supplementary materials


lh5560 scheme

Acta Cryst. (2013). E69, o40-o41    [ doi:10.1107/S1600536812047976 ]

Ethyl 2,7,7-trimethyl-4-(1-methyl-1H-indol-3-yl)-5-oxo-1,4,5,6,7,8-hexahydroquinoline-3-carboxylate

S. Öztürk Yildirim, R. J. Butcher, M. G. Gündüz, A. El-Khouly, R. Simsek and C. Safak

Abstract top

In the title molecule, C24H28N2O3, the cyclohexene ring is in a sofa conformation and the 1,4-dihydropyridine ring is in a slight boat conformation. In the indole ring system, the pyrrole and benzene rings form a dihedral angle of 2.63 (7)°. In the crystal, N-H...O hydrogen bonds connect the molecules into C(6) chains parallel to the b axis and pairs of weak C-H...O hydrogen bonds link inversion-related chains into a ladder motif through R22(18) rings. A weak intramolecular C-H...O hydrogen bond is also observed.

Comment top

Calcium ions play a critical role in various biological functions such as muscle contraction, release of neurotransmitters and regulation of neuronal excitability (Triggle & Swamy, 1980). Calcium entry into the cytosol is mediated by different types of calcium channels with distinct physiological roles (Zamponi, 1997). L-type channels are confined to cell bodies and regulate contractions in muscle cells. Calcium channel antagonists reversibly block Ca2+ influx through L-type calcium channels (Dolphin, 2006). 1,4-Dihydropyridines (DHP), of which nifedipine is the prototype, are one of the known classes of calcium antagonists which are frequently used for the treatment of cardiovascular diseases like angina, hypertension and supraventricular tachycardia (Vaghy et al., 1987; Triggle, 2003; Şafak & Şimşek, 2006). DHPs have attracted interest since their introduction into clinical medicine, because of their high potency and selectivity of action (Zhou et al., 2011). Many modifications have been carried out on the structure of nifedipine in order to enhance calcium modulating effects and lead to new active compounds (Gordeev et al., 1998). According information obtained from structure-activity relationships and our experience in this field, we synthesized ethyl 2,7,7-trimethyl-4-(1-methyl-1H-indol-3-yl)-5-oxo-1,4,5,6,7,8-hexahydroquinoline-3-carboxylate and determined its crystal structure.

The molecular structure of the title compound is shown in Fig. 1. The (C1—C6) cyclohexene ring is in a sofa conformation with puckering parameters (Cremer & Pople, 1975) of QT = 0.492 (1) Å, θ = 120.6 (1) ° and φ = 302.2 (1)°. The 1,4-dihydropyridine ring (N1/C1/C6—C9) is in a slight boat conformation. In the 1H-indole ring system, the 2,3-dihydro-1H-pyrrole and benzene rings form a dihedral angle of 2.63 (7)°. The values of the bond lengths and bond angles are comparable with those of the related structures previously reported (El-Khouly et al., 2012; Öztürk Yildirim et al., 2012; Gündüz, et al., 2012).

In the crystal, N—H···O hydrogen bonds connect molecules via C(6) motifs (Bernstein et al. 1995) into chains parallel to the b axis and pairs weak C—H···O hydrogen bonds link inversion related chains into a ladder motif through R22(18) rings (Fig. 2). A weak intramolecular C—H···O hydrogen bond is also observed.

Related literature top

For the biological functions of calcium ions, see: Triggle & Swamy (1980) and for the biological functions and physiological roles of calcium channels, see: Zamponi (1997); Dolphin (2006). For the biological properties of 1,4-dihydro pyridines (DHP), see: Vaghy et al. (1987); Triggle (2003); Şafak & Şimşek (2006); Zhou et al., (2011). For nifedipine (the prototypical DHP) in clinical use, see: Gordeev et al. (1998). For geometric analysis, see: Cremer & Pople (1975). For hydrogen-bond motifs, see: Bernstein et al. (1995). For similar structures, see: El-Khouly et al.(2012); Öztürk Yildirim et al. (2012); Gündüz, et al. (2012).

