research communications\(\def\hfill{\hskip 5em}\def\hfil{\hskip 3em}\def\eqno#1{\hfil {#1}}\)

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ISSN: 2056-9890

Different intra- and inter­molecular hydrogen-bonding patterns in (3S,4aS,8aS)-2-[(2R,3S)-3-(2,5-X2-benzamido)-2-(2,5-X2-benzo­yl­oxy)-4-phenyl­butyl]-N-tert-butyldeca­hydro­iso­quinoline-3-carboxamides (X = H or Cl): compounds with moderate aspartyl protease inhibition activity

CROSSMARK_Color_square_no_text.svg

aDepartamento de Química Orgânica, Universidade Federal de Pelotas (UFPel), Campus Universitário, s/n, Caixa Postal 354, 96010-900 Pelotas, RS, Brazil, bInstituto de Tecnologia em Fármacos – Farmanguinhos, Fiocruz. R. Sizenando, Nabuco, 100, Manguinhos, 21041-250, Rio de Janeiro, RJ, Brazil, and cDepartment of Chemistry, University of Aberdeen, Meston Walk, Aberdeen AB24 3UE, Scotland
*Correspondence e-mail: w.harrison@abdn.ac.uk

Edited by S. Parkin, University of Kentucky, USA (Received 20 May 2017; accepted 25 May 2017; online 31 May 2017)

The crystal structures of (3S,4aS,8aS)-2-[(2R,3S)-3-benzamido-2-benzo­yloxy-4-phenyl­but­yl]-N-tert-butyldeca­hydro­iso­quinoline-3-carboxamide, C38H47N3O4, (I), and (3S,4aS,8aS)-2-[(2R,3S)-3-(2,5-di­chloro­benzamido)-2-(2,5-di­chloro­benzo­yloxy)-4-phenyl­but­yl]-N-tert-butyldeca­hydro­iso­quinoline-3-carboxamide, C38H43Cl4N3O4, (II), are described. Despite their chemical similarity, they adopt different conformations in the solid state: (I) features a bifurcated intra­molecular N—H⋯(N,O) hydrogen bond from the tert-butylamide NH group to the piperidine N atom and the benzoate O atom, whereas (II) has an intra­molecular N—H⋯O link from the benzamide NH group to the tert-butyl­amide O atom. In the crystal of (I), mol­ecules are linked by C(4) amide N—H⋯O hydrogen bonds into chains propagating in the [010] direction, with both donor and acceptor parts of the benzamide group. In the extended structure of (II), C(11) N—H⋯O chains propagating in the [010] direction arise, with the donor being the tert-butylamide NH group and the acceptor being the O atom of the benzamide group.

1. Chemical context

Malaria remains one of the most devastating infectious diseases with over 200 million cases and more than 600 000 deaths each year – primarily children under the age of five in sub-Saharan Africa. There is an urgent need for effective drugs with new mechanisms of action, due to the high rate of mutation of the parasite, which leads to the development of resistance of current drugs.

One of the critical stages of the life cycle of the parasite during human infection is the degradation of haemoglobin, which provides nutrients for its growth and maturation (Coombs et al., 2001[Coombs, G. H., Goldberg, D. E., Klemba, M., Berry, C., Kay, J. & Mottram, J. C. (2001). Trends Parasitol. 17, 532-537.]). Plasmepsins are a family of aspartic proteases involved in the degradation of human haemoglobin by Plasmodium falciparum (Huizing et al., 2015[Huizing, A. P., Mondal, M. & Hirsch, A. K. (2015). J. Med. Chem. 58, 5151-5163.]). As the parasite needs the resulting amino acid building blocks for its growth and development, plasmepsins are an important anti­malarial drug target. Secondary alcohols (Muthas et al., 2005[Muthas, D., Noteberg, D., Sabnis, Y. A., Hamelink, E., Vrang, L., Samuelsson, B., Karlén, A. & Hallberg, A. (2005). Bioorg. Med. Chem. 13, 5371-5390.]; Ersmark et al., 2006[Ersmark, K., Nervall, M., Gutiérrez-de-Terán, H., Hamelink, E., Janka, L. K., Clemente, J. C., Dunn, B. M., Gogoll, A., Samuelsson, B., Aqvist, J. & Hallberg, A. (2006). Bioorg. Med. Chem. 14, 2197-2208.]) and tertiary alcohols (Motwani et al., 2015[Motwani, H. V., De Rosa, M., Odell, L. R., Hallberg, A. & Larhed, M. (2015). Eur. J. Med. Chem. 90, 462-490.]) have been successfully used to develop potent inhibitors of these enzymes.

Cunico et al. (2008[Cunico, W., Ferreira, M. L. G., Ferreira, T. G., Penido, C., Henriques, M. G. M. O., Krettli, L. G., Varottic, F. P. & Krettli, A. U. (2008). Lett. Drug Des. Discov. pp. 178-181.]) reported the moderate in vitro anti­malarial activities of the products of reactions of the 2-amino­ethyl compound, 3 (see Scheme 1[link]) with various sulfonyl chlorides and acyl chlorides. In the present article, we report the crystal structures of two compounds (see Scheme 2[link]), C38H47N3O4, (I)[link], and C38H43Cl4N3O4, (II)[link], obtained in that study from reactions with acyl chlorides.

[Scheme 1]

2. Structural commentary

Compound (I)[link] crystallizes in the space group P21 with a single mol­ecule in the asymmetric unit (Fig. 1[link]). The absolute structure was not definitively established based on refinement of the Flack parameter (Parsons et al., 2013[Parsons, S., Flack, H. D. & Wagner, T. (2013). Acta Cryst. B69, 249-259.]) and the configurations of the stereogenic centres (C2 R, C3 S, C7 S, C9 S, C14 S) were set to match those in (II)[link]: they are those expected based on the known starting materials. Each atom in the C1—C2—C3—C4 `backbone' of (I)[link] bears a different substituent: C1 is attached to a piperidine+cyclo­hexane fused-ring system, which in turn bears a tert-butylamide group. C2 is attached to a benzoate group and C3 bears a benzamide group. Finally, C4 is attached to a simple phenyl ring, i.e. a benzyl group. Some key torsion angles are presented in Table 1[link]. These show that with respect to the C2—C3 bond, the C1 + C4, C1 + N3 and N3 + O4 pairings are gauche, whereas the C4 + O4 atoms are mutually anti. In terms of the H atoms, H2 is anti to N3 (171°) and H3 is anti to C1 (176°); the gauche torsion angle between the H atoms is 54°. The N1—C1—C2—C3 torsion angle of 170.4 (3)° indicates an anti conformation and the N1/C7/C8/C9/C14/C5 and C9–C14 rings have a cis-fused junction (H9—C9—C14—H14 = −52°). The amide torsion angles C3—N3—C5—C27 and C17—N2—C16—C7 are −178.3 (3) and −164.7 (4)°, respectively, which reflect the expected near-planar conformations for these groups. The dihedral angles between the aromatic rings C21–C26 (A), C27–C32 (B) and C33–C38 (C) are A/B = 85.7 (2), A/C = 79.2 (2) and B/C = 17.3 (2)°. The conformation of (I)[link] is supported by a bifurcated intra­molecular N—H⋯(N,O) hydrogen bond (Table 2[link]) arising from the tert-butylamide group: the acceptor atoms are the N atom of the piperidine ring and the O atom of the C=O group of the benzoate group. The bifurcated bond is very asymmetric in terms of angles and the H⋯O link is long, but given that the assemblage is close to planar (bond-angle sum for the H atom = 353°), we regard it as being just significant.

[Scheme 2]

Table 1
Selected torsion angles (°) for (I)[link]

N1—C1—C2—C3 170.4 (3) C1—C2—C3—C4 59.4 (4)
C1—C2—C3—N3 −66.3 (4) C4—C3—N3—C5 138.6 (4)
O4—C2—C3—C4 178.4 (3) C3—C2—O4—C6 131.5 (3)

Table 2
Hydrogen-bond geometry (Å, °) for (I)[link]

D—H⋯A D—H H⋯A DA D—H⋯A
N2—H1N⋯O5 0.90 (5) 2.55 (5) 3.384 (5) 154 (4)
N2—H1N⋯N1 0.90 (5) 2.32 (5) 2.773 (4) 111 (4)
N3—H3N⋯O3i 0.93 (5) 2.04 (5) 2.929 (4) 161 (4)
C18—H18B⋯O2ii 0.98 2.39 3.310 (5) 157
C20—H20A⋯O2 0.98 2.35 2.963 (6) 120
C29—H29⋯O5i 0.95 2.58 3.467 (5) 157
Symmetry codes: (i) [-x, y+{\script{1\over 2}}, -z]; (ii) [-x+1, y-{\script{1\over 2}}, -z+1].
[Figure 1]
Figure 1
The asymmetric unit of (I)[link], showing 50% probability displacement ellipsoids, with most H atoms omitted for clarity. The bifurcated intra­molecular hydrogen bond is shown as a double-dashed line.

