Cyclo-oxygenase-1-selective inhibitor SC-560.

In the title compound, 5-(4-chloro-phen-yl)-1-(4-methoxy-phen-yl)-3-(trifluoro-meth-yl)-1H-pyrazole (SC-560), C(17)H(12)ClF(3)N(2)O, a COX-1-selective inhibitor, the dihedral angles between the heterocycle and the chlorobenzene and methoxybenzene rings are 41.66 (6) and 43.08 (7)°, respectively. The dihedral angle between the two phenyl rings is 59.94 (6)°. No classic hydrogen bonds are possible in the crystal, and intermolecular interactions must be mainly of the dispersion type. This information may aid the identification of dosage formulations with improved oral bioavailability.

Related literature

For background literature, see: Choi et al. (2008 ▶); Cusimano et al. (2007 ▶); Kundu & Fulton (2002 ▶); Penning et al. (1997 ▶); Smith et al. (2000 ▶); Teng et al. (2003 ▶); Tiano et al. (2002 ▶); For related structures, see: Allen (2002 ▶); Charlier et al. (2004 ▶); Norris et al. (2005 ▶); Sonar et al. (2004 ▶); Zhu et al. (2004 ▶).

Experimental

Crystal data

C17H12ClF3N2O

M = 352.74

Monoclinic,

a = 15.585 (3) Å

b = 7.1671 (14) Å

c = 15.789 (3) Å

β = 116.81 (3)°

V = 1574.1 (5) Å3

Z = 4

Mo Kα radiation

μ = 0.28 mm−1

T = 90 (2) K

0.20 × 0.10 × 0.10 mm

Data collection

Nonius KappaCCD diffractometer

Absorption correction: multi-scan (SCALEPACK; Otwinowski & Minor, 1997 ▶) T min = 0.946, T max = 0.972

6895 measured reflections

3608 independent reflections

3030 reflections with I > 2σ(I)

R int = 0.020

Refinement

R[F 2 > 2σ(F 2)] = 0.035

wR(F 2) = 0.094

S = 1.04

3608 reflections

218 parameters

H-atom parameters constrained

Δρmax = 0.34 e Å−3

Δρmin = −0.29 e Å−3

Data collection: COLLECT (Hooft, 1998 ▶); cell refinement: DENZO-SMN (Otwinowski & Minor, 1997 ▶); data reduction: DENZO-SMN; 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 and local procedures.

Crystal structure: contains datablocks global, I. DOI: 10.1107/S1600536809001779/pv2130sup1.cif

Structure factors: contains datablocks I. DOI: 10.1107/S1600536809001779/pv2130Isup2.hkl

Additional supplementary materials: crystallographic information; 3D view; checkCIF report

C17H12ClF3N2O	F(000) = 720
Mr = 352.74	Dx = 1.488 Mg m−3
Monoclinic, P21/n	Mo Kα radiation, λ = 0.71073 Å
a = 15.585 (3) Å	Cell parameters from 3880 reflections
b = 7.1671 (14) Å	θ = 1.0–27.5°
c = 15.789 (3) Å	µ = 0.28 mm−1
β = 116.81 (3)°	T = 90 K
V = 1574.1 (5) Å3	Block, colorless
Z = 4	0.20 × 0.10 × 0.10 mm

Nonius KappaCCD diffractometer	3608 independent reflections
Radiation source: fine-focus sealed tube	3030 reflections with I > 2σ(I)
graphite	Rint = 0.020
Detector resolution: 18 pixels mm-1	θmax = 27.5°, θmin = 1.5°
ω scans at fixed χ = 55°	h = −20→20
Absorption correction: multi-scan (SCALEPACK; Otwinowski & Minor, 1997)	k = −9→9
Tmin = 0.946, Tmax = 0.972	l = −20→20
6895 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)] = 0.035	Hydrogen site location: inferred from neighbouring sites
wR(F2) = 0.094	H-atom parameters constrained
S = 1.04	w = 1/[σ2(Fo2) + (0.0421P)2 + 0.7994P] where P = (Fo2 + 2Fc2)/3
3608 reflections	(Δ/σ)max = 0.004
218 parameters	Δρmax = 0.34 e Å−3
0 restraints	Δρmin = −0.29 e Å−3