Experimental top

The compound was prepared by refluxing 5,5-dimethyl-cyclohexane-1,3-dione (0.001 mol), ethyl acetoacetate (0.001 mol), 1-methyl-3-indolecarbaldehyde (0.001 mol) and ammonium acetate (0.005 mol) in methanol for 8 h. After cooling, the mixture was poured into ice-water. The obtained precipitate was crystallized from ethanol (m.p. 507 K). Pure crystals suitable for X-ray structure analysis were obtained by slow evaporation method using methanol as a solvent. Its structure was elucidated by IR, 1H-NMR and elemental analysis. IR (cm-1): 3288, 3072, 2970, 1685; 1H-NMR δ (p.p.m.) 0.9–1.0 (6H; s; 2xCH3), 1.1 (3H; t; CH2CH3), 1.9–2.2 (4H; m; quinoline H6,8), 2.3 (3H; s; CH3), 3.6 (3H; s; N—CH3), 3.9 (2H; m; CH2CH3), 5.0 (1H; s; quinoline H4), 6.8 (1H; s; indole H2), 6.9–7.6 (4H; m; aromatic), 9.2 (1H; s; NH). Anal. for C24H28N2O3 calculated: C, 73.44; H, 7.19; N, 7.14; found: C, 74.05; H, 6.82; N, 7.41. The title compound demonstrated calcium channel blocker activity in isolated rat ileum and lamb carotid artery.

Refinement top

The N-bound H1N atom was located in a difference map and refined freely [N—H = 0.86 (2) Å]. The remaining H atoms were positioned geometrically (C—H = 0.95–1.00 Å) and allowed to ride on their parent atoms, with Uiso(H) = 1.2Ueq(C) or 1.5Ueq(Cmethyl). A rotating group model was used for methyl groups.

Computing details top

Data collection: CrysAlis PRO (Agilent, 2011); cell refinement: CrysAlis PRO (Agilent, 2011); data reduction: CrysAlis PRO (Agilent, 2011); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: SHELXTL (Sheldrick, 2008); software used to prepare material for publication: SHELXTL (Sheldrick, 2008).

Figures top
[Figure 1] Fig. 1. The molecular structure of (I), showing 30% probability displacement ellipsoids. The dashed line indicates the intramolecular C—H···O interaction.
[Figure 2] Fig. 2. The packing and hydrogen bonding of the title molecule in the unit cell, viewing down b axis. Hydrogen bonds and C—H···O interactions are shown as dashed lines.
Ethyl 2,7,7-trimethyl-4-(1-methyl-1H-indol-3-yl)-5-oxo-1,4,5,6,7,8- hexahydroquinoline-3-carboxylate top
Crystal data top
C24H28N2O3F(000) = 840
Mr = 392.48Dx = 1.240 Mg m3
Monoclinic, P21/cCu Kα radiation, λ = 1.54184 Å
Hall symbol: -P 2ybcCell parameters from 3252 reflections
a = 17.4656 (4) Åθ = 3.7–75.7°
b = 10.1883 (2) ŵ = 0.65 mm1
c = 12.3465 (3) ÅT = 123 K
β = 106.806 (2)°Block, colorless
V = 2103.16 (8) Å30.55 × 0.40 × 0.35 mm
Z = 4
Data collection top
Agilent Xcalibur (Ruby, Gemini)
diffractometer
4246 independent reflections
Radiation source: Enhance (Cu) X-ray Source3533 reflections with I > 2σ(I)
Graphite monochromatorRint = 0.025
Detector resolution: 10.5081 pixels mm-1θmax = 75.9°, θmin = 5.1°
ω scansh = 2021
Absorption correction: multi-scan
[CrysAlis RED (Agilent, 2011), based on expressions derived from Clark & Reid (1995)]
k = 1210
Tmin = 0.715, Tmax = 0.804l = 1415
8035 measured reflections
Refinement top
Refinement on F2Primary atom site location: structure-invariant direct methods
Least-squares matrix: fullSecondary atom site location: difference Fourier map
R[F2 > 2σ(F2)] = 0.044Hydrogen site location: inferred from neighbouring sites
wR(F2) = 0.125H atoms treated by a mixture of independent and constrained refinement
S = 1.03 w = 1/[σ2(Fo2) + (0.0707P)2 + 0.4192P]
where P = (Fo2 + 2Fc2)/3
4246 reflections(Δ/σ)max = 0.001
271 parametersΔρmax = 0.27 e Å3
0 restraintsΔρmin = 0.23 e Å3
Crystal data top
C24H28N2O3V = 2103.16 (8) Å3
Mr = 392.48Z = 4
Monoclinic, P21/cCu Kα radiation
a = 17.4656 (4) ŵ = 0.65 mm1
b = 10.1883 (2) ÅT = 123 K
c = 12.3465 (3) Å0.55 × 0.40 × 0.35 mm
β = 106.806 (2)°
Data collection top
Agilent Xcalibur (Ruby, Gemini)
diffractometer
4246 independent reflections
Absorption correction: multi-scan
[CrysAlis RED (Agilent, 2011), based on expressions derived from Clark & Reid (1995)]
3533 reflections with I > 2σ(I)
Tmin = 0.715, Tmax = 0.804Rint = 0.025
8035 measured reflectionsθmax = 75.9°
Refinement top
R[F2 > 2σ(F2)] = 0.044H atoms treated by a mixture of independent and constrained refinement
wR(F2) = 0.125Δρmax = 0.27 e Å3
S = 1.03Δρmin = 0.23 e Å3
4246 reflectionsAbsolute structure: ?
271 parametersFlack parameter: ?
0 restraintsRogers parameter: ?
Special details top

