Modulators of cellular adhesion
View Patent ↗The present invention provides compounds having formula (I): and pharmaceutically acceptable derivatives thereof, wherein R 1 -R 4 , n, p, A, B, D, E, L and AR 1 are as described generally and in classes and subclasses herein, and additionally provides pharmaceutical compositions thereof, and methods for the use thereof for the treatment of disorders mediated by the CD11/CD18 family of cellular adhesion molecules (e.g., LFA-1).
1. A compound of the following structure:
or pharmaceutically acceptable salts thereof; wherein
—C(═O)NHC(R 1 )(R 2 )R 3 is a moiety having the following structure:
R 3A is hydrogen;
R S is hydrogen;
Ar 2 is:
s is an integer of 1;
each occurrence of R P1 is independently hydrogen, halogen, or -GR G1 , wherein G is —SO 2 —, or —SO 2 NR G2 —; and R G1 and R G2 are independently hydrogen, an aliphatic, alicyclic, heteroaliphatic, heterocyclic, aromatic or heteroaromatic moiety;
R B1 , R B2 and R E are hydrogen;
R 4A and R 4B are each Cl;
L is C═O; and
AR 1 is
wherein R Q1 is independently hydrogen, OR Q3 , OCF 3 , SR Q3 , halogen, CN, isocyanate, NO 2 , CF 3 , NR Q3 R Q4 , —SO 2 R Q3 , alkyl-NR Q3 R Q4 , alkyl-C(═O)—NR Q3 R Q4 , alkyl-C(═O)R Q3 , or an aliphatic, alicyclic, heteroaliphatic, heterocyclic, aryl, heteroaryl, alkylaryl, alkylheteroaryl, heteroalkylaryl, or heteroalkylheteroaryl moiety, wherein each occurrence of R Q3 and R Q4 is independently hydrogen, a protecting group, or an aliphatic, heteroaliphatic, aryl or heteroaryl moiety;
and r is an integer from 0-6.
2. The compound of claim 1 , wherein R P1 is selected from the group consisting of halogen and -GR G1 , wherein G is —SO 2 — and R G1 is methyl.
3. The compound of claim 2 , wherein R P1 is selected from the group consisting of F and SO 2 CH 3 .
4. A pharmaceutical composition comprising a compound of claim 1 and a pharmaceutically acceptable carrier or diluent.
5. A pharmaceutical composition comprising a compound of claim 2 and a pharmaceutically acceptable carrier or diluent.
6. A pharmaceutical composition comprising a compound of claim 3 and a pharmaceutically acceptable carrier or diluent.