Method for treating glaucoma V

A method of decreasing intraocular pressure in an animal, including a human, comprising administering an intraocular pressure decreasing amount of a compound of the formula IA and or IB:

• wherein:
• a. A and D are N and B and Z are respectively, CRB and CRZ;
• b. RB and RZ are independently hydrogen, alkyl, alkoxy, allyl, alkylalkynyl, amino, acylamino, aroylamino, (aryl)(alkyl)amino, diarylamino, dialkcylamino, pyrrolidin-1-yl, piperidin-1-yl, 4-arylpiperidin-1-yl, 4-arylpiperazin-1-yl, 1-morpholin-4-yl, 1-thiamorpholin-4-yl, alkylthio, alkoxycarbonyl, carboxy, (C1-C6)-hydroxyalkyl, H2NS(O)2, H2NC(O), (alkyl)(alkyl)NC(O), 4-arylpiperazin-1-yl-C(O), fluoromethyl, difluoromethyl, trifluoromethyl, alkyl sulfonyl, alkylsulfinyl or arylsulfonyl;
• c. X and Y are independently N, N+(O—), or, respectively, CRX or CRY, with the proviso that there is only zero to one N-oxide;
• d. RX and RY are independently acetamido, hydrogen, alkyl, amino, —C≡CRE, CH2—C≡CRE, alkylamino, dialkylamino, alkylthio, aryl, arylthio, arylalkyl, hydroxyalkyl, fluoromethyl, difluoromethyl, trifluoromethyl, cyanomethyl, alkoxycarbonylmethyl, 1-(alkoxycarbonyl)-1-hydroxyalkyl or aminocarbonylmethyl, wherein RE is alkyl, hydrogen or hydroxyalkyl;
• e. W is C═O, CH(OH), S(O)2 or S(O), or together with Q forms W—Q;
• f. Q is Ar* or NR′R″, or, W—Q together are Ar, cyano or —C≡CRQ;
• g. RQ is hydrogen, acylaminoalkyl, aroylaminoalkyl, alkyl, hydroxyalkyl, alkylaminoalkyl, dialkylaminoalkyl, (aryl)(alkyl)aminoalkyl, fluoromethyl, difluoromethyl, trifluoromethyl, Ar, ArCO, ArS(O)n, where n=1 or 2, H2NC(O), or 4-arylpiperazin-1-yl-C(O);
• h. R′ and R″ are independently hydrogen, alkyl, Ar, or together, NR′R″ form a pyrrolidin-1-yl, piperidin-1-yl, 4-arylpiperidin-1-yl, 4-arylpiperazin-1-yl, 4-alkyl-piperazin-1-yl, 1-morpholin-4-yl or 1-thiamorpholin-4-yl ring;
• i. Aryl is a C6 to C10 aromatic ring and Ar or Ar*, are each a C6 or C10 aromatic ring or a 5- or 6-membered heteroaromatic ring containing at least one and up to three atoms of N for the 6-membered heteroaryl ring and from one to three atoms of N or one atom of O or S and zero to two atoms of N for the 5-membered heteroaryl ring;
• each heteroaryl ring may be optionally substituted with up to two amino-, dialkylamino-, pyrrolidin-1-yl, piperidin-1-yl, 1-morpholin-4-yl, 1-thiamorpholin-4-yl, 4-arylpiperidin-1-yl, 4-arylpiperazin-1-yl-, or halo groups, or fused to a substituted benzene, pyridine, pyrimidine, pyridazine or triazine ring, and wherein C6 or C10 aromatic and heteroaromatic rings can be additionally substituted as set forth below;
• j. An− is a pharmaceutically acceptable anion;
• k. C6 or C10 aromatic rings (including Ar, Ar*, or aryl), can be additionally substituted with acylamino, acyloxyalkyl, alkanoyl, alkanoylalkyl, alkenyl, alkoxy, alkoxycarbonyl, alkoxycarbonylalkyl, alkyl, —C≡CRE, alkylamino, (C1-C3)-alkylenedioxy, alkylsulfonyl, alkylthio, allyl, amino, benzoyl, carboxy, carboxyalkyl, cyano, cycloalkyl, dialkylamino, halo, fluoromethyl, difluoromethyl, trifluoromethyl, hydroxy, (C1-C6)-hydroxyalkyl, mercapto, nitro, phenoxy, phenyl, phenylalkyl, sulfamoyl, sulfo (—SO3H), aminosulfonyl (H2NSO2—), phenylsulfonyl, or phenylsulfinyl;
• and
• l. heteroaromatic rings (Ar or Ar*), can be additionally substituted with acylamino, alkanoyl, alkoxy, alkoxycarbonyl, alkoxycarbonylalkyl, alkyl, alkylamino, alkylsulfonyl, alkylthio, amino, arylsulfonyl, aryl sulfonyl, benzoyl, carboxy, cyano, dialkylamino, halo, fluoralkyl, hydroxy, mercapto, nitro, phenyl, phenoxy, pyrrolidin-1-yl, piperidin-1-yl, 4-arylpiperidin-1-yl, 1-morpholin-4-yl, 1-thiamorpholin-4-yl, 4-arylpiperazin-1-yl, sulfamoyl, aminosulfonyl (H2NSO2—), fluoromethyl, difluoromethyl or trifluoromethyl;
• and pharmaceutically acceptable salts of said compounds.