Experimental. Absorption correction: CrysAlis RED, (Agilent, 2011) Empirical absorption correction using spherical harmonics, implemented in SCALE3 ABSPACK scaling algorithm. (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.

Refinement. Refinement of F2 against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F2, conventional R-factors R are based on F, with F set to zero for negative F2. The threshold expression of F2 > σ(F2) is used only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F2 are statistically about twice as large as those based on F, and R- factors based on ALL data will be even larger.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å2) top
xyzUiso*/Ueq
O10.80036 (6)0.10674 (11)0.14843 (8)0.0291 (2)
O20.50682 (7)0.45404 (15)0.20829 (11)0.0444 (3)
O30.53584 (6)0.31811 (11)0.08329 (9)0.0281 (2)
N10.74838 (7)0.40267 (13)0.41035 (10)0.0250 (3)
N20.70297 (7)0.49919 (13)0.07455 (10)0.0254 (3)
C10.79738 (8)0.31973 (14)0.37441 (11)0.0235 (3)
C20.87530 (9)0.28770 (16)0.46042 (12)0.0289 (3)
H2A0.86620.21850.51160.035*
H2B0.89520.36680.50660.035*
C30.93922 (9)0.24060 (16)0.40645 (12)0.0301 (3)
C40.90135 (9)0.13072 (16)0.32375 (13)0.0312 (3)
H4A0.93970.10370.28250.037*
H4B0.89210.05400.36750.037*
C50.82268 (8)0.16811 (14)0.23802 (11)0.0240 (3)
C60.77439 (8)0.26933 (14)0.26782 (11)0.0221 (3)
C70.69728 (8)0.31300 (14)0.18198 (11)0.0218 (3)
H7A0.67040.23330.14090.026*
C80.64109 (8)0.37442 (14)0.24284 (11)0.0232 (3)
C90.66851 (8)0.42081 (14)0.34996 (12)0.0242 (3)
C100.71174 (8)0.40744 (14)0.09521 (11)0.0223 (3)
C110.75097 (8)0.53337 (14)0.11377 (12)0.0233 (3)
C120.78991 (8)0.60792 (15)0.20974 (12)0.0269 (3)
H12A0.79700.57360.28350.032*
C130.81773 (9)0.73194 (16)0.19525 (13)0.0308 (3)
H13A0.84380.78270.25990.037*
C140.80824 (9)0.78432 (16)0.08691 (14)0.0317 (3)
H14A0.82770.87000.07960.038*
C150.77111 (9)0.71327 (16)0.00918 (13)0.0297 (3)
H15A0.76470.74850.08250.036*
C160.74337 (8)0.58779 (15)0.00536 (12)0.0249 (3)
C170.68333 (8)0.39281 (14)0.01990 (11)0.0246 (3)
H17A0.65400.31890.05680.029*
C180.55550 (8)0.38803 (15)0.18007 (12)0.0266 (3)
C190.45226 (9)0.32978 (17)0.01690 (13)0.0317 (3)
H19A0.43820.42320.00000.038*
H19B0.41710.29370.05980.038*
C200.44107 (10)0.2548 (2)0.09068 (15)0.0436 (4)
H20A0.38500.26060.13640.065*
H20B0.45530.16260.07310.065*
H20C0.47550.29200.13300.065*
C210.62218 (9)0.49093 (17)0.41785 (13)0.0313 (3)
H21A0.58440.55220.36880.047*
H21B0.65920.53960.47960.047*
H21C0.59270.42670.44940.047*
