Supporting information
Crystallographic Information File (CIF) https://doi.org/10.1107/S2053229620014217/ky3199sup1.cif | |
Structure factor file (CIF format) https://doi.org/10.1107/S2053229620014217/ky3199Isup2.hkl | |
Chemical Markup Language (CML) file https://doi.org/10.1107/S2053229620014217/ky3199Isup3.cml |
CCDC reference: 2011624
Data collection: CrysAlis PRO (Rigaku OD, 2019); cell refinement: CrysAlis PRO (Rigaku OD, 2019); data reduction: CrysAlis PRO (Rigaku OD, 2019); program(s) used to solve structure: SHELXT (Sheldrick, 2015a); program(s) used to refine structure: SHELXL2018 (Sheldrick, 2015b); molecular graphics: ORTEP-3 (Farrugia, 2012); software used to prepare material for publication: SHELXL2018 (Sheldrick, 2015b) and WinGX (Farrugia, 2012).
C19H17Cl2NO2 | F(000) = 376 |
Mr = 362.23 | Dx = 1.462 Mg m−3 |
Monoclinic, P21 | Cu Kα radiation, λ = 1.54184 Å |
a = 3.96521 (9) Å | Cell parameters from 17383 reflections |
b = 16.7005 (4) Å | θ = 2.6–77.8° |
c = 12.4252 (2) Å | µ = 3.64 mm−1 |
β = 91.185 (2)° | T = 100 K |
V = 822.63 (3) Å3 | Prism, yellow |
Z = 2 | 0.15 × 0.13 × 0.12 mm |
Rigaku XtaLAB Synergy Dualflex HyPix diffractometer | 3089 independent reflections |
Radiation source: micro-focus sealed X-ray tube, PhotonJet (Cu) X-ray Source | 3079 reflections with I > 2σ(I) |
Mirror monochromator | Rint = 0.028 |
Detector resolution: 10.0000 pixels mm-1 | θmax = 72.4°, θmin = 3.6° |
ω scans | h = −4→4 |
Absorption correction: multi-scan (CrysAlis PRO; Rigaku OD, 2019) | k = −17→20 |
Tmin = 0.790, Tmax = 1.000 | l = −15→15 |
17673 measured reflections |
Refinement on F2 | Hydrogen site location: inferred from neighbouring sites |
Least-squares matrix: full | H-atom parameters constrained |
R[F2 > 2σ(F2)] = 0.024 | w = 1/[σ2(Fo2) + (0.0463P)2 + 0.1638P] where P = (Fo2 + 2Fc2)/3 |
wR(F2) = 0.064 | (Δ/σ)max < 0.001 |
S = 1.07 | Δρmax = 0.18 e Å−3 |
3089 reflections | Δρmin = −0.20 e Å−3 |
217 parameters | Absolute structure: Flack x determined using 1385 quotients [(I+)-(I-)]/[(I+)+(I-)] (Parsons et al., 2013) |
1 restraint | Absolute structure parameter: 0.002 (9) |
Primary atom site location: dual |
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. The crystal used for analysis was a yellow cube cut down from a needle prism to ca 0.12 × 0.13 × 0.15 mm. This was mounted in oil on a small loop and fixed in the cold nitrogen stream on a Rigaku Oxford Diffraction XtaLAB Synergy diffractometer, equipped with Cu Kα radiation, HyPix detector and mirror monochromator. Intensity data were measured by thin-slice ω-scans. Total no. of reflections recorded, to θmax = 72.5°, was 17673 of which 3089 were unique (Rint = 0.028); 3079 were 'observed' with