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

Journal logoCRYSTALLOGRAPHIC
COMMUNICATIONS
ISSN: 2056-9890
Volume 71| Part 5| May 2015| Pages 505-508
https://doi.org/10.1107/S2056989015007367

Crystal structure of 5-{3-[2,6-di­methyl-4-(5-methyl-1,2,4-oxa­diazol-3-yl)phen­­oxy]prop­yl}-N-(11-hy­dr­oxy­undec­yl)isoxazole-3-carboxamide hemihydrate

K. Salorinnea and T. Lahtinena*

aDepartment of Chemistry, Nanoscience Center, University of Jyväskylä, PO Box 35, 40014 JYU, Finland
*Correspondence e-mail: tanja.m.lahtinen@jyu.fi

Edited by A. J. Lough, University of Toronto, Canada (Received 27 March 2015; accepted 14 April 2015; online 18 April 2015)

The title compound, C29H42N4O5·0.5H2O, comprises four structural units. A flexible prop­yloxy unit in a gauche conformation, with a –C(H2)—C(H2)—C(H2)—O– torsion angle of −64.32 (18)°, connects an isoxazole ring and an approximately planar phenyl­oxa­diazole ring system [with a maxixmum devation of 0.061 (2) Å], which are oriented almost parallel to one another with a dihedral angle of 10.75 (7)°. Furthermore, a C11-alkyl chain with a terminal hy­droxy group links to the 3-position of the isoxazole ring via an amide bond. In the crystal, a half-occupancy solvent water mol­ecule connects to a neighbouring mol­ecule via an inter­molecular O—H⋯O(water) hydrogen bond to the C11-alkyl chain hy­droxy group.

CCDC reference: 1059505

Similar articles

1. Chemical context

An anti­viral drug family of the so-called `WIN compounds' was developed against various human illnesses caused by enteroviruses including common respiratory infections, rash or mild fever and serious or life-threatening infections, such as meningitis, myocarditis, encephalitis and paralytic poliomyelitis (De Palma et al., 2008[De Palma, A. M., Vliegen, I., Clercq, E. D. & Neyts, I. (2008). Med. Res. Rev. 28, 823-884.]; Diana, 2003[Diana, G. D. (2003). Curr. Med. Chem. 2, 1-12.]). The WIN compounds were particularly designed to target the early events (attachment, entry and uncoating) of viral replication and they have been shown to bind specifically into the inter­ior hydro­phobic pocket located at the VP1 protein of the enterovirus capsid and replacing the naturally occurring myristic acid (Reisdorph et al., 2003[Reisdorph, N., Thomas, J. J., Katpally, U., Chase, E., Harris, K., Siuzdak, G. & Smith, T. J. (2003). Virology, 314, 34-44.]; Giranda et al., 1995[Giranda, V. L., Russo, G. R., Felock, P. J., Bailey, T. R., Draper, T., Aldous, D. J., Guiles, J., Dutko, F. J., Diana, G. D., Pevear, D. C. & McMillan, M. (1995). Acta Cryst. D51, 496-503.]; Zhang et al., 2004[Zhang, Y., Simpson, A. A., Ledford, R. M., Bator, C. M., Chakravarty, S., Skochko, G. A., Demenczuk, T. M., Watanyar, A., Pevear, D. C. & Rossmann, M. G. (2004). J. Virol. 78, 11061-11069.]; Thibaut et al., 2012[Thibaut, H. J., De Palma, A. M. & Neyts, J. (2012). Biochem. Pharmacol. 83, 185-192.]). The anti­viral drug candidate development finally led to the WIN 63843 analogue, better known as Pleconaril, which showed a drastic decrease in the metabolic degradation of the mol­ecule and a broad range of anti­viral activity against enteroviruses (Pevear et al., 1999[Pevear, D. C., Tull, T. M., Seipel, M. E. & Groarke, J. M. (1999). Antimicrob. Agents Chemother. 43, 2109-2115.]; Wildenbeest et al., 2012[Wildenbeest, J. G., van den Broek, P. J., Benschop, K. S. M., Koen, G., Wierenga, P. C., Vossen, A. C. T. M., Kuijpers, T. W. & Wolthers, K. C. (2012). Antiviral Ther. 17, 459-466.]). The design of the title compound is based on the chemical structure of the WIN 61893 analogue (Diana et al., 1995[Diana, G. D., Rudewicz, P., Pevear, D. C., Nitz, T. J., Aldous, S. C., Aldous, D. J., Robinson, D. T., Draper, T., Dutko, F. J., Aldi, C., Gendron, G., Oglesby, R. C., Volkots, D. L., Reuman, M., Bailey, T. R., Czerniak, R., Block, T., Roland, R. & Opperman, J. (1995). J. Med. Chem. 38, 1355-1371.]), to which an additional C11-alkyl linker arm having a hy­droxy end group was attached at the 3-position of the isoxazole ring via an amide bond.

