Alkene azetidine derivatives as sphingosine 1-phosphate (s1p) receptor modulators

A method of treating an immunosuppressant disorder associated with the sphingosine-1-phosphate receptor modulation, wherein the immunosuppressant disorder is selected from:

• rheumatoid arthritis, psoriasis, atherosclerosis, autoimmune uveitis, dry eye, inflammatory bowel diseases, atopic allergy, atopic dermatitis, contact dermatitis, multiple sclerosis, Sjogren's syndrome and organ transplant rejection, in a mammal in need thereof, which comprises administering to a mammal in need thereof, a pharmaceutical composition comprising a therapeutically effective amount of at least one compound represented by Formula I or a pharmaceutically acceptable salt thereof:
• wherein:
• A is optionally substituted C6-10 aryl, optionally substituted heterocycle, optionally substituted C3-8 cycloalkyl or optionally substituted C3-8 cycloalkenyl;
• B is optionally substituted C6-10 aryl, optionally substituted heterocycle, optionally substituted C3-8 cycloalkyl or optionally substituted C3-8 cycloalkenyl;
• R1 is H, halogen, —OC1-8 alkyl, optionally substituted C1-8 alkyl, CN, C(O)R11, NR12R13 or hydroxyl;
• R2 is H, halogen, —OC1-8 alkyl, optionally substituted C1-8 alkyl, CN, C(O)R11, NR12R13 or hydroxyl;
• R3 is H, halogen, —OC1-8 alkyl, optionally substituted C1-8 alkyl, CN, C(O)R11, NR12R13 or hydroxyl;
• R4 is H, halogen, —OC1-8 alkyl, optionally substituted C1-8 alkyl, CN, C(O)R11, NR12R13 or hydroxyl;
• R5 is H, halogen, —OC1-8 alkyl, optionally substituted C1-8 alkyl, CN, C(O)R11, NR12R13 or hydroxyl;
• R6 is H, halogen, —OC1-8 alkyl, optionally substituted C1-8 alkyl, CN, C(O)R11, NR12R13 or hydroxyl;
• R7 is H, halogen, —OC1-8 alkyl, optionally substituted C1-8 alkyl, CN, C(O)R11, optionally substituted C6-10 aryl, optionally substituted heterocycle, optionally substituted C3-8 cycloalkyl, optionally substituted C3-8 cycloalkenyl, NR12R13 or hydroxyl;
• R8 is H, halogen, —OC1-8 alkyl, optionally substituted C1-8 alkyl, CN, C(O)R11, optionally substituted C6-10 aryl, optionally substituted heterocycle, optionally substituted C3-8 cycloalkyl, optionally substituted C3-8 cycloalkenyl, NR12R13 or hydroxyl;
• R9 is H, halogen, —OC1-8 alkyl, optionally substituted C1-8 alkyl, CN, C(O)R11, optionally substituted C6-10 aryl, optionally substituted heterocycle, optionally substituted C3-8 cycloalkyl, optionally substituted C3-8 cycloalkenyl, NR12R13 or hydroxyl;
• R10 is H, halogen, —OC1-8 alkyl, optionally substituted C1-8 alkyl, CN, C(O)R11, optionally substituted C6-10 aryl, optionally substituted heterocycle, optionally substituted C3-8 cycloalkyl, optionally substituted C3-8 cycloalkenyl, NR12R13 or hydroxyl;
• L1 is O, S, S(O), NH or CH2;
• L2 is O, S or CHR12,
• R11 is OH or optionally substituted C1-8 alkyl;
• a is 1, 2, 3, 4, 5 or 6;
• R12 is H or optionally substituted C1-8 alkyl;
• and
• R13 is H or optionally substituted C1-8 alkyl.