-
1
-
-
79251515252
-
-
For a discussion on the inhibition of LFA-1/ICAM-1as an approach to treating autoimmune diseases see
-
For a discussion on the inhibition of LFA-1/ICAM-1as an approach to treating autoimmune diseases see
-
-
-
-
2
-
-
0036174736
-
-
Yusuf-Makagiansar, H.; Anderson, M. E.; Yakovleva, T. V.; Murray, J. S.; Siahaan, T. J. Med. Res. Rev. 2002, 22, 146
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(2002)
J. Med. Res. Rev.
, vol.22
, pp. 146
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Yusuf-Makagiansar, H.1
Anderson, M.E.2
Yakovleva, T.V.3
Murray, J.S.4
Siahaan, T.5
-
3
-
-
79251471524
-
-
For a discussion of therapeutic options for treatment of psoriasis, see
-
For a discussion of therapeutic options for treatment of psoriasis, see
-
-
-
-
5
-
-
79251486063
-
-
Larson, R. S.; Davis, T.; Bologa, C.; Semenuk, G.; Vijayan, S.; Li, Y.; Oprea, T.; Chigaev, A.; Buranda, T.; Wagner, C. R.; Sklar, L. A.
-
-
-
Larson, R.S.1
Davis, T.2
Bologa, C.3
Semenuk, G.4
Vijayan, S.5
Li, Y.6
Oprea, T.7
Chigaev, A.8
Buranda, T.9
Wagner, C.R.10
Sklar, L.A.11
-
6
-
-
79251531411
-
-
For other small-molecule LFA-1/ICAM-1 antagonists as potential drugs please see
-
For other small-molecule LFA-1/ICAM-1 antagonists as potential drugs please see
-
-
-
-
7
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0035974743
-
-
Pei, Z.; Xin, Z.; Liu, G.; Li, Y.; Reilly, E. B.; Lubbers, N. L.; Huth, J. R.; Link, J. T.; von Geldern, T. W.; Cox, B. F.; Leitza, S.; Gao, Y.; Marsh, K. C.; DeVries, P.; Okasinski, G. F. J. Med. Chem. 2001, 44, 2913
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(2001)
J. Med. Chem.
, vol.44
, pp. 2913
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Pei, Z.1
Xin, Z.2
Liu, G.3
Li, Y.4
Reilly, E.B.5
Lubbers, N.L.6
Huth, J.R.7
Link, J.T.8
Von Geldern, T.W.9
Cox, B.F.10
Leitza, S.11
Gao, Y.12
Marsh, K.C.13
Devries, P.14
Okasinski, G.F.15
-
8
-
-
0035848575
-
-
Liu, G.; Huth, J. R.; Olejniczak, E. T.; Mendoza, R.; DeVries, P.; Leitza, S.; Reilly, E. B.; Olasinski, G. F.; Fesik, S. W.; von Geldern, T. W. J. Med. Chem. 2001, 44, 1202
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(2001)
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, vol.44
, pp. 1202
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Liu, G.1
Huth, J.R.2
Olejniczak, E.T.3
Mendoza, R.4
Devries, P.5
Leitza, S.6
Reilly, E.B.7
Olasinski, G.F.8
Fesik, S.W.9
Von Geldern, T.W.10
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9
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-
6044244851
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-
Wu, J.-P.; Emeigh, J.; Gao, D. A.; Goldberg, D. R.; Kuzmich, D.; Miao, C.; Potocki, I.; Qian, K. C.; Sorcek, R. J.; Jeanfavre, D. D.; Kishimoto, K.; Mainolfi, E. A.; Nabozny, G.; Peng, C.; Reilly, P; Rothlein, R.; Sellati, R. H.; Woska, J. R.; Chen, S.; Gunn, J. A.; OBrien, D.; Norris, S. H.; Kelly, T. A. J. Med. Chem. 2004, 47, 5356
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J. Med. Chem.
, vol.47
, pp. 5356
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Wu, J.-P.1
Emeigh, J.2
Gao, D.A.3
Goldberg, D.R.4
Kuzmich, D.5
Miao, C.6
Potocki, I.7
Qian, K.C.8
Sorcek, R.J.9
Jeanfavre, D.D.10
Kishimoto, K.11
Mainolfi, E.A.12
Nabozny, G.13
Peng, C.14
Reilly, P.15
Rothlein, R.16
Sellati, R.H.17
Woska, J.R.18
Chen, S.19
Gunn, J.A.20
Obrien, D.21
Norris, S.H.22
Kelly, T.A.23
more..