[Scheme 1]

2. Structural commentary

The mol­ecular structure of the title compound is shown in Fig. 1[link]. The structure contains three essentially planar heterocyclic or aromatic rings, i.e. isoxazole (atoms C19–C21/N22/O23), benzene (C7–C12) and oxa­diazole (C2/O3/N4/C5/N6), of which the latter two are directly connected via atoms C7 and C5. The three heterocyclic rings are approximately coplanar to one another, having dihedral angles between the rings of 11.57 (8) (C19–C21/N22/O23 and C7–C12), 10.68 (9) (C19–C21/N22/O23 and C2/O3/N4/C5/N6) and 4.81 (9)° (C7–C12 and C2/O3/N4/C5/N6), maintaining the WIN framework in a linear conformation. The dihedral angle between the isoxazole ring (C19–C21/N22/O23) and the approximately planar phenyl­oxa­diazole ring system [C7–C12/C2/O3/N4/C5/N6, with a maximum devation of 0.061 (2)Å for atom C12] is 10.75 (7)°. The isoxazole and phenyl­oxa­diazole ring systems are connected by a prop­yloxy unit (O15–C18), which is in a gauche conformation, with a C18—C17—C16—O15 torsion angle of −64.32 (18)°. The amide group (N26–C24) at the 3-position of the isoxazole ring which joins the C11-alkyl chain (C27–O38) and the WIN framework is likewise almost coplanar with the isoxazole ring, with a dihedral angle of 10.92 (9)° between the amide (H26/N26/C24/O25) and isoxazole planes. The amide hydrogen (H26) and the acidic isoxazole hydrogen (H20) are on opposite sides, with a torsion angle (N26—C24—C21—C20) of 172.31 (15)°. The C11-alkyl chain (C27–C37) is in an all-anti conformation, with an average torsion angle of 178.80°. The WIN framework and the C11-linker arm structural units are aligned roughly in a 160° angle and the total length of the title mol­ecule measures up to 3.4 nm.

[Figure 1]
Figure 1
The mol­ecular structure of the title compound with the atom labelling. Displacement ellipsoids are drawn at the 50% probability level.

3. Supra­molecular features

The title compound packs in the crystal lattice in layers, in which the mol­ecules are held together by solvent-mediated O—H⋯O and C—H⋯O hydrogen bonds (motif 1), as well as C—H⋯N and C—H⋯O inter­molecular inter­actions between the heterocyclic isoxazole and phenyl­oxa­diazole units of neighbouring mol­ecules (motif 2) (Table 1[link]). In the solvent-mediated assembly, an inter­molecular hydrogen-bonded network of the type R33(9) is formed between the C11-alkyl chain hy­droxy [O—H⋯O = 1.90 (1) Å], solvent water [O—H⋯O = 1.87 (1) Å], amide carbonyl and isoxazole hydrogen (C—H⋯O = 2.56 Å) groups of two parallel neighbouring mol­ecules (Fig. 2[link]). In a similar manner, two pairs of C—H⋯N and C—H⋯O hydrogen bonds connect three opposite-facing neighbouring mol­ecules via R22(8) and R22(16) loops between the isoxazole (C—H⋯O = 2.51 Å) and phenyl­oxa­diazole (C—H⋯O = 2.64 Å and C—H⋯N = 2.65 Å) groups (Fig. 2[link]).

Table 1
Hydrogen-bond geometry (Å, °)

D—H⋯A D—H H⋯A D⋯A D—H⋯A
C28—H28A⋯O3i 0.99 2.64 3.2567 (19) 120
C20—H20⋯O38ii 0.95 2.56 3.505 (2) 175
C13—H13B⋯O23i 0.98 2.51 3.416 (2) 154
C1—H1B⋯N6 0.98 2.65 3.622 (2) 174
O100—H10B⋯O25iii 0.84 (1) 1.87 (1) 2.710 (3) 180 (6)
O38—H38⋯O100 0.82 (1) 1.90 (1) 2.695 (4) 164 (2)
Symmetry codes: (i) -x+3, -y+1, -z+1; (ii) x+2, y+1, z+1; (iii) x-2, y-1, z-1.
[Figure 2]
Figure 2
A view along the c axis of the crystal packing of the title compound. Inter­molecular inter­actions formed between neighbouring mol­ecules highlighting the solvent water mediated hydrogen bonding network (motif 1, orange box) and the two coordination loops between the heterocyclic isoxazole and phenyl- oxa­diazole units (motif 2, blue box).

4. Database survey

A search of the Cambridge Structural Database (CSD; Version 5.36, November 2014; Groom & Allen, 2014[Groom, C. R. & Allen, F. H. (2014). Angew. Chem. Int. Ed. 53, 662-671.]) revealed the presence of nine structures (CSD refcode VOGDAY contains two independent mol­ecules; Salorinne et al., 2014[Salorinne, K., Lahtinen, T., Marjomäki, V. & Häkkinen, H. (2014). CrystEngComm, 16, 9001-9009.]) with the substructure 3-{3,5-dimethyl-4-[3-(3-methyl­isoxazol-5-yl)prop­oxy]phen­yl}-5-methyl-1,2,4-oxa­diazole. These nine structures belong to three similar compounds of 5-{3-[2,6-dimethyl-4-(5-methyl-1,2,4-oxa­diazol-3-yl)phen­oxy]prop­yl}iso­xazole-3-carb­oxy­lic acid (Salorinne et al., 2014[Salorinne, K., Lahtinen, T., Marjomäki, V. & Häkkinen, H. (2014). CrystEngComm, 16, 9001-9009.]), ethyl 5-{3-[2,6-dimethyl-4-(5-methyl-1,2,4-oxa­diazol-3-yl)phen­oxy]prop­yl}iso­xazole-3-carboxyl­ate (Salorinne et al., 2014[Salorinne, K., Lahtinen, T., Marjomäki, V. & Häkkinen, H. (2014). CrystEngComm, 16, 9001-9009.]) and 3-{3,5-di­methyl-4-[3-(3-methyl­isoxazol-5-yl)prop­oxy]phen­yl}-5-tri­fluoro­methyl-1,2,4-oxa­diazole (Coste et al., 2004[Coste, S., Schneider, J. M., Petit, M. N. & Coquerel, G. (2004). Cryst. Growth Des. 4, 1237-1244.]). In six of the nine structures (CSD refcodes VOGCOL01, VOGDAY, HAJYUN, HAJYUN01, HAJYUN02 and HAJYUN03; Salorinne et al., 2014[Salorinne, K., Lahtinen, T., Marjomäki, V. & Häkkinen, H. (2014). CrystEngComm, 16, 9001-9009.]; Coste et al., 2004[Coste, S., Schneider, J. M., Petit, M. N. & Coquerel, G. (2004). Cryst. Growth Des. 4, 1237-1244.]), the isoxazole and phenyl­oxa­diazole heterocyclic rings of the WIN framework are almost coplanar, similar to the title compound. However, in two of the structures (CSD refcodes VOGCOL and VOGDEL; Salorinne et al., 2014[Salorinne, K., Lahtinen, T., Marjomäki, V. & Häkkinen, H. (2014). CrystEngComm, 16, 9001-9009.]), the heterocyclic ring systems are tilted slightly with angles of 34–38° between the ring planes, whereas in one of the structures (CSD refcode VOGCOL; Salorinne et al., 2014[Salorinne, K., Lahtinen, T., Marjomäki, V. & Häkkinen, H. (2014). CrystEngComm, 16, 9001-9009.]), the heterocyclic ring systems are closer to a perpendicular orientation, with an angle of ca 60.8°. In all of the structures, the prop­yloxy unit is in a gauche conformation, with torsion angles in the range 62.4–69.2°.

