organic compounds
Ethyl 2,7,7-trimethyl-4-(1-methyl-1H-indol-3-yl)-5-oxo-1,4,5,6,7,8-hexahydroquinoline-3-carboxylate
aDepartment of Chemistry, Howard University, 525 College Street NW, Washington, DC 20059, USA, bDepartment of Physics, Faculty of Sciences, Erciyes University, 38039 Kayseri, Turkey, and cHacettepe University, Faculty of Pharmacy, Dept. of Pharmaceutical Chemistry, 06100 Sihhiye-Ankara, Turkey
*Correspondence e-mail: rbutcher99@yahoo.com
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.
Related literature
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
Crystal data
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Refinement
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Data collection: CrysAlis PRO (Agilent, 2011); cell CrysAlis PRO; data reduction: CrysAlis PRO; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: SHELXTL; software used to prepare material for publication: SHELXTL.
Supporting information
https://doi.org/10.1107/S1600536812047976/lh5560sup1.cif
contains datablocks I, global. DOI:Structure factors: contains datablock I. DOI: https://doi.org/10.1107/S1600536812047976/lh5560Isup2.hkl
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.
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.
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.
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).
Data collection: CrysAlis PRO (Agilent, 2011); cell
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).C24H28N2O3 | F(000) = 840 |
Mr = 392.48 | Dx = 1.240 Mg m−3 |
Monoclinic, P21/c | Cu Kα radiation, λ = 1.54184 Å |
Hall symbol: -P 2ybc | Cell parameters from 3252 reflections |
a = 17.4656 (4) Å | θ = 3.7–75.7° |
b = 10.1883 (2) Å | µ = 0.65 mm−1 |
c = 12.3465 (3) Å | T = 123 K |
β = 106.806 (2)° | Block, colorless |
V = 2103.16 (8) Å3 | 0.55 × 0.40 × 0.35 mm |
Z = 4 |
Agilent Xcalibur (Ruby, Gemini) diffractometer | 4246 independent reflections |
Radiation source: Enhance (Cu) X-ray Source | 3533 reflections with I > 2σ(I) |
Graphite monochromator | Rint = 0.025 |
Detector resolution: 10.5081 pixels mm-1 | θmax = 75.9°, θmin = 5.1° |
ω scans | h = −20→21 |
Absorption correction: multi-scan [CrysAlis RED (Agilent, 2011), based on expressions derived from Clark & Reid (1995)] | k = −12→10 |
Tmin = 0.715, Tmax = 0.804 | l = −14→15 |
8035 measured reflections |
Refinement on F2 | Primary atom site location: structure-invariant direct methods |
