J. Med. Chem., 1996, 39(14), , DOI: /jm960098l

J. Med. Chem., 1996, 39(14), 2835-2843, DOI:10.1021/jm960098l Terms & Conditions Electronic Supporting Information files are available without a subscription to ACS Web Editions. The American Chemical Society holds a copyright ownership interest in any copyrightable Supporting Information. Files available from the ACS website may be downloaded for personal use only. Users are not otherwise permitted to reproduce, republish, redistribute, or sell any Supporting Information from the ACS website, either in whole or in part, in either machinereadable form or any other form without permission from the American Chemical Society. For permission to reproduce, republish and redistribute this material, requesters must process their own requests via the RightsLink permission system. Information about how to use the RightsLink permission system can be found at http://pubs.acs.org/page/copyright/permissions.html Copyright 1996 American Chemical Society

(01996 American Chemical Society Journal Of Medicinal Chemistry V39 Page 2835 Ma Supplemental Page 1 Experimental Data Collection 0183 Fvzos- A colorless rocks crystal of einyephg-having approximate dimensions of 0.30 x 0.20 x 0.10 mm was mounted on a glass fiber. All measurements were made on an Enraf-Nonius CAD4 diffractometer with filtered Cu-Ka radiation. Cell constants and an orientation matrix for data collection, obtained from a least-squares refinement using the setting angles of 25 carefully centered reflections in the range 18.00 < 20 < 40.000 corresponded to amonoclinic cell with dimensions: a = 10.4326 A b = 10.8549 A = 108.87160 c = 10.5575 A V = 1131.3208 A3 For Z = 4 and F.W. = 228.22, the calculated density is 1.34 g/cm 3. Based on the systematic absences of: OkO: k # 2n packing considerations, a statistical analysis of intensity distribution, and the successful solution and refinement of the structure, the space group was determined to be: P2 1 (#4) The data were collected at a temperature of 25 j 1 0 C using the w scan technique to a maximum 20 value of 149.80. Omega scans of several intense reflections, made prior to data collection, had an average width at half-height of 0.300 with a take-off angle of 2.80. Scans of (0.65 + 0.14 tan 0)* were made at a speed of l6.5*/min (in omega). The weak reflections (I < 3.0o-(I)) were rescanned (maximum of 1 scans) and the counts were accumulated to ensure good counting statistics. Moving-crystal moving counter background measurements were made by scanning an additional 25% above and below the scan range. The counter aperture consisted of a variable horizontal slit with a width ranging from 2.0 to 2.5 mm and a vertical slit set to 2.0 mm. The diameter of the incident beam collimator was 0.7 mm and the crystal to detector distance wasm2+ cm. For intense reflections an attenuator was automatically inserted in front of the detector. Data Reduction Of the 2594 reflections which were collected, 2502 were unique (Rit = 0.033). The intensities of three representative reflection were measured after every 120 minutes of X-ray exposure time. No decay correction was applied. The linear absorption coefficient, p, for Cu-Ka radiation is 9.4 cm- 1. Azimuthal scans of several reflections indicated no need for an absorption correction. The data were corrected for Lorentz and polarization effects. A correction for secondary extinction was applied (coefficient = 5.69604e-06). 2

(01996 American Chemical Society Journal Of Medicinal Chemistry V39 Page 2835 Ma Supplemental Page 2 Structure Solution and Refinement The structure was solved by direct methods' and expanded using Fourier techniques'. The non-hydrogen atoms were refined anisotropically. Hydrogen atoms were included but not refined. The final cycle of fullmatrix least-squares refinement' was based on 1942 observed reflections (I > 3.00<r(I)) and 325 variable parameters and converged (largest parameter shift was 1.37 times its esd) with unweighted and weighted agreement factors of: R = ElIFo - Fc /EFo = 0.062 R,; = V(Ew( Fo - IFcj) 2 /EwFo 2 )] = 0.081 The standard deviation of an observation of unit weight 4 was 5.11. The weighting scheme was based on counting statistics and included a factor (p = 0.005) to downweight the intense reflections. Plots of Ew(IFo - Fc ) 2 versus Fo, reflection order in data collection, sin 0/A and various classes of indices showed no unusual trends. The maximum and minimum peaks on the final difference Fourier map corresponded to 0.00 and 0.00 e-/v, respectively. Neutral atom scattering factors were taken from Cromer and Waber'. Anomalous dispersion effects were included in Fcalc 6 ; the values for Af' and Af' were those of Creagh and McAuley 7. The values for the mass attenuation coefficients are those of Creagh and Hubbel'. All calculations were performed using the texsan 9 crystallographic software package of Molecular Structure Corporation. References (1) SIR92: Altomare, A., Burla, M.C., Camalli, M., Cascarano, M., Giacovazzo, C., Guagliardi, A., Polidori, G. (1994). J. Appl. Cryst., in preparation. (2) DIRDIF94: Beurskens, P.T., Admiraal, G., Beurskens, G., Bosman, W.P., de Gelder, R., Israel, R. and Smits, J.M.M. (1994). The DIRDIF-94 program system, Technical Report of the Crystallography Laboratory, University of Nijmegen, The Netherlands. (3) Least-Squares: Function minimized: Ew( Foj - Fc ) 2 where w = I = 4Fo 2 2 (FO 2 ) S S = Scan rate 2 (C+RB+(pFo 2 ) 2 Lp C = Total integrated peak count R = Ratio of scan time to background counting time B = Total background count Lp = Lorentz-polarization factor p = p-factor 3