5. Synthesis and crystallization

An amide coupling reaction of 5-{3-[2,6-dimethyl-4-(5-methyl-1,2,4-oxa­diazol-3-yl)phen­oxy]prop­yl}isoxazole-3-carb­oxy­lic acid (0.17 mmol, Salorinne et al., 2014[Salorinne, K., Lahtinen, T., Marjomäki, V. & Häkkinen, H. (2014). CrystEngComm, 16, 9001-9009.]) with 11-amino-1-undeca­nol (0.18 mmol) in di­chloro­methane (20 ml) in the presence of N-[3-(di­methyl­amino)­prop­yl]-N-ethyl­carbodi­imide (0.19 mmol) and a catalytic amount of 1-hy­droxy­benzotriazole at 273 K gave the title compound in 68% yield after subsequent chromatographic purification in silica with a di­chloro­methane–methanol mixture (95:5 v/v). Needle-like crystals of the title compound were obtained from an ethanol solution by vapor diffusion with water.

6. Refinement

Crystal data, data collection and structure refinement details are summarized in Table 2[link]. All H atoms were positioned geometrically and allowed to ride on their parent atoms, with C—H = 0.95–0.99 Å, and with Uiso(H) = 1.5Ueq(C) for methyl and 1.2Ueq(C) for other H atoms, and N—H = 0.88 Å and Uiso(H) = 1.2Ueq(N). The positions of the O-bound H atoms were located in a difference Fourier map and refined as riding atoms with Uiso(H) = 1.5Ueq(O). The O—H distance of the half-occupied water molecule was restrained to 0.84 (1) Å.

Table 2
Experimental details

Crystal data
Chemical formula 2C29H42N4O5·H2O
Mr 1071.34
Crystal system, space group Triclinic, P[\overline{1}]
Temperature (K) 170
a, b, c (Å) 6.7137 (3), 14.0263 (5), 16.6757 (8)
α, β, γ (°) 113.889 (4), 94.515 (4), 90.976 (4)
V (Å3) 1429.29 (12)
Z 1
Radiation type Mo Kα
μ (mm−1) 0.09
Crystal size (mm) 0.42 × 0.15 × 0.09
 
Data collection
Diffractometer Agilent SuperNova, Single source at offset, Eos
Absorption correction Analytical [CrysAlis PRO (Agilent, 2013[Agilent (2013). CrysAlis PRO. Agilent Technologies Ltd, Yarnton, Oxfordshire, England.]), based on expressions derived by Clark & Reid (1995[Clark, R. C. & Reid, J. S. (1995). Acta Cryst. A51, 887-897.])]
Tmin, Tmax 0.990, 0.998
No. of measured, independent and observed [I > 2σ(I)] reflections 13976, 7670, 5463
Rint 0.016
(sin θ/λ)max (Å−1) 0.716
 
Refinement
R[F2 > 2σ(F2)], wR(F2), S 0.053, 0.148, 1.05
No. of reflections 7670
No. of parameters 364
No. of restraints 3
H-atom treatment H atoms treated by a mixture of independent and constrained refinement
Δρmax, Δρmin (e Å−3) 0.36, −0.26
Computer programs: CrysAlis PRO (Agilent, 2013[Agilent (2013). CrysAlis PRO. Agilent Technologies Ltd, Yarnton, Oxfordshire, England.]), SHELXS97 (Sheldrick, 2008[Sheldrick, G. M. (2008). Acta Cryst. A64, 112-122.]), SHELXL2013 (Sheldrick, 2015[Sheldrick, G. M. (2015). Acta Cryst. C71, 3-8.]) and OLEX2 (Dolomanov et al., 2009[Dolomanov, O. V., Bourhis, L. J., Gildea, R. J., Howard, J. A. K. & Puschmann, H. (2009). J. Appl. Cryst. 42, 339-341.]).

Supporting information

CCDC reference: 1059505

Crystal structure: contains datablock I. DOI: https://doi.org/10.1107/S2056989015007367/lh5758sup1.cif

Structure factors: contains datablock I. DOI: https://doi.org/10.1107/S2056989015007367/lh5758Isup2.hkl

Supporting information file. DOI: https://doi.org/10.1107/S2056989015007367/lh5758Isup3.cml

checkCIF report


Computing details top

Data collection: CrysAlis PRO (Agilent, 2013); cell refinement: CrysAlis PRO (Agilent, 2013); data reduction: CrysAlis PRO (Agilent, 2013); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL2013 (Sheldrick, 2015); molecular graphics: OLEX2 (Dolomanov et al., 2009); software used to prepare material for publication: OLEX2 (Dolomanov et al., 2009).