I > 2σI. Data were processed using the CrysAlisPro CCD and RED (Rigaku Oxford Diffraction Ltd., 2018) programs. The structure was determined by the intrinsic phasing routines in the SHELXT program (Sheldrick, 2015a) and refined by full-matrix least-squares methods, on F2's, in SHELXL (Sheldrick, 2015b). The non-hydrogen atoms were refined with anisotropic thermal parameters. Scattering factors for neutral atoms were taken from International Tables (1992). Computer programs used in this analysis have been noted above, and were run through WinGX (Farrugia, 2012) on a Dell Optiplex 780 PC at the University of East Anglia. The crystallographic data were deposited at the Cambridge Crystallographic Data Centre (CCDC) under a CCDC number:2011624. Copies of the data can be obtained, via www. ccdc.cam.ac.uk. |
x | y | z | Uiso*/Ueq | ||
C1 | 0.9545 (5) | 0.73931 (13) | 0.27433 (17) | 0.0152 (4) | |
C2 | 1.0426 (5) | 0.73678 (13) | 0.38359 (17) | 0.0149 (4) | |
Cl2 | 1.22361 (12) | 0.65138 (3) | 0.44086 (4) | 0.01875 (13) | |
C3 | 1.0024 (6) | 0.80261 (15) | 0.45034 (16) | 0.0163 (4) | |
H3 | 1.067736 | 0.800400 | 0.522597 | 0.020* | |
C4 | 0.8631 (5) | 0.87136 (14) | 0.40690 (17) | 0.0162 (4) | |
Cl4 | 0.81245 (14) | 0.95350 (3) | 0.49102 (4) | 0.02188 (14) | |
C5 | 0.7663 (6) | 0.87689 (14) | 0.29907 (18) | 0.0189 (4) | |
H5 | 0.670026 | 0.923528 | 0.271425 | 0.023* | |
C6 | 0.8174 (6) | 0.81078 (14) | 0.23391 (17) | 0.0186 (4) | |
H6 | 0.758946 | 0.813997 | 0.161163 | 0.022* | |
C7 | 1.0117 (5) | 0.67207 (13) | 0.19629 (16) | 0.0156 (4) | |
O7 | 1.1582 (4) | 0.68791 (10) | 0.11275 (13) | 0.0218 (3) | |
C8 | 0.8765 (6) | 0.59292 (15) | 0.22078 (18) | 0.0165 (4) | |
H8 | 0.758501 | 0.585203 | 0.283861 | 0.020* | |
C9 | 0.9208 (5) | 0.53076 (14) | 0.15283 (17) | 0.0150 (4) | |
H9 | 1.047509 | 0.540990 | 0.092192 | 0.018* | |
C11 | 0.7933 (5) | 0.45028 (14) | 0.16393 (16) | 0.0151 (4) | |
C12 | 0.8317 (5) | 0.39453 (14) | 0.08094 (17) | 0.0160 (4) | |
H12 | 0.938062 | 0.410480 | 0.018466 | 0.019* | |
C13 | 0.7172 (5) | 0.31664 (14) | 0.08860 (17) | 0.0155 (4) | |
H13 | 0.740596 | 0.281911 | 0.030725 | 0.019* | |
C14 | 0.5650 (5) | 0.28933 (13) | 0.18344 (16) | 0.0132 (4) | |
C15 | 0.5209 (5) | 0.34556 (14) | 0.26673 (16) | 0.0159 (4) | |
H15 | 0.415507 | 0.329814 | 0.329461 | 0.019* | |
C16 | 0.6316 (5) | 0.42367 (14) | 0.25670 (17) | 0.0156 (4) | |
H16 | 0.598026 | 0.459444 | 0.312836 | 0.019* | |
N17 | 0.4798 (4) | 0.20947 (12) | 0.19637 (14) | 0.0145 (4) | |
C18 | 0.3753 (5) | 0.16042 (14) | 0.10351 (16) | 0.0165 (4) | |
H18A | 0.500315 | 0.176468 | 0.040801 | 0.020* | |
H18B | 0.137091 | 0.168634 | 0.087878 | 0.020* | |
C19 | 0.4400 (6) | 0.07279 (14) | 0.12729 (18) | 0.0187 (4) | |
