Literature DB >> 23476166

N-[4-(9-Chloro-quino[3,2-b]benzo[1,4]thia-zin-6-yl)but-yl]acetamide.

Małgorzata Jeleń¹, Kinga Suwińska, Krystian Pluta, Beata Morak-Młodawska.

Abstract

In the title mol-ecule, C21H20ClN3OS, the tetra-cyclic system is close to planar [r.m.s. deviation = 0.110 (4) Å]. The dihedral angle between the quinoline ring system and the benzene ring is 178.3 (1)° and the angle between two (S-C=C-N) halves of the thia-zine ring is 173.4 (1)°. In the crystal, mol-ecules are arranged via π-π inter-actions [centroid-centroid distances = 3.603 (2)-3.739 (2) Å] into slipped stacks extending along [010]. Inter-molecular N-H⋯O hydrogen bonds link the amide groups of neighbouring mol-ecules along the stack, generating a C(4) motif. The title compound shows promising anti-proliferative and anti-cancer activity.

Entities: Chemical Disease Gene Species

Year: 2012 PMID： 23476166 PMCID： PMC3588930 DOI： 10.1107/S1600536812045680

Source DB: PubMed Journal: Acta Crystallogr Sect E Struct Rep Online ISSN： 1600-5368

Related literature

For recent literature on biological activity of phenothiazines, see: Aaron et al. (2009 ▶); Pluta et al. (2011 ▶). For the synthesis and biological activity of 6-substituted quinobenzothiazines, see: Jeleń & Pluta (2009 ▶); Pluta et al. (2012 ▶). For the folded structures of similar tetracyclic systems, see: Jeleń et al. (2012 ▶); Luck et al. (2003 ▶); Yoshida et al. (1994 ▶). For crystal structures of phenothiazines, see: Chu (1988 ▶). For information on azaphenothiazines, and their nomenclature and synthesis, see: Pluta et al. (2009 ▶).

Experimental

Crystal data

C21H20ClN3OS M = 397.92 Monoclinic, a = 12.7800 (4) Å b = 4.9530 (11) Å c = 28.781 (2) Å β = 97.726 (5)° V = 1805.3 (4) Å3 Z = 4 Mo Kα radiation μ = 0.35 mm−1 T = 100 K 0.60 × 0.10 × 0.05 mm

Data collection

Nonius KappaCCD diffractometer upgraded with an APEXII detector 17434 measured reflections 3032 independent reflections 1987 reflections with I > 2σ(I) R int = 0.121

Refinement

R[F 2 > 2σ(F 2)] = 0.067 wR(F 2) = 0.127 S = 1.10 3032 reflections 245 parameters H-atom parameters constrained Δρmax = 0.32 e Å−3 Δρmin = −0.29 e Å−3 Data collection: COLLECT (Nonius, 1998 ▶); cell refinement: DENZO and SCALEPACK (Otwinowski & Minor, 1997 ▶); data reduction: DENZO and SCALEPACK; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 ▶); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 ▶); molecular graphics: ORTEPIII (Burnett & Johnson, 1996 ▶) and Mercury (Macrae et al., 2008 ▶); software used to prepare material for publication: publCIF (Westrip, 2010 ▶). Click here for additional data file. Crystal structure: contains datablock(s) I, global. DOI: 10.1107/S1600536812045680/gk2524sup1.cif Click here for additional data file. Structure factors: contains datablock(s) I. DOI: 10.1107/S1600536812045680/gk2524Isup2.hkl Additional supplementary materials: crystallographic information; 3D view; checkCIF report

C₂₁H₂₀ClN₃OS	F(000) = 832
M_r = 397.92	D_x = 1.464 Mg m⁻³
Monoclinic, P2₁/c	Mo Kα radiation, λ = 0.71073 Å
Hall symbol: -P 2ybc	Cell parameters from 5229 reflections
a = 12.7800 (4) Å	θ = 2.9–24.7°
b = 4.9530 (11) Å	µ = 0.35 mm⁻¹
c = 28.781 (2) Å	T = 100 K
β = 97.726 (5)°	Needle, yellow
V = 1805.3 (4) Å³	0.60 × 0.10 × 0.05 mm
Z = 4