5-{3-[2,6-Dimethyl-4-(5-methyl-1,2,4-oxadiazol-3-yl)phenoxy]propyl}-N-(11-hydroxyundecyl)isoxazole-3-carboxamide hemihydrate top
Crystal data top
2C29H42N4O5·H2OZ = 1
Mr = 1071.34F(000) = 578
Triclinic, P1Dx = 1.245 Mg m−3
a = 6.7137 (3) ÅMo Kα radiation, λ = 0.71073 Å
b = 14.0263 (5) ÅCell parameters from 5261 reflections
c = 16.6757 (8) Åθ = 2.5–30.3°
α = 113.889 (4)°µ = 0.09 mm−1
β = 94.515 (4)°T = 170 K
γ = 90.976 (4)°Needle, clear colourless
V = 1429.29 (12) Å30.42 × 0.15 × 0.09 mm
Data collection top
Agilent SuperNova, Single source at offset, Eos
diffractometer		7670 independent reflections
Radiation source: SuperNova (Mo) X-ray Source5463 reflections with I > 2σ(I)
Mirror monochromatorRint = 0.016
Detector resolution: 16.0107 pixels mm-1θmax = 30.6°, θmin = 2.5°
ω scansh = −8→9
Absorption correction: analytical
[CrysAlisPro (Agilent, 2013), based on expressions derived by Clark & Reid (1995)]		k = −19→20
Tmin = 0.990, Tmax = 0.998l = −23→23
13976 measured reflections
Refinement top
Refinement on F2Primary atom site location: structure-invariant direct methods
Least-squares matrix: fullHydrogen site location: mixed
R[F2 > 2σ(F2)] = 0.053H atoms treated by a mixture of independent and constrained refinement
wR(F2) = 0.148 w = 1/[σ2(Fo2) + (0.0537P)2 + 0.3588P]
where P = (Fo2 + 2Fc2)/3
S = 1.05(Δ/σ)max = 0.001
7670 reflectionsΔρmax = 0.36 e Å−3
364 parametersΔρmin = −0.26 e Å−3
3 restraints
Special details top

Experimental. Absorption correction: [CrysAlisPro (Agilent, 2013). Analytical numeric absorption correction using a multifaceted crystal model based on expressions derived by Clark & Reid (1995)