Compound (II)[link] crystallizes in the space group P212121 with one mol­ecule in the asymmetric unit (Fig. 2[link]). Here, the absolute structure is very well established (C2 R, C3 S, C7 S, C9 S, C14 S) and is consistent with the starting materials (Cunico et al., 2008[Cunico, W., Ferreira, M. L. G., Ferreira, T. G., Penido, C., Henriques, M. G. M. O., Krettli, L. G., Varottic, F. P. & Krettli, A. U. (2008). Lett. Drug Des. Discov. pp. 178-181.]). The C1—C2—C3—C4 backbone bears the equivalent substituents to (I)[link], with the difference that the benzyl and amide rings both bear a pair of Cl atoms at the meta positions. Selected torsion angles for (II)[link] (Table 3[link]) show similarities but also one major difference with respect to (I)[link]. In terms of the central C2—C3 bond in (II)[link], the C1 + C4, C1 + N3 and N3 + O4 pairings are gauche, whereas the C4 + O4 atoms are mutually anti. With respect to the H atoms, H2 is anti to N3 (−175°) and H3 is anti to C1 (−166°); the torsion angle between the H atoms is 69°. Thus, the overall conformation of the atoms about the C2—C3 bond in (II)[link] is essentially the same as in (I)[link], although some of the torsion angles differ by as much as 20°. The N1—C1—C2—C3 gauche torsion angle of −69.1 (3)° in (II)[link] is quite different to the value for (I)[link] above, whereas the amide torsion angles C3—N3—C5—C27 [180.0 (3)°] and C17—N2—C16—C7 [–177.5 (3)°] in (II)[link] are similar. The dihedral angles between the aromatic rings C21–C26 (A), C27–C32 (B) and C33–C38 (C) are A/B = 74.84 (17), A/C = 67.99 (17) and B/C = 68.91 (15)°: it may be seen that the first two of these values are similar to the equivalent data for (I)[link], but the third value is very different, possibly reflecting a reorientation in (II)[link] to minimize unfavourable steric inter­actions between the bichlorinated rings. Compound (II)[link] features a completely different intra­molecular N—H⋯O hydrogen bond (Table 4[link]) to (I)[link]: in (II)[link], a much shorter (and presumably stronger) bond arises from the benzamide NH group to the tert-butylamide O atom, which no doubt correlates with the very different N1—C1—C2—C3 torsion angles for (I)[link] and (II)[link] already mentioned.

Table 3
Selected torsion angles (°) for (II)[link]

N1—C1—C2—C3 −69.1 (3) C1—C2—C3—C4 74.4 (3)
C1—C2—C3—N3 −49.5 (3) C4—C3—N3—C5 136.6 (3)
O4—C2—C3—C4 −167.3 (2) C3—C2—O4—C6 158.0 (2)

Table 4
Hydrogen-bond geometry (Å, °) for (II)[link]

D—H⋯A D—H H⋯A DA D—H⋯A
N2—H1N⋯O3i 0.84 (4) 2.13 (4) 2.931 (3) 160 (3)
N3—H2N⋯O2 0.88 (4) 1.99 (4) 2.834 (3) 159 (3)
C4—H4A⋯N1 0.99 2.55 3.149 (4) 119
C18—H18A⋯O2 0.98 2.36 2.975 (4) 120
C34—H34⋯O3 0.95 2.40 3.324 (4) 163
Symmetry code: (i) [-x+1, y+{\script{1\over 2}}, -z+{\script{1\over 2}}].
[Figure 2]
Figure 2
The asymmetric unit of (II)[link], showing 50% probability displacement ellipsoids, with most H atoms omitted for clarity. The intra­molecular hydrogen bond is shown as a double-dashed line.

3. Supra­molecular features

In the crystal of (I)[link], mol­ecules are linked by classical C(4) amide N—H⋯O hydrogen bonds into chains propagating in the [010] direction, with adjacent mol­ecules related by the 21 screw axis. Both donor and acceptor are part of the benzamide group (Fig. 3[link]). Two weak C—H⋯O inter­actions are also observed.

[Figure 3]
Figure 3
A fragment of a [010] hydrogen-bonded chain in (I)[link], showing 20% probability displacement ellipsoids; the pendant rings and C-bound H atoms have been omitted for clarity. [Symmetry code as in Table 2[link]; additionally (iii) −x, y − [{1\over 2}], −z.]

In the extended structure of (II)[link], C(11) [010] N—H⋯O chains arise, with the donor being the tert-butylamide NH group and the acceptor being the O atom of the benzamide ring (Fig. 4[link]). Adjacent mol­ecules are again related by a 21 screw axis.

[Figure 4]
Figure 4
A fragment of a [010] hydrogen-bonded chain in (II)[link], showing 20% probability displacement ellipsoids; the pendant rings and C-bound H atoms have been omitted for clarity. [Symmetry code as in Table 4[link]; additionally (ii) −x + 1, y − [{1\over 2}], −z + [{1\over 2}].]

In short, for (I)[link], the tert-butylamide NH moiety forms an intra­molecular hydrogen bond and the benzamide NH group forms an inter­molecular link, whereas for (II)[link], the situation is reversed: the benzamide NH group forms the intra­molecular bond and the tert-butyl NH group forms the inter­molecular link.

4. Database survey

A survey of of the Cambridge Structural Database (Groom et al., 2016[Groom, C. R., Bruno, I. J., Lightfoot, M. P. & Ward, S. C. (2016). Acta Cryst. B72, 171-179.]: updated to April 2017) for the grouping of atoms about the C1—C2—C3—C4 fragment in (I)[link] and (II)[link] yielded 24 matches. The most similar are the isostructural halide salts YURSUB and YURTAI of the anti-HIV drug saquinavir mesylate (Fandaruff et al., 2015[Fandaruff, C., Chelazzi, L., Braga, D., Cuffini, S. L., Silva, M. A. S., Resende, J. A. L. C., Dichiarante, E. & Grepioni, F. (2015). Cryst. Growth Des. 15, 5233-5239.]), which also act as protease inhibitors. The other hits have little similarity to the title compounds.

5. Synthesis and crystallisation

As summarized in Scheme 1, compounds (I)[link] and (II)[link] were prepared as described previously (Cunico et al., 2008[Cunico, W., Ferreira, M. L. G., Ferreira, T. G., Penido, C., Henriques, M. G. M. O., Krettli, L. G., Varottic, F. P. & Krettli, A. U. (2008). Lett. Drug Des. Discov. pp. 178-181.]) and recrystallized from methanol solution. (I)[link]: colourless needles, m.p. 475–476 K, ESI–HRMS (M + H): calculated for C38H48N3O4: 610.3645, found: 610.3638. (II)[link]: colourless slabs, m.p. 459–460 K, ESI–HRMS (M + H): calculated for C38H4435Cl4N3O4: 746.2086, found: 746.2078.

6. Refinement

Crystal data, data collection and structure refinement details are summarized in Table 5[link]. The N-bound H atoms were located in difference maps and their positions were freely refined. The C-bound H atoms were placed geometrically (C—H = 0.95–1.00 Å) and refined as riding atoms. The constraint Uiso(H) = 1.2Ueq(C) or 1.5Ueq(methyl C) was applied in all cases. The methyl groups were allowed to rotate, but not to tip, to best fit the electron density.

Table 5
Experimental details

  (I) (II)
Crystal data
Chemical formula C38H47N3O4 C38H43Cl4N3O4
Mr 609.78 747.55
Crystal system, space group Monoclinic, P21 Orthorhombic, P212121
Temperature (K) 100 100
a, b, c (Å) 11.4866 (3), 9.4448 (2), 16.8257 (5) 10.4539 (1), 15.1917 (1), 24.3677 (2)
α, β, γ (°) 90, 109.227 (3), 90 90, 90, 90
V3) 1723.58 (8) 3869.90 (6)
Z 2 4
Radiation type Cu Kα Cu Kα
μ (mm−1) 0.60 3.12
Crystal size (mm) 0.52 × 0.15 × 0.05 0.25 × 0.20 × 0.04
 
Data collection
Diffractometer Rigaku Mercury CCD Rigaku Mercury CCD
Absorption correction Multi-scan (SADABS; Sheldrick, 2004[Sheldrick, G. M. (2004). SADABS. University of Göttingen, Germany.]) Multi-scan (SADABS; Sheldrick, 2004[Sheldrick, G. M. (2004). SADABS. University of Göttingen, Germany.])
Tmin, Tmax 0.654, 0.971 0.611, 0.886
No. of measured, independent and observed [I > 2σ(I)] reflections 24074, 5349, 4547 44109, 7278, 7140
Rint 0.068 0.046
(sin θ/λ)max−1) 0.610 0.610
 
Refinement
R[F2 > 2σ(F2)], wR(F2), S 0.056, 0.151, 1.07 0.038, 0.100, 1.05
No. of reflections 5349 7278
No. of parameters 415 451
No. of restraints 1 0
H-atom treatment H atoms treated by a mixture of independent and constrained refinement H atoms treated by a mixture of independent and constrained refinement
Δρmax, Δρmin (e Å−3) 0.35, −0.26 0.28, −0.32
Absolute structure Flack x determined using 1316 quotients [(I+) − (I)]/[(I+) + (I)] (Parsons et al., 2013[Parsons, S., Flack, H. D. & Wagner, T. (2013). Acta Cryst. B69, 249-259.]) Flack x determined using 3021 quotients [(I+) − (I)]/[(I+) + (I)] (Parsons et al., 2013[Parsons, S., Flack, H. D. & Wagner, T. (2013). Acta Cryst. B69, 249-259.])
Absolute structure parameter −0.4 (2) −0.006 (7)
Computer programs: CrysAlis PRO (Rigaku, 2014[Rigaku (2014). CrysAlis PRO. Rigaku Corporation, Tokyo, Japan.]), SHELXS97 (Sheldrick, 2008[Sheldrick, G. M. (2008). Acta Cryst. A64, 112-122.]), SHELXL2014 (Sheldrick, 2015[Sheldrick, G. M. (2015). Acta Cryst. C71, 3-8.]), ORTEP-3 for Windows (Farrugia, 2012[Farrugia, L. J. (2012). J. Appl. Cryst. 45, 849-854.]) and publCIF (Westrip, 2010[Westrip, S. P. (2010). J. Appl. Cryst. 43, 920-925.]).

