US 7,465,799 B2
Methods and compositions for selectin inhibition
Neelu Kaila, Lexington, Mass. (US); Silvano L. Debernardo, Verona, N.J. (US); Kristin M. Jantz, Arlington, Mass. (US); Raymond T. Camphausen, Wayland, Mass. (US); and Patricia W. Bedard, Mansfield, Mass. (US)
Assigned to Wyeth, Madison, N.J. (US)
Filed on Nov. 09, 2004, as Appl. No. 10/984,093.
Claims priority of provisional application 60/518950, filed on Nov. 10, 2003.
Prior Publication US 2005/0101568 A1, May 12, 2005
Int. Cl. C07D 215/38 (2006.01)
U.S. Cl. 546—156  [546/153] 16 Claims
 
1. A compound having the Formula II:

OG Complex Work Unit Drawing
or a pharmaceutically acceptable salt thereof, wherein:
Y is O, (CR3R4)p or NR5;
p is 1 to 3;
X is OH, OR3, OC1-6 alkyl, OC(═O)aryl, OC(═O)C1-6 alkyl, OC(═O)OC1-6 alkyl or NR3R3′;
each R1, R2 R3, R3′ and R4 is independently hydrogen, C1-6 alkyl, C1-6 perhaloalkyl, OC1-6 perhaloalkyl, halogen, thioalkyl, CN, OH, SH, (CH2)nOSO3H, (CH2)nSO3H, (CH2)nCO2R6, OSO3R6, SO2R6, SO3R6, PO3R6R7, (CH2)nSO2NR8R9, (CH2)nC(═O)NR8R9, C(═O)R12, aryl, heterocyclo, C(═O)aryl, C(═O)heterocyclo, OC(═O)aryl, OC(═O)heterocyclo, Oaryl, Oheterocyclo, arylalkyl, C(═O)arylalkyl, OC(═O)arylalkyl, Oarylalkyl, alkenyl, alkynyl, or NHCOR8, wherein any of said alkyl, Oalkyl, aryl, heterocyclo, C(═O)aryl, C(═O)heterocyclo, O—C(═O)aryl, O—C(═O )heterocyclo, O-aryl, O-heterocyclo, arylalkyl, C(═O)arylalkyl, O—C(═O)arylalkyl, O-arylalkyl, alkenyl or alkynyl can optionally be substituted with up to three substituents selected from halogen, C1-6 alkyl, OC1-6 alkyl and CN;
each R6 and R7 is independently selected from the group consisting of hydrogen and C1-6 alkyl that is optionally substituted with up to three substituents selected from OH, CF3, SH and halogen;
each R5, R8 and R9 is independently selected from the group consisting of hydrogen, C1-6 alkyl, C1-6haloalkyl, thioalkyl, OH, (CH2)1OSO3H, (CH2)1SO3R10, (CH2)nCO2R10, SO3R10, PO3R10R11, (CH2)nSO2(CH2)nNR10R11, (CH2)nCONR10R11, COR10, aryl, heterocyclo, C(═O)aryl, C(═O)heterocyclo, O—C(═O)aryl, O—C(═O)heterocyclo, Oaryl, Oheterocyclo, arylalkyl, C(═O)arylalkyl, OC(═O)arylalkyl, Oarylalkyl, alkenyl, or alkynyl, wherein any of said alkyl, aryl, heterocyclo, C(═O)aryl, C(═O)heterocyclo, OC(═O)aryl, OC(═O)heterocyclo, Oaryl, Oheterocyclo, arylalkyl, C(═O)arylalkyl, OC(═O)arylalkyl, Oarylalkyl, alkenyl or alkynyl can optionally be substituted with up to three substituents selected from halogen, C1-6 alkyl, OC1-6 alkyl and CN;
each n is an independently selected integer from 0 to 6;
each l is an independently selected integer from 1 to 6;
each R10 and R11 is independently selected from the group consisting of hydrogen and C1-6 alkyl that is optionally substituted with up to three substituents selected from OH, CF3, SH and halogen;
each R12 is independently hydrogen, C1-6 alkyl, C1-6 perhaloalkyl, OC1-6 alkyl, OC1-6 perhaloalkyl, thioalkyl, OH, (CH2)1OSO3H, (CH2)1SO3H, (CH2)1CO2R6, (CH2)1SO2NR8R9,(CH2)nC(═O)NR 8R9, NR8R9, alkenyl, alkynyl, or NHCOR8, wherein any of said alkyl, Oalkyl, alkenyl or alkynyl can optionally be substituted with up to three substituents selected from halogen, C1-6 alkyl, OC1-6 alkyl and CN; and
Z is aryl, arylalkyl, heteroaryl or heterocyclo, wherein each of said aryl, arylalkyl, heteroaryl and heterocyclo is optionally substituted.