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Acta Cryst. (2010). E66, o587-o588    [ doi:10.1107/S1600536810004940 ]

Dimethyl 1,4-dihydro-4-(4-methoxyphenyl)-2,6-dimethylpyridine-3,5-dicarboxylate

W.-S. Loh, H.-K. Fun, B. P. Reddy, V. Vijayakumar and S. Sarveswari

Abstract top

In the title compound, C18H21NO5, the dihydropyridine ring adopts a flattened-boat conformation and its planar part forms a dihedral angle of 84.60 (2)° with the benzene ring. In the crystal, intermolecular N-H...O and C-H...O hydrogen bonds result in the formation of zigzag layers parallel to (001). These layers are interconnected via C-H...[pi] interactions.

Comment top

Hantzsch 1,4-dihydropyridines (1,4-DHPS) are biologically active compounds which include various vasodilator, antihypertensive, bronchodilator, heptaprotective, antitumor, antimutagenic, geroprotective and antidiabetic agents (Gaudio et al., 1994). Nifedipine, nitrendipine and nimodipine have been used commercially as calcium channel blockers (Bocker & Guengerich, 1986; Gordeev et al., 1996). For the treatment of congestive heart failure a number of DHP calcium antagonists have been introduced (Sunkel et al., 1992; Vo et al., 1995). Some DHPs have also been introduced as neuroprotectant and cognition enhancers. In addition, a number of DHPs with platelet anti-aggregatory activity have also been discovered (Cooper et al., 1992).

In the title compound (Fig. 1), the 1,4-dihydropyridine ring (C7–C11/N1) adopts a flattened-boat conformation with puckering parameter Q = 0.2368 (9) Å; Θ = 72.8 (2)° and φ = 186.1 (2)° (Cremer & Pople, 1975). The C8–C11 plane forms a dihedral angle of 84.60 (2)° with the C1–C6 benzene ring. Bond lengths (Allen et al., 1987) and angles are within the normal range and are comparable to those in closely related structures (Fun et al., 2009a,b).

In the crystal packing (Fig. 2), intermolecular N1—H1N1···O4 and C18—H18B···O4 hydrogen bonds (Table 1) link pairs of neighbouring molecules to form chains along the [100] direction; the chains contain R21(6) ring motifs (Bernstein et al., 1995). Intermolecular C14—H14A···O1 hydrogen bonds further interconnect these chains together to form zigzag layers parallel to the (001). The crystal structure is further stabilized by C—H···π interactions involving the C1–C6 benzene ring (centroid Cg1).

Related literature top

For the synthesis, see: Rathore et al. (2009). For general background and applications of 1,4-dihydropyridine derivatives, see: Bocker & Guengerich (1986); Cooper et al. (1992); Gaudio et al. (1994); Gordeev et al. (1996); Sunkel et al. (1992); Vo et al. (1995). For ring conformations, see: Cremer & Pople (1975). For bond-length data, see: Allen et al. (1987). For related structures, see: Fun et al. (2009a,b). For hydrogen-bond motifs, see: Bernstein et al. (1995). For the stability of the temperature controller used for the data collection, see: Cosier & Glazer (1986).

Experimental top

Dimethyl 1,4-dihydro-2,6-dimethyl-4-(4-methoxyphenyl)-3,5-pyridine dicarboxylate was prepared according to the Hantzsch pyridine synthesis (Rathore et al., 2009). A mixture of 4-methoxybenzaldehyde (10.0 mmol), methylacetoacetate (20.0 mmol) and ammonium acetate (10.0 mmol) was heated at 353 K for 2 h (monitored by TLC). After the completion of the reaction, the mixture was cooled to room temperature and it was kept for 24 h to get a solid product. The solid formed was washed using diethyl ether. The washed solid was collected separately and the liquid kept for solidification. The purity of the crude product was checked through TLC and recrystallized using acetone and ether.