(01996 American Chemical Society Journal Of Medicinal Chemistry V39 Page 2835 Ma Supplemental Page 3 (4) Standard deviation of an observation bf unit weight: Vrw(jFo - IFc ) 2 /(No - Nv) where: No = number of observations Nv = number of variables (5) Cromer, D. T. & Waber, J. T.; "International Tables for X-ray Crystallography", Vol. IV, The Kynoch Press, Birmingham, England, Table 2.2 A (1974). (6) Ibers, J. A. & Hamilton, W. C.; Acta Crystallogr., 17, 781 (1964). (7) Creagh, D. C. & McAuley, W.J.; "International Tables for Crystallography", Vol C, (A.J.C. Wilson, ed.), Kluwer Academic Publishers, Boston, Table 4.2.6.8, pages 219-222 (1992). (8) Creagh, D. C. & Hubbell, J.H..; "International Tables for Crystallography", Vol C, (A.J.C. Wilson, ed.), Kluwer Academic Publishers, Boston, Table 4.2.4.3, pages 200-206 (1992). (9) texsan: Crystal Structure Analysis Package, Molecular Structure Corporation (1985 & 1992). 4

(01996 American Chemical Society Journal Of Medicinal Chemistry V39 Page 2835 Ma Supplemental Page 4 EXPERIMENTAL DETAILS A. Crystal Data 3 Empirical Formula 9- Formula Weight -. Crystal Color, Habit Crystal Dimensions Crystal System Lattice Type No. of Reflections Used for Unit Cell Determination (20 range) C 1 0 N 2 0 3 FH 13 228.22 colorless, rocks 0.30 X 0.20 X 0.10 mm monoclinic Primitive 25 ( 18.0-40.00 ) Omega Scan Peak Width at Half-height 6 Lattice Parameters 0.300 a = 10.4326A b = 10.8549 A (t ( o c = 10.5575 A ) = 108.87160 ~ca~3 '~> V = 1131.3208 A 3 7 Space Group P2 1 (#4) Z value 4 \\\$\ V-1 1.340 g/cm 3 Fooo 480.00 pu(cuka) 9.44 cm- 1 B. Intensity Measurements J U / Diffractometer CAD4 5

(01996 American Chemical Society Journal Of Medicinal Chemistry V39 Page 2835 Ma Supplemental Page 5 Radiation Attenuator Take-off Angle Detector Aperture Crystal to Detector Distance Temperature Scan Type Scan Rate Scan Width 20max No. of Reflections Measured Corrections CuKa (A = 1.54178 A) Ni foil (factor = 24.04) 2.80 2.0-2.5 mm horizontal 2.0 mm vertical 4l mm 25.00 C w 16.5 0 /min (in w) (0.65 + 0.14 tan 0)0 149.80 Total: 2594 Unique: 2502 (Rina = 0.033) Lorentz-polarization Secondary Extinction (coefficient: 5.69604e-06) C. Structure Solution and Refinement Structure Solution Refinement Function Minimized Least Squares Weights p-factor Anomalous Dispersion No. Observations (I>3.00o-(I)) No. Variables Reflection/Parameter Ratio Residuals: R; Rw Goodness of Fit Indicator Max Shift/Error in Final Cycle Direct Methods (SIR92) Full-matrix least-squares Ew(jFo - ffcj) 2 I 4Fo 2 c 2 TFo) -- FC(Fo2) 0.0050 All non-hydrogen atoms 1942 325 5.98 0.062 ; 0.081 5.11 1.37 6

(01996 American Chemical Society Journal Of Medicinal Chemistry V39 Page 2835 Ma Supplemental Page 6 Table 1. Atomic coordinates and Biso/Beq atom x Y z Beg F -0.1152(3) 0-0.095 7.13(8) F(1*) -0.6307(2) -0.8304(3) -0.626 5.05(6) 0(1) -0.3998(3) -0.4669(3) -0.0515(2) 3.99(5) 0(1*) -0.6746(2) -0.3798(3) -0.349 3.25(5) -0.5055(3) -0.0909(3) -0.2368(3) 4.73(6) 0(2*) -0.4929(2) -0.7539(3) -0.2125(2) 2.85(5) 0(3*) -0.7986(2) -0.9284(3) -0.4786(2) 2.75(4) -0.2514(2) 0.0737(3) 0.089 2.89(5) -0.2145(3) 0.295-0.1429(3) 4.96(7) 0(4*) -0.5529(2) -1.136-0.5167(3) 4.20(6) 0.0141(4) 0.1976(5) 0.2247(4) 8.7(1) 0(5*) -0.9395(3) -1.0582(4) -0.7397(3) 5.05(6) -0.3347(3) -0.1041(4) -0.0376(3) 2.41(5) N(1*) -0.6802(3) -0.7456(4) -0.3989(2) 2.49(5) -0.4574(3) -0.2761(3) -0.1333(3) 3.21(5) N(3*) -0.5949(3) -0.5694(3) -0.2778(3) 2.45(5) C(1') -0.3139(3) 0.0304(4) -0.0405(3) 2.25(6) C(1"*) -0.6683(3) -0.8778(4) -0.4183(3) 2.58(5) -0.4396(3) -0.1524(4) -0.141 3.31(6) C(2') -0.2241(4) 0.0701(5) -0.1223(4) 4.08(8) C(2*) -0.5819(3) -0.694-0.2917(3) 2.64(6) C(2'*) -0.5921(3) -0.9104(4) -0.5152(4) 2.86(6) ((3') -0.1667(3) 0.1935(4) -0.054 3.64(7) C(3'*) -0.6496(3) -1.0394(4) -0.564 2.82(6) 8