Least-squares matrix: full | Secondary atom site location: difference Fourier map |
R[F2 > 2σ(F2)] = 0.044 | Hydrogen site location: inferred from neighbouring sites |
wR(F2) = 0.125 | H 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 parameters | Δρmax = 0.27 e Å−3 |
0 restraints | Δρmin = −0.23 e Å−3 |
C24H28N2O3 | V = 2103.16 (8) Å3 |
Mr = 392.48 | Z = 4 |
Monoclinic, P21/c | Cu Kα radiation |
a = 17.4656 (4) Å | µ = 0.65 mm−1 |
b = 10.1883 (2) Å | T = 123 K |
c = 12.3465 (3) Å | 0.55 × 0.40 × 0.35 mm |
β = 106.806 (2)° |
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 = 0.804 | Rint = 0.025 |
8035 measured reflections |
R[F2 > 2σ(F2)] = 0.044 | 0 restraints |
wR(F2) = 0.125 | H atoms treated by a mixture of independent and constrained refinement |
S = 1.03 | Δρmax = 0.27 e Å−3 |
4246 reflections | Δρmin = −0.23 e Å−3 |
271 parameters |
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. |
x | y | z | Uiso*/Ueq | ||
O1 | 0.80036 (6) | 0.10674 (11) | 0.14843 (8) | 0.0291 (2) | |
O2 | 0.50682 (7) | 0.45404 (15) | 0.20829 (11) | 0.0444 (3) | |
O3 | 0.53584 (6) | 0.31811 (11) | 0.08329 (9) | 0.0281 (2) | |
N1 | 0.74838 (7) | 0.40267 (13) | 0.41035 (10) | 0.0250 (3) | |
N2 | 0.70297 (7) | 0.49919 (13) | −0.07455 (10) | 0.0254 (3) | |
C1 | 0.79738 (8) | 0.31973 (14) | 0.37441 (11) | 0.0235 (3) | |
C2 | 0.87530 (9) | 0.28770 (16) | 0.46042 (12) | 0.0289 (3) | |
H2A | 0.8662 | 0.2185 | 0.5116 | 0.035* | |
H2B | 0.8952 | 0.3668 | 0.5066 | 0.035* | |
C3 | 0.93922 (9) | 0.24060 (16) | 0.40645 (12) | 0.0301 (3) | |
C4 | 0.90135 (9) | 0.13072 (16) | 0.32375 (13) | 0.0312 (3) | |
H4A | 0.9397 | 0.1037 | 0.2825 | 0.037* | |
H4B | 0.8921 | 0.0540 | 0.3675 | 0.037* | |
C5 | 0.82268 (8) | 0.16811 (14) | 0.23802 (11) | 0.0240 (3) | |
C6 | 0.77439 (8) | 0.26933 (14) | 0.26782 (11) | 0.0221 (3) | |
C7 | 0.69728 (8) | 0.31300 (14) | 0.18198 (11) | 0.0218 (3) | |
H7A | 0.6704 | 0.2333 | 0.1409 | 0.026* | |
C8 | 0.64109 (8) | 0.37442 (14) | 0.24284 (11) | 0.0232 (3) | |
C9 | 0.66851 (8) | 0.42081 (14) | 0.34996 (12) | 0.0242 (3) | |
C10 | 0.71174 (8) | 0.40744 (14) | 0.09521 (11) | 0.0223 (3) | |
C11 | 0.75097 (8) | 0.53337 (14) | 0.11377 (12) | 0.0233 (3) | |
C12 | 0.78991 (8) | 0.60792 (15) | 0.20974 (12) | 0.0269 (3) | |
H12A | 0.7970 | 0.5736 | 0.2835 | 0.032* | |
C13 | 0.81773 (9) | 0.73194 (16) | 0.19525 (13) | 0.0308 (3) | |