Refinement top

Atom H1N1 was located in a difference Fourier map and was refined freely [N–H = 0.854 (18) Å]. The remaining H atoms were positioned geometrically [C–H = 0.93–0.98 Å] and were refined using a riding model, with Uiso(H) = 1.2-1.5 Ueq(C). A rotating-group model was applied for the methyl groups. Reflection 010 was partially obscured by the beam stop and hence was omitted. In addition, the most disagreeable reflections 114, 414 amd 248 were also omitted during the refinement.

Computing details top

Data collection: APEX DUO (Bruker, 2009); cell refinement: SAINT (Bruker, 2009); data reduction: SAINT (Bruker, 2009); program(s) used to solve structure: SHELXTL (Sheldrick, 2008); program(s) used to refine structure: SHELXTL (Sheldrick, 2008); molecular graphics: SHELXTL (Sheldrick, 2008); software used to prepare material for publication: SHELXTL (Sheldrick, 2008) and PLATON (Spek, 2009).

Figures top
[Figure 1] Fig. 1. The molecular structure of the title compound, showing 50% probability displacement ellipsoids and the atom-numbering scheme.
[Figure 2] Fig. 2. The crystal packing of the title compound, viewed approximately along the c axis, showing R12(6) ring motifs. H atoms not involved in hydrogen bonding (dashed lines) have been omitted for clarity.
Dimethyl 1,4-dihydro-4-(4-methoxyphenyl)-2,6-dimethylpyridine-3,5-dicarboxylate top
Crystal data top
C18H21NO5Z = 2
Mr = 331.36F(000) = 352
Triclinic, P1Dx = 1.365 Mg m−3
Hall symbol: -P 1Mo Kα radiation, λ = 0.71073 Å
a = 7.4106 (3) ÅCell parameters from 9874 reflections
b = 9.5715 (5) Åθ = 2.8–37.5°
c = 11.7771 (6) ŵ = 0.10 mm−1
α = 83.029 (1)°T = 100 K
β = 83.834 (1)°Block, colourless
γ = 77.424 (1)°0.35 × 0.34 × 0.24 mm
V = 806.46 (7) Å3
Data collection top
Bruker SMART APEX DUO CCD area-detector
diffractometer		4664 independent reflections
Radiation source: fine-focus sealed tube4319 reflections with I > 2σ(I)
graphiteRint = 0.019
φ and ω scansθmax = 30.0°, θmin = 2.7°
Absorption correction: multi-scan
(SADABS; Bruker, 2009)		h = −10→10
Tmin = 0.966, Tmax = 0.976k = −13→13
19600 measured reflectionsl = −15→16
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)] = 0.037Hydrogen site location: inferred from neighbouring sites
wR(F2) = 0.110H atoms treated by a mixture of independent and constrained refinement
S = 1.05 w = 1/[σ2(Fo2) + (0.0628P)2 + 0.2437P]
where P = (Fo2 + 2Fc2)/3
4664 reflections(Δ/σ)max = 0.001
226 parametersΔρmax = 0.48 e Å−3
0 restraintsΔρmin = −0.22 e Å−3
Crystal data top
C18H21NO5γ = 77.424 (1)°
Mr = 331.36V = 806.46 (7) Å3
Triclinic, P1Z = 2
a = 7.4106 (3) ÅMo Kα radiation
b = 9.5715 (5) ŵ = 0.10 mm−1
c = 11.7771 (6) ÅT = 100 K
α = 83.029 (1)°0.35 × 0.34 × 0.24 mm
β = 83.834 (1)°
Data collection top
Bruker SMART APEX DUO CCD area-detector
diffractometer		4664 independent reflections
Absorption correction: multi-scan
(SADABS; Bruker, 2009)		4319 reflections with I > 2σ(I)
Tmin = 0.966, Tmax = 0.976Rint = 0.019
19600 measured reflectionsθmax = 30.0°
Refinement top
R[F2 > 2σ(F2)] = 0.037H atoms treated by a mixture of independent and constrained refinement
wR(F2) = 0.110Δρmax = 0.48 e Å−3
S = 1.05Δρmin = −0.22 e Å−3
4664 reflectionsAbsolute structure: ?
226 parametersFlack parameter: ?
0 restraintsRogers parameter: ?
Special details top

Experimental. The crystal was placed in the cold stream of an Oxford Cryosystems Cobra open-flow nitrogen cryostat (Cosier & Glazer, 1986) operating at 100.0 (1) K.