C221.01088 (10)0.1881 (2)0.49980 (15)0.0404 (4)
H22A1.05110.15400.46590.061*
H22B0.99310.11740.54080.061*
H22C1.03420.25920.55250.061*
C230.96694 (10)0.35270 (19)0.34418 (15)0.0390 (4)
H23A1.00710.31970.30950.058*
H23B0.99040.42270.39800.058*
H23C0.92110.38740.28520.058*
C240.67642 (9)0.52313 (17)0.19626 (12)0.0307 (3)
H24A0.65080.44380.23540.046*
H24B0.72260.54590.22250.046*
H24C0.63800.59580.21260.046*
H1N0.7596 (11)0.414 (2)0.4823 (17)0.033 (5)*
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
O10.0361 (5)0.0295 (6)0.0207 (5)0.0038 (4)0.0064 (4)0.0004 (4)
O20.0284 (6)0.0622 (9)0.0387 (6)0.0099 (6)0.0033 (5)0.0156 (6)
O30.0226 (5)0.0304 (5)0.0266 (5)0.0016 (4)0.0001 (4)0.0026 (4)
N10.0275 (6)0.0286 (6)0.0166 (5)0.0006 (5)0.0029 (4)0.0013 (5)
N20.0297 (6)0.0276 (6)0.0183 (5)0.0048 (5)0.0058 (4)0.0028 (5)
C10.0251 (6)0.0241 (7)0.0198 (6)0.0004 (5)0.0040 (5)0.0022 (5)
C20.0279 (7)0.0352 (8)0.0196 (6)0.0020 (6)0.0007 (5)0.0001 (6)
C30.0255 (7)0.0353 (8)0.0253 (7)0.0036 (6)0.0007 (6)0.0006 (6)
C40.0301 (7)0.0331 (8)0.0273 (7)0.0089 (6)0.0034 (6)0.0000 (6)
C50.0277 (7)0.0246 (7)0.0193 (6)0.0008 (5)0.0060 (5)0.0028 (5)
C60.0231 (6)0.0229 (6)0.0187 (6)0.0008 (5)0.0033 (5)0.0023 (5)
C70.0238 (6)0.0218 (6)0.0174 (6)0.0001 (5)0.0020 (5)0.0005 (5)
C80.0246 (7)0.0232 (7)0.0209 (6)0.0010 (5)0.0050 (5)0.0025 (5)
C90.0261 (7)0.0233 (7)0.0230 (6)0.0003 (5)0.0064 (5)0.0015 (5)
C100.0234 (6)0.0226 (7)0.0192 (6)0.0032 (5)0.0036 (5)0.0003 (5)
C110.0234 (6)0.0236 (7)0.0226 (6)0.0037 (5)0.0063 (5)0.0026 (5)
C120.0271 (7)0.0280 (7)0.0242 (6)0.0011 (6)0.0051 (5)0.0000 (6)
C130.0302 (7)0.0283 (8)0.0320 (8)0.0017 (6)0.0062 (6)0.0036 (6)
C140.0301 (7)0.0243 (7)0.0411 (9)0.0003 (6)0.0113 (6)0.0050 (6)
C150.0302 (7)0.0300 (8)0.0303 (7)0.0052 (6)0.0113 (6)0.0084 (6)
C160.0237 (6)0.0272 (7)0.0239 (7)0.0053 (5)0.0070 (5)0.0026 (6)
C170.0273 (7)0.0239 (7)0.0209 (6)0.0036 (5)0.0045 (5)0.0001 (5)
C180.0255 (7)0.0286 (7)0.0244 (6)0.0002 (6)0.0052 (5)0.0013 (6)
C190.0220 (7)0.0335 (8)0.0334 (8)0.0026 (6)0.0019 (6)0.0030 (6)
C200.0343 (8)0.0480 (10)0.0385 (9)0.0068 (8)0.0056 (7)0.0127 (8)
C210.0309 (7)0.0358 (8)0.0267 (7)0.0018 (6)0.0075 (6)0.0048 (6)
C220.0294 (8)0.0494 (10)0.0349 (8)0.0077 (7)0.0025 (6)0.0011 (8)
C230.0295 (7)0.0459 (10)0.0399 (9)0.0019 (7)0.0074 (6)0.0033 (8)
C240.0369 (8)0.0364 (8)0.0186 (6)0.0082 (6)0.0078 (6)0.0047 (6)
Geometric parameters (Å, º) top
O1—C51.2317 (18)C10—C111.441 (2)
O2—C181.2115 (19)C11—C121.406 (2)