Geometry. All e.s.d.'s (except the e.s.d. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell e.s.d.'s are taken into account individually in the estimation of e.s.d.'s in distances, angles and torsion angles; correlations between e.s.d.'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell e.s.d.'s is used for estimating e.s.d.'s involving l.s. planes.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å2) top
xyzUiso*/UeqOcc. (<1)
N260.4579 (2)0.58797 (10)0.29818 (9)0.0368 (3)
H260.51680.52820.27940.044*
O151.50948 (17)0.80964 (8)0.69521 (7)0.0345 (3)
O230.98187 (18)0.57258 (8)0.43787 (8)0.0419 (3)
C33−0.5511 (2)0.30398 (12)−0.11261 (10)0.0345 (4)
H33A−0.65040.3164−0.06910.041*
H33B−0.55190.3632−0.13050.041*
C280.1978 (2)0.49429 (12)0.17862 (10)0.0333 (3)
H28A0.20240.43470.19600.040*
H28B0.29440.48320.13420.040*
C270.2593 (2)0.59363 (13)0.25821 (10)0.0367 (4)
H27A0.25980.65310.24060.044*
H27B0.16070.60610.30210.044*
C35−0.8237 (3)0.20232 (12)−0.23541 (10)0.0364 (4)
H35A−0.83200.2614−0.25340.044*
H35B−0.92110.2122−0.19150.044*
O250.4853 (2)0.75915 (9)0.38872 (8)0.0472 (3)
C31−0.2796 (2)0.40101 (12)0.01197 (10)0.0333 (3)
H31A−0.37820.41290.05580.040*
H31B−0.28100.4607−0.00530.040*
C72.0845 (2)0.78185 (12)0.79254 (10)0.0327 (3)
C30−0.0726 (2)0.39840 (12)0.05502 (10)0.0337 (3)
H30A0.02670.38890.01190.040*
H30B−0.06980.33740.07070.040*
O32.54720 (19)0.71434 (9)0.87183 (8)0.0418 (3)
C32−0.3442 (2)0.30171 (12)−0.06881 (10)0.0348 (4)
H32A−0.34330.2421−0.05140.042*
H32B−0.24500.2897−0.11240.042*
C122.0006 (3)0.87875 (12)0.82186 (10)0.0365 (4)
H122.07470.93780.86530.044*
N62.3818 (2)0.85718 (11)0.90254 (9)0.0388 (3)
N42.3705 (2)0.68521 (11)0.81288 (9)0.0389 (3)
C29−0.0119 (2)0.49672 (12)0.13743 (10)0.0339 (3)
H29A−0.10900.50530.18130.041*
H29B−0.01780.55800.12220.041*
C101.7059 (2)0.80337 (12)0.72431 (10)0.0311 (3)
C34−0.6142 (2)0.20383 (12)−0.19294 (10)0.0357 (4)
H34A−0.51770.1933−0.23740.043*
H34B−0.60670.1444−0.17540.043*
C81.9776 (2)0.69561 (12)0.72722 (10)0.0323 (3)
H82.03530.62950.70650.039*
N220.7992 (2)0.55954 (11)0.38631 (9)0.0413 (4)
C91.7885 (2)0.70490 (12)0.69204 (10)0.0314 (3)
C240.5515 (2)0.67201 (12)0.36269 (10)0.0331 (3)
C36−0.8799 (3)0.10077 (13)−0.31550 (11)0.0409 (4)
H36A−0.78080.0904−0.35880.049*
H36B−0.87320.0420−0.29710.049*
C181.2226 (2)0.70293 (12)0.53997 (10)0.0337 (3)
H18A1.33080.67020.50250.040*
H18B1.21890.67370.58490.040*
C200.8824 (2)0.73138 (12)0.46614 (10)0.0313 (3)
H200.87420.80510.48950.038*
C52.2806 (2)0.77262 (12)0.83423 (10)0.0329 (3)
C210.7448 (2)0.65460 (12)0.40427 (10)0.0309 (3)
C111.8104 (3)0.89102 (12)0.78886 (10)0.0354 (4)
C37−1.0859 (3)0.09851 (13)−0.35931 (10)0.0387 (4)
H37A−1.18720.1026−0.31810.046*
H37B−1.09700.1597−0.37440.046*
C171.2696 (3)0.82027 (12)0.58603 (11)0.0380 (4)
H17A1.24540.85170.54280.046*
H17B1.17800.85110.63260.046*
C191.0283 (2)0.67627 (12)0.48446 (10)0.0314 (3)
C161.4831 (3)0.84709 (13)0.62690 (11)0.0380 (4)
H16A1.57660.81390.58170.046*
H16B1.51110.92360.65190.046*
C22.5404 (3)0.81666 (13)0.92158 (11)0.0374 (4)
C131.6694 (3)0.61197 (12)0.62341 (11)0.0401 (4)
H13A1.53760.60640.64310.060*
H13B1.74010.54840.61460.060*
H13C1.65280.62050.56780.060*
C12.7090 (3)0.86781 (15)0.98960 (12)0.0469 (4)
H1A2.70960.84021.03500.070*
H1B2.69340.94331.01650.070*
H1C2.83540.85370.96230.070*
C141.7185 (3)0.99591 (13)0.82549 (12)0.0475 (5)
H14A1.77981.03710.88540.071*
H14B1.57420.98570.82680.071*
H14C1.74191.03300.78800.071*
O100−1.4973 (6)−0.0308 (2)−0.5193 (2)0.0642 (9)0.5
H10A−1.586 (8)0.012 (4)−0.504 (4)0.096*0.5
H10B−1.503 (9)−0.0960 (10)−0.548 (3)0.096*0.5
O38−1.1236 (2)0.00445 (10)−0.43770 (9)0.0517 (4)
H38−1.238 (2)0.006 (2)−0.4585 (15)0.077*
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
N260.0317 (8)0.0351 (7)0.0377 (7)0.0030 (6)−0.0097 (6)0.0109 (6)
O150.0290 (6)0.0373 (6)0.0372 (6)0.0034 (5)−0.0018 (5)0.0159 (5)
O230.0362 (7)0.0310 (6)0.0464 (7)0.0040 (5)−0.0147 (5)0.0066 (5)
C330.0279 (8)0.0327 (8)0.0349 (8)0.0021 (6)−0.0032 (6)0.0067 (6)
C280.0285 (8)0.0344 (8)0.0335 (8)0.0024 (6)−0.0040 (6)0.0114 (6)
C270.0296 (9)0.0393 (9)0.0353 (8)0.0039 (7)−0.0063 (7)0.0109 (7)