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

Refinement. 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
O10.19666 (9)0.64176 (7)0.02070 (6)0.01872 (14)
O20.45751 (9)−0.03547 (8)0.19907 (6)0.02053 (15)
O30.76827 (9)−0.08374 (7)0.16829 (6)0.01754 (14)
O40.13686 (9)0.26414 (7)0.49736 (6)0.01760 (14)
O50.29405 (9)0.35204 (8)0.61485 (6)0.01934 (14)
N10.78947 (10)0.17746 (8)0.42720 (6)0.01437 (14)
C10.22940 (12)0.30263 (9)0.19929 (7)0.01528 (16)
H1A0.16360.22910.21320.018*
C20.17064 (12)0.41859 (9)0.11955 (7)0.01588 (16)
H2A0.06670.42210.08060.019*
C30.26760 (11)0.52967 (9)0.09799 (7)0.01404 (16)
C40.42555 (12)0.52171 (9)0.15453 (8)0.01685 (17)
H4A0.49300.59420.13930.020*
C50.48191 (12)0.40434 (9)0.23414 (8)0.01621 (17)
H5A0.58750.39970.27180.019*
C60.38473 (11)0.29392 (9)0.25892 (7)0.01226 (15)
C70.44663 (11)0.16962 (9)0.34963 (7)0.01211 (15)
H7A0.35130.11140.36310.015*
C80.62773 (11)0.07428 (8)0.30836 (7)0.01266 (15)
C90.79129 (11)0.08547 (9)0.34450 (7)0.01310 (15)
C100.63106 (11)0.23953 (9)0.49133 (7)0.01351 (15)
C110.46306 (11)0.22785 (9)0.46145 (7)0.01275 (15)
C120.28140 (14)0.76387 (10)0.00644 (9)0.02215 (19)
H12A0.21510.8376−0.04550.033*
H12B0.40790.7363−0.02430.033*
H12C0.27820.79980.07940.033*
C130.60706 (12)−0.01947 (9)0.22266 (7)0.01414 (16)
C140.74903 (14)−0.16612 (11)0.07708 (9)0.02279 (19)
H14A0.8698−0.20910.04440.034*
H14B0.6814−0.10380.01880.034*
H14C0.6831−0.24030.10730.034*
C150.28484 (11)0.28084 (9)0.52454 (7)0.01380 (16)
C160.11938 (13)0.41561 (11)0.67270 (8)0.02036 (18)
H16A0.14160.46590.73380.031*
H16B0.05400.34140.70370.031*
H16C0.04620.48190.61910.031*
C170.98251 (11)0.00466 (9)0.30817 (8)0.01614 (16)
H17A0.9862−0.09690.32060.024*
H17B1.07120.02810.35260.024*
H17C1.01220.03120.22820.024*
C180.67039 (12)0.31346 (10)0.58865 (8)0.01716 (17)
H18A0.59850.41010.58480.026*
H18B0.80000.31560.58300.026*
H18C0.63790.26190.66040.026*
H1N10.895 (2)0.1892 (17)0.4467 (13)0.030 (4)*
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
O10.0186 (3)0.0164 (3)0.0206 (3)−0.0040 (2)−0.0063 (2)0.0048 (2)
O20.0147 (3)0.0233 (3)0.0262 (3)−0.0051 (2)−0.0037 (2)−0.0088 (3)
O30.0143 (3)0.0177 (3)0.0218 (3)−0.0029 (2)−0.0008 (2)−0.0080 (2)
O40.0111 (3)0.0237 (3)0.0187 (3)−0.0042 (2)−0.0016 (2)−0.0036 (2)
O50.0127 (3)0.0272 (3)0.0193 (3)−0.0035 (2)0.0003 (2)−0.0099 (3)
N10.0095 (3)0.0180 (3)0.0168 (3)−0.0037 (2)−0.0026 (2)−0.0036 (3)
C10.0140 (4)0.0160 (4)0.0171 (4)−0.0055 (3)−0.0041 (3)0.0002 (3)
C20.0139 (4)0.0177 (4)0.0168 (4)−0.0039 (3)−0.0055 (3)0.0001 (3)