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10
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0034816320
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Last-Barney, K.; Davidson, W.; Cardozo, M.; Frye, L. L.; Grygon, C. a.; Hopkins, J. L.; Jeanfavre, D. D.; Pav, S.; Qian, C.; Stevenson, J. M.; Tong, L.; Zindell, R.; Kelly, T. A. J. Am. Chem. Soc. 2001, 123, 5643
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(2001)
J. Am. Chem. Soc.
, vol.123
, pp. 5643
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Last-Barney, K.1
Davidson, W.2
Cardozo, M.3
Frye, L.L.4
C, A.G.5
Hopkins, J.L.6
Jeanfavre, D.D.7
Pav, S.8
Qian, C.9
Stevenson, J.M.10
Tong, L.11
Zindell, R.12
Kelly, T.A.13
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11
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-
9644290863
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Wang, G. T.; Wang, S.; Gentles, R.; Sowin, T.; Leitza, S.; Reilly, E. B.; von Geldern, T. W. Bioorg. Med. Chem. Lett. 2005, 15, 195
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(2005)
Bioorg. Med. Chem. Lett.
, vol.15
, pp. 195
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Wang, G.T.1
Wang, S.2
Gentles, R.3
Sowin, T.4
Leitza, S.5
Reilly, E.B.6
Von Geldern, T.W.7
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12
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0037325580
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Wattanasin, S.; Albert, R.; Ehrhardt, C.; Roche, D.; Savio, M.; Hommel, U.; Welzenbach, K.; Weitz-Schmidt, G. Bioorg. Med. Chem. Lett. 2003, 12, 499
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(2003)
Bioorg. Med. Chem. Lett.
, vol.12
, pp. 499
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-
Wattanasin, S.1
Albert, R.2
Ehrhardt, C.3
Roche, D.4
Savio, M.5
Hommel, U.6
Welzenbach, K.7
Weitz-Schmidt, G.8
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13
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77952041008
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Watterson, S. H.; Xiao, Z.; Dodd, D. S.; Tortolani, D. R.; Vaccaro, W.; Potin, D.; Launay, M.; Stetsko, D. K.; Skala, S.; Davis, P. M.; Lee, D.; Yang, X.; McIntyre, K. W.; Balimane, R.; Patel, K.; Yang, Z.; Marathe, P.; Kadiyala, P.; Tebben, A. J.; Sheriff, S.; Chang, C. Y. Y.; Ziemba, T.; Zhang, H.; Chen, B.-C.; DelMonte, A. J.; Aranibar, N.; McKinnon, M.; Barrish, J. C.; Suchard, S. J.; Dhar, T. G. M. J. Med. Chem. 2010, 53, 3814
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(2010)
J. Med. Chem.
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-
Watterson, S.H.1
Xiao, Z.2
Dodd, D.S.3
Tortolani, D.R.4
Vaccaro, W.5
Potin, D.6
Launay, M.7
Stetsko, D.K.8
Skala, S.9
Davis, P.M.10
Lee, D.11
Yang, X.12
McIntyre, K.W.13
Balimane, R.14
Patel, K.15
Yang, Z.16
Marathe, P.17
Kadiyala, P.18
Tebben, A.J.19
Sheriff, S.20
Chang, C.Y.Y.21
Ziemba, T.22
Zhang, H.23
Chen, B.-C.24
Delmonte, A.J.25
Aranibar, N.26
McKinnon, M.27
Barrish, J.C.28
Suchard, S.J.29
Dhar, T.G.M.30
more..
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14
-
-
79251490446
-
-
Due to the higher level of reactivity of isopropanol relative to that of tert -butanol, the isopropyl impurity 6 is enriched to a higher level than the level of isopropanol observed in the tert -butanol.
-
Due to the higher level of reactivity of isopropanol relative to that of tert -butanol, the isopropyl impurity 6 is enriched to a higher level than the level of isopropanol observed in the tert -butanol.
