Supporting information for J. Med. Chem., 1994, 37(5), 674 688, DOI: 10.1021/jm00031a018 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 machine-readable 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 1994 American Chemical Society
11 WO- (1%%-m Compound homogeneity was determined by analytical reverse phase HPLC using a Dynamax-60A column (5µ; 250 mm 4.6 mm; C18) using eluents A: water, 0.1% TFA, and B: acetonitrile, 0.1% TFA, with gradient elution from 85% A : 15% to 20% A : 80% over 30 min with a flow rate of 1.5 ml/min. The eluent was monitored by UV absorption at 215 nm. Compounds were characterized by NMR using a Varian Unity 300 spectrometer using TMS or solvent as an internal standard. 70
DELAY FILE 1 VIAL 1.05 INJ 1 OF 1 VOL. 1010 TRAY 14 EQUIL. TIME.00 GRAD..00 CHANNEL A INJECT 29-10-91 15:03:23 STORED TO BIN # 66??? ER 0 DATA SAVED TO BIN# 66 INPUT OVERRANGE AT RT = 2.39 29-10-91 FILE 1. METHOD 1. ^ INDEX 58 " ro CH= "A" PS= BIN 0. RUN 58 PEAK# AREA% RT 66 58 BIN 66 AREA BC 1 9.066 2.07 1029572 01 2 2.037 2.69 231330 02 3 6.776 3.64 769476 03 4 1.401 4.85 159145 01 5 1.274 5.96 144659 02 6 1.615 6.57 183380 02 / 1.116 7.61 126772 03 V 0.68 8.39 77183 r --* r 01 * 3
m. DIALOGl AUTOSAMPLER FILE...PRESS ERASE? (Y OR ) Y <ENTER> TO SKIP TO NEXT QUERY VIAL INJ VOL I J/VIAL CAL INT CAL VIAL FILE 1.01 1010 1 1 LAST VIAL? (0 ) 1.04 SYRINGE RATE? ( 2) END A/S DIALOG FILE 1 VIAL 1.01 INJ 1 OF 1 VOL 1010 TRAY 1 EQUIL. TIME.00 GRAD. DELAY.00 CHANNEL A INJECT 09-06-92 13:09:13 STORED TO BIN # 45 It78???ER 0 DATA SAVED TO BIN # 45
CHANNEL A INJECT 05-08-91 08:33:33 STORED TO BIN # 103??? DATA SAVED TO BIN # 103 INPUT OVERRANGE AT RT= 14.1 17 05-08-91 08:33:33 CH= "A" PS= 1. FILE 1. METHOD 0. RUN 127 INDEX 127 BIN 103 PEAK# AREA% RT AREA BC 4 97.909 14.06 24087188 0150.363 15.68 89387 01 6 1.728 16.94 425058 01 TOTAL 100. 24601633 100. 24601633
CHANNEL A INJECT 28-05-91 14:22:49 STORED TO BIN # 34??? DATA SAVED TO BIN # 34 LC CONDITIONS UNIT1 RUN FILE 1 TIME %A %B %C FLOW 0.0 85.0 0.0 15.0 1.50 30.0 20.0 0.0 80.0 1.50 35.0 85.0 0.0 15.0 1.50 MAX. PRESS. LIMIT=3500 PSl M1N. PRESS. LIMIT0PSl 3 j* oo INPUT OVERRANGE AT RT= 2.12 28-05-91 14:22:49 CH= "A" PS= 1. FILE 1. METHOD 0. RUN 55 INDEX 28 BIN 34 PEAK# AREA% RT AREA BL AREA BL
??? DATA SAVED TO BIN # 45 INPUT OVERRANGE AT RT= 2.08 18-06-91 15:17:47 CH= "A" PS= 1. FILE 1. METHOD 0. RUN 63 INDEX 63 BIN 45 PEAK# AREA% RT AREA BC 3 3.195 5.97 336478 01 4 1.573 10.75 165639 01 5 92.181 14.5 9708475 01 6 1.895 16.62 199597 01 7 1.156 19.53 121741 01 3 c 3 TOTAL 100. 10531930
