Patent ID: 6376507
Filing Date: 2002-04-23
Classification: A61K,A61P

Abstract:
A method of treating or preventing a disorder selected from stroke, epilepsy, head trauma, ischemic neuronal damage such as cerebral ischemic damage from stroke or vascular occlusion, excitotoxic neuronal damage and amyotrophic lateral sclerosis in a mammal, comprising administering to said mammal(a) an amount of a compound of the formula â€ƒwherein A is a ring system selected from phenyl, naphthyl, thienyl, quinolinyl and indolinyl, and wherein the sidechain containing NR2R3 is attached to a carbon atom of ring system A; A is an aryl group selected from phenyl, naphthyl, thienyl, dihydroquinolinyl and indolinyl, and wherein the sidechain containing NR2R3 is attached to a carbon atom of AA; AAA is an aryl group selected from phenyl, naphthyl, thienyl, dihydroquinolinyl and indolinyl, and wherein the â€”CH2PR3 sidechain is attached to a carbon atom of ring AAA; P is NR2, O, S, SO or SO2; Q is SO2, NH, â€”N(C1-C6)alkyl or â€ƒwherein the point of attachment of said â€ƒto ring AAA is the nitrogen atom and the point of attachment to X5 is the sulfur atom; W1 is hydrogen, halo or (C1-C6)alkyl, Sâ€”(C1-C3)alkyl, halo or (C1-C6)alkoxy optionally substituted with from one to three fluorine atoms; W2 is hydrogen, (C1-C6)alkyl, Sâ€”(C1-C3)alkyl, halo or (C1-C6)alkoxy optionally substituted with from one to three fluorine atoms; W is hydrogen, (C1-C6)alkyl optionally substituted with from one to three fluorine atoms, â€”S(O)vâ€”(C1-C6)alkyl wherein v is zero, one or two, halo or (C1-C6)alkoxy optionally substituted with from one to three fluorine atoms; X1 is hydrogen, (C1-C10)alkoxy optionally substituted with from one to three fluorine atoms or (C1-C10)alkyl optionally substituted with from one to three fluorine atoms; X2 and X3 are independently selected from hydrogen, halo, nitro, (C1-C10)alkyl optionally substituted with from one to three fluorine atoms, (C1-C10)alkoxy optionally substituted with from one to three fluorine atoms, trifluoromethyl, hydroxy, phenyl, cyano, amino, (C1-C6yalkylamino, di-(C1-C6)alkylamino, â€”(C&boxH;O)â€”NHâ€”(C1-C6)alkyl, (C1-C6)-alkyl-(C&boxH;O)â€”NHâ€”(C1-C6)alkyl, hydroxy(C1-C4)alkyl, C1-C4)alkoxy(C1-C4)alkyl, â€”NHCHO and â€”NHCOâ€”(C1-C6)alkyl; X5 is a four to six membered heterocyclic ring containing from one to three heteroatoms selected from sulfur, nitrogen and oxygen, wherein said heterocyclic ring may optionally be substituted with from one to three substituents, preferably with from zero to two substituents, independently selected from phenyl, (C1-C6)alkyl optionally substituted with from one to three fluorine atoms, (C1-C6)alkoxy optionally substituted with from one to three fluorine atoms and halo; R is a 4, 5 or 6 membered heterocyclic ring containing from one to three heteroatoms selected from oxygen, nitrogen and sulfur wherein said heterocyclic ring may contain from zero to three double bonds and may optionally be substituted with one or more substituents, preferably one or two substituents, independently selected from (C1-C6)alkyl optionally substituted with from one to three fluorine atoms and (C1-C6)alkoxy optionally substituted with from one to three fluorine atoms; R1 is selected from amino, (C1-C6)alkylamino, di-(C1-C6)alkylamino, â€”S(O)vâ€”(C1-C10)-alkyl wherein v is zero, one or two, â€”S(O)v-aryl wherein v is zero, one or two, â€”O-aryl, â€”SO2NR4R5 