H13A | 0.8438 | 0.7827 | 0.2599 | 0.037* | |
C14 | 0.80824 (9) | 0.78432 (16) | 0.08691 (14) | 0.0317 (3) | |
H14A | 0.8277 | 0.8700 | 0.0796 | 0.038* | |
C15 | 0.77111 (9) | 0.71327 (16) | −0.00918 (13) | 0.0297 (3) | |
H15A | 0.7647 | 0.7485 | −0.0825 | 0.036* | |
C16 | 0.74337 (8) | 0.58779 (15) | 0.00536 (12) | 0.0249 (3) | |
C17 | 0.68333 (8) | 0.39281 (14) | −0.01990 (11) | 0.0246 (3) | |
H17A | 0.6540 | 0.3189 | −0.0568 | 0.029* | |
C18 | 0.55550 (8) | 0.38803 (15) | 0.18007 (12) | 0.0266 (3) | |
C19 | 0.45226 (9) | 0.32978 (17) | 0.01690 (13) | 0.0317 (3) | |
H19A | 0.4382 | 0.4232 | 0.0000 | 0.038* | |
H19B | 0.4171 | 0.2937 | 0.0598 | 0.038* | |
C20 | 0.44107 (10) | 0.2548 (2) | −0.09068 (15) | 0.0436 (4) | |
H20A | 0.3850 | 0.2606 | −0.1364 | 0.065* | |
H20B | 0.4553 | 0.1626 | −0.0731 | 0.065* | |
H20C | 0.4755 | 0.2920 | −0.1330 | 0.065* | |
C21 | 0.62218 (9) | 0.49093 (17) | 0.41785 (13) | 0.0313 (3) | |
H21A | 0.5844 | 0.5522 | 0.3688 | 0.047* | |
H21B | 0.6592 | 0.5396 | 0.4796 | 0.047* | |
H21C | 0.5927 | 0.4267 | 0.4494 | 0.047* | |
C22 | 1.01088 (10) | 0.1881 (2) | 0.49980 (15) | 0.0404 (4) | |
H22A | 1.0511 | 0.1540 | 0.4659 | 0.061* | |
H22B | 0.9931 | 0.1174 | 0.5408 | 0.061* | |
H22C | 1.0342 | 0.2592 | 0.5525 | 0.061* | |
C23 | 0.96694 (10) | 0.35270 (19) | 0.34418 (15) | 0.0390 (4) | |
H23A | 1.0071 | 0.3197 | 0.3095 | 0.058* | |
H23B | 0.9904 | 0.4227 | 0.3980 | 0.058* | |
H23C | 0.9211 | 0.3874 | 0.2852 | 0.058* | |
C24 | 0.67642 (9) | 0.52313 (17) | −0.19626 (12) | 0.0307 (3) | |
H24A | 0.6508 | 0.4438 | −0.2354 | 0.046* | |
H24B | 0.7226 | 0.5459 | −0.2225 | 0.046* | |
H24C | 0.6380 | 0.5958 | −0.2126 | 0.046* | |
H1N | 0.7596 (11) | 0.414 (2) | 0.4823 (17) | 0.033 (5)* |
U11 | U22 | U33 | U12 | U13 | U23 | |
O1 | 0.0361 (5) | 0.0295 (6) | 0.0207 (5) | 0.0038 (4) | 0.0064 (4) | −0.0004 (4) |
O2 | 0.0284 (6) | 0.0622 (9) | 0.0387 (6) | 0.0099 (6) | 0.0033 (5) | −0.0156 (6) |
O3 | 0.0226 (5) | 0.0304 (5) | 0.0266 (5) | 0.0016 (4) | −0.0001 (4) | −0.0026 (4) |
N1 | 0.0275 (6) | 0.0286 (6) | 0.0166 (5) | 0.0006 (5) | 0.0029 (4) | −0.0013 (5) |
N2 | 0.0297 (6) | 0.0276 (6) | 0.0183 (5) | 0.0048 (5) | 0.0058 (4) | 0.0028 (5) |
C1 | 0.0251 (6) | 0.0241 (7) | 0.0198 (6) | −0.0004 (5) | 0.0040 (5) | 0.0022 (5) |
C2 | 0.0279 (7) | 0.0352 (8) | 0.0196 (6) | 0.0020 (6) | 0.0007 (5) | 0.0001 (6) |