Supporting information


Computing details top

For both compounds, data collection: CrysAlis PRO (Rigaku, 2014); cell refinement: CrysAlis PRO (Rigaku, 2014); data reduction: CrysAlis PRO (Rigaku, 2014); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL2014 (Sheldrick, 2015); molecular graphics: ORTEP-3 (Farrugia, 2012); software used to prepare material for publication: publCIF (Westrip, 2010).

(I) (3S,4aS,8aS)-2-[(2R,3S)-3-Benzamido-2-benzoyloxy-4-phenylbutyl]-N-tert-butyldecahydroisoquinoline-3-carboxamide top
Crystal data top
C38H47N3O4F(000) = 656
Mr = 609.78Dx = 1.175 Mg m3
Monoclinic, P21Cu Kα radiation, λ = 1.54184 Å
a = 11.4866 (3) ÅCell parameters from 8813 reflections
b = 9.4448 (2) Åθ = 5.4–69.6°
c = 16.8257 (5) ŵ = 0.60 mm1
β = 109.227 (3)°T = 100 K
V = 1723.58 (8) Å3Needle, colourless
Z = 20.52 × 0.15 × 0.05 mm
Data collection top
Rigaku Mercury CCD
diffractometer
4547 reflections with I > 2σ(I)
ω scansRint = 0.068
Absorption correction: multi-scan
(SADABS; Sheldrick, 2004)
θmax = 70.1°, θmin = 2.8°
Tmin = 0.654, Tmax = 0.971h = 1413
24074 measured reflectionsk = 119
5349 independent reflectionsl = 2019
Refinement top
Refinement on F2Hydrogen site location: mixed
Least-squares matrix: fullH atoms treated by a mixture of independent and constrained refinement
R[F2 > 2σ(F2)] = 0.056 w = 1/[σ2(Fo2) + (0.0894P)2 + 0.2672P]
where P = (Fo2 + 2Fc2)/3
wR(F2) = 0.151(Δ/σ)max < 0.001
S = 1.07Δρmax = 0.35 e Å3
5349 reflectionsΔρmin = 0.26 e Å3
415 parametersAbsolute structure: Flack x determined using 1316 quotients [(I+)-(I-)]/[(I+)+(I-)] (Parsons et al., 2013)
1 restraintAbsolute structure parameter: 0.4 (2)
Primary atom site location: structure-invariant direct methods
Special details top