(01996 American Chemical Society Journal Of Medicinal Chemistry V39 Page 2835 Ma Supplemental Page 7 Table 1. Atomic coordinates and Bio/Beq (continued) atom x Y z Beq C(4*) -0.6835(3) -0.4921(4) -0.3666(3) 2.31(6) C(4) -0.3743(3) -0.3549(4) -0.0417(3) 2.83(6) C(4') -0.2103(3) 0.1984(4) 0.0716(3) 3.00(6) C(4'*) -0.7704(3) -1.0523(4) -0.514 2.79(6) -0.2621(3) -0.299 0.059 2.67(6) C(5*) -0.7814(3) -0.5513(4) -0.4791(3) 2.82(6) C(5') -0.1034(5) 0.2421(5) 0.1996(5) 6.07(10) C(5'*) -0.8954(4) -1.1097(5) -0.6106(5) 4.47(8) C(6*) -0.7749(3) -0.6752(4) -0.4921(3) 2.62(6) C(6) -0.2459(3) -0.1773(4) 0.0574(3) 2.62(6) C(7) -0.1654(4) -0.3819(4) 0.1577(4) 3.92(8) C(7*) -0.8846(4) -0.4743(4) -0.5759(4) 3.67(8) 11(1) 0 0 0 3 11(2) 0 0 0 3 H(3) 0 0 0 3 11(4) 0 0 0 4 11(5) 0 0 0 4 11(6) 0 0 0 5 11(7) 0 0 0 4 II(8) 0 0 0 3 II(9) 0 0 0 3 H(10) 0-1 0 3 H(11) 0 0 0 3 11(12) 0 0 0 3 9

(01996 American Chemical Society Journal Of Medicinal Chemistry V39 Page 2835 Ma Supplemental Page 8 Table 1. Atomic coordinates and Biso/Beq (continued) atom x y z Beq H(14) 0 0 0 3 H(15) 0 0 0 2 Beq - 2 (aa*) 2 + U 22 (bb*) 2 + U 33 (cc*) 2 + 2Ui 2 aa*bb* cosy + 2U 3 aa*cc* cosfl + 2U 23 bb*cc* cos a) 10

(01996 American Chemical Society Journal Of Medicinal Chemistry V39 Page 2835 Ma Supplemental Page 9 Table 2. Anisotropic Displacement Parameters atom U 11 U 2 2 Us33 U12 U 13 U 23 F 0.108(2) 0.056(2) 0.147(3) 0.014(2) 0.099(2) 0.007(2) F(1*) 0.097(2) 0.040(1) 0.067(1) -0.009(1) 0.043(1) 0.003(1) 0(1) 0.063(2) 0.027(1) 0.047(1) -0.004(1) -0.003(1) 0.004(1) O(1*) 0.044(1) 0.0258(10) 0.044(1) -0.003(1) 0.001(1) -0.0025(10) 0.072(2) 0.032(1) 0.046(1) 0.007(1) -0.021(1) 0.004(1) 0(2*) 0.030(1) 0.023(1) 0.040(1) 0.0015(10) -0.0108(10) 0.0011(10) 14 0(3*) 0.0273(10) 0.025(1) 0.048(1) -0.0016(9) 0.0053(9) -0.008(1) 0.045(1) 0.033(1) 0.030(1) -0.010(1) 0.009-0.0023(9) 0.055(2) 0.052(2) 0.073(2) -0.002(1) 0.009(1) 0.037(1) 0(4*) 0.047(1) 0.041(2) 0.068(2) 0.020(1) 0.013(1) -0.005(1) 0.088(2) 0.119(3) 0.086(2) -0.002(2) -0.023(2) -0.007(3) 0(5*) 0.046(1) 0.064(2) 0.062(2) 0.006(1) -0.011(1) -0.019(1) 0.034(1) 0.019(1) 0.031(1) -0.001(1) 0.000(1) 0.001(1) N(1*) 0.028(1) 0.024(1) 0.037(1) 0.001(1) 0.0024(10) -0.006(1) 0.038(1) 0.032(1) 0.036(1) 0.002(1) -0.010(1) -0.003(1) N(3*) 0.035(1) 0.023(1) 0.027(1) -0.003(1) -0.002(1) -0.0040(9) C(1') 0.028(2) 0.017(1) 0.031(1) -0.002(1) -0.004(1) -0.001(1) C(1*) 0.027(1) 0.026(1) 0.037(2) 0.002(1) 0.000(1) -0.002(1) 0.04 0.029(1) 0.04 0.004(1) -0.010(1) -0.006(1) C(2') 0.07 0.05 0.041(2) -0.016(1) 0.027(2) 0.001(2) C(2*) 0.031(1) 0.028(1) 0.032(2) 0.002(1) -0.003(1) -0.001(1) C(2'*) 0.029(2) 0.027(2) 0.05-0.004(1) 0.010(1) -0.008(1) C(3') 0.044(2) 0.041(2) 0.045(2) -0.003(2) 0.003(1) 0.013(1) C(3'*) 0.041(2) 0.027(1) 0.034(2) 0.004(1) 0.004(1) -0.004(1) 11