wherein each of R4 and R5 is, independently, (C1-C6)alkyl, or R4 and R5, together with the nitrogen to which they are attached, form a saturated ring containing one nitrogen and from 3 to 6 carbons, â€”NH(C&boxH;O)(C1-C6)alkyl, â€”NH(C&boxH;O)CF3, â€ƒwherein one or both of the alkyl moieties may optionally be substituted with from one to three fluorine atoms, â€”N(SO2â€”(C1-C10)alkyl)2 and â€ƒand wherein the aryl moieties of said â€”S(O)v-aryl, â€”O-aryl and â€ƒare independently selected from phenyl and benzyl and may optionally be substituted with from one to three substituents independently selected from (C1-C4)alkyl, (C1-C4)alkoxy and halo; or R1 is a group having the formula â€ƒwherein a is 0, 1 or 2 and the asterisk represents a position meta to the R2R3NCH2 side chain; the dotted lines in formula Ib represent that one of the Xâ€”Y and Yâ€”Z bonds may optionally be a double bond; X is selected from &boxH;CHâ€”, â€”CH2â€”, â€”Oâ€”, â€”Sâ€”, â€”SOâ€”, â€”SO2â€”, â€”N(R4)â€”, â€”NHâ€”, &boxH;Nâ€”, â€”CH[(C1-C6)alkyl]â€”, &boxH;C[(C1-C6)alkyl]â€”, â€”CH(C6H5)â€” and &boxH;C(C6H5)â€”; Y is selected from C&boxH;O, C&boxH;NR4, C&boxH;S, &boxH;CHâ€”, â€”CH2â€”, &boxH;C[(C1-C6)alkyl]â€”, â€”CH[(C1-C6)alkyl]â€”, &boxH;C(C6H5Y, â€”CH(C6H5)â€”, &boxH;Nâ€”, â€”NHâ€”, â€”N(R4)â€”, &boxH;C(halo)â€”, &boxH;C(oR4)â€”, &boxH;C(SR4)â€”, &boxH;C(NR4)â€”, â€”Oâ€”, â€”Sâ€”, and SO2, wherein the phenyl moieties of said &boxH;C(C6H5)â€” and â€”CH(C6H5)â€” may optionally be substituted with from one to three substituents independently selected from trifluoromethyl and halo, and wherein the alkyl moieties of said &boxH;[(C1-C6)alkyl]â€” and â€”CH[C1-C6)alkyl]â€” may optionally be substituted with from one to three fluorine atoms; Z is selected from &boxH;CHâ€”, â€”CH2â€”, &boxH;Nâ€”, â€”NHâ€”, â€”Sâ€”, â€”N(R4)â€”, &boxH;C(C6H5)â€”, â€”CH(C6H5)â€”, &boxH;C[(C1-C6) alkyl]â€” and â€”CH[(C1-C6)alkyl]â€”; or X, Y and Z, together with the two carbon atoms shared between the benzo ring and the XYZ ring, form a fused pyridine or pyrimidine ring; R4 is (C1-C6)alkyl or phenyl; R2 is hydrogen or â€”CO2(C1-C10)alkyl; R3 is selected from â€ƒwherein R6 and R10 are independently selected from furyl, thienyl, pyridyl, indolyl, biphenyl and phenyl, wherein said phenyl may optionally be substituted with one or two substituents independently selected from halo, (C1-C10)alkyl optionally substituted with from one to three fluorine atoms, (C1-C10)alkoxy optionally substituted with from one to three fluorine atoms, carboxy, benzyloxycarbonyl and (C1-C3)alkoxy-carbonyl; R7 is selected from (C3-C4) branched alkyl, (C5-C6) branched alkenyl, (C5-C7)cycloalkyl, a radicals named in the definition of R6; R8 is hydrogen or (C1-C6)alkyl; R9 and R19 are independently selected from phenyl, biphenyl, naphthyl, pyridyl, benzhydryl, thienyl and furyl, and R9 and R19 may optionally be substituted with from one to three substituents independently selected from halo, (C1-C10)alkyl optionally substituted with from one to three fluorine atoms and (C1-C10)alkoxy optionally substituted with from one to three fluorine atoms; Y1 is (CH2)I wherein I is an integer from one to three, or Y1 is a group of the formula â€ƒZ1 is oxygen, sulfur, amino, (C1-C3)alkylamino or (CH2)n wherein n is zero, one or two; x is an integer from zero to four; y is an integer from zero to four; z is an integer from one to six, wherein the ring containing (CH2)z may