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.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å2) top
xyzUiso*/Ueq
C10.1094 (4)0.3195 (4)0.1956 (2)0.0347 (8)
H1A0.19500.35300.20690.042*
H1B0.05660.36720.14380.042*
C20.1046 (3)0.1585 (4)0.1806 (2)0.0322 (8)
H20.16680.11130.22950.039*
C30.1262 (3)0.1138 (4)0.0997 (2)0.0310 (8)
H30.12650.00790.09880.037*
C40.2513 (3)0.1625 (4)0.0978 (2)0.0353 (8)
H4A0.24910.26650.09000.042*
H4B0.31400.14140.15300.042*
C50.0678 (3)0.0764 (4)0.0162 (2)0.0322 (8)
C60.0309 (4)0.0410 (4)0.2415 (2)0.0344 (9)
C70.1555 (3)0.4553 (4)0.3252 (2)0.0362 (8)
H70.16680.54060.29330.043*
C80.1086 (4)0.5037 (5)0.3955 (3)0.0408 (9)
H8A0.16740.57330.43110.049*
H8B0.10600.42130.43120.049*
C90.0194 (4)0.5709 (5)0.3631 (3)0.0408 (9)
H90.01350.65870.33140.049*
C100.0665 (4)0.6127 (5)0.4343 (3)0.0469 (10)
H10A0.14080.67260.41140.056*
H10B0.00270.66980.47590.056*
C110.0984 (4)0.4852 (5)0.4784 (3)0.0510 (12)
H11A0.02240.43070.50690.061*
H11B0.13300.51790.52180.061*
C120.1913 (4)0.3899 (5)0.4161 (3)0.0497 (11)
H12A0.27020.44150.39170.060*
H12B0.20720.30540.44570.060*
C130.1435 (4)0.3435 (5)0.3454 (3)0.0430 (10)
H13A0.07040.28210.36910.052*
H13B0.20790.28710.30380.052*
C140.1088 (4)0.4686 (5)0.3014 (2)0.0381 (9)
H140.18630.52250.27320.046*
C150.0557 (3)0.4256 (4)0.2330 (3)0.0379 (9)
H15A0.11280.35800.19440.046*
H15B0.05010.51050.19990.046*
C160.2805 (4)0.3896 (5)0.3683 (3)0.0389 (9)
C170.3889 (4)0.1660 (5)0.4317 (3)0.0395 (9)
C180.4024 (4)0.1975 (5)0.5232 (3)0.0430 (10)
H18A0.41440.29950.53360.064*
H18B0.47370.14620.56040.064*
H18C0.32770.16730.53450.064*
C190.3574 (4)0.0085 (5)0.4131 (3)0.0484 (11)
H19A0.27640.01130.41820.073*
H19B0.42000.04990.45330.073*
H19C0.35560.01350.35570.073*
C200.5072 (4)0.1970 (6)0.4129 (3)0.0516 (12)
H20A0.52840.29730.42350.077*
H20B0.49520.17510.35380.077*
H20C0.57420.13860.44920.077*
C210.2909 (3)0.0951 (4)0.0296 (2)0.0345 (8)
C220.3112 (4)0.0514 (5)0.0303 (3)0.0381 (9)
H220.29600.10890.07210.046*
C230.3533 (4)0.1124 (5)0.0299 (3)0.0449 (10)
H230.36800.21150.02820.054*
C240.3743 (4)0.0325 (6)0.0919 (3)0.0508 (11)
H240.40340.07560.13280.061*
C250.3523 (4)0.1131 (6)0.0941 (3)0.0523 (11)
H250.36570.16980.13690.063*
C260.3109 (4)0.1745 (5)0.0337 (3)0.0444 (10)
H260.29590.27360.03580.053*
C270.1602 (3)0.1360 (4)0.0933 (2)0.0315 (8)
C280.1291 (4)0.2311 (4)0.1467 (2)0.0335 (8)
H280.04700.26530.13230.040*
C290.2175 (4)0.2756 (4)0.2206 (3)0.0370 (9)
H290.19550.33950.25680.044*
C300.3380 (4)0.2273 (4)0.2417 (3)0.0386 (9)
H300.39840.25820.29230.046*
C310.3700 (4)0.1339 (4)0.1889 (3)0.0382 (9)
H310.45250.10110.20330.046*
C320.2825 (3)0.0883 (4)0.1156 (3)0.0353 (8)
H320.30520.02400.07980.042*
C330.1626 (3)0.0098 (4)0.2289 (2)0.0346 (8)
C340.2557 (4)0.0418 (5)0.1540 (3)0.0400 (9)
H340.23540.08060.10810.048*
C350.3772 (4)0.0176 (5)0.1463 (3)0.0481 (11)
H350.44060.04050.09520.058*
C360.4071 (4)0.0400 (5)0.2126 (3)0.0493 (11)
H360.49100.05660.20680.059*
C370.3155 (4)0.0735 (5)0.2872 (3)0.0506 (11)
H370.33630.11270.33280.061*
C380.1931 (4)0.0496 (5)0.2950 (3)0.0449 (10)
H380.12980.07380.34580.054*
N10.0677 (3)0.3598 (3)0.26662 (19)0.0332 (7)
N20.2845 (3)0.2467 (4)0.3755 (2)0.0369 (8)
H1N0.208 (4)0.209 (6)0.358 (3)0.044*
N30.0279 (3)0.1602 (3)0.02500 (19)0.0301 (7)
H3N0.027 (4)0.252 (6)0.005 (3)0.036*
O20.3711 (3)0.4674 (3)0.3992 (2)0.0506 (8)
O30.0799 (2)0.0457 (3)0.00716 (17)0.0344 (6)
O40.0177 (2)0.1111 (3)0.17533 (16)0.0329 (6)
O50.0540 (2)0.0080 (4)0.30361 (18)0.0449 (7)
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
C10.036 (2)0.0253 (19)0.040 (2)0.0010 (16)0.0092 (16)0.0009 (15)
C20.0261 (17)0.0251 (19)0.043 (2)0.0008 (15)0.0086 (15)0.0016 (16)
C30.0292 (17)0.0212 (18)0.0410 (19)0.0052 (15)0.0094 (14)0.0021 (15)
C40.0318 (18)0.027 (2)0.045 (2)0.0015 (16)0.0095 (15)0.0010 (17)
C50.0328 (19)0.023 (2)0.039 (2)0.0003 (15)0.0090 (15)0.0032 (15)
C60.037 (2)0.030 (2)0.038 (2)0.0008 (16)0.0138 (17)0.0014 (16)
C70.037 (2)0.0251 (19)0.042 (2)0.0047 (16)0.0062 (16)0.0014 (17)
C80.042 (2)0.031 (2)0.045 (2)0.0043 (18)0.0092 (17)0.0029 (17)
C90.045 (2)0.027 (2)0.047 (2)0.0004 (18)0.0100 (18)0.0000 (17)
C100.050 (2)0.032 (2)0.057 (3)0.006 (2)0.015 (2)0.005 (2)
C110.057 (3)0.049 (3)0.048 (2)0.008 (2)0.020 (2)0.002 (2)
C120.052 (3)0.043 (3)0.059 (3)0.002 (2)0.024 (2)0.005 (2)
C130.043 (2)0.033 (2)0.053 (2)0.0001 (18)0.0147 (18)0.0012 (19)
C140.035 (2)0.033 (2)0.044 (2)0.0068 (17)0.0097 (16)0.0013 (17)
C150.033 (2)0.032 (2)0.045 (2)0.0014 (16)0.0073 (16)0.0013 (16)
C160.039 (2)0.030 (2)0.043 (2)0.0064 (17)0.0076 (17)0.0028 (16)
C170.0319 (19)0.033 (2)0.046 (2)0.0001 (17)0.0033 (16)0.0008 (18)
C180.041 (2)0.035 (2)0.047 (2)0.0005 (18)0.0055 (17)0.0029 (18)
C190.044 (2)0.030 (2)0.059 (3)0.0076 (19)0.001 (2)0.004 (2)
C200.041 (2)0.051 (3)0.060 (3)0.003 (2)0.013 (2)0.004 (2)
C210.0264 (17)0.032 (2)0.043 (2)0.0004 (16)0.0082 (14)0.0002 (17)
C220.036 (2)0.031 (2)0.047 (2)0.0002 (17)0.0132 (16)0.0019 (18)
C230.036 (2)0.036 (2)0.060 (3)0.0019 (18)0.0131 (19)0.007 (2)
C240.048 (2)0.050 (3)0.057 (3)0.008 (2)0.020 (2)0.011 (2)
C250.059 (3)0.055 (3)0.050 (2)0.006 (2)0.026 (2)0.001 (2)
C260.047 (2)0.035 (2)0.052 (2)0.0017 (19)0.0174 (18)0.003 (2)
C270.0311 (18)0.0192 (18)0.042 (2)0.0015 (15)0.0095 (15)0.0018 (15)
C280.0353 (19)0.0226 (18)0.041 (2)0.0007 (16)0.0099 (16)0.0031 (16)
C290.043 (2)0.023 (2)0.042 (2)0.0030 (16)0.0095 (17)0.0019 (16)
C300.038 (2)0.028 (2)0.043 (2)0.0039 (17)0.0031 (17)0.0025 (17)
C310.0310 (18)0.031 (2)0.048 (2)0.0012 (16)0.0063 (16)0.0010 (17)
C320.0333 (19)0.0219 (19)0.048 (2)0.0015 (16)0.0099 (16)0.0005 (16)
C330.0347 (19)0.0245 (18)0.046 (2)0.0012 (16)0.0156 (16)0.0015 (16)
C340.038 (2)0.034 (2)0.047 (2)0.0014 (17)0.0115 (17)0.0035 (18)
C350.036 (2)0.045 (3)0.059 (3)0.004 (2)0.0104 (19)0.003 (2)
C360.040 (2)0.043 (3)0.065 (3)0.008 (2)0.018 (2)0.004 (2)
C370.047 (2)0.047 (3)0.062 (3)0.002 (2)0.024 (2)0.010 (2)
C380.042 (2)0.042 (3)0.051 (2)0.001 (2)0.0156 (18)0.008 (2)
N10.0307 (16)0.0262 (17)0.0396 (17)0.0022 (13)0.0075 (13)0.0028 (13)
N20.0325 (16)0.0274 (18)0.0445 (18)0.0014 (14)0.0040 (14)0.0008 (14)
N30.0289 (15)0.0188 (16)0.0398 (16)0.0015 (12)0.0075 (12)0.0012 (13)
O20.0407 (16)0.0357 (17)0.0652 (19)0.0084 (14)0.0038 (14)0.0029 (15)
O30.0356 (13)0.0185 (13)0.0470 (15)0.0024 (11)0.0111 (11)0.0009 (11)
O40.0303 (12)0.0283 (14)0.0391 (13)0.0033 (11)0.0100 (10)0.0022 (11)
O50.0361 (15)0.0494 (18)0.0457 (16)0.0009 (14)0.0087 (12)0.0121 (14)
Geometric parameters (Å, º) top
C1—N11.476 (5)C17—N21.472 (5)
C1—C21.539 (5)C17—C201.522 (6)
C1—H1A0.9900C17—C181.526 (6)
C1—H1B0.9900C17—C191.538 (6)
C2—O41.449 (4)C18—H18A0.9800
C2—C31.521 (5)C18—H18B0.9800
C2—H21.0000C18—H18C0.9800
C3—N31.453 (4)C19—H19A0.9800
C3—C41.519 (5)C19—H19B0.9800
C3—H31.0000C19—H19C0.9800
C4—C211.507 (6)C20—H20A0.9800
C4—H4A0.9900C20—H20B0.9800
C4—H4B0.9900C20—H20C0.9800
C5—O31.241 (5)C21—C261.383 (6)
C5—N31.346 (5)C21—C221.403 (6)
C5—C271.490 (5)C22—C231.383 (6)
C6—O51.213 (5)C22—H220.9500
C6—O41.346 (5)C23—C241.372 (7)
C6—C331.486 (5)C23—H230.9500
C7—N11.465 (5)C24—C251.397 (8)
C7—C161.512 (6)C24—H240.9500
C7—C81.522 (6)C25—C261.383 (7)
C7—H71.0000C25—H250.9500
C8—C91.527 (6)C26—H260.9500
C8—H8A0.9900C27—C281.397 (5)
C8—H8B0.9900C27—C321.403 (5)
C9—C101.520 (6)C28—C291.386 (5)