C350.0291 (8)0.0341 (8)0.0362 (8)0.0043 (7)−0.0038 (7)0.0055 (6)
O250.0417 (7)0.0386 (6)0.0514 (7)0.0096 (6)−0.0092 (6)0.0104 (5)
C310.0280 (8)0.0327 (8)0.0331 (8)0.0018 (6)−0.0032 (6)0.0084 (6)
C70.0304 (8)0.0343 (8)0.0336 (8)0.0039 (6)0.0003 (6)0.0145 (6)
C300.0291 (8)0.0341 (8)0.0335 (8)0.0019 (6)−0.0024 (6)0.0102 (6)
O30.0372 (7)0.0394 (6)0.0455 (7)0.0085 (5)−0.0034 (5)0.0150 (5)
C320.0298 (9)0.0353 (8)0.0314 (8)0.0017 (7)−0.0030 (6)0.0064 (6)
C120.0367 (9)0.0308 (8)0.0366 (8)0.0010 (7)−0.0048 (7)0.0098 (6)
N60.0373 (8)0.0369 (7)0.0375 (7)0.0054 (6)−0.0039 (6)0.0114 (6)
N40.0345 (8)0.0379 (7)0.0417 (7)0.0047 (6)−0.0034 (6)0.0147 (6)
C290.0281 (8)0.0343 (8)0.0329 (8)0.0011 (6)−0.0047 (6)0.0086 (6)
C100.0285 (8)0.0327 (8)0.0316 (7)0.0034 (6)−0.0004 (6)0.0133 (6)
C340.0293 (8)0.0344 (8)0.0328 (8)0.0055 (7)−0.0035 (6)0.0038 (6)
C80.0329 (9)0.0300 (7)0.0334 (8)0.0051 (6)0.0029 (6)0.0120 (6)
N220.0348 (8)0.0352 (7)0.0421 (8)0.0040 (6)−0.0131 (6)0.0067 (6)
C90.0326 (9)0.0304 (7)0.0302 (7)0.0017 (6)0.0009 (6)0.0116 (6)
C240.0301 (8)0.0370 (8)0.0314 (7)0.0006 (7)−0.0029 (6)0.0141 (6)
C360.0328 (9)0.0357 (8)0.0389 (9)0.0042 (7)−0.0078 (7)0.0013 (7)
C180.0278 (8)0.0345 (8)0.0339 (8)0.0029 (6)−0.0032 (6)0.0099 (6)
C200.0287 (8)0.0297 (7)0.0320 (7)0.0015 (6)−0.0006 (6)0.0095 (6)
C50.0321 (9)0.0341 (8)0.0334 (8)0.0039 (7)0.0025 (6)0.0147 (6)
C210.0277 (8)0.0329 (8)0.0294 (7)0.0026 (6)−0.0012 (6)0.0106 (6)
C110.0355 (9)0.0298 (7)0.0373 (8)0.0041 (7)−0.0022 (7)0.0110 (6)
C370.0308 (9)0.0386 (9)0.0355 (8)0.0003 (7)−0.0039 (7)0.0049 (7)
C170.0330 (9)0.0354 (8)0.0414 (9)0.0001 (7)−0.0076 (7)0.0134 (7)
C190.0292 (8)0.0302 (7)0.0302 (7)0.0025 (6)−0.0008 (6)0.0082 (6)
C160.0351 (9)0.0383 (8)0.0413 (9)−0.0027 (7)−0.0082 (7)0.0192 (7)
C20.0366 (9)0.0378 (8)0.0367 (8)0.0060 (7)0.0005 (7)0.0143 (7)
C130.0367 (10)0.0320 (8)0.0429 (9)0.0028 (7)−0.0029 (7)0.0076 (7)
C10.0397 (10)0.0508 (10)0.0451 (10)0.0044 (8)−0.0072 (8)0.0164 (8)
C140.0488 (12)0.0321 (8)0.0512 (10)0.0087 (8)−0.0088 (9)0.0085 (7)
O1000.0418 (18)0.0401 (18)0.085 (3)−0.0014 (17)−0.0171 (18)0.0032 (16)
O380.0355 (7)0.0480 (7)0.0479 (7)−0.0014 (6)−0.0147 (6)−0.0013 (6)
Geometric parameters (Å, º) top
N26—H260.8800C10—C91.406 (2)
N26—C271.4614 (19)C10—C111.394 (2)
N26—C241.3352 (19)C34—H34A0.9900
O15—C101.3854 (18)C34—H34B0.9900
O15—C161.4356 (19)C8—H80.9500
O23—N221.4056 (17)C8—C91.387 (2)
O23—C191.3591 (18)N22—C211.308 (2)
C33—H33A0.9900C9—C131.504 (2)
C33—H33B0.9900C24—C211.494 (2)
C33—C321.525 (2)C36—H36A0.9900
C33—C341.521 (2)C36—H36B0.9900
C28—H28A0.9900C36—C371.506 (2)
C28—H28B0.9900C18—H18A0.9900
C28—C271.507 (2)C18—H18B0.9900
C28—C291.524 (2)C18—C171.523 (2)
C27—H27A0.9900C18—C191.487 (2)
C27—H27B0.9900C20—H200.9500
C35—H35A0.9900C20—C211.412 (2)
C35—H35B0.9900C20—C191.349 (2)
C35—C341.520 (2)C11—C141.510 (2)
C35—C361.522 (2)C37—H37A0.9900
O25—C241.2242 (19)C37—H37B0.9900
C31—H31A0.9900C37—O381.4329 (19)
C31—H31B0.9900C17—H17A0.9900
C31—C301.521 (2)C17—H17B0.9900
C31—C321.520 (2)C17—C161.510 (2)
C7—C121.391 (2)C16—H16A0.9900
C7—C81.394 (2)C16—H16B0.9900
C7—C51.473 (2)C2—C11.481 (2)
C30—H30A0.9900C13—H13A0.9800
C30—H30B0.9900C13—H13B0.9800
C30—C291.521 (2)C13—H13C0.9800
O3—N41.4194 (18)C1—H1A0.9800
O3—C21.339 (2)C1—H1B0.9800
C32—H32A0.9900C1—H1C0.9800
C32—H32B0.9900C14—H14A0.9800
C12—H120.9500C14—H14B0.9800
C12—C111.392 (2)C14—H14C0.9800
N6—C51.387 (2)O100—O100i0.847 (5)
N6—C21.293 (2)O100—H10A0.834 (10)
N4—C51.304 (2)O100—H10B0.841 (10)
C29—H29A0.9900O38—H380.819 (10)
C29—H29B0.9900
C27—N26—H26119.5C8—C9—C10118.41 (14)
C24—N26—H26119.5C8—C9—C13121.52 (14)
C24—N26—C27121.03 (13)N26—C24—C21116.22 (14)
C10—O15—C16115.72 (13)O25—C24—N26123.45 (15)
C19—O23—N22109.09 (11)O25—C24—C21120.32 (14)
H33A—C33—H33B107.7C35—C36—H36A108.9
C32—C33—H33A108.9C35—C36—H36B108.9
C32—C33—H33B108.9H36A—C36—H36B107.7
C34—C33—H33A108.9C37—C36—C35113.23 (14)
C34—C33—H33B108.9C37—C36—H36A108.9
C34—C33—C32113.38 (13)C37—C36—H36B108.9
H28A—C28—H28B107.9H18A—C18—H18B107.8
C27—C28—H28A109.1C17—C18—H18A109.1
C27—C28—H28B109.1C17—C18—H18B109.1
C27—C28—C29112.36 (13)C19—C18—H18A109.1
C29—C28—H28A109.1C19—C18—H18B109.1
C29—C28—H28B109.1C19—C18—C17112.46 (13)