Nonius KappaCCD diffractometer upgraded with an APEXII detector	1987 reflections with I > 2σ(I)
Radiation source: fine-focus sealed tube	R_int = 0.121
Graphite monochromator	θ_max = 24.7°, θ_min = 3.1°
Detector resolution: 8.3 pixels mm^-1	h = −15→15
ω scan	k = −5→5
17434 measured reflections	l = −32→33
3032 independent 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)] = 0.067	Hydrogen site location: inferred from neighbouring sites
wR(F²) = 0.127	H-atom parameters constrained
S = 1.10	w = 1/[σ²(F_o²) + (0.016P)² + 1.5516P] where P = (F_o² + 2F_c²)/3
3032 reflections	(Δ/σ)_max < 0.001
245 parameters	Δρ_max = 0.32 e Å⁻³
0 restraints	Δρ_min = −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 > 2σ(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	U_iso*/U_eq
C1	1.1591 (3)	0.0335 (8)	0.38503 (15)	0.0286 (11)
H1	1.1969	0.0022	0.4153	0.034*
C2	1.1827 (3)	−0.1165 (8)	0.34779 (14)	0.0298 (11)
H2	1.2360	−0.2513	0.3520	0.036*
C3	1.1264 (3)	−0.0669 (8)	0.30318 (15)	0.0285 (11)
H3	1.1426	−0.1689	0.2771	0.034*
C4	1.0484 (3)	0.1260 (8)	0.29646 (14)	0.0252 (10)
H4	1.0116	0.1557	0.2660	0.030*
C4A	1.0226 (3)	0.2802 (8)	0.33455 (14)	0.0240 (10)
C5A	0.9204 (3)	0.6158 (8)	0.36259 (14)	0.0249 (10)
C6A	0.8031 (3)	0.9780 (8)	0.38605 (14)	0.0249 (10)
C7	0.7205 (3)	1.1593 (8)	0.37258 (14)	0.0251 (10)
H7	0.6895	1.1630	0.3407	0.030*
C8	0.6820 (3)	1.3348 (8)	0.40429 (14)	0.0281 (11)
H8	0.6289	1.4636	0.3939	0.034*
C9	0.7229 (3)	1.3170 (8)	0.45101 (14)	0.0278 (11)
C10	0.8017 (3)	1.1362 (8)	0.46564 (14)	0.0283 (11)
H10	0.8280	1.1239	0.4980	0.034*
C10A	0.8439 (3)	0.9705 (8)	0.43379 (14)	0.0258 (10)
C11A	0.9741 (3)	0.5778 (8)	0.40921 (14)	0.0244 (10)
C12	1.0516 (3)	0.3889 (8)	0.41680 (14)	0.0246 (10)
H12	1.0871	0.3616	0.4476	0.030*
C12A	1.0802 (3)	0.2326 (8)	0.37939 (14)	0.0243 (10)
C14	0.8053 (3)	0.8667 (8)	0.30219 (13)	0.0257 (10)
H14A	0.8611	0.8131	0.2833	0.031*
H14B	0.7936	1.0632	0.2978	0.031*
C15	0.7036 (3)	0.7195 (8)	0.28324 (13)	0.0252 (10)
H15A	0.6482	0.7613	0.3031	0.030*
H15B	0.7160	0.5222	0.2843	0.030*
C16	0.6666 (3)	0.8062 (8)	0.23276 (13)	0.0272 (11)
H16A	0.6422	0.9960	0.2327	0.033*
H16B	0.7271	0.7982	0.2147	0.033*
C17	0.5779 (3)	0.6321 (9)	0.20864 (14)	0.0316 (11)
H17A	0.5948	0.4398	0.2154	0.038*
H17B	0.5119	0.6750	0.2215	0.038*
C19	0.5476 (3)	0.4691 (9)	0.12731 (15)	0.0290 (11)
C20	0.5415 (3)	0.5422 (9)	0.07638 (14)	0.0362 (12)
H20A	0.5999	0.4565	0.0631	0.054*
H20B	0.5463	0.7387	0.0733	0.054*
H20C	0.4742	0.4791	0.0595	0.054*
N5	0.9431 (2)	0.4684 (6)	0.32683 (11)	0.0227 (8)
N6	0.8438 (3)	0.8161 (6)	0.35178 (11)	0.0237 (8)
N18	0.5615 (3)	0.6734 (7)	0.15804 (11)	0.0279 (9)
H18	0.5607	0.8396	0.1472	0.033*
O21	0.5405 (2)	0.2316 (6)	0.14005 (10)	0.0400 (8)
S11	0.94961 (9)	0.7684 (2)	0.45749 (4)	0.0304 (3)
Cl13	0.67276 (9)	1.5212 (2)	0.49241 (4)	0.0364 (3)