C9—C141.537 (6)C28—H280.9500
C9—H91.0000C29—C301.388 (6)
C10—C111.522 (7)C29—H290.9500
C10—H10A0.9900C30—C311.384 (6)
C10—H10B0.9900C30—H300.9500
C11—C121.520 (7)C31—C321.380 (6)
C11—H11A0.9900C31—H310.9500
C11—H11B0.9900C32—H320.9500
C12—C131.529 (6)C33—C381.390 (6)
C12—H12A0.9900C33—C341.391 (5)
C12—H12B0.9900C34—C351.378 (6)
C13—C141.516 (6)C34—H340.9500
C13—H13A0.9900C35—C361.382 (6)
C13—H13B0.9900C35—H350.9500
C14—C151.524 (6)C36—C371.384 (7)
C14—H141.0000C36—H360.9500
C15—N11.479 (5)C37—C381.387 (6)
C15—H15A0.9900C37—H370.9500
C15—H15B0.9900C38—H380.9500
C16—O21.240 (5)N2—H1N0.90 (5)
C16—N21.354 (5)N3—H3N0.93 (5)
N1—C1—C2112.5 (3)N2—C17—C18109.8 (3)
N1—C1—H1A109.1C20—C17—C18111.8 (3)
C2—C1—H1A109.1N2—C17—C19106.4 (3)
N1—C1—H1B109.1C20—C17—C19108.1 (4)
C2—C1—H1B109.1C18—C17—C19109.5 (4)
H1A—C1—H1B107.8C17—C18—H18A109.5
O4—C2—C3107.4 (3)C17—C18—H18B109.5
O4—C2—C1107.3 (3)H18A—C18—H18B109.5
C3—C2—C1114.4 (3)C17—C18—H18C109.5
O4—C2—H2109.2H18A—C18—H18C109.5
C3—C2—H2109.2H18B—C18—H18C109.5
C1—C2—H2109.2C17—C19—H19A109.5
N3—C3—C4111.1 (3)C17—C19—H19B109.5
N3—C3—C2112.4 (3)H19A—C19—H19B109.5
C4—C3—C2111.7 (3)C17—C19—H19C109.5
N3—C3—H3107.1H19A—C19—H19C109.5
C4—C3—H3107.1H19B—C19—H19C109.5
C2—C3—H3107.1C17—C20—H20A109.5
C21—C4—C3114.4 (3)C17—C20—H20B109.5
C21—C4—H4A108.7H20A—C20—H20B109.5
C3—C4—H4A108.7C17—C20—H20C109.5
C21—C4—H4B108.7H20A—C20—H20C109.5
C3—C4—H4B108.7H20B—C20—H20C109.5
H4A—C4—H4B107.6C26—C21—C22118.1 (4)
O3—C5—N3122.8 (3)C26—C21—C4121.7 (4)
O3—C5—C27120.3 (3)C22—C21—C4120.1 (4)
N3—C5—C27116.9 (3)C23—C22—C21120.2 (4)
O5—C6—O4124.2 (4)C23—C22—H22119.9
O5—C6—C33124.3 (4)C21—C22—H22119.9
O4—C6—C33111.5 (3)C24—C23—C22121.3 (4)
N1—C7—C16113.8 (3)C24—C23—H23119.4
N1—C7—C8111.5 (3)C22—C23—H23119.4
C16—C7—C8105.9 (3)C23—C24—C25119.0 (4)
N1—C7—H7108.5C23—C24—H24120.5
C16—C7—H7108.5C25—C24—H24120.5
C8—C7—H7108.5C26—C25—C24119.8 (5)
C7—C8—C9113.1 (3)C26—C25—H25120.1
C7—C8—H8A109.0C24—C25—H25120.1
C9—C8—H8A109.0C25—C26—C21121.5 (4)
C7—C8—H8B109.0C25—C26—H26119.2
C9—C8—H8B109.0C21—C26—H26119.2
H8A—C8—H8B107.8C28—C27—C32118.7 (3)
C10—C9—C8112.2 (3)C28—C27—C5122.9 (3)
C10—C9—C14111.3 (4)C32—C27—C5118.3 (3)
C8—C9—C14109.3 (3)C29—C28—C27120.3 (4)
C10—C9—H9108.0C29—C28—H28119.9
C8—C9—H9108.0C27—C28—H28119.9
C14—C9—H9108.0C28—C29—C30120.3 (4)
C9—C10—C11112.6 (4)C28—C29—H29119.9
C9—C10—H10A109.1C30—C29—H29119.9
C11—C10—H10A109.1C31—C30—C29119.8 (4)
C9—C10—H10B109.1C31—C30—H30120.1
C11—C10—H10B109.1C29—C30—H30120.1
H10A—C10—H10B107.8C32—C31—C30120.3 (4)
C12—C11—C10111.0 (4)C32—C31—H31119.9
C12—C11—H11A109.4C30—C31—H31119.9
C10—C11—H11A109.4C31—C32—C27120.6 (4)
C12—C11—H11B109.4C31—C32—H32119.7
C10—C11—H11B109.4C27—C32—H32119.7
H11A—C11—H11B108.0C38—C33—C34119.5 (4)
C11—C12—C13110.8 (4)C38—C33—C6118.6 (3)
C11—C12—H12A109.5C34—C33—C6121.9 (4)
C13—C12—H12A109.5C35—C34—C33120.1 (4)
C11—C12—H12B109.5C35—C34—H34119.9
C13—C12—H12B109.5C33—C34—H34119.9
H12A—C12—H12B108.1C34—C35—C36120.2 (4)
C14—C13—C12112.1 (4)C34—C35—H35119.9
C14—C13—H13A109.2C36—C35—H35119.9
C12—C13—H13A109.2C35—C36—C37120.4 (4)
C14—C13—H13B109.2C35—C36—H36119.8
C12—C13—H13B109.2C37—C36—H36119.8
H13A—C13—H13B107.9C36—C37—C38119.5 (4)
C13—C14—C15113.3 (4)C36—C37—H37120.2
C13—C14—C9112.6 (3)C38—C37—H37120.2
C15—C14—C9109.4 (3)C37—C38—C33120.3 (4)
C13—C14—H14107.0C37—C38—H38119.8
C15—C14—H14107.0C33—C38—H38119.8
C9—C14—H14107.0C7—N1—C1111.6 (3)
N1—C15—C14113.2 (3)C7—N1—C15111.0 (3)
N1—C15—H15A108.9C1—N1—C15108.9 (3)
C14—C15—H15A108.9C16—N2—C17124.8 (3)
N1—C15—H15B108.9C16—N2—H1N111 (3)
C14—C15—H15B108.9C17—N2—H1N120 (3)
H15A—C15—H15B107.7C5—N3—C3122.5 (3)
O2—C16—N2123.6 (4)C5—N3—H3N117 (3)
O2—C16—C7119.5 (4)C3—N3—H3N121 (3)
N2—C16—C7116.8 (3)C6—O4—C2118.2 (3)
N2—C17—C20111.1 (4)
N1—C1—C2—O451.4 (4)N3—C5—C27—C32151.0 (4)
N1—C1—C2—C3170.4 (3)C32—C27—C28—C290.7 (6)
O4—C2—C3—N352.7 (4)C5—C27—C28—C29175.6 (4)
C1—C2—C3—N366.3 (4)C27—C28—C29—C300.7 (6)
O4—C2—C3—C4178.4 (3)C28—C29—C30—C310.2 (6)
C1—C2—C3—C459.4 (4)C29—C30—C31—C320.2 (6)
N3—C3—C4—C2166.6 (4)C30—C31—C32—C270.1 (6)
C2—C3—C4—C21167.0 (3)C28—C27—C32—C310.3 (6)
N1—C7—C8—C954.5 (5)C5—C27—C32—C31176.2 (3)
C16—C7—C8—C9178.9 (3)O5—C6—C33—C386.1 (6)
C7—C8—C9—C10177.6 (4)O4—C6—C33—C38173.6 (4)
C7—C8—C9—C1453.6 (5)O5—C6—C33—C34175.7 (4)
C8—C9—C10—C1170.2 (5)O4—C6—C33—C344.6 (6)
C14—C9—C10—C1152.6 (5)C38—C33—C34—C351.3 (7)
C9—C10—C11—C1255.8 (5)C6—C33—C34—C35176.8 (4)
C10—C11—C12—C1356.2 (5)C33—C34—C35—C360.6 (7)
C11—C12—C13—C1455.1 (5)C34—C35—C36—C370.1 (8)
C12—C13—C14—C15177.6 (3)C35—C36—C37—C380.3 (8)
C12—C13—C14—C952.7 (5)C36—C37—C38—C331.0 (7)
C10—C9—C14—C1351.0 (5)C34—C33—C38—C371.5 (7)
C8—C9—C14—C1373.5 (4)C6—C33—C38—C37176.7 (4)
C10—C9—C14—C15178.0 (3)C16—C7—N1—C163.7 (4)
C8—C9—C14—C1553.6 (4)C8—C7—N1—C1176.5 (3)
C13—C14—C15—N169.4 (4)C16—C7—N1—C15174.5 (3)
C9—C14—C15—N157.3 (4)C8—C7—N1—C1554.8 (4)
N1—C7—C16—O2159.3 (4)C2—C1—N1—C7130.4 (3)
C8—C7—C16—O277.9 (5)C2—C1—N1—C15106.6 (3)
N1—C7—C16—N225.0 (5)C14—C15—N1—C757.9 (4)
C8—C7—C16—N297.9 (4)C14—C15—N1—C1178.8 (3)
C3—C4—C21—C26117.9 (4)O2—C16—N2—C1710.8 (7)
C3—C4—C21—C2263.6 (5)C7—C16—N2—C17164.7 (4)
C26—C21—C22—C231.7 (6)C20—C17—N2—C1657.7 (6)
C4—C21—C22—C23176.8 (3)C18—C17—N2—C1666.5 (5)
C21—C22—C23—C241.0 (6)C19—C17—N2—C16175.1 (4)
C22—C23—C24—C250.1 (7)O3—C5—N3—C31.0 (6)
C23—C24—C25—C260.5 (7)C27—C5—N3—C3178.3 (3)
C24—C25—C26—C210.2 (7)C4—C3—N3—C5138.6 (4)
C22—C21—C26—C251.3 (6)C2—C3—N3—C595.4 (4)
C4—C21—C26—C25177.2 (4)O5—C6—O4—C24.2 (6)
O3—C5—C27—C28146.7 (4)C33—C6—O4—C2175.5 (3)
N3—C5—C27—C2832.6 (5)C3—C2—O4—C6131.5 (3)
O3—C5—C27—C3229.7 (5)C1—C2—O4—C6105.0 (4)
Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
N2—H1N···O50.90 (5)2.55 (5)3.384 (5)154 (4)
N2—H1N···N10.90 (5)2.32 (5)2.773 (4)111 (4)
N3—H3N···O3i0.93 (5)2.04 (5)2.929 (4)161 (4)
C18—H18B···O2ii0.982.393.310 (5)157
C20—H20A···O20.982.352.963 (6)120
C29—H29···O5i0.952.583.467 (5)157
Symmetry codes: (i) x, y+1/2, z; (ii) x+1, y1/2, z+1.
(II) (3S,4aS,8aS)-2-[(2R,3S)-3-(2,5-Dichlorobenzamido)-2-(2,5-dichlorobenzoyloxy)-4-phenylbutyl]-N-tert-butyldecahydroisoquinoline-3-carboxamide top
Crystal data top
C38H43Cl4N3O4Dx = 1.283 Mg m3
Mr = 747.55Cu Kα radiation, λ = 1.54184 Å
Orthorhombic, P212121Cell parameters from 40379 reflections
a = 10.4539 (1) Åθ = 3.4–70.0°
b = 15.1917 (1) ŵ = 3.12 mm1
c = 24.3677 (2) ÅT = 100 K
V = 3869.90 (6) Å3Slab, colourless
Z = 40.25 × 0.20 × 0.04 mm
F(000) = 1568
Data collection top
Rigaku Mercury CCD
diffractometer
7140 reflections with I > 2σ(I)
ω scansRint = 0.046
Absorption correction: multi-scan
(SADABS; Sheldrick, 2004)
θmax = 70.1°, θmin = 3.4°
Tmin = 0.611, Tmax = 0.886h = 1212
44109 measured reflectionsk = 1518
7278 independent reflectionsl = 2929
Refinement top
Refinement on F2Hydrogen site location: mixed
Least-squares matrix: fullH atoms treated by a mixture of independent and constrained refinement
R[F2 > 2σ(F2)] = 0.038 w = 1/[σ2(Fo2) + (0.0552P)2 + 1.8039P]
where P = (Fo2 + 2Fc2)/3
wR(F2) = 0.100(Δ/σ)max < 0.001
S = 1.05Δρmax = 0.28 e Å3
7278 reflectionsΔρmin = 0.32 e Å3
451 parametersAbsolute structure: Flack x determined using 3021 quotients [(I+)-(I-)]/[(I+)+(I-)] (Parsons et al., 2013)
0 restraintsAbsolute structure parameter: 0.006 (7)
Primary atom site location: structure-invariant direct methods
Special details top