(01996 American Chemical Society Journal Of Medicinal Chemistry V39 Page 2835 Ma Supplemental Page 10 Table 2. Anisotropic Displacement Parameters (continued) atom U 11 U 2 2 U 3 3 U 1 2 U 13 U 23 C(4*) 0.03 0.022(1) 0.033(2) 0.002(1) 0.005(1) 0.000(1) C(4) 0.04 0.029(1) 0.032(2) 0.002(1) 0.003(1) 0.000(1) C(4') 0.034(2) 0.029(1) 0.045(2) 0.001(1) 0.004(1) 0.006(1) C(4'*) 0.036(1) 0.023(1) 0.042(2) 0.001(1) 0.007(1) -0.001(1) 0.030(1) 0.031(1) 0.035(2) 0.001(1) 0.003(1) 0.003(1) C(5*) 0.03 0.030(1) 0.041(2) 0.000(1) 0.002(1) -0.001(1) C(5') 0.077(2) 0.045(2) 0.075(3) -0.032(2) -0.023(2) 0.013(2) C(5'*) 0.047(2) 0.042(2) 0.073(2) -0.014(2) 0.007(2) -0.019(2) C(6*) 0.024(1) 0.029(1) 0.039(2) -0.002(1) -0.001(1) -0.004(1) C(6) 0.027(1) 0.032(1) 0.032(2) 0.000(1) -0.003(1) -0.003(1) C(7) 0.045(2) 0.041(2) 0.049(2) 0.004(2) -0.005(2) 0.013(2) C(7*) 0.048(2) 0.032(2) 0.046(2) 0.008(2) -0.004(2) 0.004(1) The general temperature factor expression: exp(-27r 2 (a* 2 Unjh 2 + b* 2 U 2 2 k 2 + c* 2 U 33 1 2 + 2a*b*Ul 2 hk + 2a*c*Uishl + 2b*c*U 23 kl)) 12

(01996 American Chemical Society Journal Of Medicinal Chemistry V39 Page 2835 Ma Supplemental Page 11 Table 3. Bond Lengths(A) atom atom distance atom atom distance 1.41(1) 1.409(9) 0(1) 1.243(9) 1.221(9) 1.449(9) 1.396(9) 1.43 1.234(9) 1.456(9) 1.413(8) 1.41(1) 0(9) 1.27(1) 1.214(8) 1.427(8) 1.476(9) 1.381(9) 1.376(9) 1.369(9) 1.36(1) 1.460(9) 1.378(8) 1.380(9) 1.370(9) 1.371(10) 1.52(1) 1.51(1) 1.53(1) 1.445(10) 1.35(1) 1.49(1) 1.53(1) 1.54(1) 1.53(1) 1.44(1) 1.49(1) 1.54(1) 1.55(1) 1.33(1) 13

(01996 American Chemical Society Journal Of Medicinal Chemistry V39 Page 2835 Ma Supplemental Page 12 Table 4. Bond Lengths(A) atom atom distance atom atom distance H(8) 0.93 H(9) 0.98 H(10) 0.97 H(11) 0.96 H(1) 0.98 H(3) 0.96 H(14) 0.95 H(4) 0.95 H(5) 0.96 H(19) 0.96 H(15) 0.95 H(23) 0.99 H(24) 0.99 H(16) 0.97 H(17) 0.94 H(20) 0.95 H(6) 0.94 H(7) 0.93 H(18) 0.96 H(21) 0.97 H(22) 0.98 H(2) 0.96 14

(01996 American Chemical Society Journal Of Medicinal Chemistry V39 Page 2835 Ma Supplemental Page 13 Table 5. Bond Angles(o) atom atom atom angle atom atom atom angle 104.6(5) 103.3(5) 116.2(6) 121.4(6) 122.1(7) 126.5(7) 116.0(6) 121.2(6) 122.3(6) 126.9(6) 105.2(6) 110.6(6) 115.9(7) 109.3(6) 104.0(6) 114.2(6) 118.8(7) 118.5(7) 122.7(7) 120.1(7) 124.4(7) 115.5(6) 109.7(7) 105.1(6) 117. 123.2(7) 122.4(7) 114.4(6) 109.5(6) 106.5(6) 114.2(7) 119.1(7) 125.1(7) 115.8(7) 121.7(7) 110.0(6) 107.8(6) 101.9(6) 114(1) 107.8(7) 107. 101.3(7) 113.4(8) 111.4(7) 104.7(7) 112.4(6) 113.2(6) 104.1(6) 15