C3 | 0.0255 (7) | 0.0353 (8) | 0.0253 (7) | 0.0036 (6) | 0.0007 (6) | 0.0006 (6) |
C4 | 0.0301 (7) | 0.0331 (8) | 0.0273 (7) | 0.0089 (6) | 0.0034 (6) | 0.0000 (6) |
C5 | 0.0277 (7) | 0.0246 (7) | 0.0193 (6) | 0.0008 (5) | 0.0060 (5) | 0.0028 (5) |
C6 | 0.0231 (6) | 0.0229 (6) | 0.0187 (6) | 0.0008 (5) | 0.0033 (5) | 0.0023 (5) |
C7 | 0.0238 (6) | 0.0218 (6) | 0.0174 (6) | −0.0001 (5) | 0.0020 (5) | 0.0005 (5) |
C8 | 0.0246 (7) | 0.0232 (7) | 0.0209 (6) | 0.0010 (5) | 0.0050 (5) | 0.0025 (5) |
C9 | 0.0261 (7) | 0.0233 (7) | 0.0230 (6) | −0.0003 (5) | 0.0064 (5) | 0.0015 (5) |
C10 | 0.0234 (6) | 0.0226 (7) | 0.0192 (6) | 0.0032 (5) | 0.0036 (5) | 0.0003 (5) |
C11 | 0.0234 (6) | 0.0236 (7) | 0.0226 (6) | 0.0037 (5) | 0.0063 (5) | 0.0026 (5) |
C12 | 0.0271 (7) | 0.0280 (7) | 0.0242 (6) | 0.0011 (6) | 0.0051 (5) | 0.0000 (6) |
C13 | 0.0302 (7) | 0.0283 (8) | 0.0320 (8) | −0.0017 (6) | 0.0062 (6) | −0.0036 (6) |
C14 | 0.0301 (7) | 0.0243 (7) | 0.0411 (9) | −0.0003 (6) | 0.0113 (6) | 0.0050 (6) |
C15 | 0.0302 (7) | 0.0300 (8) | 0.0303 (7) | 0.0052 (6) | 0.0113 (6) | 0.0084 (6) |
C16 | 0.0237 (6) | 0.0272 (7) | 0.0239 (7) | 0.0053 (5) | 0.0070 (5) | 0.0026 (6) |
C17 | 0.0273 (7) | 0.0239 (7) | 0.0209 (6) | 0.0036 (5) | 0.0045 (5) | 0.0001 (5) |
C18 | 0.0255 (7) | 0.0286 (7) | 0.0244 (6) | −0.0002 (6) | 0.0052 (5) | 0.0013 (6) |
C19 | 0.0220 (7) | 0.0335 (8) | 0.0334 (8) | 0.0026 (6) | −0.0019 (6) | −0.0030 (6) |
C20 | 0.0343 (8) | 0.0480 (10) | 0.0385 (9) | 0.0068 (8) | −0.0056 (7) | −0.0127 (8) |
C21 | 0.0309 (7) | 0.0358 (8) | 0.0267 (7) | 0.0018 (6) | 0.0075 (6) | −0.0048 (6) |
C22 | 0.0294 (8) | 0.0494 (10) | 0.0349 (8) | 0.0077 (7) | −0.0025 (6) | 0.0011 (8) |
C23 | 0.0295 (7) | 0.0459 (10) | 0.0399 (9) | −0.0019 (7) | 0.0074 (6) | 0.0033 (8) |
C24 | 0.0369 (8) | 0.0364 (8) | 0.0186 (6) | 0.0082 (6) | 0.0078 (6) | 0.0047 (6) |
O1—C5 | 1.2317 (18) | C10—C11 | 1.441 (2) |
O2—C18 | 1.2115 (19) | C11—C12 | 1.406 (2) |
O3—C18 | 1.3475 (18) | C11—C16 | 1.4191 (19) |
O3—C19 | 1.4578 (16) | C12—C13 | 1.384 (2) |
N1—C1 | 1.3648 (19) | C12—H12A | 0.9500 |
N1—C9 | 1.3910 (18) | C13—C14 | 1.405 (2) |
N1—H1N | 0.86 (2) | C13—H13A | 0.9500 |
N2—C17 | 1.3716 (19) | C14—C15 | 1.381 (2) |
N2—C16 | 1.3724 (19) | C14—H14A | 0.9500 |
N2—C24 | 1.4594 (17) | C15—C16 | 1.397 (2) |
C1—C6 | 1.3606 (19) | C15—H15A | 0.9500 |
C1—C2 | 1.5002 (18) | C17—H17A | 0.9500 |
C2—C3 | 1.533 (2) | C19—C20 | 1.495 (2) |