H19A | 0.363274 | 0.040835 | 0.066366 | 0.022* | |
H19B | 0.680642 | 0.064173 | 0.137077 | 0.022* | |
O20 | 0.2701 (4) | 0.04708 (10) | 0.22196 (13) | 0.0193 (3) | |
C21 | 0.3857 (5) | 0.09365 (14) | 0.31143 (17) | 0.0177 (4) | |
H21A | 0.625238 | 0.084422 | 0.322896 | 0.021* | |
H21B | 0.270985 | 0.076053 | 0.375454 | 0.021* | |
C22 | 0.3253 (5) | 0.18248 (14) | 0.29586 (17) | 0.0161 (4) | |
H22A | 0.084798 | 0.193057 | 0.292522 | 0.019* | |
H22B | 0.421497 | 0.211782 | 0.356511 | 0.019* |
U11 | U22 | U33 | U12 | U13 | U23 | |
C1 | 0.0183 (10) | 0.0116 (11) | 0.0158 (10) | −0.0028 (8) | 0.0015 (8) | 0.0019 (8) |
C2 | 0.0167 (10) | 0.0114 (11) | 0.0166 (10) | 0.0002 (8) | 0.0023 (8) | 0.0020 (8) |
Cl2 | 0.0279 (3) | 0.0127 (3) | 0.0157 (2) | 0.00367 (18) | −0.00087 (17) | 0.00193 (18) |
C3 | 0.0182 (10) | 0.0162 (11) | 0.0144 (9) | −0.0017 (8) | 0.0025 (7) | 0.0003 (8) |
C4 | 0.0198 (10) | 0.0089 (10) | 0.0201 (10) | −0.0020 (8) | 0.0054 (8) | −0.0019 (8) |
Cl4 | 0.0339 (3) | 0.0124 (3) | 0.0196 (2) | 0.0030 (2) | 0.00575 (19) | −0.00228 (19) |
C5 | 0.0226 (11) | 0.0131 (11) | 0.0210 (11) | 0.0018 (8) | 0.0007 (8) | 0.0033 (8) |
C6 | 0.0267 (11) | 0.0139 (11) | 0.0151 (9) | 0.0008 (8) | −0.0014 (8) | 0.0018 (8) |
C7 | 0.0190 (10) | 0.0139 (12) | 0.0139 (9) | 0.0001 (8) | 0.0000 (8) | 0.0019 (8) |
O7 | 0.0327 (8) | 0.0164 (9) | 0.0164 (7) | −0.0016 (6) | 0.0067 (6) | 0.0020 (6) |
C8 | 0.0193 (10) | 0.0149 (11) | 0.0154 (10) | −0.0013 (8) | 0.0027 (7) | 0.0009 (8) |
C9 | 0.0160 (10) | 0.0155 (12) | 0.0135 (9) | 0.0009 (8) | 0.0007 (7) | 0.0023 (8) |
C11 | 0.0160 (9) | 0.0145 (11) | 0.0148 (9) | 0.0029 (8) | 0.0003 (7) | 0.0002 (8) |
C12 | 0.0187 (10) | 0.0150 (11) | 0.0144 (9) | 0.0014 (8) | 0.0029 (8) | 0.0012 (8) |
C13 | 0.0190 (10) | 0.0133 (11) | 0.0143 (9) | 0.0021 (8) | 0.0011 (7) | −0.0010 (8) |
C14 | 0.0130 (9) | 0.0118 (11) | 0.0146 (9) | 0.0012 (7) | −0.0013 (7) | −0.0002 (8) |
C15 | 0.0183 (10) | 0.0167 (11) | 0.0127 (9) | 0.0008 (8) | 0.0023 (7) | −0.0008 (8) |
C16 | 0.0194 (10) | 0.0134 (11) | 0.0142 (9) | 0.0001 (8) | 0.0016 (8) | −0.0019 (8) |
N17 | 0.0176 (8) | 0.0120 (10) | 0.0139 (8) | −0.0009 (7) | 0.0014 (6) | −0.0008 (7) |
C18 | 0.0186 (9) | 0.0152 (12) | 0.0156 (9) | −0.0017 (8) | −0.0004 (7) | −0.0004 (9) |
C19 | 0.0191 (10) | 0.0155 (12) | 0.0214 (11) | −0.0017 (8) | −0.0003 (8) | −0.0016 (9) |
O20 | 0.0201 (8) | 0.0150 (9) | 0.0227 (8) | −0.0043 (6) | −0.0010 (6) | 0.0017 (6) |
C21 | 0.0168 (10) | 0.0158 (11) | 0.0204 (10) | −0.0016 (8) | −0.0011 (8) | 0.0031 (8) |
C22 | 0.0170 (10) | 0.0165 (12) | 0.0148 (9) | −0.0018 (8) | 0.0005 (7) | 0.0019 (8) |
C1—C2 | 1.396 (3) | C13—C14 | 1.411 (3) |
