IMDOLIZINE DERIVATIVES AS LIGANDS OF THE CRTH2 RECEPTOR

摘要

Compounds of formula (I) are CRTH2 antagonists, useful in the treatment of, for example, asthma, chronic obstructive pulmonary disease, rhinitis, allergic airway syndrome, and allergic rhinobronchitis. Formula (I) wherein R<SUB>1</SUB>, R<SUB>2</SUB>. R<SUB>3</SUB> and R<SUB>4</SUB> each independently are hydrogen, C<SUB>1</SUB>-C<SUB>6</SUB>alkyl, fully or partially fluorinated C<SUB>1</SUB>-C<SUB>6</SUB>alkyl, halo, -S(O)<SUB>n</SUB>R<SUB>10,</SUB> -SO<SUB>2</SUB>N(R<SUB>10</SUB>)<SUB>2,</SUB> -N(R<SUB>10</SUB>)<SUB>2,</SUB> -C(O)N(R<SUB>10</SUB>)<SUB>2,</SUB> -NR<SUB>10</SUB>C(O)R<SUB>9,</SUB> -CO<SUB>2</SUB>R<SUB>10</SUB>, -C(O)R<SUB>9</SUB>, -NO<SUB>2, </SUB>-CN or -OR<SUB>11</SUB>; wherein each R<SUB>9</SUB> is independently C<SUB>1</SUB>-C<SUB>6</SUB>alkyl, aryl, heteroaryl; R<SUB>10</SUB> is independently hydrogen, C<SUB>1</SUB>-C<SUB>6</SUB>alkyl, aryl, or heteroaryl; R<SUB>11</SUB> is hydrogen, C<SUB>1</SUB>-C<SUB>6</SUB>alkyl, fully or partially fluorinated C<SUB>1</SUB>-C<SUB>6</SUB>alkyl or a group -SO<SUB>2</SUB>R<SUB>10</SUB> ; n is 0, 1 or 2; R<SUB>5</SUB> is C<SUB>1</SUB>-C<SUB>6</SUB>alkyl, fully or partially fluorinated C<SUB>1</SUB>-C<SUB>6</SUB>alkyl, C<SUB>1</SUB>-C<SUB>6</SUB>alkenyl, C<SUB>1</SUB>-C<SUB>6</SUB>alkynyl, optionally substituted aryl, or optionally substituted heteroaryl; R<SUB>6</SUB> is hydrogen, C<SUB>1</SUB>-C<SUB>6</SUB>alkyl or fully or partially fluorinated C<SUB>1</SUB>-C<SUB>6</SUB>alkyl ; R<SUB>7</SUB> and R<SUB>8</SUB> are independently hydrogen or C<SUB>1</SUB>-C<SUB>6</SUB>alkyl, or R<SUB>7</SUB> and R<SUB>8</SUB> together with the atom to which they are attached form a cycloalkyl group; and X is -CHR<SUB>6</SUB>-, -S(O)<SUB>n</SUB>-, -C(O)-, -NR<SUB>6</SUB>SO<SUB>2</SUB>- or -SO<SUB>2</SUB>NR<SUB>6</SUB>- wherein n is 0, 1 or 2.