O3—C181.3475 (18)C11—C161.4191 (19)
O3—C191.4578 (16)C12—C131.384 (2)
N1—C11.3648 (19)C12—H12A0.9500
N1—C91.3910 (18)C13—C141.405 (2)
N1—H1N0.86 (2)C13—H13A0.9500
N2—C171.3716 (19)C14—C151.381 (2)
N2—C161.3724 (19)C14—H14A0.9500
N2—C241.4594 (17)C15—C161.397 (2)
C1—C61.3606 (19)C15—H15A0.9500
C1—C21.5002 (18)C17—H17A0.9500
C2—C31.533 (2)C19—C201.495 (2)
C2—H2A0.9900C19—H19A0.9900
C2—H2B0.9900C19—H19B0.9900
C3—C41.531 (2)C20—H20A0.9800
C3—C231.531 (2)C20—H20B0.9800
C3—C221.532 (2)C20—H20C0.9800
C4—C51.5207 (19)C21—H21A0.9800
C4—H4A0.9900C21—H21B0.9800
C4—H4B0.9900C21—H21C0.9800
C5—C61.446 (2)C22—H22A0.9800
C6—C71.5197 (17)C22—H22B0.9800
C7—C101.5146 (19)C22—H22C0.9800
C7—C81.5315 (19)C23—H23A0.9800
C7—H7A1.0000C23—H23B0.9800
C8—C91.355 (2)C23—H23C0.9800
C8—C181.4781 (19)C24—H24A0.9800
C9—C211.503 (2)C24—H24B0.9800
C10—C171.3713 (18)C24—H24C0.9800
C18—O3—C19114.36 (11)C12—C13—C14121.39 (14)
C1—N1—C9122.27 (12)C12—C13—H13A119.3
C1—N1—H1N116.4 (13)C14—C13—H13A119.3
C9—N1—H1N115.4 (13)C15—C14—C13121.05 (14)
C17—N2—C16108.41 (12)C15—C14—H14A119.5
C17—N2—C24126.04 (13)C13—C14—H14A119.5
C16—N2—C24125.07 (13)C14—C15—C16117.61 (14)
C6—C1—N1120.71 (12)C14—C15—H15A121.2
C6—C1—C2123.79 (13)C16—C15—H15A121.2
N1—C1—C2115.48 (12)N2—C16—C15129.41 (13)
C1—C2—C3112.70 (12)N2—C16—C11108.03 (13)
C1—C2—H2A109.1C15—C16—C11122.51 (14)
C3—C2—H2A109.1C10—C17—N2110.91 (13)
C1—C2—H2B109.1C10—C17—H17A124.5
C3—C2—H2B109.1N2—C17—H17A124.5
H2A—C2—H2B107.8O2—C18—O3121.90 (13)
C4—C3—C23110.43 (13)O2—C18—C8126.06 (14)
C4—C3—C22110.36 (14)O3—C18—C8112.03 (12)
C23—C3—C22109.28 (14)O3—C19—C20108.07 (12)
C4—C3—C2106.87 (12)O3—C19—H19A110.1
C23—C3—C2111.12 (14)C20—C19—H19A110.1
C22—C3—C2108.75 (13)O3—C19—H19B110.1
C5—C4—C3114.23 (13)C20—C19—H19B110.1
C5—C4—H4A108.7H19A—C19—H19B108.4
C3—C4—H4A108.7C19—C20—H20A109.5
C5—C4—H4B108.7C19—C20—H20B109.5
C3—C4—H4B108.7H20A—C20—H20B109.5
H4A—C4—H4B107.6C19—C20—H20C109.5
O1—C5—C6122.29 (13)H20A—C20—H20C109.5
O1—C5—C4119.05 (13)H20B—C20—H20C109.5
C6—C5—C4118.54 (12)C9—C21—H21A109.5
C1—C6—C5118.99 (12)C9—C21—H21B109.5
C1—C6—C7121.21 (13)H21A—C21—H21B109.5
C5—C6—C7119.73 (12)C9—C21—H21C109.5
C10—C7—C6112.57 (11)H21A—C21—H21C109.5
C10—C7—C8110.43 (11)H21B—C21—H21C109.5
C6—C7—C8109.99 (11)C3—C22—H22A109.5
C10—C7—H7A107.9C3—C22—H22B109.5
C6—C7—H7A107.9H22A—C22—H22B109.5
C8—C7—H7A107.9C3—C22—H22C109.5
C9—C8—C18119.84 (13)H22A—C22—H22C109.5
C9—C8—C7121.71 (12)H22B—C22—H22C109.5
C18—C8—C7118.39 (12)C3—C23—H23A109.5
C8—C9—N1119.58 (13)C3—C23—H23B109.5