C2—H2A | 0.9900 | C19—H19A | 0.9900 |
C2—H2B | 0.9900 | C19—H19B | 0.9900 |
C3—C4 | 1.531 (2) | C20—H20A | 0.9800 |
C3—C23 | 1.531 (2) | C20—H20B | 0.9800 |
C3—C22 | 1.532 (2) | C20—H20C | 0.9800 |
C4—C5 | 1.5207 (19) | C21—H21A | 0.9800 |
C4—H4A | 0.9900 | C21—H21B | 0.9800 |
C4—H4B | 0.9900 | C21—H21C | 0.9800 |
C5—C6 | 1.446 (2) | C22—H22A | 0.9800 |
C6—C7 | 1.5197 (17) | C22—H22B | 0.9800 |
C7—C10 | 1.5146 (19) | C22—H22C | 0.9800 |
C7—C8 | 1.5315 (19) | C23—H23A | 0.9800 |
C7—H7A | 1.0000 | C23—H23B | 0.9800 |
C8—C9 | 1.355 (2) | C23—H23C | 0.9800 |
C8—C18 | 1.4781 (19) | C24—H24A | 0.9800 |
C9—C21 | 1.503 (2) | C24—H24B | 0.9800 |
C10—C17 | 1.3713 (18) | C24—H24C | 0.9800 |
C18—O3—C19 | 114.36 (11) | C12—C13—C14 | 121.39 (14) |
C1—N1—C9 | 122.27 (12) | C12—C13—H13A | 119.3 |
C1—N1—H1N | 116.4 (13) | C14—C13—H13A | 119.3 |
C9—N1—H1N | 115.4 (13) | C15—C14—C13 | 121.05 (14) |
C17—N2—C16 | 108.41 (12) | C15—C14—H14A | 119.5 |
C17—N2—C24 | 126.04 (13) | C13—C14—H14A | 119.5 |
C16—N2—C24 | 125.07 (13) | C14—C15—C16 | 117.61 (14) |
C6—C1—N1 | 120.71 (12) | C14—C15—H15A | 121.2 |
C6—C1—C2 | 123.79 (13) | C16—C15—H15A | 121.2 |
N1—C1—C2 | 115.48 (12) | N2—C16—C15 | 129.41 (13) |
C1—C2—C3 | 112.70 (12) | N2—C16—C11 | 108.03 (13) |
C1—C2—H2A | 109.1 | C15—C16—C11 | 122.51 (14) |
C3—C2—H2A | 109.1 | C10—C17—N2 | 110.91 (13) |
C1—C2—H2B | 109.1 | C10—C17—H17A | 124.5 |
C3—C2—H2B | 109.1 | N2—C17—H17A | 124.5 |
H2A—C2—H2B | 107.8 | O2—C18—O3 | 121.90 (13) |
C4—C3—C23 | 110.43 (13) | O2—C18—C8 | 126.06 (14) |
C4—C3—C22 | 110.36 (14) | O3—C18—C8 | 112.03 (12) |
C23—C3—C22 | 109.28 (14) | O3—C19—C20 | 108.07 (12) |
C4—C3—C2 | 106.87 (12) | O3—C19—H19A | 110.1 |
C23—C3—C2 | 111.12 (14) | C20—C19—H19A | 110.1 |
C22—C3—C2 | 108.75 (13) | O3—C19—H19B | 110.1 |
C5—C4—C3 | 114.23 (13) | C20—C19—H19B | 110.1 |
C5—C4—H4A | 108.7 | H19A—C19—H19B | 108.4 |
C3—C4—H4A | 108.7 | C19—C20—H20A | 109.5 |
C5—C4—H4B | 108.7 | C19—C20—H20B | 109.5 |
C3—C4—H4B | 108.7 | H20A—C20—H20B | 109.5 |
H4A—C4—H4B | 107.6 | C19—C20—H20C | 109.5 |
O1—C5—C6 | 122.29 (13) | H20A—C20—H20C | 109.5 |
O1—C5—C4 | 119.05 (13) | H20B—C20—H20C | 109.5 |
C6—C5—C4 | 118.54 (12) | C9—C21—H21A | 109.5 |
C1—C6—C5 | 118.99 (12) | C9—C21—H21B | 109.5 |
C1—C6—C7 | 121.21 (13) | H21A—C21—H21B | 109.5 |
C5—C6—C7 | 119.73 (12) | C9—C21—H21C | 109.5 |
C10—C7—C6 | 112.57 (11) | H21A—C21—H21C | 109.5 |