C30.0140 (3)0.0141 (3)0.0131 (3)−0.0013 (3)−0.0014 (3)−0.0005 (3)
C40.0166 (4)0.0161 (4)0.0192 (4)−0.0068 (3)−0.0043 (3)0.0015 (3)
C50.0140 (4)0.0178 (4)0.0182 (4)−0.0056 (3)−0.0057 (3)0.0009 (3)
C60.0111 (3)0.0132 (3)0.0125 (3)−0.0021 (3)−0.0014 (3)−0.0017 (3)
C70.0098 (3)0.0135 (3)0.0133 (3)−0.0027 (3)−0.0021 (3)−0.0010 (3)
C80.0117 (3)0.0119 (3)0.0144 (3)−0.0025 (3)−0.0016 (3)−0.0010 (3)
C90.0120 (3)0.0126 (3)0.0146 (3)−0.0029 (3)−0.0010 (3)−0.0003 (3)
C100.0124 (4)0.0148 (3)0.0134 (3)−0.0028 (3)−0.0021 (3)−0.0006 (3)
C110.0109 (3)0.0146 (3)0.0128 (3)−0.0028 (3)−0.0012 (3)−0.0010 (3)
C120.0258 (5)0.0168 (4)0.0238 (4)−0.0066 (3)−0.0043 (3)0.0043 (3)
C130.0141 (4)0.0123 (3)0.0161 (4)−0.0030 (3)−0.0017 (3)−0.0006 (3)
C140.0205 (4)0.0232 (4)0.0270 (5)−0.0042 (3)−0.0016 (3)−0.0131 (4)
C150.0131 (3)0.0148 (3)0.0132 (3)−0.0028 (3)−0.0013 (3)0.0000 (3)
C160.0149 (4)0.0243 (4)0.0218 (4)−0.0022 (3)0.0021 (3)−0.0087 (3)
C170.0101 (3)0.0161 (4)0.0223 (4)−0.0023 (3)−0.0014 (3)−0.0030 (3)
C180.0132 (4)0.0221 (4)0.0178 (4)−0.0038 (3)−0.0037 (3)−0.0059 (3)
Geometric parameters (Å, °) top
O1—C31.3697 (10)C7—C81.5180 (11)
O1—C121.4276 (11)C7—H7A0.98
O2—C131.2163 (10)C8—C91.3565 (11)
O3—C131.3516 (10)C8—C131.4698 (11)
O3—C141.4433 (11)C9—C171.5040 (11)
O4—C151.2226 (10)C10—C111.3603 (11)
O5—C151.3461 (10)C10—C181.5026 (11)
O5—C161.4416 (11)C11—C151.4637 (11)
N1—C101.3843 (10)C12—H12A0.96
N1—C91.3872 (11)C12—H12B0.96
N1—H1N10.871 (16)C12—H12C0.96
C1—C21.3885 (11)C14—H14A0.96
C1—C61.3938 (11)C14—H14B0.96
C1—H1A0.93C14—H14C0.96
C2—C31.3925 (12)C16—H16A0.96
C2—H2A0.93C16—H16B0.96
C3—C41.3912 (12)C16—H16C0.96
C4—C51.3928 (11)C17—H17A0.96
C4—H4A0.93C17—H17B0.96
C5—C61.3901 (11)C17—H17C0.96
C5—H5A0.93C18—H18A0.96
C6—C71.5252 (11)C18—H18B0.96
C7—C111.5172 (11)C18—H18C0.96
C3—O1—C12116.97 (7)C10—C11—C15124.91 (8)
C13—O3—C14115.18 (7)C10—C11—C7120.70 (7)
C15—O5—C16116.31 (7)C15—C11—C7114.13 (7)
C10—N1—C9124.03 (7)O1—C12—H12A109.5
C10—N1—H1N1116.8 (10)O1—C12—H12B109.5
C9—N1—H1N1118.7 (10)H12A—C12—H12B109.5
C2—C1—C6121.53 (8)O1—C12—H12C109.5
C2—C1—H1A119.2H12A—C12—H12C109.5
C6—C1—H1A119.2H12B—C12—H12C109.5
C1—C2—C3119.85 (8)O2—C13—O3121.96 (8)
C1—C2—H2A120.1O2—C13—C8123.36 (8)
C3—C2—H2A120.1O3—C13—C8114.65 (7)
O1—C3—C4124.45 (8)O3—C14—H14A109.5
O1—C3—C2115.92 (7)O3—C14—H14B109.5
C4—C3—C2119.63 (8)H14A—C14—H14B109.5
C3—C4—C5119.49 (8)O3—C14—H14C109.5
C3—C4—H4A120.3H14A—C14—H14C109.5
C5—C4—H4A120.3H14B—C14—H14C109.5
C6—C5—C4121.82 (8)O4—C15—O5121.67 (8)
C6—C5—H5A119.1O4—C15—C11123.13 (8)