(01996 American Chemical Society Journal Of Medicinal Chemistry V39 Page 2835 Ma Supplemental Page 14 Table 5. Bond Angles(*) (continued) atom atom atom angle atom atom atom angle 115.8(8) 122.4(7) 122.8(7) 114.6(7) 121.9(7) 118. 118.8(7) 123.2(7) 16

(01996 American Chemical Society Journal Of Medicinal Chemistry V39 Page 2835 Ma Supplemental Page 15 Table 6. Bond Angles(*) atom atom atom angle atom atom atom angle H(8) 118.2 H(8) 115.3 H(9) 115.1 H(9) 116.9 H(10) 107.4 H(10) 108.4 H(10) 108.9 H(11) 121.5 H(11) 110.2 H(11) 97.1 H(1) 108.7 H(1) 109.6 H(l) 106.4 H(3) 119.5 H(3) 101.7 H(3) 105.7 H(14) 116.9 H(14) 120.9 H(4) 111.3 H(5) 110.3 H(19) 109.8 B(4) H(5) 109.0 H(4) H(19) 108.5 H(5) H(19) 107.9 H(15) 110.6 H(15) 113.6 H(15) 112.5 H(23) 113.8 0(9) H(24) 112.0 H(23) 105.7 H(24) 105.7 H(23) H(24) 103.7 H(16) 109.4 H(17) 110.7 BH(20) 109.6 B(16) B(17) 109.2 1(16) H(20) 107.7 BH(17) B(20) 110.2 H(6) 114.7 H(6) 112.0 H(6) 113.0 H(7) 109.1 H(7) 108.2 H(7) 109.8 H(18) 108.7 H(18) 109.8 H(18) 108.5 BH(21) 108.7 17

(01996 American Chemical Society Journal Of Medicinal Chemistry V39 Page 2835 Ma Supplemental Page 16 Table 6. Bond Angles(o) (continued) atom atom atom angle atom atom atom angle H(22) 108.1 H(21) 109.1 H(22) 109.0 H(21) H(22) 105.6 H(2) 116.4 H(2) 121.3 18

(01996 American Chemical Society Journal Of Medicinal Chemistry V39 Page 2835 Ma Supplemental Page 17 Table 7. Torsion Angles(*) atom atom atom atom angle ((17) 79.7(8) 133.5(7) 77.9(7) ((25) 133.6(6) 0(1) (20) (38) -176.0(9) 0(1) 0(40) ((39) 179.6(9) -168.3(9) ((14) ((27) 0(9) 75(1) ((14) (33) 15.3(8)-r -31(1) ((33) 0(14) ((27) -101.1(9) 0(12) 0(15) -171.7(8) -4(1) 15.6(7) ((5) 0(15) 150.3(6) ((5) 0(25) -36.3(7) 0(9) -44(1) 0(15) 0(22) -175.7(8) 0(35) (37) -99. 0(17) ((14) 168.0(6) -7(1) 0(40) 178. 0(1) ((38) 0(39) 7(1) atom atom atom atom angle -41.3(9) -103.5(7) -41.1(8) -104.1(7) 0(1) 1(1) 5(1) 168.5(8) 137. 154.2(7) -32.5(8) -113.7(8) 175.4(8) 138.5(6) 69.3(10) -37.4(10) -50(1) -3(1) ((15) 0(12) 174. -110.6(7) -153.5(7) 0(1) -177.6(8) -178.5(8) ((5) 169.8(6) 19

(01996 American Chemical Society Journal Of Medicinal Chemistry V39 Page 2835 Ma Supplemental Page 18 Table 7. Torsion Angles(') (continued) atom atom atom atom angle -155.3(6) 1(1) -2(1) 179. 47.5(7) -39.3(7) -175.8(8) -4(1) 9.3(8) -163.1(8) -178.3(8) 138.1(7) -86.5(9) -4(1) atom atom atom atom angle -8(1) -178.4(8) 177.3(7) 6(1) 11.7(7) -165.2(7) 6(1) 44. -93.7(8) -36.6(7) 78.6(9) 137.2(8) 87.8(9) 3(1) 20

(01996 American Chemical Society Journal Of Medicinal Chemistry V39 Page 2835 Ma Supplemental Page 19 Table 8. Non-bonded Contacts out to 3.00 A atom atom distance ADC atom atom distance ADC 2.917(8) 45402 2.816(8) 1 2.876(9) 56501 2.805(8) 56501 2.816(9) 46402 2.871(8) 1 2.82(1) 44401 2.881(10) 44402 21