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.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å2) top
xyzUiso*/Ueq
C10.3339 (3)0.3116 (2)0.28983 (12)0.0291 (6)
H1A0.42280.30550.27640.035*
H1B0.29480.36290.27120.035*
C20.2587 (3)0.2289 (2)0.27568 (12)0.0300 (6)
H20.17020.23350.29100.036*
C30.3188 (3)0.1407 (2)0.29311 (12)0.0291 (6)
H30.27170.09290.27340.035*
C40.3109 (3)0.1206 (2)0.35483 (13)0.0330 (7)
H4A0.35950.16570.37550.040*
H4B0.22050.12350.36690.040*
C50.4901 (3)0.09795 (19)0.22901 (12)0.0283 (6)
C60.1687 (3)0.2720 (2)0.18833 (14)0.0339 (7)
C70.4476 (3)0.37726 (19)0.36694 (12)0.0269 (6)
H70.44500.43680.34950.032*
C80.4452 (3)0.3883 (2)0.42941 (12)0.0304 (6)
H8A0.45000.32970.44710.036*
H8B0.52090.42280.44110.036*
C90.3234 (3)0.4354 (2)0.44809 (13)0.0327 (7)
H90.32380.49520.43090.039*
C100.3151 (4)0.4484 (2)0.51013 (14)0.0399 (7)
H10A0.39680.47350.52350.048*
H10B0.24640.49130.51830.048*
C110.2880 (4)0.3630 (3)0.54077 (14)0.0455 (8)
H11A0.27580.37600.58020.055*
H11B0.36250.32320.53720.055*
C120.1691 (4)0.3171 (3)0.51853 (16)0.0503 (9)
H12A0.09300.35420.52570.060*
H12B0.15710.26030.53780.060*
C130.1815 (3)0.3005 (2)0.45668 (14)0.0407 (8)
H13A0.25340.25960.44980.049*
H13B0.10210.27270.44280.049*
C140.2048 (3)0.3865 (2)0.42625 (13)0.0347 (7)
H140.12890.42520.43270.042*
C150.2175 (3)0.3736 (2)0.36460 (13)0.0318 (6)
H15A0.14280.33990.35110.038*
H15B0.21640.43190.34640.038*
C160.5715 (3)0.33129 (19)0.35033 (12)0.0255 (6)
C170.7959 (3)0.3617 (2)0.31935 (14)0.0311 (6)
C180.8574 (3)0.2958 (3)0.3576 (2)0.0518 (10)
H18A0.80610.24180.35840.078*
H18B0.86220.32080.39470.078*
H18C0.94390.28210.34460.078*
C190.7847 (4)0.3250 (3)0.26108 (16)0.0478 (9)
H19A0.73270.27140.26160.072*
H19B0.87020.31120.24700.072*
H19C0.74410.36890.23730.072*
C200.8752 (3)0.4461 (2)0.31835 (15)0.0369 (7)
H20A0.83310.48970.29490.055*
H20B0.96060.43330.30380.055*
H20C0.88290.46940.35570.055*
C210.3644 (4)0.0305 (2)0.36758 (13)0.0378 (7)
C220.4947 (4)0.0212 (3)0.38043 (15)0.0451 (8)
H220.54640.07230.38430.054*
C230.5494 (5)0.0614 (3)0.38766 (17)0.0558 (10)
H230.63760.06640.39650.067*
C240.4763 (6)0.1352 (3)0.38198 (17)0.0620 (12)
H240.51440.19160.38580.074*
C250.3478 (5)0.1284 (3)0.37081 (18)0.0601 (12)
H250.29690.18000.36790.072*
C260.2912 (4)0.0445 (2)0.36356 (16)0.0503 (9)
H260.20240.04000.35590.060*
C270.6317 (3)0.10128 (19)0.21805 (13)0.0296 (6)
C280.7207 (3)0.0856 (2)0.25959 (14)0.0335 (7)
H280.69340.07220.29580.040*
C290.8505 (3)0.0899 (2)0.24673 (15)0.0363 (7)
C300.8922 (3)0.1106 (2)0.19463 (16)0.0385 (7)
H300.98100.11480.18670.046*
C310.8013 (3)0.1254 (2)0.15382 (15)0.0365 (7)
C320.6711 (3)0.12013 (19)0.16489 (13)0.0318 (6)
H320.61000.12930.13660.038*
C330.1663 (3)0.2464 (2)0.12927 (13)0.0331 (7)
C340.2152 (3)0.1651 (2)0.11265 (14)0.0341 (7)
H340.25830.12780.13790.041*
C350.1993 (3)0.1402 (2)0.05848 (14)0.0361 (7)
C360.1413 (3)0.1945 (2)0.02003 (14)0.0396 (7)
H360.13300.17690.01720.047*
C370.0960 (3)0.2754 (2)0.03776 (15)0.0396 (7)
C380.1059 (3)0.3019 (2)0.09184 (15)0.0377 (7)
H380.07210.35700.10330.045*
N10.3352 (2)0.32700 (16)0.34911 (10)0.0269 (5)
N20.6672 (2)0.38628 (17)0.33856 (10)0.0271 (5)
H1N0.651 (4)0.440 (3)0.3363 (14)0.033*
N30.4523 (2)0.13695 (16)0.27536 (10)0.0278 (5)
H2N0.510 (4)0.166 (2)0.2945 (15)0.033*
O20.58152 (19)0.24951 (13)0.34972 (9)0.0289 (4)
O30.4177 (2)0.06170 (14)0.19576 (9)0.0328 (5)
O40.2526 (2)0.22167 (14)0.21627 (9)0.0322 (4)
O50.1021 (2)0.32785 (16)0.20878 (10)0.0423 (6)
Cl10.96231 (8)0.07105 (6)0.29804 (4)0.0481 (2)
Cl20.85139 (8)0.14928 (6)0.08777 (4)0.0480 (2)
Cl30.24876 (9)0.03602 (6)0.03774 (4)0.0465 (2)
Cl40.01738 (10)0.34193 (6)0.00931 (4)0.0512 (2)
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
C10.0196 (12)0.0323 (15)0.0355 (15)0.0010 (11)0.0018 (12)0.0014 (12)
C20.0208 (13)0.0339 (15)0.0352 (15)0.0008 (12)0.0024 (12)0.0035 (12)
C30.0211 (13)0.0293 (14)0.0370 (15)0.0019 (11)0.0016 (12)0.0011 (12)
C40.0298 (15)0.0296 (15)0.0395 (16)0.0019 (12)0.0019 (13)0.0014 (13)
C50.0230 (14)0.0251 (13)0.0369 (15)0.0010 (11)0.0014 (12)0.0036 (12)
C60.0234 (14)0.0331 (16)0.0452 (17)0.0005 (13)0.0064 (13)0.0006 (13)
C70.0178 (13)0.0267 (14)0.0362 (15)0.0012 (11)0.0003 (11)0.0007 (11)
C80.0228 (13)0.0319 (15)0.0364 (15)0.0038 (12)0.0005 (12)0.0019 (12)
C90.0299 (15)0.0318 (15)0.0365 (16)0.0012 (13)0.0037 (13)0.0006 (12)
C100.0424 (18)0.0403 (18)0.0370 (16)0.0024 (14)0.0042 (14)0.0017 (14)
C110.054 (2)0.047 (2)0.0358 (17)0.0020 (16)0.0048 (15)0.0032 (15)
C120.052 (2)0.052 (2)0.048 (2)0.0100 (18)0.0109 (17)0.0066 (17)
C130.0362 (17)0.0417 (18)0.0442 (18)0.0095 (14)0.0065 (15)0.0009 (15)
C140.0253 (14)0.0387 (17)0.0401 (17)0.0016 (13)0.0059 (12)0.0006 (13)
C150.0199 (14)0.0337 (16)0.0417 (17)0.0023 (12)0.0016 (12)0.0036 (13)
C160.0180 (12)0.0292 (15)0.0292 (13)0.0016 (11)0.0014 (10)0.0004 (11)
C170.0180 (13)0.0272 (14)0.0480 (17)0.0006 (11)0.0045 (12)0.0042 (13)
C180.0219 (15)0.046 (2)0.088 (3)0.0029 (14)0.0063 (17)0.026 (2)
C190.049 (2)0.044 (2)0.051 (2)0.0072 (16)0.0195 (17)0.0077 (16)
C200.0225 (14)0.0325 (16)0.0557 (19)0.0026 (12)0.0025 (14)0.0076 (14)
C210.0472 (19)0.0304 (16)0.0358 (16)0.0009 (15)0.0006 (14)0.0002 (13)
C220.049 (2)0.0421 (19)0.0438 (19)0.0047 (16)0.0052 (16)0.0011 (15)
C230.062 (3)0.053 (2)0.052 (2)0.012 (2)0.006 (2)0.0051 (18)
C240.096 (4)0.042 (2)0.048 (2)0.016 (2)0.006 (2)0.0015 (17)
C250.091 (4)0.0340 (19)0.056 (2)0.012 (2)0.006 (2)0.0001 (17)
C260.066 (3)0.0379 (19)0.0471 (19)0.0139 (18)0.0119 (18)0.0062 (16)
C270.0217 (14)0.0256 (14)0.0416 (16)0.0008 (11)0.0001 (12)0.0066 (12)
C280.0255 (15)0.0314 (15)0.0437 (17)0.0010 (12)0.0003 (12)0.0056 (13)
C290.0214 (14)0.0329 (16)0.0546 (19)0.0036 (12)0.0048 (14)0.0096 (14)
C300.0255 (15)0.0283 (15)0.062 (2)0.0003 (12)0.0058 (14)0.0119 (14)
C310.0311 (16)0.0308 (16)0.0476 (18)0.0032 (12)0.0060 (14)0.0076 (14)
C320.0256 (14)0.0263 (14)0.0436 (17)0.0019 (12)0.0003 (13)0.0057 (12)
C330.0241 (14)0.0340 (16)0.0411 (16)0.0003 (13)0.0041 (13)0.0017 (13)
C340.0244 (14)0.0362 (16)0.0418 (16)0.0002 (12)0.0024 (12)0.0021 (14)
C350.0332 (16)0.0354 (16)0.0397 (16)0.0014 (13)0.0010 (13)0.0010 (13)
C360.0371 (18)0.0451 (18)0.0365 (17)0.0038 (15)0.0013 (14)0.0021 (14)
C370.0325 (16)0.0402 (18)0.0460 (18)0.0040 (14)0.0052 (14)0.0090 (15)
C380.0287 (15)0.0354 (17)0.0491 (19)0.0012 (13)0.0061 (14)0.0028 (14)
N10.0177 (11)0.0294 (12)0.0336 (12)0.0025 (10)0.0009 (10)0.0021 (10)
N20.0201 (11)0.0249 (12)0.0364 (13)0.0005 (10)0.0006 (10)0.0002 (10)
N30.0198 (11)0.0277 (12)0.0358 (13)0.0006 (10)0.0018 (10)0.0039 (10)
O20.0217 (9)0.0253 (10)0.0395 (11)0.0011 (8)0.0028 (8)0.0001 (8)
O30.0254 (10)0.0300 (11)0.0432 (12)0.0010 (8)0.0046 (9)0.0076 (9)
O40.0250 (10)0.0356 (11)0.0361 (11)0.0038 (9)0.0054 (9)0.0030 (9)
O50.0332 (11)0.0429 (13)0.0507 (14)0.0121 (10)0.0066 (10)0.0081 (11)
Cl10.0266 (4)0.0544 (5)0.0632 (5)0.0083 (4)0.0099 (4)0.0119 (4)
Cl20.0419 (4)0.0490 (5)0.0529 (5)0.0093 (4)0.0139 (4)0.0051 (4)
Cl30.0514 (5)0.0428 (4)0.0452 (4)0.0061 (4)0.0023 (4)0.0044 (3)