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
Cl13	0.06492 (3)	0.90044 (6)	0.10611 (2)	0.02831 (12)
N2	0.38203 (8)	0.87316 (17)	0.67980 (8)	0.0188 (2)
O20	0.12419 (8)	0.14611 (15)	0.54981 (7)	0.0287 (3)
F3	0.56584 (7)	1.19886 (15)	0.74065 (7)	0.0382 (3)
F2	0.52162 (8)	1.04490 (15)	0.83041 (6)	0.0443 (3)
N1	0.32413 (8)	0.81035 (16)	0.59070 (7)	0.0169 (2)
C10	0.14398 (10)	0.89725 (19)	0.22720 (9)	0.0199 (3)
C5	0.33171 (9)	0.91657 (19)	0.52240 (9)	0.0171 (3)
C18	0.21726 (10)	0.3440 (2)	0.50702 (9)	0.0196 (3)
H18	0.2135	0.2529	0.4618	0.023*
F1	0.44389 (7)	1.28688 (15)	0.75784 (7)	0.0448 (3)
C11	0.10734 (10)	0.8619 (2)	0.29082 (10)	0.0199 (3)
H11	0.0408	0.8367	0.2688	0.024*
C19	0.26912 (9)	0.50583 (19)	0.51716 (9)	0.0179 (3)
H19	0.3033	0.5239	0.4809	0.021*
C7	0.26748 (10)	0.89925 (18)	0.41982 (9)	0.0170 (3)
C14	0.27105 (9)	0.64202 (19)	0.58060 (9)	0.0173 (3)
C16	0.17333 (11)	0.4491 (2)	0.62713 (10)	0.0244 (3)
H16	0.1419	0.4285	0.6657	0.029*
C6	0.48912 (10)	1.1368 (2)	0.74825 (10)	0.0222 (3)
C12	0.16930 (10)	0.86393 (19)	0.38715 (9)	0.0190 (3)
H12	0.1449	0.8411	0.4315	0.023*
C4	0.39888 (9)	1.0532 (2)	0.56958 (9)	0.0189 (3)
H4	0.4216	1.1482	0.5428	0.023*
C8	0.30233 (10)	0.9337 (2)	0.35415 (10)	0.0211 (3)
H8	0.3689	0.9576	0.3757	0.025*
C3	0.42585 (9)	1.0204 (2)	0.66545 (9)	0.0190 (3)
C15	0.22267 (10)	0.6153 (2)	0.63461 (10)	0.0222 (3)
H15	0.2231	0.7102	0.6768	0.027*
C17	0.17048 (10)	0.3143 (2)	0.56306 (10)	0.0217 (3)
C9	0.24066 (11)	0.9335 (2)	0.25715 (10)	0.0238 (3)
H9	0.2645	0.9578	0.2124	0.029*
C21	0.07544 (14)	0.1110 (3)	0.60633 (11)	0.0403 (5)
H21A	0.1214	0.1185	0.6737	0.060*
H21B	0.0468	−0.0138	0.5921	0.060*
H21C	0.0248	0.2043	0.5919	0.060*

