) |
C7—C6—C1—C2 | 179.01 (18) | O1—C14—C15—C10 | −178.14 (16) |
C5—C6—C1—Cl2 | −177.27 (13) | C13—C14—C15—C10 | 1.9 (3) |
C7—C6—C1—Cl2 | 0.4 (2) | C2—C3—C4—C5 | 0.9 (4) |
C6—C1—C2—C3 | −0.9 (3) | C3—C4—C5—C6 | −0.3 (3) |
Cl2—C1—C2—C3 | 177.78 (18) | C3—C4—C5—Cl1 | −179.69 (18) |
C1—C2—C3—C4 | −0.3 (4) | C1—C6—C5—C4 | −0.7 (3) |
C11—C7—C8—C9 | −9.1 (2) | C7—C6—C5—C4 | −178.35 (17) |
C6—C7—C8—C9 | 116.24 (18) | C1—C6—C5—Cl1 | 178.63 (13) |
C11—C7—C8—C22 | 173.69 (15) | C7—C6—C5—Cl1 | 1.0 (2) |
C6—C7—C8—C22 | −61.0 (2) |
D—H···A | D—H | H···A | D···A | D—H···A |
C7—H7···Cl2 | 0.98 | 2.50 | 3.078 (3) | 117 |
N2—HNB···O1i | 0.86 | 2.19 | 3.048 (2) | 173 |
O1—HO1···N1ii | 0.85 (3) | 1.95 (3) | 2.762 (2) | 160 (3) |
Symmetry codes: (i) −x+2, −y+1, −z; (ii) x+1, y−1, z. |
Acknowledgements
The authors thank Dr Babu Varghese, Senior Scientific Officer, SAIF, IIT Madras, Chennai, India, for the data collection.
References
Allen, F. H., Kennard, O., Watson, D. G., Brammer, L., Orpen, A. G. & Taylor, R. (1987). J. Chem. Soc. Perkin Trans. 2, pp. S1–19. CrossRef Web of Science Google Scholar
Anderson, D. R., Hegde, S., Reinhard, E., Gomez, L., Vernier, W. F., Lee, L., Liu, S., Sambandam, A., Snider, P. A. & Masih, L. (2005). Bioorg. Med. Chem. Lett. 15, 1587–1590. Web of Science CrossRef PubMed CAS Google Scholar
Bi, Q., Ruan, W.-W., Cao, L. & Xu, Y.-J. (2017). Biomed. Res. India, 28, 1290–1293. CAS Google Scholar
Bianchi, G. & Tava, A. (1987). Agric. Biol. Chem. 51, 2001–2002. CrossRef CAS Google Scholar
Bisht, S. S., Jaiswal, N., Sharma, A., Fatima, S., Sharma, R., Rahuja, N., Srivastava, A. K., Bajpai, V., Kumar, B. & Tripathi, R. P. (2011). Carbohydr. Res. 346, 1191–1201. CrossRef CAS PubMed Google Scholar
Brandenburg, K. (2007). DIAMOND. Crystal Impact GbR, Bonn, Germany. Google Scholar
Bruker (2018). APEX3, SAINT and SADABS. Bruker AXS Inc., Madison, Wisconsin, USA. Google Scholar
Cingolani, G., Gualtieri, F. & Pigini, M. (1969). J. Med. Chem. 12, 531–532. CrossRef CAS PubMed Google Scholar
Eiden, F. & Denk, F. (1991). Arch. Pharm. Pharm. Med. Chem. 324, 353–354. CrossRef CAS Web of Science Google Scholar
Emmadi, N. R., Atmakur, K., Chityal, G. K., Pombala, S. & Nanubolu, J. B. (2012). Bioorg. Med. Chem. Lett. 22, 7261–7264. Web of Science CSD CrossRef CAS PubMed Google Scholar
Groom, C. R., Bruno, I. J., Lightfoot, M. P. & Ward, S. C. (2016). Acta Cryst. B72, 171–179. Web of Science CrossRef IUCr Journals Google Scholar
Hiramoto, K., Nasuhara, A., Michikoshi, K., Kato, T. & Kikugawa, K. (1997). Mutat. Res. 395, 47–56. CrossRef CAS PubMed Google Scholar
Horton, P. N., Akkurt, M., Mohamed, S. K., Younes, S. H. H. & Albayati, M. R. (2015). Acta Cryst. E71, o546–o547. CSD CrossRef IUCr Journals Google Scholar