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
C1	0.025 (3)	0.028 (3)	0.032 (3)	−0.002 (2)	0.003 (2)	0.005 (2)
C2	0.025 (3)	0.026 (3)	0.040 (3)	0.000 (2)	0.008 (2)	0.002 (2)
C3	0.030 (3)	0.022 (3)	0.035 (3)	−0.006 (2)	0.007 (2)	0.000 (2)
C4	0.027 (3)	0.023 (2)	0.026 (2)	−0.009 (2)	0.002 (2)	−0.001 (2)
C4A	0.025 (2)	0.016 (2)	0.032 (2)	−0.004 (2)	0.007 (2)	0.003 (2)
C5A	0.026 (3)	0.019 (2)	0.030 (2)	−0.002 (2)	0.005 (2)	0.002 (2)
C6A	0.023 (2)	0.023 (2)	0.029 (2)	−0.004 (2)	0.003 (2)	0.003 (2)
C7	0.027 (3)	0.024 (3)	0.025 (2)	−0.009 (2)	0.005 (2)	0.001 (2)
C8	0.026 (3)	0.022 (3)	0.037 (3)	−0.003 (2)	0.006 (2)	0.005 (2)
C9	0.030 (3)	0.021 (3)	0.034 (3)	−0.002 (2)	0.008 (2)	−0.003 (2)
C10	0.031 (3)	0.027 (3)	0.027 (2)	−0.005 (2)	0.001 (2)	0.001 (2)
C10A	0.024 (2)	0.024 (2)	0.029 (2)	−0.002 (2)	0.004 (2)	0.002 (2)
C11A	0.027 (3)	0.019 (2)	0.028 (2)	−0.004 (2)	0.007 (2)	0.0015 (19)
C12	0.024 (2)	0.021 (2)	0.029 (2)	−0.006 (2)	0.004 (2)	0.005 (2)
C12A	0.021 (2)	0.021 (2)	0.031 (2)	−0.003 (2)	0.005 (2)	0.003 (2)
C14	0.033 (3)	0.021 (2)	0.023 (2)	0.002 (2)	0.003 (2)	0.0061 (19)
C15	0.028 (3)	0.021 (2)	0.026 (2)	−0.003 (2)	0.001 (2)	0.0018 (19)
C16	0.032 (3)	0.020 (2)	0.032 (2)	0.000 (2)	0.009 (2)	−0.0005 (19)
C17	0.037 (3)	0.028 (3)	0.029 (2)	−0.002 (2)	0.001 (2)	0.008 (2)
C19	0.022 (2)	0.029 (3)	0.034 (3)	0.002 (2)	−0.003 (2)	0.000 (2)
C20	0.037 (3)	0.033 (3)	0.040 (3)	0.002 (2)	0.009 (2)	−0.011 (2)
N5	0.0211 (19)	0.018 (2)	0.029 (2)	0.0004 (17)	0.0033 (16)	0.0048 (16)
N6	0.027 (2)	0.021 (2)	0.0228 (19)	−0.0017 (17)	0.0043 (16)	0.0008 (16)
N18	0.035 (2)	0.018 (2)	0.029 (2)	−0.0034 (17)	−0.0004 (17)	0.0051 (16)
O21	0.050 (2)	0.0159 (18)	0.050 (2)	−0.0015 (16)	−0.0054 (16)	−0.0007 (15)
S11	0.0343 (7)	0.0290 (7)	0.0271 (6)	0.0036 (6)	0.0006 (5)	−0.0018 (5)
Cl13	0.0404 (7)	0.0309 (7)	0.0391 (7)	0.0040 (6)	0.0105 (6)	−0.0054 (5)

C1—C2	1.371 (5)	C10A—S11	1.745 (4)
C1—C12A	1.405 (5)	C11A—C12	1.359 (5)
C1—H1	0.9500	C11A—S11	1.743 (4)
C2—C3	1.406 (5)	C12—C12A	1.413 (5)
C2—H2	0.9500	C12—H12	0.9500
C3—C4	1.376 (5)	C14—N6	1.468 (4)
C3—H3	0.9500	C14—C15	1.526 (5)
C4—C4A	1.411 (5)	C14—H14A	0.9900
C4—H4	0.9500	C14—H14B	0.9900
C4A—N5	1.374 (5)	C15—C16	1.528 (5)
C4A—C12A	1.417 (5)	C15—H15A	0.9900
C5A—N5	1.325 (5)	C15—H15B	0.9900
C5A—N6	1.399 (5)	C16—C17	1.515 (5)
C5A—C11A	1.435 (5)	C16—H16A	0.9900
C6A—C7	1.400 (5)	C16—H16B	0.9900
C6A—C10A	1.403 (5)	C17—N18	1.458 (5)
C6A—N6	1.423 (5)	C17—H17A	0.9900
C7—C8	1.397 (5)	C17—H17B	0.9900
C7—H7	0.9500	C19—O21	1.239 (5)
C8—C9	1.378 (5)	C19—N18	1.340 (5)
C8—H8	0.9500	C19—C20	1.502 (5)
C9—C10	1.371 (5)	C20—H20A	0.9800
C9—Cl13	1.749 (4)	C20—H20B	0.9800
C10—C10A	1.392 (5)	C20—H20C	0.9800
C10—H10	0.9500	N18—H18	0.8800