CHANNEL A INJECT 29-08-91 09:44: 18 STORED TO BIN # 29??? DATA SAVED TO BIN # 29 INPUT OVERRANGE AT RT= 11.62 29-08--91 09:44:18 CH= "A" PS= 1. FILE 1 METHOD 0. RUN 312 INDEX 312 BIN 29 3 " PEAK# AREA% RT AREA BC c 4 0.537 8.52 163952 01 D u 5 0.602 10.42 183965 02 6 0.402 10.64 122760 02 in 7 3.43 10.86 1047661 03 8 3.569 11.3 1090155 02 9 85.686 11.55 26170205 02 10 5.773 12.1 1763336 03 TOTAL 100. 30542034
CHANNEL A INJECT 13-09-91 14:27: 57 STORED TO BIN # 9??? DATA SAVED TO BIN # 9 c/i CO INPUT OVERRANGE AT RT= 8.24 RUN2068 13-09- 91 FILE1. METHOD 0. RUN 419 PEAK# AREA% "A" PS= 1. INDEX 419 BIN 9 BIN 9 RT AREA BC 1 1.753 2.12 299873 01 2 0.197 6.11 33634 01 3 0.212 7.52 36315 02 4 0.77 7.81 131780 03 5 93.16 8.21 15936692 016 0.657 9.24 112403 01 7 2.332 10.1 398896 01 8 0.919 10.68 157241 01 TOTAL 100. 17106834 4:27:57 CH=
' W if??? DATA SAVED TO BIN tt 6 3 INPUT OVERRANGE AT RT= 17.2 5 Q. cn 10-05-92 11:49:34 CH= "A" PS= 1. (71 FILE 1. METHOD 0. RUN 772 INDEX 772 BIN 6 PEAK# AREA% RT AREA BC 1 0.259 16.06 151583 01 2 97.463 17.07 56969944 02 3 1.666 17.7 974063 02 4 0.611 18.18 357341 03 TOTAL 100. 58452931 c WARNING - MEMORY AT 10. - UNPROTECTED CHROMATOGRAMS WILL BE REPLACED
01? FILE 1 VIAL 2.04 INJ 1 OF 1 VOL 1010 TRAY 15 EQUIL. TIME.00 GRAD. DELAY.00 CHANNEL A INJECT 16-02-92 23:52:20 STORED TO BIN # 128??? DATA SAVED TO BIN # 128
. CHANNEL A INJECT 05/03/91 09:18:59 REPLAYED FROM BIN # 48 4^.??? INPUT OVERRANGE AT RT= 15.83 Q 3 05/03/91 09:18:59 CH= "A" PS= 1. FILE 1. METHOD 0. RUN 205 INDEX 205 BIN 48 PEAK# AREA% RT AREA BC 1 0.899 2.05 551072 01 2 0.032 2.21 19860 01 3 0.312 2.27 191345 02 4 0.34 2.32 208309 03 5 0.117 11.19 71990 01 6 0.345 14.95 211261 01 7 97.708 15.54 59914230 01 8 0.067 16.98 41041 01 9 0.103 21.73 63222 01 10 0.078 24.02 47584 01 > * r 1 orx OO 1
CHANNEL A INJECT 31-05-91 10:44:13 STORED TO BIN # 50??? DATA SAVED TO BIN # 50 LC CONDITIONS UNIT 1 RUN FILE 1 TIME XA XB XC FLOW 0.0 85.0 0.0 15.0 1.50 30.0 20.0 0.0 80.0 1.50 35.0 85.0 0.0 15.0 1.50 MAX. PRESS. LIMIT = 3500 PSI M1N. PRESS. LIMIT = 0 PSI INPUT OVERRANGE AT RT= 2.15 -Q 31-05-91 10:44:13 CH= "A" PS= 1 3 FILE 1. METHOD 0. RUN 72 INDEX 45 BIN 50 Q) CO PEAK# AREA% RT AREA BC 1 3.545 2.04 403159 01 2 1.832 8.98 208311 01 3 2.531 12.21 287815 01
pj CHANNEL A INJECT 02-08-91 1 1 :03: 56 STORED TO BIN tt 100??? DATA SAVED TO BIN # 100 > A INPUT OVERRANGE AT RT= 16.51
U1514/62/1 CRUDE DS1.A FAULT 10 CHANNEL A INJECT 16-09-91 08:05:13 STORED TO BIN # 97??? DATA SAVED TO BIN # 97
CHANNEL A INJECT 16-08-91 08:55:22 REPLAYED FROM BIN # 46 AZ 1??? INPUT OVERRANGE AT RT= 10.08 16-08-91 08:55:22 CH= "A" PS= 1. FILE 1. METHOD 0. RUN 320 INDEX 320 BIN 46 PEAK# AREA% RT AREA BC 1 0.1 0.97 38620 01 2 0.082 1.14 31423 01 3 0.866 1.36 333201 01 4 1.073 1.68 412551 01 5 1.369 2.06 526567 01 6 13.088 3.28 5034255 02 7 72.781 10.03 27994983 02 8 0.967 10.75 372130 02 9 1.935 11.36 744308 02 10 7.739 1 1.92 2976585 03