C8—C9—C21127.93 (13)H23A—C23—H23B109.5
N1—C9—C21112.48 (12)C3—C23—H23C109.5
C17—C10—C11105.93 (12)H23A—C23—H23C109.5
C17—C10—C7125.43 (13)H23B—C23—H23C109.5
C11—C10—C7128.46 (12)N2—C24—H24A109.5
C12—C11—C16118.31 (13)N2—C24—H24B109.5
C12—C11—C10134.96 (13)H24A—C24—H24B109.5
C16—C11—C10106.70 (12)N2—C24—H24C109.5
C13—C12—C11119.12 (14)H24A—C24—H24C109.5
C13—C12—H12A120.4H24B—C24—H24C109.5
C11—C12—H12A120.4
C9—N1—C1—C612.1 (2)C6—C7—C10—C17126.79 (14)
C9—N1—C1—C2166.63 (13)C8—C7—C10—C17109.86 (15)
C6—C1—C2—C323.2 (2)C6—C7—C10—C1158.89 (18)
N1—C1—C2—C3158.12 (13)C8—C7—C10—C1164.47 (17)
C1—C2—C3—C451.15 (17)C17—C10—C11—C12177.98 (16)
C1—C2—C3—C2369.39 (17)C7—C10—C11—C122.8 (3)
C1—C2—C3—C22170.29 (14)C17—C10—C11—C160.02 (15)
C23—C3—C4—C567.55 (17)C7—C10—C11—C16175.22 (13)
C22—C3—C4—C5171.52 (13)C16—C11—C12—C131.4 (2)
C2—C3—C4—C553.44 (17)C10—C11—C12—C13176.46 (15)
C3—C4—C5—O1157.14 (14)C11—C12—C13—C140.3 (2)
C3—C4—C5—C626.6 (2)C12—C13—C14—C150.4 (2)
N1—C1—C6—C5171.47 (13)C13—C14—C15—C160.1 (2)
C2—C1—C6—C57.2 (2)C17—N2—C16—C15175.84 (14)
N1—C1—C6—C75.7 (2)C24—N2—C16—C153.4 (2)
C2—C1—C6—C7175.67 (13)C17—N2—C16—C111.48 (15)
O1—C5—C6—C1170.63 (13)C24—N2—C16—C11173.94 (13)
C4—C5—C6—C15.5 (2)C14—C15—C16—N2178.00 (14)
O1—C5—C6—C76.6 (2)C14—C15—C16—C111.0 (2)
C4—C5—C6—C7177.32 (13)C12—C11—C16—N2179.29 (12)
C1—C6—C7—C10103.36 (15)C10—C11—C16—N20.90 (15)
C5—C6—C7—C1079.50 (16)C12—C11—C16—C151.7 (2)
C1—C6—C7—C820.24 (19)C10—C11—C16—C15176.65 (13)
C5—C6—C7—C8156.90 (12)C11—C10—C17—N20.95 (16)
C10—C7—C8—C9104.62 (15)C7—C10—C17—N2176.33 (12)
C6—C7—C8—C920.22 (19)C16—N2—C17—C101.55 (16)
C10—C7—C8—C1872.63 (16)C24—N2—C17—C10173.91 (13)
C6—C7—C8—C18162.53 (12)C19—O3—C18—O20.3 (2)
C18—C8—C9—N1177.22 (13)C19—O3—C18—C8178.99 (12)
C7—C8—C9—N15.6 (2)C9—C8—C18—O211.2 (2)
C18—C8—C9—C211.5 (2)C7—C8—C18—O2166.16 (16)
C7—C8—C9—C21175.75 (14)C9—C8—C18—O3169.60 (13)
C1—N1—C9—C812.1 (2)C7—C8—C18—O313.10 (18)
C1—N1—C9—C21166.76 (13)C18—O3—C19—C20176.22 (14)
Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
C21—H21A···O20.982.282.8073 (19)113
N1—H1N···O1i0.86 (2)1.98 (2)2.8161 (15)163.9 (19)
C24—H24C···O2ii0.982.603.1693 (19)118
Symmetry codes: (i) x, y+1/2, z+1/2; (ii) x+1, y+1, z.
Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
C21—H21A···O20.982.282.8073 (19)112.5
N1—H1N···O1i0.86 (2)1.98 (2)2.8161 (15)163.9 (19)
C24—H24C···O2ii0.982.603.1693 (19)117.5
Symmetry codes: (i) x, y+1/2, z+1/2; (ii) x+1, y+1, z.
Acknowledgements top