N26—C27—C28111.29 (13)C21—C20—H20127.9
N26—C27—H27A109.4C19—C20—H20127.9
N26—C27—H27B109.4C19—C20—C21104.27 (13)
C28—C27—H27A109.4N6—C5—C7121.88 (14)
C28—C27—H27B109.4N4—C5—C7123.71 (14)
H27A—C27—H27B108.0N4—C5—N6114.37 (14)
H35A—C35—H35B107.8N22—C21—C24120.05 (14)
C34—C35—H35A109.1N22—C21—C20112.71 (14)
C34—C35—H35B109.1C20—C21—C24127.21 (14)
C34—C35—C36112.48 (13)C12—C11—C10118.13 (14)
C36—C35—H35A109.1C12—C11—C14120.24 (15)
C36—C35—H35B109.1C10—C11—C14121.58 (15)
H31A—C31—H31B107.7C36—C37—H37A109.6
C30—C31—H31A108.8C36—C37—H37B109.6
C30—C31—H31B108.8H37A—C37—H37B108.1
C32—C31—H31A108.8O38—C37—C36110.40 (13)
C32—C31—H31B108.8O38—C37—H37A109.6
C32—C31—C30113.69 (13)O38—C37—H37B109.6
C12—C7—C8119.31 (15)C18—C17—H17A109.1
C12—C7—C5118.79 (14)C18—C17—H17B109.1
C8—C7—C5121.86 (14)H17A—C17—H17B107.8
C31—C30—H30A108.9C16—C17—C18112.46 (14)
C31—C30—H30B108.9C16—C17—H17A109.1
C31—C30—C29113.32 (13)C16—C17—H17B109.1
H30A—C30—H30B107.7O23—C19—C18115.49 (13)
C29—C30—H30A108.9C20—C19—O23109.31 (13)
C29—C30—H30B108.9C20—C19—C18135.17 (14)
C2—O3—N4106.40 (12)O15—C16—C17108.21 (14)
C33—C32—H32A108.8O15—C16—H16A110.1
C33—C32—H32B108.8O15—C16—H16B110.1
C31—C32—C33113.98 (13)C17—C16—H16A110.1
C31—C32—H32A108.8C17—C16—H16B110.1
C31—C32—H32B108.8H16A—C16—H16B108.4
H32A—C32—H32B107.7O3—C2—C1117.70 (15)
C7—C12—H12119.3N6—C2—O3113.45 (15)
C7—C12—C11121.41 (15)N6—C2—C1128.85 (16)
C11—C12—H12119.3C9—C13—H13A109.5
C2—N6—C5102.68 (13)C9—C13—H13B109.5
C5—N4—O3103.10 (12)C9—C13—H13C109.5
C28—C29—H29A109.0H13A—C13—H13B109.5
C28—C29—H29B109.0H13A—C13—H13C109.5
C30—C29—C28112.80 (13)H13B—C13—H13C109.5
C30—C29—H29A109.0C2—C1—H1A109.5
C30—C29—H29B109.0C2—C1—H1B109.5
H29A—C29—H29B107.8C2—C1—H1C109.5
O15—C10—C9117.88 (13)H1A—C1—H1B109.5
O15—C10—C11120.18 (14)H1A—C1—H1C109.5
C11—C10—C9121.74 (14)H1B—C1—H1C109.5
C33—C34—H34A108.7C11—C14—H14A109.5
C33—C34—H34B108.7C11—C14—H14B109.5
C35—C34—C33114.39 (13)C11—C14—H14C109.5
C35—C34—H34A108.7H14A—C14—H14B109.5
C35—C34—H34B108.7H14A—C14—H14C109.5
H34A—C34—H34B107.6H14B—C14—H14C109.5
C7—C8—H8119.5O100i—O100—H10A45 (5)
C9—C8—C7120.98 (14)O100i—O100—H10B166 (4)
C9—C8—H8119.5H10A—O100—H10B132 (6)
C21—N22—O23104.61 (12)C37—O38—H38107.1 (18)
C10—C9—C13120.03 (14)
N26—C24—C21—N22−9.9 (2)C34—C33—C32—C31−179.60 (14)
N26—C24—C21—C20172.31 (15)C34—C35—C36—C37−179.10 (15)
O15—C10—C9—C8−173.62 (14)C8—C7—C12—C111.5 (3)
O15—C10—C9—C134.2 (2)C8—C7—C5—N6−176.35 (15)
O15—C10—C11—C12174.16 (14)C8—C7—C5—N41.3 (3)
O15—C10—C11—C14−3.2 (3)N22—O23—C19—C18−177.78 (14)
O23—N22—C21—C24−178.41 (14)N22—O23—C19—C200.63 (18)
O23—N22—C21—C20−0.32 (19)C9—C10—C11—C12−0.6 (2)
C27—N26—C24—O25−4.6 (3)C9—C10—C11—C14−177.98 (16)
C27—N26—C24—C21174.35 (14)C24—N26—C27—C28171.58 (14)
C27—C28—C29—C30177.88 (14)C36—C35—C34—C33179.91 (15)
C35—C36—C37—O38175.68 (15)C18—C17—C16—O15−64.32 (18)
O25—C24—C21—N22169.10 (16)C5—C7—C12—C11−175.97 (15)
O25—C24—C21—C20−8.7 (3)C5—C7—C8—C9176.58 (15)
C31—C30—C29—C28−178.56 (14)C5—N6—C2—O3−0.4 (2)
C7—C12—C11—C10−0.8 (3)C5—N6—C2—C1179.90 (18)
C7—C12—C11—C14176.62 (17)C21—C20—C19—O23−0.78 (18)
C7—C8—C9—C10−0.5 (2)C21—C20—C19—C18177.18 (18)
C7—C8—C9—C13−178.27 (15)C11—C10—C9—C81.2 (2)
C30—C31—C32—C33−179.69 (14)C11—C10—C9—C13179.01 (15)
O3—N4—C5—C7−178.08 (14)C17—C18—C19—O23176.76 (14)
O3—N4—C5—N6−0.30 (19)C17—C18—C19—C20−1.1 (3)
C32—C33—C34—C35177.44 (14)C19—O23—N22—C21−0.18 (18)
C32—C31—C30—C29−178.21 (14)C19—C18—C17—C16−168.20 (14)
C12—C7—C8—C9−0.8 (2)C19—C20—C21—N220.69 (19)
C12—C7—C5—N61.1 (2)C19—C20—C21—C24178.63 (16)
C12—C7—C5—N4178.67 (16)C16—O15—C10—C9−100.42 (16)
N4—O3—C2—N60.2 (2)C16—O15—C10—C1184.64 (18)
N4—O3—C2—C1179.98 (15)C2—O3—N4—C50.04 (17)
C29—C28—C27—N26178.10 (14)C2—N6—C5—C7178.26 (15)
C10—O15—C16—C17164.12 (13)C2—N6—C5—N40.4 (2)
Symmetry code: (i) −x−3, −y, −z−1.
Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
C28—H28A···O3ii0.992.643.2567 (19)120
C20—H20···O38iii0.952.563.505 (2)175
C13—H13B···O23ii0.982.513.416 (2)154
C1—H1B···N60.982.653.622 (2)174
O100—H10B···O25iv0.84 (1)1.87 (1)2.710 (3)180 (6)
O38—H38···O1000.82 (1)1.90 (1)2.695 (4)164 (2)
Symmetry codes: (ii) −x+3, −y+1, −z+1; (iii) x+2, y+1, z+1; (iv) x−2, y−1, z−1.
 