CHANNEL A INJECT 06-08-91 13:49:32 REPLAYED FROM BIN # 121??? INPUT OVERRANGE AT RT= 2.11 06-08-91 13:49:32 CH= "A" PS= 1. FILE 1. METHOD 0. RUN 147 INDEX 147 BIN 121 PEAK# AREA%. RT AREA BC 2 100. 9.27 20672991 01 TOTAL 100. 20672991 INK LOW - CHANGE PRINT CARTRIDGE AND PRESS [CTRL-SHIFT-C]
VIAL 4.05 INJ 1 OF 1 VOL 1010 TRAY 12 EQUIL TIME.00 GRAD DELAY.00 CHANNEL A INJECT 01-01-92 15:01:46 STORED TO BIN # 55??? 3 > < DATA SAVED TO BIN # 55 INPUT OVERRANGE AT RT= 2.32 01-01--92 FILE 1 METHOD 0. RUN 315 5:01:46 CH= "A" PS= 1. INDEX 315 BIN 55 PEAK# AREA% RT AREA BC 1 4.283 1.9 1019355 01 2 5.854 2.38 1393389 02 3 6.028 3.5 1434662 02 4 6.244 4.08 1486262 02 5 7.226 4.99 1719940 02 6 4.598 5.9 1094305 02 7 7.035 6.59 1674578 02 8 4.08 7.71 971097 02 A OC"J / rs r\ 4
CHANNEL A INJECT 10-02-92 21:32:27 STORED TO BIN # 71??? DATA SAVED TO BIN # 71 INPUT OVERRANGE AT RT= 2.24 3 01-02-92 21:32:27 CH= "A" PS= 1. C FILE 1. METHOD 0. RUN 464 INDEX 464 BIN 71 V PEAK# AREA% RT AREA BC -%l 1 4.216 1.84 1112057 01 2 1.647 2.34 434399 01 3 2.041 3.46 538290 02 4 5.088 3.99 1341811 03 5 2.046 7.55 539495 02 6 1.306 9.26 344374 02 7 1.919 11.28 505991 02 8 0.438 12.99 115599 02 9 0.193 13.36 50984 02 10 81.107 14.16 21391186 03 1 ( (?f,r74 1 fl*
CHANNEL A INJECT 13-11-91 09:54:32 STORED TO BIN # 120 AZ1??? DATA SAVED TO BIN # 120 INPUT OVERRANGE AT RT= 2.24 g 13-11-91 09:54:32 CH= "A" PS= 1. C D FILE 1. METHOD 0. RUN 117 INDEX 117 BIN 120 Q PEAK# AREA% RT AREA BC 1 2.129 0.92 992404 02 2 2.963 1.77 1381228 02 3 3.065 2.3 1428648 02 4 4.541 3.32 2116403 02 5 8.255 4.22 3847638 02 6 2.606 5.88 1214769 02 >1 3.183 6.68 1483709 02 " T-*/-. -» / /-«I OO
END A/S DIALOG FILE 1 VIAL 2.01 INJ 1 OF 1 VOL 1010 TRAY 15 EQUIL. TIME.00 GRAD. DELAY.00 CHANNEL A INJECT 30-10-91 15:39:51 STORED TO BIN # 80??? 24.44 3 ER 0 2 DATA SAVED TO BIN # 80. -J ro c INPUT OVERRANGE AT RT= 13.46 30-10-91 15:39:51 CH= "A" PS= 1. FILE 1. METHOD 0. RUN 72 INDEX 72 BIN 80 PEAK# AREA% RT AREA BC 1 n nn ooo / m
. 13. 8... 5,098.41 56068.1 02 vi:a- v:v<:3 i "' 9.32.15' V 2.594 10.14! 285331 <32. 16 1.619 10.93 178079 02 17 0.907 11.32 99810 02 18 3.244 11.94 356792 03 19 3.278 28.17 360588 02 20 11.328 28.46 1245956 03 : :/47856 ;40 '> TOTAL 100. 10998989 WARNING - MEMORY AT 0. - UNPROTECTED FILE 1 VIAL 3.02 INJ 1 OF 1 VOL 1010 TRAY 9 EQUIL. TIME.00 GRAD. DELAY.00 CHANNEL A INJECT 13-11-91 09:13:22 STORED TO BIN It 119 AZ 1??? DATA SAVED TO BIN # 119 W INPUT OVERRANGE AT RT= 2.24
U1514/81/ AFTER FREEZE-DRYER DS1.A FAULT 10 CHANNEL A INJECT 07-10-91 08:52:21 STORED TO BIN # 102??? DATA SAVED TO BIN # 102 INPUT OVERRANGE AT RT= 16.94