C01996 American Chemical Society Journal Of Medicinal Chemistry V39 Page 2835 Ma Supplemental Page 20 The ADC (atom designator code) specifies the position of an atom in a crystal. The 5-digit number shown in the table is a composite of three one-digit numbers and one two-digit number: TA (first digit) + TB (second digit) + TC (third digit) + SN (last two digits). TA, TB and TC are the crystal lattice translation digits along cell edges a, b and c. A translation digit of 5 indicates the origin unit cell. If TA = 4, this indicates a translation of one unit cell length along the a-axis in the negative direction. Each translation digit can range in value from 1 to 9 and thus -4 lattice translations from the origin (TA=5, TB=5, TC=5) can be represented. The SN, or symmetry operator number, refers to the number of the symmetry operator used to generate the coordinates of the target atom. A list of symmetry operators relevant to this structure are given below. For a given intermolecular contact, the first atom (origin atom) is located in the origin unit cell and its position can be generated using the identity operator (SN=1). Thus, the ADC for an origin atom is always 55501. The position of the second atom (target atom) can be generated using the ADC and the coordinates of the atom in the parameter table. For example, an ADC of 47502 refers to the target atom moved through symmetry operator two, then translated -1 cell translations along the a axis, +2 cell translations along the b axis, and 0 cell translations along the c axis. An ADC of 1 indicates an intermolecular contact between two fragments (eg. cation and anion) that reside in the same asymmetric unit. Symmetry Operators: (1) X, Y, Z (2) -X, 1/2+Y, -Z 22

(01996 American Chemical Society Journal Of Medicinal Chemistry V39 Page 2835 Ma Supplemental Page 21 Table 9. Non-bonded Angles(*) atom atom atom angle atom atom atom angle 37.8(4) 38.5(5) 66.3(5) 52.6(4) 60. 32.6(2) 28.3(2) 92.5(3) 52. 48.9(2) 38. 36.6(4) 64.5(4) 52.2(4) 90.5(4) 93.2(4) 59.6(3) 91.4(3) 52.1(2) 108.4(3) 130.2(3) 31.8(2) 29.1(2) 54.5(3) 87.6(3) 48.8(2) 28. 65.7(2) 56.9(2) 113.5(2) 71.8(2) 32.1(4) 29.7(4) 122.2(5) 60.8(5) 61.8(3) 90.5(3) 92.9(3) 151. 31.2(3) 169.3(4) 30.3(4) 30.7(4) 63.7(5) 128.2(6) 60.9(3) 93.9(3) 106.4(3) 23

(01996 American Chemical Society Journal Of Medicinal Chemistry V39 Page 2835 Ma Supplemental Page 22 0(27) 0(9) 33. 135. 38.7(4) 73.2(4) 64.4(4) 133.4(5) 139.9(5) 36.3(4) 89.4(4) 65.1(3) 103.1(4) 28.5(3) 103.4(3) 30. 139.1(3) 116. 65.2(3) 101.7(4) 64.1(2) 83.6(3) 34.7(5) 126.5(5) 76.4(3) 82.6(3) 132.9(3) 30.2(4) 120.7(5) 139.5(4) 104.6(5) 36.4(4) 138.7(5) 53.8(4) 76.3(5) 38.8(4) 153. 51.3(4) 38.3(3) 81.5(4) 94.9(3) 162.4(4) 61.5(2) 65.9(4) 52.3(3) 140.4(4) 24.5(4) 116.8(3) 35.8(4) 97.9(5) 59.3(3) 130.1(4) 142.7(3) 31.7(4) 61.3(5) 61.9(3) 24

(01996 American Chemical Society Journal Of Medicinal Chemistry V39 Page 2835 Ma Supplemental Page 23 93. 31.2(2) 176.2(3) 39.7(4) 73.3(4) 63.2(4) 75.9(4) 38.4(4) 151.3(5) 65.1(3) 102. 28.7(2) 164.1(4) 62.7(2) 113.9(3) 143. 61.8(2) 98.6(5) 96.2(3) 126.6(4) 121.2(8) 52.7(6) 31.5(3) 98.3(4) 47.2(2) 30.4(4) 125. 0(22) 89. 150.6(3) 103.3(5) 36. 137.1(5) 55.8(4) 138.6(4) 35.4(4) 89.6(4) 38.5(3) 78.8(3) 103.5(3) 29.9(2) 64.6(3) 52.8(2) 101.5(3) 33.3(4) 120.4(6) 98.2(3) 35.9(6) 63.2(7) 100.5(4) 28.5(2) 73.4(3) 30.7(4) 63.1(4) 61.1(2) 25

(01996 American Chemical Society Journal Of Medicinal Chemistry V39 Page 2835 Ma Supplemental Page 24 93.8(3) 32.7(2) 133. 34.9(4) 111.3(5) 58.7(3) 138.7(3) 78.4(3) 142.3(3) 74.2(2) 122.1(7) 148. 91.4(4) 114.6(5) 60.1(4) 26.8(4) 145. 109.8(5) 62.1(4) 148.6(5) 150. 60.2(4) 59.2(3) 120. 103.4(3) 165.1(4) 134.6(4) 26 104.9(3) 138.2(3) 35.1(4) 95.9(4) 169.2(5) 77.2(3) 135.8(3) 109.8(3) 143. 79.5(2) 121.4(6) 89.8(5) 28.6(4) 87.5(5) 116.2(6) 32.4(4) 93.6(5) 117.8(5) 89.5(4) 34.1(4) 33.5(4) 177.7(5) 120.6(3) 86.2(3) 88.7(3) 61.3(3) 125.4(4)

