- Kilogram synthesis of a LFA-1/ICAM inhibitor
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The process development and the kilogram-scale synthesis of BMS-587101 (1) are described. The synthesis features a [3 + 2] azomethine ylide cycloaddition to efficiently build the spirocyclic core in a diastereoselective fashion followed by a classical res
- Delmonte, Albert J.,Waltermire, Robert E.,Fan, Yu,McLeod, Douglas D.,Gao, Zhinong,Gesenberg, Kirsten D.,Girard, Kevin P.,Rosingana, Miguel,Wang, Xuebao,Kuehne-Willmore, Jennifer,Braem, Alan D.,Castoro, John A.
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scheme or table
p. 553 - 561
(2011/07/30)
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- Small molecule antagonist of leukocyte function associated antigen-1 (LFA-1): Structure-activity relationships leading to the identification of 6-((5 S,9 R)-9-(4-Cyanophenyl)-3-(3,5-dichlorophenyl)-1-methyl-2,4-dioxo-1,3,7- triazaspiro[4.4]nonan-7-yl)nico
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Leukocyte function-associated antigen-1 (LFA-1), also known as CD11a/CD18 or αLβ2, belongs to the β2 integrin subfamily and is constitutively expressed on all leukocytes. The major ligands of LFA-1 include three intercellu
- Watterson, Scott H.,Xiao, Zili,Dodd, Dharmpal S.,Tortolani, David R.,Vaccaro, Wayne,Potin, Dominique,Launay, Michele,Stetsko, Dawn K.,Skala, Stacey,Davis, Patric M.,Lee, Deborah,Yang, Xiaoxia,McIntyre, Kim W.,Balimane, Praveen,Patel, Karishma,Yang, Zheng,Marathe, Punit,Kadiyala, Pathanjali,Tebben, Andrew J.,Sheriff, Steven,Chang, Chiehying Y.,Ziemba, Theresa,Zhang, Huiping,Chen, Bang-Chi,Delmonte, Albert J.,Aranibar, Nelly,McKinnon, Murray,Barrish, Joel C.,Suchard, Suzanne J.,Murali Dhar
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scheme or table
p. 3814 - 3830
(2010/07/05)
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- Synthesis of lead LFA-1 antagonist [14C]spyrocyclic hydantoin
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Radiolabelled drug lead candidate leukocyte function-associated antigen 1 antagonist [14C]spyrocyclic hydantoin: 5-(((5S,9R)-9-(4-[ 14C]-cyanophenyl)-3-(3,5-dichlorophenyl)-1-methyl-2,4-dioxo-1,3, 7-triazaspiro[4.4]nonan-7-yl)methyl)
- Tran, Scott B.,Maxwell, Brad D.,Chen, Shiang-Yuan,Bonacorsi, Samuel J.,Leith, Leslie,Ogan, Marc,Rinehart, J. Kent,Balasubramanian, Balu
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experimental part
p. 236 - 242
(2010/06/16)
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- CRYSTALLINE FORMS OF6- [(5S, 9R) -9- (4-CYANOPHENYL) -3-(3, 5-DICHLOROPHENYL) -1-METHYL-2, 4-DIOXO-1, 3, 7-TRIAZASPIRO [4.4] NON-7-YL] NICOTINIC
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The invention provides crystalline forms of 6-[(5S,9R)-9-(4-cyanophenyl)-3-(3,5-dichlorophenyl)-1-methyl-2,4-dioxo-1,3,7-triazaspiro[4.4]non-7-yl]nicotinic acid, its pharmaceutically acceptable salts, or solvates, thereof Further, a process is provided fo
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Page/Page column 66
(2010/11/08)
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- Discovery and development of 5-[(5S,9R)-9-(4-cyanophenyl)-3-(3,5- dichlorophenyl)-1-methyl-2,4-dioxo-1,3,7-triazaspiro[4.4]non-7-yl-methyl] -3-thiophenecarboxylic Acid (BMS-587101) - A small molecule antagonist of leukocyte function associated antigen-1
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LFA-1 (leukocyte function-associated antigen-1), is a member of the β2-integrin family and is expressed on all leukocytes. This letter describes the discovery and preliminary SAR of spirocyclic hydantoin based LFA-1 antagonists that culminated in the iden
- Potin, Dominiques,Launay, Michele,Monatlik, Francoise,Malabre, Patrice,Fabreguettes, Maud,Fouquet, Andre,Maillet, Magali,Nicolai, Eric,Dorgeret, Lo?c,Chevallier, Fran?ois,Besse, Dominique,Dufort, Monique,Caussade, Fran?ois,Ahmad, Syed Z.,Stetsko, Dawn K.,Skala, Stacey,Davis, Patricia M.,Balimane, Praveen,Patel, Karishma,Yang, Zheng,Marathe, Punit,Postelneck, Jennifer,Townsend, Robert M.,Goldfarb, Valentina,Sheriff, Steven,Einspahr, Howard,Kish, Kevin,Malley, Mary F.,DiMarco, John D.,Gougoutas, Jack Z.,Kadiyala, Pathanjali,Cheney, Daniel L.,Tejwani, Ravindra W.,Murphy, Denette K.,Mcintyre, Kim W.,Yang, Xiaoxia,Chao, Sam,Leith, Leslie,Xiao, Zili,Mathur, Arvind,Chen, Bang-Chi,Wu, Daugh-Rurng,Traeger, Sarah C.,McKinnon, Murray,Barrish, Joel C.,Robl, Jeffrey A.,Iwanowicz, Edwin J.,Suchard, Suzanne J.,Dhar, T. G. Murali
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p. 6946 - 6949
(2007/10/03)
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- Spiro-hydantoin compounds useful as anti-inflammatory agents
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Compounds having the formula (I), and pharmaceutically-acceptable salts, hydrates, enantiomers, and diastereomers, and prodrugs thereof, are useful as inhibitors of LFA-1/ICAM and as anti-inflammatory agents, wherein L and K are O or S; Z is N or CR4b; Ar is an optionally-substituted aryl or heteroaryl; G is a linker attached to T or M or is absent; J, M and T are selected to define a three to six membered saturated or partially unsaturated non-aromatic ring; and R2 R4a, R4b, and R4c are as defined in the specification.
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Page/Page column 45
(2008/06/13)
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