C10—C7—C8 | 110.43 (11) | H21B—C21—H21C | 109.5 |
C6—C7—C8 | 109.99 (11) | C3—C22—H22A | 109.5 |
C10—C7—H7A | 107.9 | C3—C22—H22B | 109.5 |
C6—C7—H7A | 107.9 | H22A—C22—H22B | 109.5 |
C8—C7—H7A | 107.9 | C3—C22—H22C | 109.5 |
C9—C8—C18 | 119.84 (13) | H22A—C22—H22C | 109.5 |
C9—C8—C7 | 121.71 (12) | H22B—C22—H22C | 109.5 |
C18—C8—C7 | 118.39 (12) | C3—C23—H23A | 109.5 |
C8—C9—N1 | 119.58 (13) | C3—C23—H23B | 109.5 |
C8—C9—C21 | 127.93 (13) | H23A—C23—H23B | 109.5 |
N1—C9—C21 | 112.48 (12) | C3—C23—H23C | 109.5 |
C17—C10—C11 | 105.93 (12) | H23A—C23—H23C | 109.5 |
C17—C10—C7 | 125.43 (13) | H23B—C23—H23C | 109.5 |
C11—C10—C7 | 128.46 (12) | N2—C24—H24A | 109.5 |
C12—C11—C16 | 118.31 (13) | N2—C24—H24B | 109.5 |
C12—C11—C10 | 134.96 (13) | H24A—C24—H24B | 109.5 |
C16—C11—C10 | 106.70 (12) | N2—C24—H24C | 109.5 |
C13—C12—C11 | 119.12 (14) | H24A—C24—H24C | 109.5 |
C13—C12—H12A | 120.4 | H24B—C24—H24C | 109.5 |
C11—C12—H12A | 120.4 | ||
C9—N1—C1—C6 | 12.1 (2) | C6—C7—C10—C17 | 126.79 (14) |
C9—N1—C1—C2 | −166.63 (13) | C8—C7—C10—C17 | −109.86 (15) |
C6—C1—C2—C3 | 23.2 (2) | C6—C7—C10—C11 | −58.89 (18) |
N1—C1—C2—C3 | −158.12 (13) | C8—C7—C10—C11 | 64.47 (17) |
C1—C2—C3—C4 | −51.15 (17) | C17—C10—C11—C12 | 177.98 (16) |
C1—C2—C3—C23 | 69.39 (17) | C7—C10—C11—C12 | 2.8 (3) |
C1—C2—C3—C22 | −170.29 (14) | C17—C10—C11—C16 | −0.02 (15) |
C23—C3—C4—C5 | −67.55 (17) | C7—C10—C11—C16 | −175.22 (13) |
C22—C3—C4—C5 | 171.52 (13) | C16—C11—C12—C13 | 1.4 (2) |
C2—C3—C4—C5 | 53.44 (17) | C10—C11—C12—C13 | −176.46 (15) |
C3—C4—C5—O1 | 157.14 (14) | C11—C12—C13—C14 | −0.3 (2) |
C3—C4—C5—C6 | −26.6 (2) | C12—C13—C14—C15 | −0.4 (2) |
N1—C1—C6—C5 | −171.47 (13) | C13—C14—C15—C16 | 0.1 (2) |
C2—C1—C6—C5 | 7.2 (2) | C17—N2—C16—C15 | −175.84 (14) |
N1—C1—C6—C7 | 5.7 (2) | C24—N2—C16—C15 | −3.4 (2) |
C2—C1—C6—C7 | −175.67 (13) | C17—N2—C16—C11 | 1.48 (15) |
O1—C5—C6—C1 | 170.63 (13) | C24—N2—C16—C11 | 173.94 (13) |
C4—C5—C6—C1 | −5.5 (2) | C14—C15—C16—N2 | 178.00 (14) |
O1—C5—C6—C7 | −6.6 (2) | C14—C15—C16—C11 | 1.0 (2) |
C4—C5—C6—C7 | 177.32 (13) | C12—C11—C16—N2 | −179.29 (12) |
C1—C6—C7—C10 | 103.36 (15) | C10—C11—C16—N2 | −0.90 (15) |
C5—C6—C7—C10 | −79.50 (16) | C12—C11—C16—C15 | −1.7 (2) |
C1—C6—C7—C8 | −20.24 (19) | C10—C11—C16—C15 | 176.65 (13) |
C5—C6—C7—C8 | 156.90 (12) | C11—C10—C17—N2 | 0.95 (16) |
C10—C7—C8—C9 | −104.62 (15) | C7—C10—C17—N2 | 176.33 (12) |
C6—C7—C8—C9 | 20.22 (19) | C16—N2—C17—C10 | −1.55 (16) |