C4—C5—H5A119.1O5—C15—C11115.20 (7)
C5—C6—C1117.64 (7)O5—C16—H16A109.5
C5—C6—C7120.39 (7)O5—C16—H16B109.5
C1—C6—C7121.96 (7)H16A—C16—H16B109.5
C11—C7—C8111.44 (6)O5—C16—H16C109.5
C11—C7—C6109.82 (6)H16A—C16—H16C109.5
C8—C7—C6110.88 (6)H16B—C16—H16C109.5
C11—C7—H7A108.2C9—C17—H17A109.5
C8—C7—H7A108.2C9—C17—H17B109.5
C6—C7—H7A108.2H17A—C17—H17B109.5
C9—C8—C13125.21 (7)C9—C17—H17C109.5
C9—C8—C7120.89 (7)H17A—C17—H17C109.5
C13—C8—C7113.77 (7)H17B—C17—H17C109.5
C8—C9—N1118.88 (7)C10—C18—H18A109.5
C8—C9—C17127.61 (8)C10—C18—H18B109.5
N1—C9—C17113.47 (7)H18A—C18—H18B109.5
C11—C10—N1118.71 (7)C10—C18—H18C109.5
C11—C10—C18127.85 (8)H18A—C18—H18C109.5
N1—C10—C18113.43 (7)H18B—C18—H18C109.5
C6—C1—C2—C3−0.14 (13)C10—N1—C9—C812.37 (12)
C12—O1—C3—C4−6.29 (13)C10—N1—C9—C17−165.74 (7)
C12—O1—C3—C2173.39 (8)C9—N1—C10—C11−10.00 (12)
C1—C2—C3—O1−178.08 (8)C9—N1—C10—C18169.89 (7)
C1—C2—C3—C41.62 (13)N1—C10—C11—C15176.50 (7)
O1—C3—C4—C5178.06 (8)C18—C10—C11—C15−3.38 (14)
C2—C3—C4—C5−1.60 (13)N1—C10—C11—C7−9.74 (12)
C3—C4—C5—C60.12 (14)C18—C10—C11—C7170.39 (8)
C4—C5—C6—C11.32 (13)C8—C7—C11—C1024.10 (10)
C4—C5—C6—C7−177.87 (8)C6—C7—C11—C10−99.17 (9)
C2—C1—C6—C5−1.31 (13)C8—C7—C11—C15−161.50 (7)
C2—C1—C6—C7177.87 (8)C6—C7—C11—C1575.23 (8)
C5—C6—C7—C1153.55 (10)C14—O3—C13—O22.95 (12)
C1—C6—C7—C11−125.60 (8)C14—O3—C13—C8−174.88 (7)
C5—C6—C7—C8−70.05 (10)C9—C8—C13—O2173.87 (8)
C1—C6—C7—C8110.80 (9)C7—C8—C13—O2−10.26 (12)
C11—C7—C8—C9−21.76 (10)C9—C8—C13—O3−8.34 (12)
C6—C7—C8—C9100.90 (9)C7—C8—C13—O3167.53 (7)
C11—C7—C8—C13162.17 (7)C16—O5—C15—O4−4.05 (12)
C6—C7—C8—C13−75.16 (8)C16—O5—C15—C11175.05 (7)
C13—C8—C9—N1−179.23 (7)C10—C11—C15—O4−177.44 (8)
C7—C8—C9—N15.17 (12)C7—C11—C15—O48.43 (11)
C13—C8—C9—C17−1.42 (14)C10—C11—C15—O53.48 (12)
C7—C8—C9—C17−177.01 (8)C7—C11—C15—O5−170.65 (7)
Hydrogen-bond geometry (Å, °) top
Cg1 is the centroid of the C1–C6 ring.
D—H···AD—HH···AD···AD—H···A
N1—H1N1···O4i0.87 (2)2.23 (2)3.0906 (10)169 (1)
C14—H14A···O1ii0.962.543.4631 (13)162
C18—H18B···O4i0.962.563.4558 (12)156
C12—H12B···Cg1iii0.962.793.6549 (11)151
Symmetry codes: (i) x+1, y, z; (ii) x+1, y−1, z; (iii) −x+1, −y+1, −z.
Table 1
Hydrogen-bond geometry (Å, °) top
Cg1 is the centroid of the C1–C6 ring.
D—H···AD—HH···AD···AD—H···A
N1—H1N1···O4i0.87 (2)2.23 (2)3.0906 (10)169 (1)
C14—H14A···O1ii0.962.543.4631 (13)162
C18—H18B···O4i0.962.563.4558 (12)156
C12—H12B···Cg1iii0.962.793.6549 (11)151
Symmetry codes: (i) x+1, y, z; (ii) x+1, y−1, z; (iii) −x+1, −y+1, −z.
Acknowledgements top