C2—C1—C12A	121.4 (4)	C1—C12A—C4A	119.9 (4)
C2—C1—H1	119.3	C12—C12A—C4A	116.6 (4)
C12A—C1—H1	119.3	N6—C14—C15	115.1 (3)
C1—C2—C3	118.7 (4)	N6—C14—H14A	108.5
C1—C2—H2	120.7	C15—C14—H14A	108.5
C3—C2—H2	120.7	N6—C14—H14B	108.5
C4—C3—C2	121.4 (4)	C15—C14—H14B	108.5
C4—C3—H3	119.3	H14A—C14—H14B	107.5
C2—C3—H3	119.3	C14—C15—C16	110.2 (3)
C3—C4—C4A	120.5 (4)	C14—C15—H15A	109.6
C3—C4—H4	119.8	C16—C15—H15A	109.6
C4A—C4—H4	119.8	C14—C15—H15B	109.6
N5—C4A—C4	119.1 (4)	C16—C15—H15B	109.6
N5—C4A—C12A	122.8 (4)	H15A—C15—H15B	108.1
C4—C4A—C12A	118.1 (4)	C17—C16—C15	113.1 (3)
N5—C5A—N6	115.9 (4)	C17—C16—H16A	109.0
N5—C5A—C11A	121.8 (4)	C15—C16—H16A	109.0
N6—C5A—C11A	122.2 (4)	C17—C16—H16B	109.0
C7—C6A—C10A	117.1 (4)	C15—C16—H16B	109.0
C7—C6A—N6	120.1 (4)	H16A—C16—H16B	107.8
C10A—C6A—N6	122.8 (4)	N18—C17—C16	112.1 (3)
C8—C7—C6A	122.5 (4)	N18—C17—H17A	109.2
C8—C7—H7	118.8	C16—C17—H17A	109.2
C6A—C7—H7	118.8	N18—C17—H17B	109.2
C9—C8—C7	118.5 (4)	C16—C17—H17B	109.2
C9—C8—H8	120.8	H17A—C17—H17B	107.9
C7—C8—H8	120.8	O21—C19—N18	122.0 (4)
C10—C9—C8	120.5 (4)	O21—C19—C20	121.4 (4)
C10—C9—Cl13	119.3 (3)	N18—C19—C20	116.5 (4)
C8—C9—Cl13	120.1 (3)	C19—C20—H20A	109.5
C9—C10—C10A	121.1 (4)	C19—C20—H20B	109.5
C9—C10—H10	119.5	H20A—C20—H20B	109.5
C10A—C10—H10	119.5	C19—C20—H20C	109.5
C10—C10A—C6A	120.3 (4)	H20A—C20—H20C	109.5
C10—C10A—S11	115.4 (3)	H20B—C20—H20C	109.5
C6A—C10A—S11	124.3 (3)	C5A—N5—C4A	118.8 (3)
C12—C11A—C5A	119.2 (4)	C5A—N6—C6A	123.8 (3)
C12—C11A—S11	116.7 (3)	C5A—N6—C14	118.1 (3)
C5A—C11A—S11	124.1 (3)	C6A—N6—C14	118.2 (3)
C11A—C12—C12A	120.8 (4)	C19—N18—C17	122.8 (3)
C11A—C12—H12	119.6	C19—N18—H18	118.6
C12A—C12—H12	119.6	C17—N18—H18	118.6
C1—C12A—C12	123.5 (4)	C11A—S11—C10A	102.2 (2)

D—H···A	D—H	H···A	D···A	D—H···A
N18—H18···O21ⁱ	0.88	1.97	2.819 (4)	163

Table 1

Hydrogen-bond geometry (Å, °)

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
N18—H18⋯O21ⁱ	0.88	1.97	2.819 (4)	163

Symmetry code: (i) .

2 in total

1. A short history of SHELX.

Authors: George M Sheldrick
Journal: Acta Crystallogr A Date: 2007-12-21 Impact factor: 2.290

Review 2. Recent progress in biological activities of synthesized phenothiazines.

Authors: Krystian Pluta; Beata Morak-Młodawska; Małgorzata Jeleń
Journal: Eur J Med Chem Date: 2011-05-12 Impact factor: 6.514

2 in total