C1—C6 | 1.400 (3) | C13—H13 | 0.9300 |
C1—C7 | 1.504 (3) | C14—N17 | 1.386 (3) |
C2—C3 | 1.388 (3) | C14—C15 | 1.411 (3) |
C2—Cl2 | 1.742 (2) | C15—C16 | 1.383 (3) |
C3—C4 | 1.379 (3) | C15—H15 | 0.9300 |
C3—H3 | 0.9300 | C16—H16 | 0.9300 |
C4—C5 | 1.389 (3) | N17—C22 | 1.462 (3) |
C4—Cl4 | 1.739 (2) | N17—C18 | 1.468 (3) |
C5—C6 | 1.387 (3) | C18—C19 | 1.514 (3) |
C5—H5 | 0.9300 | C18—H18A | 0.9700 |
C6—H6 | 0.9300 | C18—H18B | 0.9700 |
C7—O7 | 1.229 (3) | C19—O20 | 1.433 (3) |
C7—C8 | 1.461 (3) | C19—H19A | 0.9700 |
C8—C9 | 1.352 (3) | C19—H19B | 0.9700 |
C8—H8 | 0.9300 | O20—C21 | 1.425 (3) |
C9—C11 | 1.444 (3) | C21—C22 | 1.514 (3) |
C9—H9 | 0.9300 | C21—H21A | 0.9700 |
C11—C12 | 1.400 (3) | C21—H21B | 0.9700 |
C11—C16 | 1.403 (3) | C22—H22A | 0.9700 |
C12—C13 | 1.382 (3) | C22—H22B | 0.9700 |
C12—H12 | 0.9300 | ||
C2—C1—C6 | 117.5 (2) | N17—C14—C15 | 121.41 (19) |
C2—C1—C7 | 124.5 (2) | C13—C14—C15 | 117.3 (2) |
C6—C1—C7 | 117.90 (18) | C16—C15—C14 | 121.16 (19) |
C3—C2—C1 | 121.8 (2) | C16—C15—H15 | 119.4 |
C3—C2—Cl2 | 117.12 (16) | C14—C15—H15 | 119.4 |
C1—C2—Cl2 | 121.00 (17) | C15—C16—C11 | 121.6 (2) |
C4—C3—C2 | 118.39 (19) | C15—C16—H16 | 119.2 |
C4—C3—H3 | 120.8 | C11—C16—H16 | 119.2 |
C2—C3—H3 | 120.8 | C14—N17—C22 | 120.14 (18) |
C3—C4—C5 | 122.2 (2) | C14—N17—C18 | 120.77 (17) |
C3—C4—Cl4 | 118.15 (17) | C22—N17—C18 | 112.09 (17) |
C5—C4—Cl4 | 119.62 (18) | N17—C18—C19 | 110.01 (17) |
C6—C5—C4 | 118.0 (2) | N17—C18—H18A | 109.7 |
C6—C5—H5 | 121.0 | C19—C18—H18A | 109.7 |
C4—C5—H5 | 121.0 | N17—C18—H18B | 109.7 |
C5—C6—C1 | 122.0 (2) | C19—C18—H18B | 109.7 |
C5—C6—H6 | 119.0 | H18A—C18—H18B | 108.2 |
C1—C6—H6 | 119.0 | O20—C19—C18 | 111.65 (18) |
O7—C7—C8 | 123.6 (2) | O20—C19—H19A | 109.3 |
O7—C7—C1 | 117.66 (19) | C18—C19—H19A | 109.3 |
C8—C7—C1 | 118.71 (18) | O20—C19—H19B | 109.3 |
C9—C8—C7 | 120.8 (2) | C18—C19—H19B | 109.3 |
C9—C8—H8 | 119.6 | H19A—C19—H19B | 108.0 |
C7—C8—H8 | 119.6 | C21—O20—C19 | 109.14 (16) |
C8—C9—C11 | 127.2 (2) | O20—C21—C22 | 112.81 (17) |
C8—C9—H9 | 116.4 | O20—C21—H21A | 109.0 |
C11—C9—H9 | 116.4 | C22—C21—H21A | 109.0 |
C12—C11—C16 | 116.9 (2) | O20—C21—H21B | 109.0 |
C12—C11—C9 | 120.35 (19) | C22—C21—H21B | 109.0 |
C16—C11—C9 | 122.7 (2) | H21A—C21—H21B | 107.8 |
C13—C12—C11 | 122.3 (2) | N17—C22—C21 | 110.01 (18) |
C13—C12—H12 | 118.8 | N17—C22—H22A | 109.7 |
C11—C12—H12 | 118.8 | C21—C22—H22A | 109.7 |
C12—C13—C14 | 120.6 (2) | N17—C22—H22B | 109.7 |
C12—C13—H13 | 119.7 | C21—C22—H22B | 109.7 |
C14—C13—H13 | 119.7 | H22A—C22—H22B | 108.2 |
N17—C14—C13 | 121.16 (19) | ||
C6—C1—C2—C3 | −1.0 (3) | C16—C11—C12—C13 | 0.0 (3) |
C7—C1—C2—C3 | 176.0 (2) | C9—C11—C12—C13 | 179.2 (2) |
C6—C1—C2—Cl2 | −178.56 (17) | C11—C12—C13—C14 | −2.2 (3) |