RJB acknowledges the NSF–MRI program (grant No. CHE-0619278) for funds to purchase the diffractometer.

references
References top

Agilent (2011). CrysAlis PRO and CrysAlis RED. Agilent Technologies, Yarnton, Oxfordshire, England.

Bernstein, J., Davis, R. E., Shimoni, L. & Chang, N.-L. (1995). Angew. Chem. Int. Ed. Engl. 34, 1555–1573.

Clark, R. C. & Reid, J. S. (1995). Acta Cryst. A51, 887–897.

Cremer, D. & Pople, J. A. (1975). J. Am. Chem. Soc. 97, 1354–1358.

Dolphin, A. C. (2006). Br. J. Pharmacol. 147, 56–62.

El-Khouly, A., Öztürk Yildirim, S., Butcher, R. J., Şimsek, R. & Şafak, C. (2012). Acta Cryst. E68, o3337.

Gordeev, M. F., Patel, D. V., England, B. P., Jonnalagadda, S., Combs, J. D. & Gordon, E. M. (1998). Bioorg. Med. Chem. 6, 883–889.

Gündüz, M. G., Butcher, R. J., Öztürk Yildirim, S., El-Khouly, A., Safak, C. & Şimsek, R. (2012). Acta Cryst. E68, o3404–o3405.

Öztürk Yildirim, S., Butcher, R. J., El-Khouly, A., Safak, C. & Şimsek, R. (2012). Acta Cryst. E68, o3365–o3366.

Şafak, C. & Şimşek, R. (2006). Mini Rev. Med. Chem. 6, 747–755.

Sheldrick, G. M. (2008). Acta Cryst. A64, 112–122.

Triggle, D. J. (2003). Mini Rev. Med. Chem. 3, 215–223.

Triggle, D. J. & Swamy, V. C. (1980). Chest, 78, 174–179.

Vaghy, P. L., Williams, J. S. & Schwartz, A. (1987). Am. J. Cardiol. 23, 9A–17A.

Zamponi, G. W. (1997). Drug Dev. Res. 42, 131–143.

Zhou, K., Wang, X.-M., Zhao, Y.-Z., Cao, Y.-X., Fu, Q. & Zhang, S. (2011). Med. Chem. Res. 20, 1325–1330.