(01996 American Chemical Society Journal Of Medicinal Chemistry V39 Page 2835 Ma Supplemental Page 25 0(1) 0(1) 29.7(2) 57.4(3) 148.1(3) 104. 30.8(3) 118.9(3) 155.2(6) 33. 63.8(4) 28.8(4) 93.7(5) 62.8(4) 172.7(4) 61.8(3) 89.2(3) 120. 88.3(3) 30.9(2) 29.8(3) 176.4(4) 116.0(6) 32.7(4) 93.5(5) 123.1(5) 121.2(6) 89.7(5) 28.8(4) 0(15) 118.8(3) 69.5(2) 134.7(4) 31.5(2) 144.8(4) 126.5(7) 26.9(4) 93.5(5) 115.1(5) 152.5(5) 33. 118. 122.5(3) 91.6(3) 59.9(3) 90.5(3) 60.7(3) 148.1(3) 150.8(4) 122.3(6) 26.4(4) 143.6(5) 113.4(5) 62.1(4) 148.6(5) 92.3(4) 109.7(5) 27

(01996 American Chemical Society Journal Of Medicinal Chemistry V39 Page 2835 Ma Supplemental Page 26 0(1) 0(1) 81.8(4) 89.6(4) 34.7(3) 33.7(4) 175.3(5) 118.8(3) 92.6(3) 88.5(3) 60.9(3) 127.4(3) 119.9(3) 68.5(2) 130.3(4) 31.4(2) 142.1(4) 126.9(6) 153.5(5) 33.2(4) 118.7(4) 26.9(3) 93.9(5) 114.1(5) 122.4(3) 91.6(3) 59.8(2) 90.6(3) 61.1(3) 60.2(4) 148.7(5) 149.9(5) 60.2(4) 59.1(2) 119.9(3) 112.6(3) 164.1(4) 136.4(4) 29.5(2) 57. 149. 99.8(3) 30.5(2) 116.7(3) 28.2(4) 94.3(4) 63.4(4) 154.6(5) 32.9(3) 63.7(4) 173.2(4) 61.4(3) 90.5(3) 120.7(3) 87.2(2) 30.9(2) 28

(01996 American Chemical Society Journal Of Medicinal Chemistry V39 Page 2835 Ma Supplemental Page 27 147. 151.9(3) 110.6(6) 37.7(3) 127.6(5) 115.9(7) 139.3(7) 30.8(5) 38.2(4) 94.6(5) 90.6(3) 61.3(3) 110.8(4) 104.0(6) 72. 134.8(5) 149.1(5) 147.3(5) 87.9(4) 28.5(3) 77. 33.4(4) 105.9(5) 38.2(3) 170.5(5) 151.7(4) 150.9(4) 30.2(3) 177.8(3) 105.2(6) 68.3(4) 97.6(4) 146.3(6) 116.4(6) 75.6(4) 32.6(3) 37.9(3) 122.9(4) 108.8(4) 109.3(6) 39. 95.2(4) 86.1(4) 114.2(6) 147.4(6) 31. 57.6(4) 39.3(4) 112.4(5) 106.8(5) 87.9(3) 120.5(4) 59.8(3) 124.9(4) 29

C01996 American Chemical Society Journal Of Medicinal Chemistry V39 Page 2835 Ma Supplemental Page 28 0(15) 135.2(4) 73.2(3) 59.3(3) 86. 122.7(7) 87.5(5) 58.6(4) 25.4(4) 89.3(5) 93.2(5) 152.2(6) 56.7(3) 85.5(3) 28.9(2) 120.1(7) 153.7(6) 93.3(5) 115.5(6) 26.6(3) 56.2(4) 89.1(5) 59.3(4) 60.7(3) 120.3(4) 90.5(3) 105.1(6) 100.2(5) 100.7(4) 110.9(3) 26.7(2) 118.8(7) 144.1(6) 29.5(4) 118.5(7) 31.3(4) 60.2(4) 149.8(6) 178.7(6) 114.6(3) 58. 29.1(2) 124.4(7) 146.2(6) 175.1(6) 86.1(5) 146.7(5) 29.5(4) 31.2(4) 59.6(3) 29.9(2) 29.8(2) 109.7(7) 36.9(3) 68.6(4) 30

(01996 American Chemical Society Journal Of Medicinal Chemistry V39 Page 2835 Ma Supplemental Page 29 0(32) 117. 126.5(5) 144.1(6) 139.4(7) 75.1(5) 37.8(4) 123.8(5) 90. 110.1(4) 122.4(7) 90.2(5) 148.7(6) 99.3(5) 147.4(5) 26.5(3) 87.1(5) 28.9(4) 57.4(4) 61.8(3) 90.3(3) 59.3(3) 79.9(3) 80.6(3) 109.5(6) 38.5(4) 72.7(4) 85.2(4) 114.2(7) 31 29.1(6) 118.4(6) 94.9(5) 31.9(4) 37.7(3) 110.3(5) 60. 123.2(7) 152.0(6) 178.0(6) 114.4(6) 85.7(5) 57.2(4) 33. 88.1(4) 85.2(4) 121. 88.4(3) 28.5(2) 30.7(2) 78.7(3) 106.5(6) 97.9(5) 136.1(5) 155.5(6) 146.7(6)