Cl40.0557 (5)0.0457 (5)0.0523 (5)0.0007 (4)0.0155 (4)0.0113 (4)
Geometric parameters (Å, º) top
C1—N11.463 (4)C17—N21.473 (4)
C1—C21.522 (4)C17—C181.512 (5)
C1—H1A0.9900C17—C201.527 (4)
C1—H1B0.9900C17—C191.530 (5)
C2—O41.453 (4)C18—H18A0.9800
C2—C31.540 (4)C18—H18B0.9800
C2—H21.0000C18—H18C0.9800
C3—N31.462 (4)C19—H19A0.9800
C3—C41.537 (4)C19—H19B0.9800
C3—H31.0000C19—H19C0.9800
C4—C211.511 (4)C20—H20A0.9800
C4—H4A0.9900C20—H20B0.9800
C4—H4B0.9900C20—H20C0.9800
C5—O31.238 (4)C21—C261.376 (5)
C5—N31.335 (4)C21—C221.405 (5)
C5—C271.505 (4)C22—C231.391 (5)
C6—O51.206 (4)C22—H220.9500
C6—O41.348 (4)C23—C241.364 (7)
C6—C331.491 (5)C23—H230.9500
C7—N11.467 (3)C24—C251.374 (8)
C7—C161.526 (4)C24—H240.9500
C7—C81.532 (4)C25—C261.416 (6)
C7—H71.0000C25—H250.9500
C8—C91.530 (4)C26—H260.9500
C8—H8A0.9900C27—C321.389 (5)
C8—H8B0.9900C27—C281.395 (4)
C9—C101.527 (4)C28—C291.395 (4)
C9—C141.540 (4)C28—H280.9500
C9—H91.0000C29—C301.379 (5)
C10—C111.523 (5)C29—Cl11.735 (3)
C10—H10A0.9900C30—C311.393 (5)
C10—H10B0.9900C30—H300.9500
C11—C121.525 (6)C31—C321.391 (4)
C11—H11A0.9900C31—Cl21.731 (4)
C11—H11B0.9900C32—H320.9500
C12—C131.534 (5)C33—C381.394 (5)
C12—H12A0.9900C33—C341.397 (5)
C12—H12B0.9900C34—C351.383 (5)
C13—C141.522 (5)C34—H340.9500
C13—H13A0.9900C35—C361.388 (5)
C13—H13B0.9900C35—Cl31.740 (3)
C14—C151.521 (4)C36—C371.385 (5)
C14—H141.0000C36—H360.9500
C15—N11.470 (4)C37—C381.382 (5)
C15—H15A0.9900C37—Cl41.736 (3)
C15—H15B0.9900C38—H380.9500
C16—O21.247 (4)N2—H1N0.84 (4)
C16—N21.335 (4)N3—H2N0.88 (4)
N1—C1—C2111.1 (2)N2—C17—C20106.8 (2)
N1—C1—H1A109.4C18—C17—C20109.6 (3)
C2—C1—H1A109.4N2—C17—C19108.5 (3)
N1—C1—H1B109.4C18—C17—C19111.4 (3)
C2—C1—H1B109.4C20—C17—C19109.4 (3)
H1A—C1—H1B108.0C17—C18—H18A109.5
O4—C2—C1108.1 (2)C17—C18—H18B109.5
O4—C2—C3103.1 (2)H18A—C18—H18B109.5
C1—C2—C3116.5 (2)C17—C18—H18C109.5
O4—C2—H2109.6H18A—C18—H18C109.5
C1—C2—H2109.6H18B—C18—H18C109.5
C3—C2—H2109.6C17—C19—H19A109.5
N3—C3—C4109.5 (2)C17—C19—H19B109.5
N3—C3—C2110.0 (2)H19A—C19—H19B109.5
C4—C3—C2114.9 (2)C17—C19—H19C109.5
N3—C3—H3107.4H19A—C19—H19C109.5
C4—C3—H3107.4H19B—C19—H19C109.5
C2—C3—H3107.4C17—C20—H20A109.5
C21—C4—C3111.2 (3)C17—C20—H20B109.5
C21—C4—H4A109.4H20A—C20—H20B109.5
C3—C4—H4A109.4C17—C20—H20C109.5
C21—C4—H4B109.4H20A—C20—H20C109.5
C3—C4—H4B109.4H20B—C20—H20C109.5
H4A—C4—H4B108.0C26—C21—C22118.2 (3)
O3—C5—N3124.7 (3)C26—C21—C4122.0 (3)
O3—C5—C27120.0 (3)C22—C21—C4119.7 (3)
N3—C5—C27115.3 (3)C23—C22—C21121.2 (4)
O5—C6—O4124.5 (3)C23—C22—H22119.4
O5—C6—C33124.9 (3)C21—C22—H22119.4
O4—C6—C33110.5 (3)C24—C23—C22119.9 (4)
N1—C7—C16111.3 (2)C24—C23—H23120.0
N1—C7—C8109.8 (2)C22—C23—H23120.0
C16—C7—C8109.1 (2)C23—C24—C25120.4 (4)
N1—C7—H7108.9C23—C24—H24119.8
C16—C7—H7108.9C25—C24—H24119.8
C8—C7—H7108.9C24—C25—C26120.1 (4)
C9—C8—C7111.1 (2)C24—C25—H25120.0
C9—C8—H8A109.4C26—C25—H25120.0
C7—C8—H8A109.4C21—C26—C25120.3 (4)
C9—C8—H8B109.4C21—C26—H26119.9
C7—C8—H8B109.4C25—C26—H26119.9
H8A—C8—H8B108.0C32—C27—C28121.0 (3)
C10—C9—C8113.7 (3)C32—C27—C5117.6 (3)
C10—C9—C14111.0 (3)C28—C27—C5121.4 (3)
C8—C9—C14110.0 (2)C29—C28—C27118.5 (3)
C10—C9—H9107.3C29—C28—H28120.7
C8—C9—H9107.3C27—C28—H28120.7
C14—C9—H9107.3C30—C29—C28121.7 (3)
C11—C10—C9112.7 (3)C30—C29—Cl1119.2 (2)
C11—C10—H10A109.1C28—C29—Cl1119.1 (3)
C9—C10—H10A109.1C29—C30—C31118.6 (3)
C11—C10—H10B109.1C29—C30—H30120.7
C9—C10—H10B109.1C31—C30—H30120.7
H10A—C10—H10B107.8C32—C31—C30121.3 (3)
C10—C11—C12111.5 (3)C32—C31—Cl2119.2 (3)
C10—C11—H11A109.3C30—C31—Cl2119.4 (3)
C12—C11—H11A109.3C27—C32—C31118.9 (3)
C10—C11—H11B109.3C27—C32—H32120.6
C12—C11—H11B109.3C31—C32—H32120.6
H11A—C11—H11B108.0C38—C33—C34120.8 (3)
C11—C12—C13110.8 (3)C38—C33—C6118.8 (3)
C11—C12—H12A109.5C34—C33—C6120.3 (3)
C13—C12—H12A109.5C35—C34—C33118.3 (3)
C11—C12—H12B109.5C35—C34—H34120.8
C13—C12—H12B109.5C33—C34—H34120.8
H12A—C12—H12B108.1C34—C35—C36122.3 (3)
C14—C13—C12110.6 (3)C34—C35—Cl3119.3 (3)
C14—C13—H13A109.5C36—C35—Cl3118.3 (3)
C12—C13—H13A109.5C37—C36—C35117.8 (3)
C14—C13—H13B109.5C37—C36—H36121.1
C12—C13—H13B109.5C35—C36—H36121.1
H13A—C13—H13B108.1C38—C37—C36122.1 (3)
C15—C14—C13112.6 (3)C38—C37—Cl4119.7 (3)
C15—C14—C9109.5 (2)C36—C37—Cl4118.2 (3)
C13—C14—C9112.0 (3)C37—C38—C33118.7 (3)
C15—C14—H14107.5C37—C38—H38120.6
C13—C14—H14107.5C33—C38—H38120.6
C9—C14—H14107.5C1—N1—C7112.5 (2)
N1—C15—C14112.9 (3)C1—N1—C15108.8 (2)
N1—C15—H15A109.0C7—N1—C15110.1 (2)
C14—C15—H15A109.0C16—N2—C17126.5 (3)
N1—C15—H15B109.0C16—N2—H1N118 (3)
C14—C15—H15B109.0C17—N2—H1N114 (3)
H15A—C15—H15B107.8C5—N3—C3123.4 (3)
O2—C16—N2123.9 (3)C5—N3—H2N118 (2)
O2—C16—C7122.1 (2)C3—N3—H2N119 (2)
N2—C16—C7114.0 (2)C6—O4—C2119.3 (2)
N2—C17—C18111.1 (3)
N1—C1—C2—O4175.5 (2)C27—C28—C29—Cl1179.7 (2)
N1—C1—C2—C369.1 (3)C28—C29—C30—C311.6 (5)
O4—C2—C3—N368.7 (3)Cl1—C29—C30—C31179.8 (2)
C1—C2—C3—N349.5 (3)C29—C30—C31—C320.5 (5)
O4—C2—C3—C4167.3 (2)C29—C30—C31—Cl2178.7 (2)
C1—C2—C3—C474.4 (3)C28—C27—C32—C311.6 (5)
N3—C3—C4—C2159.4 (3)C5—C27—C32—C31178.7 (3)
C2—C3—C4—C21176.4 (3)C30—C31—C32—C271.1 (5)
N1—C7—C8—C958.6 (3)Cl2—C31—C32—C27179.7 (2)
C16—C7—C8—C9179.2 (2)O5—C6—C33—C3815.3 (5)
C7—C8—C9—C10179.9 (3)O4—C6—C33—C38167.0 (3)
C7—C8—C9—C1454.7 (3)O5—C6—C33—C34159.9 (3)
C8—C9—C10—C1172.6 (4)O4—C6—C33—C3417.8 (4)
C14—C9—C10—C1152.1 (4)C38—C33—C34—C351.6 (5)
C9—C10—C11—C1253.9 (4)C6—C33—C34—C35173.5 (3)
C10—C11—C12—C1355.9 (4)C33—C34—C35—C362.6 (5)
C11—C12—C13—C1457.1 (4)C33—C34—C35—Cl3175.4 (2)
C12—C13—C14—C15179.9 (3)C34—C35—C36—C371.5 (5)
C12—C13—C14—C956.2 (4)Cl3—C35—C36—C37176.5 (3)
C10—C9—C14—C15179.2 (3)C35—C36—C37—C380.7 (5)
C8—C9—C14—C1552.4 (3)C35—C36—C37—Cl4177.4 (3)
C10—C9—C14—C1353.5 (4)C36—C37—C38—C331.7 (5)
C8—C9—C14—C1373.3 (3)Cl4—C37—C38—C33178.3 (2)
C13—C14—C15—N169.1 (3)C34—C33—C38—C370.5 (5)
C9—C14—C15—N156.2 (3)C6—C33—C38—C37175.6 (3)
N1—C7—C16—O235.0 (4)C2—C1—N1—C7153.7 (2)
C8—C7—C16—O286.4 (3)C2—C1—N1—C1584.0 (3)
N1—C7—C16—N2147.1 (2)C16—C7—N1—C157.2 (3)
C8—C7—C16—N291.6 (3)C8—C7—N1—C1178.2 (2)
C3—C4—C21—C2685.2 (4)C16—C7—N1—C15178.8 (2)
C3—C4—C21—C2290.5 (4)C8—C7—N1—C1560.3 (3)
C26—C21—C22—C231.5 (5)C14—C15—N1—C1175.6 (2)
C4—C21—C22—C23174.3 (3)C14—C15—N1—C760.7 (3)
C21—C22—C23—C240.4 (6)O2—C16—N2—C174.7 (5)
C22—C23—C24—C252.0 (6)C7—C16—N2—C17177.5 (3)
C23—C24—C25—C261.8 (7)C18—C17—N2—C1653.9 (4)
C22—C21—C26—C251.7 (5)C20—C17—N2—C16173.3 (3)
C4—C21—C26—C25174.0 (4)C19—C17—N2—C1668.9 (4)
C24—C25—C26—C210.1 (6)O3—C5—N3—C30.8 (5)
O3—C5—C27—C3242.1 (4)C27—C5—N3—C3180.0 (3)
N3—C5—C27—C32137.1 (3)C4—C3—N3—C5136.6 (3)
O3—C5—C27—C28137.6 (3)C2—C3—N3—C596.3 (3)
N3—C5—C27—C2843.2 (4)O5—C6—O4—C24.8 (5)
C32—C27—C28—C290.5 (5)C33—C6—O4—C2172.9 (2)
C5—C27—C28—C29179.8 (3)C1—C2—O4—C678.2 (3)
C27—C28—C29—C301.2 (5)C3—C2—O4—C6158.0 (2)
Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
N2—H1N···O3i0.84 (4)2.13 (4)2.931 (3)160 (3)
N3—H2N···O20.88 (4)1.99 (4)2.834 (3)159 (3)
C4—H4A···N10.992.553.149 (4)119
C18—H18A···O20.982.362.975 (4)120
C34—H34···O30.952.403.324 (4)163
Symmetry code: (i) x+1, y+1/2, z+1/2.
 