References

First citationAgilent (2013). CrysAlis PRO. Agilent Technologies Ltd, Yarnton, Oxfordshire, England.  Google Scholar
 First citationClark, R. C. & Reid, J. S. (1995). Acta Cryst. A51, 887–897.  CrossRef CAS Web of Science IUCr Journals Google Scholar
 First citationCoste, S., Schneider, J. M., Petit, M. N. & Coquerel, G. (2004). Cryst. Growth Des. 4, 1237–1244.  CSD CrossRef CAS Google Scholar
 First citationDe Palma, A. M., Vliegen, I., Clercq, E. D. & Neyts, I. (2008). Med. Res. Rev. 28, 823–884.  CrossRef PubMed CAS Google Scholar
 First citationDiana, G. D. (2003). Curr. Med. Chem. 2, 1–12.  CAS Google Scholar
 First citationDiana, G. D., Rudewicz, P., Pevear, D. C., Nitz, T. J., Aldous, S. C., Aldous, D. J., Robinson, D. T., Draper, T., Dutko, F. J., Aldi, C., Gendron, G., Oglesby, R. C., Volkots, D. L., Reuman, M., Bailey, T. R., Czerniak, R., Block, T., Roland, R. & Opperman, J. (1995). J. Med. Chem. 38, 1355–1371.  CrossRef CAS PubMed Google Scholar
 First citationDolomanov, O. V., Bourhis, L. J., Gildea, R. J., Howard, J. A. K. & Puschmann, H. (2009). J. Appl. Cryst. 42, 339–341.  Web of Science CrossRef CAS IUCr Journals Google Scholar
 First citationGiranda, V. L., Russo, G. R., Felock, P. J., Bailey, T. R., Draper, T., Aldous, D. J., Guiles, J., Dutko, F. J., Diana, G. D., Pevear, D. C. & McMillan, M. (1995). Acta Cryst. D51, 496–503.  CrossRef IUCr Journals Google Scholar
 First citationGroom, C. R. & Allen, F. H. (2014). Angew. Chem. Int. Ed. 53, 662–671.  Web of Science CSD CrossRef CAS Google Scholar
 First citationPevear, D. C., Tull, T. M., Seipel, M. E. & Groarke, J. M. (1999). Antimicrob. Agents Chemother. 43, 2109–2115.  PubMed CAS Google Scholar
 First citationReisdorph, N., Thomas, J. J., Katpally, U., Chase, E., Harris, K., Siuzdak, G. & Smith, T. J. (2003). Virology, 314, 34–44.  Web of Science CrossRef PubMed CAS Google Scholar
 First citationSalorinne, K., Lahtinen, T., Marjomäki, V. & Häkkinen, H. (2014). CrystEngComm, 16, 9001–9009.  CSD CrossRef CAS 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 citationThibaut, H. J., De Palma, A. M. & Neyts, J. (2012). Biochem. Pharmacol. 83, 185–192.  CrossRef CAS PubMed Google Scholar
 First citationWildenbeest, J. G., van den Broek, P. J., Benschop, K. S. M., Koen, G., Wierenga, P. C., Vossen, A. C. T. M., Kuijpers, T. W. & Wolthers, K. C. (2012). Antiviral Ther. 17, 459–466.  CrossRef CAS Google Scholar
 First citationZhang, Y., Simpson, A. A., Ledford, R. M., Bator, C. M., Chakravarty, S., Skochko, G. A., Demenczuk, T. M., Watanyar, A., Pevear, D. C. & Rossmann, M. G. (2004). J. Virol. 78, 11061–11069.  CrossRef PubMed CAS Google Scholar

This is an open-access article distributed under the terms of the Creative Commons Attribution (CC-BY) Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original authors and source are cited.

Journal logoCRYSTALLOGRAPHIC
COMMUNICATIONS
ISSN: 2056-9890
Volume 71| Part 5| May 2015| Pages 505-508
https://doi.org/10.1107/S2056989015007367
Follow Acta Cryst. E
Sign up for e-alerts
E-alerts
Follow Acta Cryst. on Twitter
Twitter
Follow us on facebook
Facebook
Sign up for RSS feeds
RSS