-
-
-
-
15
-
-
77955358076
-
-
Zhang, H.; Watterson, S. H.; Xiao, Z.; Dhar, T. G. M.; Balasubramanian, B.; Barrish, J. C.; Chen, B.-C. Org. Process Res. Dev. 2010, 14, 936
-
(2010)
Org. Process Res. Dev.
, vol.14
, pp. 936
-
-
Zhang, H.1
Watterson, S.H.2
Xiao, Z.3
Dhar, T.G.M.4
Balasubramanian, B.5
Barrish, J.C.6
Chen, B.-C.7
-
16
-
-
79251500422
-
-
note
-
Identification of alternative reagents for the tert -butyl ester formation was desired to avoid the use of the very odiferous thionyl chloride. Ideally, an alternative procedure would also obviate the need to source ultra-pure tert -butanol which was free of isopropanol.
-
-
-
-
18
-
-
79251503050
-
-
note
-
To the best of our knowledge, this mechanism has not been studied in detail. Our hypothesis regarding the induction period is that at the beginning of the reaction the majority of the DMAP is not initially available to enter the catalytic cycle as it forms a salt with the nicotinic acid.
-
-
-
-
19
-
-
79251489849
-
-
note
-
2O was utilized on scale-up with a molar feed rate of 0.163 mol/min. Since the gas evolution was addition controlled, the maximum potential offgassing rate was ∼7.4 L/min.
-
-
-
-
20
-
-
77952932810
-
-
The DTTA salt 4b was readily available as it was a common intermediate with BMS-578101, a first-generation molecule. For a description of its synthesis, see
-
The DTTA salt 4b was readily available as it was a common intermediate with BMS-578101, a first-generation molecule. For a description of its synthesis, see: DelMonte, A. J.; Waltermire, R. E.; Fan, Y.; McLeod, D. D.; Gao, Z.; Gesenberg, K. D.; Girard, K. P.; Rosingana, M.; Wang, X.; Kuehne-Willmore, J.; Braem, A. D.; Castoro, J. Org. Process Res. Dev. 2010, 14, 553
-
(2010)
Org. Process Res. Dev.
, vol.14
, pp. 553
-
-
Delmonte, A.J.1
Waltermire, R.E.2
Fan, Y.3
McLeod, D.D.4
Gao, Z.5
Gesenberg, K.D.6
Girard, K.P.7
Rosingana, M.8
Wang, X.9
Kuehne-Willmore, J.10
Braem, A.D.11
Castoro, J.12
-
21
-
-
79251489552
-
-
Throughout this publication mL/g refers to mL of solvent to grams of input material.
-
Throughout this publication mL/g refers to mL of solvent to grams of input material.
-
-
-
-
22
-
-
79251487265
-
-
The same impurity was also observed during the Discovery development work (see ref. 6).
-
The same impurity was also observed during the Discovery development work (see ref. 6).
-
-
-
-
23
-
-
79251469497
-
-
note
-
7 in the presence of 2 equiv of DBU. After 2 h, NMR and HPLC indicated ∼15% formation of the undesired diastereomer 10. This amount increased to ∼30% after 4 h of heating.
-
-
-
-
24
-
-
79251475339
-
-
2O was evidenced by absence of the tert -butyl carboxylate of 4a which could be observed if 4b was charged to the mixture immediately.
-
2O was evidenced by absence of the tert -butyl carboxylate of 4a which could be observed if 4b was charged to the mixture immediately.
-
-
-
-
25
-
-
79251513370
-
-
Yields reported are corrected yields, and the HPLC area percent purity reported is the combined HPLC area percent purity for the spirocyclic hydantoin 5a and p -TSA.
-
Yields reported are corrected yields, and the HPLC area percent purity reported is the combined HPLC area percent purity for the spirocyclic hydantoin 5a and p -TSA.
-
-
-
-
26
-
-
79251481235
-
-
A D90 < 60 -m was desired.
-
A D90 < 60 -m was desired.
-
-
-
-
27
-
-
79251488547
-
-
For a review on the Ritter reaction see
-
For a review on the Ritter reaction see
-
-
-
-
29
-
-
79251487595
-
-
note
-
The high loss of 1 to mother liquor may have been due to the uncontrolled crystallization, the new morphology or the higher than previously observed level of impurities. It is notable that pXRD indicated 1 had the correct polymorphic form with little to no amorphous content.
-
-
-
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