Kale, S. R., Kahandal, S. S., Burange, A. S., Gawande, M. B. & Jayaram, R. V. (2013). Catal. Sci. Technol. 3, 2050–2056. Web of Science CrossRef CAS Google Scholar
Khafagy, M. M., Abd El-Wahab, A. H. F., Eid, F. A. & El-Agrody, A. M. (2002). Farmaco, 57, 715–722. Web of Science CrossRef PubMed CAS Google Scholar
Kidwai, M., Poddar, R., Bhardwaj, S., Singh, S. & Luthra, M. P. (2010). Eur. J. Med. Chem. 45, 5031–5038. Web of Science CrossRef CAS PubMed Google Scholar
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. Web of Science CrossRef CAS IUCr Journals Google Scholar
Martínez-Grau, A. & Marco, J. (1997). Bioorg. Med. Chem. Lett. 7, 3165–3170. Google Scholar
Mohr, S. J., Chirigos, M. A., Fuhrman, F. S. & Pryor, J. W. (1975). Cancer Res. 35, 3750–3754. PubMed CAS Web of Science Google Scholar
Mungra, D. C., Patel, M. P., Rajani, D. P. & Patel, R. G. (2011). Eur. J. Med. Chem. 46, 4192–4200. Web of Science CrossRef CAS PubMed Google Scholar
Osman, S., Albert, B. J., Wang, Y., Li, M., Czaicki, N. L. & Koide, K. (2011). Chem. Eur. J. 17, 895–904. CrossRef CAS PubMed Google Scholar
Patil, A. D., Freyer, A. J., Eggleston, D. S., Haltiwanger, R. C., Bean, M. F., Taylor, P. B., Caranfa, M. J., Breen, A. L., Bartus, H. R., Johnson, R. K., Hertzberg, R. P. & Westley, J. W. (1993). J. Med. Chem. 36, 4131–4138. CSD CrossRef CAS PubMed Web of Science Google Scholar
Perrella, F. W., Chen, S. F., Behrens, D. L., Kaltenbach, R. F. & Seitz, S. P. (1994). J. Med. Chem. 37, 2232–2237. CrossRef CAS PubMed Web of Science Google Scholar
Sabry, N. M., Mohamed, H. M., Khattab, E. S. A. E. H., Motlaq, S. & El-Agrody, A. M. (2011). Eur. J. Med. Chem. 46, 765–772. Web of Science CrossRef CAS PubMed Google Scholar
Schiller, R., Tichotová, L., Pavlík, J., Buchta, V., Melichar, B., Votruba, I., Kuneš, J., Špulák, M. & Pour, M. (2010). Bioorg. Med. Chem. Lett. 20, 7358–7360. CrossRef CAS PubMed Google Scholar
Shahrisa, A., Zirak, M., Mehdipour, A. R. & Miri, R. (2011). Chem. Heterocycl. Compd. 46, 1354–1363. CrossRef CAS Google Scholar
Sheldrick, G. M. (2015a). Acta Cryst. A71, 3–8. Web of Science CrossRef IUCr Journals Google Scholar
Sheldrick, G. M. (2015b). Acta Cryst. C71, 3–8. Web of Science CrossRef IUCr Journals Google Scholar
Spek, A. L. (2009). Acta Cryst. D65, 148–155. Web of Science CrossRef CAS IUCr Journals Google Scholar
Wang, S. M., Milne, G. W. A., Yan, X. J., Posey, I. J., Nicklaus, M. C., Graham, L. & Rice, W. G. (1996). J. Med. Chem. 39, 2047–2054. CrossRef CAS PubMed Google Scholar
Wang, Y., Mo, S. Y., Wang, S. J., Li, S., Yang, Y. C. & Shi, J. G. (2005). Org. Lett. 7, 1675–1678. CrossRef PubMed CAS Google Scholar
Wu, J. Y. C., Fong, W. F., Zhang, J. X., Leung, C. H., Kwong, H. L., Yang, M. S., Li, D. & Cheung, H. (2003). Eur. J. Pharmacol. 473, 9–17. Web of Science CrossRef PubMed CAS Google Scholar
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