C7—C1—C2—Cl2 | −1.6 (3) | C12—C13—C14—N17 | −173.46 (19) |
C1—C2—C3—C4 | 1.7 (3) | C12—C13—C14—C15 | 3.0 (3) |
Cl2—C2—C3—C4 | 179.31 (17) | N17—C14—C15—C16 | 174.66 (19) |
C2—C3—C4—C5 | −0.7 (3) | C13—C14—C15—C16 | −1.8 (3) |
C2—C3—C4—Cl4 | 179.84 (16) | C14—C15—C16—C11 | −0.3 (3) |
C3—C4—C5—C6 | −0.9 (3) | C12—C11—C16—C15 | 1.2 (3) |
Cl4—C4—C5—C6 | 178.58 (17) | C9—C11—C16—C15 | −178.0 (2) |
C4—C5—C6—C1 | 1.5 (3) | C13—C14—N17—C22 | 179.40 (18) |
C2—C1—C6—C5 | −0.6 (3) | C15—C14—N17—C22 | 3.0 (3) |
C7—C1—C6—C5 | −177.8 (2) | C13—C14—N17—C18 | −32.2 (3) |
C2—C1—C7—O7 | −128.3 (2) | C15—C14—N17—C18 | 151.44 (19) |
C6—C1—C7—O7 | 48.7 (3) | C14—N17—C18—C19 | 155.90 (18) |
C2—C1—C7—C8 | 54.8 (3) | C22—N17—C18—C19 | −53.4 (2) |
C6—C1—C7—C8 | −128.2 (2) | N17—C18—C19—O20 | 57.1 (2) |
O7—C7—C8—C9 | 3.1 (4) | C18—C19—O20—C21 | −59.5 (2) |
C1—C7—C8—C9 | 179.78 (19) | C19—O20—C21—C22 | 58.9 (2) |
C7—C8—C9—C11 | −177.70 (19) | C14—N17—C22—C21 | −156.88 (18) |
C8—C9—C11—C12 | 173.4 (2) | C18—N17—C22—C21 | 52.2 (2) |
C8—C9—C11—C16 | −7.4 (4) | O20—C21—C22—N17 | −55.5 (2) |
D—H···A | D—H | H···A | D···A | D—H···A |
C13—H13···O7i | 0.93 | 2.42 | 3.343 (3) | 176 |
C18—H18A···O7i | 0.97 | 2.37 | 3.326 (3) | 168 |
Symmetry code: (i) −x+2, y−1/2, −z. |
C16—C11—C9—C8 | C11—C9—C8—C7 | C9—C8—C7—O7 | C9—C8—C7—C1 | C8—C7—C1—C6 | Reference |
-7.4 (4) | -177.70 (19) | 3.1 (4) | 179.78 (19) | -128.2 (2) | This study |
35.7 | -177..6 | 20.2 | -162.9 | -47.3 | This study* |
11.0 | -176.8 | 16.3 | -163.0 | -157.5 | Treadwell (2006) |
12.8 | 178.5 | 7.0 | -173.0 | 169.0 | Li & Su (1994) |
2.5 | -169.5 | 11.8 | -179.8 | 163.8 | Wu et al., (2014b) |
-7.1 | 179.9 | -8.5 | 170.7 | 166.8 | Barsky et al. (2008); compound 3 |
Note: (*) the torsion angles for the keto–ethene after the interaction with 7bqy. |
ADD SCHEME HERE |
O7—C7 | C7—C8 | C8═C9 | Reference |
1.229 (3) | 1.461 (3) | 1.352 (3) | This study |
1.224 (2) | 1.474 (4) | 1.326 (3) | Treadwell (2006) |
1.227 (4) | 1.474 (4) | 1.313 (4) | Li & Su (1994) |
1.240 (2) | 1.459 (2) | 1.327 (3) | Wu et al. (2014a,b) |
1.226 (2) | 1.471 (2) | 1.325 (2) | Tang (2009) |
Poses | Binding affinities (kcal mol-1) | RMSD lower limit | RMSD upper limit | No. of hydrogen bonds, residue, D (Å) |
1 | -7.0 | 0.0 | 0.0 | 1, Arg 188(A), 2.89 |
2 | -7.0 | 1.535 | 2.045 | 3, Arg 188(A), 2.70; Gly 143(A), 3.08; Thr190(A), 3.10 |
3 | -6.9 | 4.271 | 9.538 | 1, His164(A), 2.7 |
4 | -6.8 | 1.291 | 1.722 | 1, Glu166(A), 2.68 |
5 | -6.7 | 4.417 | 9.652 | 1, Gly143(A), 3.05 |
6 | -6.7 | 5.001 | 10.53 | 1, Glu166(A), 3.00 |
7 | -6.6 | 4.414 | 9.585 | 0 |
8 | -6.6 | 2.759 | 3.767 | 1, Thr190(A), 2.70 |
9 | -6.4 | 1.652 | 2.114 | 1, Glu166(A), 2.80 |