Stereoisomeric compounds and methods for the treatment of gastrointestinal and central nervous system disorders

A method of treating a gastrointestinal disorder selected from the group consisting of gastroesophageal reflux disease (GERD), emesis, dyspepsia, gastroparesis, constipation, intestinal pseudo-obstruction, post-operative ileus comprising administering to a patient in need of such treatment a therapeutically effective amount of a compound of the formula

• and pharmaceutically acceptable salts thereof, wherein
• the bonds at positions 3 and 4 are cis relative to each other;
• R1 is halogen;
• R2 is amino, NH(C1-C4 alkyl) or N(C1-C4 alkyl)(C1-C4 alkyl);
• R3 is OH or C1-C4 alkoxy;
• R4 is H or methyl;
• and
• R5 is —O—C3-C8 cycloalkyl, —O-heterocycloalkyl or heterocycloalkyl, wherein the heterocycloalkyl portion of the —O-heterocycloalkyl or heterocycloalkyl is aza-bicyclo-octyl, aza-bicyclo-nonyl, aza-bicyclo-decyl, piperidinyl, piperazinyl, or pyrrolidinyl, wherein
• the piperidinyl, piperazinyl, and pyrrolidinyl groups are unsubstituted or substituted at one or two positions with groups that are independently C1-C4 alkyl, C1-C4 alkoxy, halogen, C1-C4 haloalkyl, C1-C4 haloalkoxy, hydroxyl, hydroxy C1-C4 alkyl, amino, —NH(C1-C4 alkyl), —N(C1-C4 alkyl)(C1-C4 alkyl), —(C0-C6 alkyl)-C(O)R11, or NO2, and wherein
• the aza-bicyclo-octyl, aza-bicyclo-nonyl, and aza-bicyclo-decyl nitrogen is optionally substituted with methyl or ethyl;
• R9 at each occurrence is independently H or C1-C4 alkyl;
• R11 is C1-C6 alkoxy, optionally substituted with 1 or 2 groups that are independently C1-C4 alkoxy, amino, —NH(C1-C6 alkyl), —N(C1-C6 alkyl)(C1-C6 alkyl), —(C0-C6 alkyl)-C(O)N(R9)-heterocycloalkyl, O-heterocycloalkyl, or heterocycloalkyl, wherein the heterocycloalkyl is pyrrolidinyl, piperidinyl, piperazinyl, or morpholinyl, wherein the heterocycloalkyl groups are optionally substituted with 1, 2, or 3 groups that are independently halogen, C1-C6 alkyl, C1-C6 alkoxy, hydroxy, hydroxy C1C6 alkyl, C1-C6 alkoxycarbonyl, —CO2H, CF3, or OCF3;
• and
• R20 is C1-C6 alkoxy (preferably C1-C4 alkoxy, more preferably methoxy), or OH.