C01996 American Chemical Society Journal Of Medicinal Chemistry V39 Page 2835 Ma Supplemental Page 30 0(17) 87.2(5) 30.7(3) 57.4(4) 34.4(5) 108.9(6) 98. 38.7(3) 119.3(4) 60.1(3) 76.4(3) 148.3(5) 130.3(4) 26.8(2) 119.1(7) 154.4(6) 93.6(5) 115.8(7) 26.6(4) 56.6(4) 89.2(5) 59.2(4) 60.8(3) 120.7(4) 90.8(4) 31.8(4) 151.8(6) 62.3(4) 0(1) 146.8(6) 28.2(3) 78. 39.7(5) 110.2(6) 88.9(4) 173. 155. 96.9(4) 101.7(4) 126.5(4) 58.8(3) 85.3(3) 125.1(7) 145.6(6) 175.7(6) 86.5(5) 147.3(6) 29.3(4) 31.6(4) 60. 30. 30. 121.7(7) 92.9(5) 30.1(4) 166.3(6) 32

(01996 American Chemical Society Journal Of Medicinal Chemistry V39 Page 2835 Ma Supplemental Page 31 0(1) O(ll) 132.3(6) 28.8(3) 151.8(6) 57.8(4) 61.1(3) 61.9(3) 144.7(4) 59. 30.6(2) 87.6(3) 89.5(3) 52.3(3) 148.3(4) 115.4(3) 61.3(2) 30.5(4) 57.2(3) 25.6(2) 107.8(6) 112.6(5) 85. 36.3(3) 110.9(5) 72.5(4) 31.9(3) 35.7(2) 58. 0(22) 89.9(4) 30.3(4) 59.3(4) 70.2(4) 120.1(4) 30.6(2) 124.7(3) 123. 86.1(3) 177.6(4) 30.6(2) 92.4(3) 125.7(4) 108.9(3) 26.7(4) 56.1(4) 82.8(3) 110.0(6) 99.1(5) 127.4(6) 101.9(6) 65. 32.1(4) 37.6(4) 130.3(5) 94.8(3) 60. 33

C01996 American Chemical Society Journal Of Medicinal Chemistry V39 Page 2835 Ma Supplemental Page 32 0(27) 92.8(4) 114(1) 91.1(9) 31.6(5) 27.2(4) 55.7(4) 82.8(3) 107.8(7) 98.8(6) 127.1(7) 101.3(7) 64.3(5) 32.3(4) 37.5(4) 129.3(6) 94.9(4) 60.8(4) 144.2(5) 111.4(7) 121.3(5) 115.5(7) 104.7(7) 66.2(5) 31.4(4) 69.8(5) 34.5(5) 120.5(6) 142.6(4) 102.8(8) 34. 55.8(3) 30.3(4) 57.4(3) 25.4(2) 107. 111.6(6) 83. 34.8(4) 112.2(7) 71.8(5) 32.7(4) 35.1(3) 57.5(3) 92.1(4) 113.4(8) 135.8(6) 131.6(6) 128.0(6) 36.1(4) 109.7(5) 53.6(4) 39. 126.0(6) 34.2(2) 34

C01996 American Chemical Society Journal Of Medicinal Chemistry V39 Page 2835 Ma Supplemental Page 33 A 75.7(3) 58.2(3) 0(9) 67.6(3) 59.9(3) 92.3(4) 99.7(4) 112.7(4) 95.1(4) 25.7(3) 112.4(6) 113.2(6) 135.8(5) 120.7(5) 133. 113.6(5) 104.1(6) 36.4(4) 66.1(4) 109.5(5) 31.9(4) 69. 38.8(4) 34.2(4) 126. 34.6(2) 75.1(3) 59. 60.5(3) 93.3(4) 113.2(4) 115.8(8) 100.5(6) 93.6(6) 34. 32.2(4) 56.4(3) 122.8(7) 122.4(7) 150.4(7) 89.5(5) 148.8(6) 171.9(7) 114.6(7) 85.8(5) 147.6(6) 26.9(4) 57.7(4) 28.9(4) 33.1(4) 87.9(5) 57.1(4) 61.9(3) 59.1(3) 28.2(2) 35

C01996 American Chemical Society Journal Of Medicinal Chemistry V39 Page 2835 Ma Supplemental Page 34 a 0(1) 0(1) 120.9(4) 30.8(2) 31.9(4) 30.1(4) 62.6(4) 89.9(5) 151.9(6) 59.3(4) 61. 120.3(4) 145.4(4) 59.3(3) 87.2(3) 92.6(4) 89.7(3) 116.3(3) 123.2(7) 87.6(5) 58.9(5) 89.2(5) 25.2(4) 152.7(6) 92.7(6) 58.1(3) 29.3(2) 28.8(2) 0(1) 90.1(3) 121.9(7) 92.9(5) 152.2(6) 166.9(7) 29. 30.4(4) 58.6(4) 62. 30.7(2) 122.9(4) 30.4(2) 177. 148.3(4) 30.4(2) 118.8(7) 29.6(4) 144.0(6) 118. 31.2(4) 60. 149.1(6) 176.0(6) 114.5(3) 56.4(3) 85.2(3) 36

C01996 American Chemical Society Journal Of Medicinal Chemistry V39 Page 2835 Ma Supplemental Page 35 & Hydrogen Bonds A H B A-H H...B A...B A-H...B H(8) H(9) 0(1) 0.93 1.95 0.98 1.85 2.871(8) 172 2.816(8) 170 37