Acknowledgements

We thank the EPSRC National Crystallography Service (University of Southampton) for the X-ray data collections.

References

First citationCoombs, G. H., Goldberg, D. E., Klemba, M., Berry, C., Kay, J. & Mottram, J. C. (2001). Trends Parasitol. 17, 532–537.  Web of Science CrossRef PubMed CAS Google Scholar
First citationCunico, W., Ferreira, M. L. G., Ferreira, T. G., Penido, C., Henriques, M. G. M. O., Krettli, L. G., Varottic, F. P. & Krettli, A. U. (2008). Lett. Drug Des. Discov. pp. 178–181.  CrossRef Google Scholar
First citationErsmark, K., Nervall, M., Gutiérrez-de-Terán, H., Hamelink, E., Janka, L. K., Clemente, J. C., Dunn, B. M., Gogoll, A., Samuelsson, B., Aqvist, J. & Hallberg, A. (2006). Bioorg. Med. Chem. 14, 2197–2208.  CrossRef PubMed CAS Google Scholar
First citationFandaruff, C., Chelazzi, L., Braga, D., Cuffini, S. L., Silva, M. A. S., Resende, J. A. L. C., Dichiarante, E. & Grepioni, F. (2015). Cryst. Growth Des. 15, 5233–5239.  CrossRef CAS Google Scholar
First citationFarrugia, L. J. (2012). J. Appl. Cryst. 45, 849–854.  Web of Science CrossRef CAS IUCr Journals Google Scholar
First citationGroom, C. R., Bruno, I. J., Lightfoot, M. P. & Ward, S. C. (2016). Acta Cryst. B72, 171–179.  Web of Science CSD CrossRef IUCr Journals Google Scholar
First citationHuizing, A. P., Mondal, M. & Hirsch, A. K. (2015). J. Med. Chem. 58, 5151–5163.  CrossRef CAS PubMed Google Scholar
First citationMotwani, H. V., De Rosa, M., Odell, L. R., Hallberg, A. & Larhed, M. (2015). Eur. J. Med. Chem. 90, 462–490.  CrossRef CAS PubMed Google Scholar
First citationMuthas, D., Noteberg, D., Sabnis, Y. A., Hamelink, E., Vrang, L., Samuelsson, B., Karlén, A. & Hallberg, A. (2005). Bioorg. Med. Chem. 13, 5371–5390.  CrossRef PubMed CAS Google Scholar
First citationParsons, S., Flack, H. D. & Wagner, T. (2013). Acta Cryst. B69, 249–259.  Web of Science CrossRef CAS IUCr Journals Google Scholar
First citationRigaku (2014). CrysAlis PRO. Rigaku Corporation, Tokyo, Japan.  Google Scholar
First citationSheldrick, G. M. (2004). SADABS. University of Göttingen, Germany.  Google Scholar
First citationSheldrick, G. M. (2008). Acta Cryst. A64, 112–122.  Web of Science CrossRef CAS IUCr Journals Google Scholar
First citationSheldrick, G. M. (2015). Acta Cryst. C71, 3–8.  Web of Science CrossRef IUCr Journals Google Scholar
First citationWestrip, S. P. (2010). J. Appl. Cryst. 43, 920–925.  Web of Science CrossRef CAS IUCr Journals Google Scholar

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