	U11	U22	U33	U12	U13	U23
Cl13	0.0288 (2)	0.0370 (2)	0.01330 (17)	0.00223 (16)	0.00434 (14)	0.00022 (14)
N2	0.0178 (6)	0.0216 (6)	0.0138 (5)	−0.0009 (5)	0.0044 (4)	−0.0028 (4)
O20	0.0349 (6)	0.0259 (6)	0.0258 (5)	−0.0125 (5)	0.0143 (5)	−0.0024 (4)
F3	0.0326 (5)	0.0472 (6)	0.0402 (5)	−0.0209 (5)	0.0211 (4)	−0.0206 (5)
F2	0.0533 (6)	0.0441 (6)	0.0177 (4)	−0.0183 (5)	0.0001 (4)	−0.0012 (4)
N1	0.0180 (5)	0.0186 (6)	0.0126 (5)	−0.0015 (5)	0.0057 (4)	−0.0014 (4)
C10	0.0238 (7)	0.0184 (7)	0.0134 (6)	0.0030 (5)	0.0046 (5)	0.0000 (5)
C5	0.0177 (6)	0.0180 (7)	0.0159 (6)	0.0022 (5)	0.0080 (5)	0.0011 (5)
C18	0.0207 (7)	0.0180 (7)	0.0178 (6)	0.0029 (5)	0.0067 (5)	−0.0008 (5)
F1	0.0342 (5)	0.0427 (6)	0.0472 (6)	0.0054 (5)	0.0092 (5)	−0.0268 (5)
C11	0.0187 (6)	0.0189 (7)	0.0189 (6)	0.0009 (5)	0.0059 (5)	0.0001 (5)
C19	0.0188 (6)	0.0189 (7)	0.0170 (6)	0.0031 (5)	0.0089 (5)	0.0019 (5)
C7	0.0200 (6)	0.0141 (6)	0.0150 (6)	0.0016 (5)	0.0063 (5)	0.0008 (5)
C14	0.0171 (6)	0.0177 (7)	0.0142 (6)	−0.0010 (5)	0.0045 (5)	0.0013 (5)
C16	0.0259 (7)	0.0312 (8)	0.0191 (6)	−0.0075 (6)	0.0127 (6)	−0.0023 (6)
C6	0.0208 (7)	0.0240 (8)	0.0207 (7)	−0.0022 (6)	0.0084 (6)	−0.0033 (6)
C12	0.0215 (7)	0.0192 (7)	0.0171 (6)	0.0008 (5)	0.0093 (5)	0.0011 (5)
C4	0.0182 (6)	0.0186 (7)	0.0189 (6)	0.0001 (5)	0.0073 (5)	0.0009 (5)
C8	0.0199 (7)	0.0237 (7)	0.0193 (7)	−0.0004 (6)	0.0084 (5)	0.0003 (5)
C3	0.0166 (6)	0.0195 (7)	0.0191 (6)	0.0013 (5)	0.0066 (5)	−0.0008 (5)
C15	0.0238 (7)	0.0262 (8)	0.0172 (6)	−0.0032 (6)	0.0097 (6)	−0.0044 (6)
C17	0.0204 (7)	0.0213 (7)	0.0188 (6)	−0.0037 (6)	0.0048 (5)	0.0024 (5)
C9	0.0270 (7)	0.0280 (8)	0.0177 (6)	0.0000 (6)	0.0113 (6)	0.0009 (6)
C21	0.0495 (11)	0.0482 (11)	0.0253 (8)	−0.0297 (9)	0.0188 (8)	−0.0057 (7)