??? data saved to bin # 91.g 22-09-92 15:06:54 ch= "a" ps= 1. c 3 ci file 1. method 0. run 438 index 438 bin 91 (j\ peak# area% rt area bc 1 4.035 2.03 899666 03 2 1.483 11.28 330537 02 3 38.074 11.71 8489031 03 4 21.561 27.71 4807251 01 5 34.847 33.25 7769371 01
??? DATA SAVED TO BIN # 123 INPUT OVERRANGE AT RT= 2.2 q 3 29-09-92 08:42:42 CH= "A" PS= 1. FILE 1. METHOD 0. RUN 467 INDEX 467 BIN 123 PEAK# AREA% RT AREA BC Q. 1 1.576 1.82 679144 01 2 3.559 2.27 1534289 02 01 3 8.108 5.31 3494854 02 4 3.361 10.48 1448980 02 5 0.329 10.75 141899 02 6 69.763 12.03 30071680 03 7 0.244 15.5 105326 01 8 0.294 25.41 126673 02 9 12.765 27.65 5502509 03
FILE 1 VIAL 4.02 INJ 1 OF 1 VOL 1010 TRAY 12 EQUIL. TIME.00 GRAD. DELAY.00 CHANNEL A INJECT 01-01-92 17:05:51 STORED TO BIN # 57??? 1 DATA SAVED TO BIN # 57 INPUT OVERRANGE AT RT= 2.29 01-01- 92 7:05:51 CH= MA" PS= 1. FILE 1 METHOD 0. RUN 317 INDEX 317 BIN 57 PEAK# AREA% RT AREA BC 1 2.239 1.88 965907 01 2 2.697 2.38 1163418 02 3 3.468 3.44 1496085 02 4 3.378 4.08 1456968 02 5 4.448 4.94 1918636 02 6 3.048 5.95 1314719 02 7 3.061 6.8 1320465 02
??? CHANNEL A INJECT 13-06-92 18:18:51 STORED TO BIN #82 AZ1 DATA SAVED TO BIN # 82 INPUT OVERRANGE AT RT 2.83 3 13-06--92 18:18:51 CH= "A" PS= 1. FILE 1 METHOD 0. RUN 80 INDEX 80 BIN 82 PEAK# AREA% RT AREA BC 00 1 4.058 1.76 940587 01 2 7.492 2.28 1736592 01 3 32.161 5.68 7455031 02 4 2.517 13.42 583423 03 5 43.673 19.34 10123370 01 6 10.1 27.86 2341153 03 TOTAL 100. 23180156 WARN 1NG - MEMORY AT 0. -- UNPROTECTED CHROMATOGRAMS W1ILL BE REPLACED
FILE 1 VIAL 2.02 INJ 1 OF 1 VOL 1010 TRAY 15 EQUIL. TIME.00 GRAD. DELAY.00 CHANNEL A INJECT 16-02-92 22:29:58 STORED TO BIN # 126??? DATA SAVED TO BIN # 126 I PUT OVERRANGE AT RT= 2.29
??? DATA SAVED TO BIN # 81 INPUT OVERRANGE AT RT 1 0.47 13-06--92 17:37:40 CH= "A" PS= 1. FILE 1 METHOD 0. RUN 79 INDEX 79 BIN 81 PEAK# AREA% RT AREA BC 1 1.965 1.75 940605 01 L 3.69 2.28 1766505 01 3 3.977 10.08 1903867 02 4 86.387 10.34 41359392 03 5 0.163 13.44 77897 01 6 0.353 18.54 168992 02 7 0.241 19.5 115364 03 8 3.225 27.86 1544072 03 TOTAL 100. 47876694 WARNING - MEMORY AT 5. - UNPROTECTED CHROMATOGRAMS W1ILL BE REPLACED
EQUIL. TIME.00 GRAD. DELAY.00 CHANNEL A INJECT 27-07-92 11:15:49 STORED TO BIN # 2 AZ 1??? DATA SAVED TO BIN # 7.86 ner 0 INPUT OVERRANGE AT RT= 14.05 " 27-07-92 11:15:49 CH= "A" PS= 1. ^ FILE 1. METHOD 0. RUN 253 PEAK# AREA% RT AREA BC 1 2.24 2.19 894738 01 2 1.525 13.35 609301 01 3 89.349 13.99 35694112 01 4 0.065 18.99 26095 01 5 6.821 27.86 2724809 03 TOTAL 100. 39949055 INDEX 253 BIN 2 00 WARNING - MEMORY AT 0. - UNPROTECTED CHROMATOGRAMS WILL BE REPLACED