C10—C7—C8—C18 | 72.63 (16) | C24—N2—C17—C10 | −173.91 (13) |
C6—C7—C8—C18 | −162.53 (12) | C19—O3—C18—O2 | 0.3 (2) |
C18—C8—C9—N1 | 177.22 (13) | C19—O3—C18—C8 | −178.99 (12) |
C7—C8—C9—N1 | −5.6 (2) | C9—C8—C18—O2 | 11.2 (2) |
C18—C8—C9—C21 | −1.5 (2) | C7—C8—C18—O2 | −166.16 (16) |
C7—C8—C9—C21 | 175.75 (14) | C9—C8—C18—O3 | −169.60 (13) |
C1—N1—C9—C8 | −12.1 (2) | C7—C8—C18—O3 | 13.10 (18) |
C1—N1—C9—C21 | 166.76 (13) | C18—O3—C19—C20 | 176.22 (14) |
D—H···A | D—H | H···A | D···A | D—H···A |
C21—H21A···O2 | 0.98 | 2.28 | 2.8073 (19) | 113 |
N1—H1N···O1i | 0.86 (2) | 1.98 (2) | 2.8161 (15) | 163.9 (19) |
C24—H24C···O2ii | 0.98 | 2.60 | 3.1693 (19) | 118 |
Symmetry codes: (i) x, −y+1/2, z+1/2; (ii) −x+1, −y+1, −z. |
Experimental details
Crystal data | |
Chemical formula | C24H28N2O3 |
Mr | 392.48 |
Crystal system, space group | Monoclinic, P21/c |
Temperature (K) | 123 |
a, b, c (Å) | 17.4656 (4), 10.1883 (2), 12.3465 (3) |
β (°) | 106.806 (2) |
V (Å3) | 2103.16 (8) |
Z | 4 |
Radiation type | Cu Kα |
µ (mm−1) | 0.65 |
Crystal size (mm) | 0.55 × 0.40 × 0.35 |
Data collection | |
Diffractometer | Agilent Xcalibur (Ruby, Gemini) |
Absorption correction | Multi-scan [CrysAlis RED (Agilent, 2011), based on expressions derived from Clark & Reid (1995)] |
Tmin, Tmax | 0.715, 0.804 |
No. of measured, independent and observed [I > 2σ(I)] reflections | 8035, 4246, 3533 |
Rint | 0.025 |
(sin θ/λ)max (Å−1) | 0.629 |
Refinement | |
R[F2 > 2σ(F2)], wR(F2), S | 0.044, 0.125, 1.03 |
No. of reflections | 4246 |
No. of parameters | 271 |
H-atom treatment | H atoms treated by a mixture of independent and constrained refinement |
Δρmax, Δρmin (e Å−3) | 0.27, −0.23 |
Computer programs: CrysAlis PRO (Agilent, 2011), SHELXS97 (Sheldrick, 2008), SHELXL97 (Sheldrick, 2008), SHELXTL (Sheldrick, 2008).
D—H···A | D—H | H···A | D···A | D—H···A |
C21—H21A···O2 | 0.98 | 2.28 | 2.8073 (19) | 112.5 |
N1—H1N···O1i | 0.86 (2) | 1.98 (2) | 2.8161 (15) | 163.9 (19) |
C24—H24C···O2ii | 0.98 | 2.60 | 3.1693 (19) | 117.5 |
Symmetry codes: (i) x, −y+1/2, z+1/2; (ii) −x+1, −y+1, −z. |
Acknowledgements
RJB acknowledges the NSF–MRI program (grant No. CHE-0619278) for funds to purchase the diffractometer.
References
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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.
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.