Cl13—C10	1.7461 (15)	C19—C14	1.3892 (19)
N2—C3	1.3307 (18)	C19—H19	0.9500
N2—N1	1.3605 (15)	C7—C8	1.3924 (19)
O20—C17	1.3714 (18)	C7—C12	1.3998 (19)
O20—C21	1.4312 (19)	C14—C15	1.383 (2)
F3—C6	1.3308 (17)	C16—C17	1.385 (2)
F2—C6	1.3345 (17)	C16—C15	1.393 (2)
N1—C5	1.3680 (17)	C16—H16	0.9500
N1—C14	1.4305 (17)	C6—C3	1.4884 (19)
C10—C11	1.384 (2)	C12—H12	0.9500
C10—C9	1.385 (2)	C4—C3	1.3962 (19)
C5—C4	1.3807 (19)	C4—H4	0.9500
C5—C7	1.4759 (18)	C8—C9	1.394 (2)
C18—C19	1.381 (2)	C8—H8	0.9500
C18—C17	1.393 (2)	C15—H15	0.9500
C18—H18	0.9500	C9—H9	0.9500
F1—C6	1.3313 (18)	C21—H21A	0.9800
C11—C12	1.3861 (19)	C21—H21B	0.9800
C11—H11	0.9500	C21—H21C	0.9800
C3—N2—N1	103.79 (11)	F1—C6—F2	106.06 (12)
C17—O20—C21	116.75 (12)	F3—C6—C3	111.98 (12)
N2—N1—C5	112.22 (11)	F1—C6—C3	112.21 (12)
N2—N1—C14	118.35 (11)	F2—C6—C3	112.80 (13)
C5—N1—C14	129.25 (11)	C11—C12—C7	120.73 (13)
C11—C10—C9	121.85 (13)	C11—C12—H12	119.6
C11—C10—Cl13	118.59 (11)	C7—C12—H12	119.6
C9—C10—Cl13	119.55 (11)	C5—C4—C3	104.46 (12)
N1—C5—C4	106.47 (11)	C5—C4—H4	127.8
N1—C5—C7	124.14 (12)	C3—C4—H4	127.8
C4—C5—C7	128.73 (12)	C7—C8—C9	120.73 (13)
C19—C18—C17	120.10 (13)	C7—C8—H8	119.6
C19—C18—H18	120.0	C9—C8—H8	119.6
C17—C18—H18	120.0	N2—C3—C4	113.05 (12)
C10—C11—C12	118.89 (13)	N2—C3—C6	118.86 (12)
C10—C11—H11	120.6	C4—C3—C6	127.88 (13)
C12—C11—H11	120.6	C14—C15—C16	119.99 (13)
C18—C19—C14	119.66 (12)	C14—C15—H15	120.0
C18—C19—H19	120.2	C16—C15—H15	120.0
C14—C19—H19	120.2	O20—C17—C16	124.47 (13)
C8—C7—C12	119.10 (12)	O20—C17—C18	115.32 (13)
C8—C7—C5	120.19 (12)	C16—C17—C18	120.21 (13)
C12—C7—C5	120.48 (12)	C10—C9—C8	118.70 (13)
C15—C14—C19	120.45 (13)	C10—C9—H9	120.6
C15—C14—N1	119.79 (12)	C8—C9—H9	120.6
C19—C14—N1	119.76 (12)	O20—C21—H21A	109.5
C17—C16—C15	119.53 (13)	O20—C21—H21B	109.5
C17—C16—H16	120.2	H21A—C21—H21B	109.5
C15—C16—H16	120.2	O20—C21—H21C	109.5
F3—C6—F1	106.49 (12)	H21A—C21—H21C	109.5
F3—C6—F2	106.86 (12)	H21B—C21—H21C	109.5
C3—N2—N1—C5	−0.10 (14)	C12—C7—C8—C9	0.1 (2)
C3—N2—N1—C14	175.45 (11)	C5—C7—C8—C9	−174.46 (13)
N2—N1—C5—C4	0.92 (15)	N1—N2—C3—C4	−0.79 (15)
C14—N1—C5—C4	−174.02 (12)	N1—N2—C3—C6	174.38 (12)
N2—N1—C5—C7	−170.48 (12)	C5—C4—C3—N2	1.34 (16)
C14—N1—C5—C7	14.6 (2)	C5—C4—C3—C6	−173.29 (13)
C9—C10—C11—C12	0.3 (2)	F3—C6—C3—N2	143.23 (13)
Cl13—C10—C11—C12	−178.35 (11)	F1—C6—C3—N2	−97.07 (16)
C17—C18—C19—C14	−2.7 (2)	F2—C6—C3—N2	22.64 (18)
N1—C5—C7—C8	−147.72 (14)	F3—C6—C3—C4	−42.4 (2)
C4—C5—C7—C8	42.9 (2)	F1—C6—C3—C4	77.29 (18)
N1—C5—C7—C12	37.8 (2)	F2—C6—C3—C4	−163.00 (14)
C4—C5—C7—C12	−131.61 (15)	C19—C14—C15—C16	1.4 (2)
C18—C19—C14—C15	1.0 (2)	N1—C14—C15—C16	−178.04 (12)
C18—C19—C14—N1	−179.52 (12)	C17—C16—C15—C14	−2.2 (2)
N2—N1—C14—C15	45.45 (17)	C21—O20—C17—C16	0.4 (2)
C5—N1—C14—C15	−139.87 (14)	C21—O20—C17—C18	179.96 (14)
N2—N1—C14—C19	−134.02 (13)	C15—C16—C17—O20	180.00 (13)
C5—N1—C14—C19	40.7 (2)	C15—C16—C17—C18	0.5 (2)
C10—C11—C12—C7	−0.6 (2)	C19—C18—C17—O20	−177.60 (12)
C8—C7—C12—C11	0.4 (2)	C19—C18—C17—C16	2.0 (2)
C5—C7—C12—C11	174.95 (13)	C11—C10—C9—C8	0.2 (2)
N1—C5—C4—C3	−1.30 (15)	Cl13—C10—C9—C8	178.84 (11)
C7—C5—C4—C3	169.57 (13)	C7—C8—C9—C10	−0.4 (2)