HKF and WSL thank Universiti Sains Malaysia (USM) for the Research University Golden Goose Grant (No. 1001/PFIZIK/811012). WSL thanks the Malaysian Government and USM for the award of a Research Fellowship. VV is grateful to the DST-India for funding through the Young Scientist Scheme (Fast Track Proposal).

references
References top

Allen, F. H., Kennard, O., Watson, D. G., Brammer, L., Orpen, A. G. & Taylor, R. (1987). J. Chem. Soc. Perkin Trans. 2, pp. S1–19.

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

Bocker, R. H. & Guengerich, F. P. (1986). J. Med. Chem. 28, 1596–1603.

Bruker (2009). APEX DUO, SAINT and SADABS. Bruker AXS Inc., Madison, Wisconsin, USA.

Cooper, K., Fray, M. J., Parry, M. J., Richardson, K. & Steele, J. (1992). J. Med. Chem. 35, 3115–3129.

Cosier, J. & Glazer, A. M. (1986). J. Appl. Cryst. 19, 105–107.

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

Fun, H.-K., Goh, J. H., Reddy, B. P., Sarveswari, S. & Vijayakumar, V. (2009a). Acta Cryst. E65, o2247–o2248.

Fun, H.-K., Quah, C. K., Reddy, B. P., Sarveswari, S. & Vijayakumar, V. (2009b). Acta Cryst. E65, o2255–o2256.

Gaudio, A. C., Korolkovas, A. & Takahata, Y. (1994). J. Pharm. Sci. 83, 1110–1115.

Gordeev, M. F., Patel, D. V. & Gordon, E. M. (1996). J. Org. Chem. 61, 924–928.

Rathore, R. S., Reddy, B. P., Vijayakumar, V., Ragavan, R. V. & Narasimhamurthy, T. (2009). Acta Cryst. B65, 375–381.

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

Spek, A. L. (2009). Acta Cryst. D65, 148–155.

Sunkel, C. E., de Casa-Juana, M. F., Santos, L., Garcia, A. G., Artalejo, C. R., Villarroya, M., González-Morales, M. A., López, M. G., Cillero, J., Alonso, S. & Priego, J. G. (1992). J. Med. Chem. 35, 2407–2414.

Vo, D., Matowe, W. C., Ramesh, M., Iqbal, N., Wolowyk, M. W., Howlett, S. E. & Knaus, E. E. (1995). J. Med. Chem. 38, 2851–2859.