contain from zero to three double bonds, and one of the carbons of (CH2)z may optionally be replaced by oxygen, sulfur or nitrogen; o is two or three; p is zero or one; r is one, two or three; R11 is thienyl, biphenyl or phenyl optionally substituted with one or two substituents independently selected from halo, (C1-C10)alkyl optionally substituted with from one to three fluorine atoms and (C1-C10)alkoxy optionally substituted with from one to three fluorine atoms; X4 is (CH2)q wherein q is an integer from 1 to 6, and wherein any one of the carbon-carbon single bonds in said (CH2)q may optionally be replaced by a carbon-carbon double bond, and wherein any one of the carbon atoms of said (CH2)q may optionally be substituted with R14, and wherein any one of the carbon atoms of said (CH2)q may optionally be substituted with R15; m is an integer from 0 to 8, and any one of the carbon-carbon single bonds of (CH2)m, wherein both carbon atoms of such bond are bonded to each other and to another carbon atom in the (CH2)m chain, may optionally be replaced by a carbon-carbon double bond or a carbon-carbon triple bond, and any one of the carbon atoms of said (CH2)m may optionally be substituted with R17; R12 is a radical selected from hydrogen, (C1-C6) straight or branched alkyl, (C3-C7)cycloalkyl wherein one of the carbon atoms may optionally be replaced by nitrogen, oxygen or sulfur; aryl selected from biphenyl, phenyl, indanyl and naphthyl; heteroaryl selected from thienyl, furyl, pyridyl, thiazolyl, isothiazolyl, oxazolyl, isoxazolyl, triazolyl, tetrazolyl and quinolyl; phenyl-(C2-C6)alkyl, benzhydryl and benzyl, wherein the point of attachment on R12 is a carbon atom unless R12 is hydrogen, and wherein each of said aryl and heteroaryl groups and the phenyl moieties of said benzyl, phenyl-(C2-C6)alkyl and benzhydryl may optionally be substituted with one or more substituents independently selected from halo, nitro, (C1-C10)alkyl optionally substituted with from one to three fluorine atoms, (C1-C10)alkoxy optionally substituted with from one to three fluorine atoms, amino, hydroxy-(C1-C6)alkyl, (C1-C6)alkoxy-(C1-C6)alkyl, (C1-C6)-alkylamino, (C1-C6)alkyl-Oâ€”(C&boxH;O)â€”, (C1-C6)alkyl-Oâ€”(C&boxH;O)â€”(C1-C6)alkyl, (C1-C6)alkyl-(C&boxH;O)â€”Oâ€”, (C1-C6)alkyl-Câ€”(C1-C6)alkyl-Oâ€”, (C1-C6)alkyl-(C&boxH;O)â€”, (C1-C6)alkyl-(C&boxH;O)â€”(C1-C6)alkyl-, di-(C1-C6)alkylamino, â€”(C&boxH;O)NHâ€”(C1-C6)alkyl, (C1-C6)-alkyl-(C&boxH;O)â€”NHâ€”(C1-C6)alkyl, â€”NH(CO)H and â€”NH(C&boxH;O)â€”(C1-C6)alkyl; and wherein one of the phenyl moieties of said benzhydryl may optionally be replaced by naphthyl, thienyl, furyl or pyridyl; R13 is hydrogen, phenyl or (C1-C6)alkyl; or R12 and R13, together with the carbon to which they are attached, form a saturated carbocyclic ring having from 3 to 7 carbon atoms wherein one of said carbon atoms that is neither the point of attachment of the spiro ring nor adjacent to it may optionally be replaced by oxygen, nitrogen or sulfur; R14 and R15 are each independently selected from hydrogen, hydroxy, halo, amino, oxo (&boxH;O), cyano, hydroxy-(C1-C6)alkyl, (C1-C6)alkoxy-(C1-C6)alkyl, (C1-C6)alkylamino, di-(C1-C6)alkylamino, (C1-C6)alkoxy, â€”(C&boxH;O)â€”OH, (C1-C6)alkyl-Oâ€”(C&boxH;O)â€”, (C1-C6)alkyl-Oâ€”(C&boxH;O)â€”(C1-C6)alkyl, (C1-C6)alkyl-(C&boxH;O)â€”Oâ€”, (C1-C6)alkyl-(C&boxH;O)â€”(C1-C6)alkyl-Oâ€”, (C1-C6)alkyl-(C&boxH;O)â€”, (C1-Cr)alkyl-(C&boxH;O)â€”(C1-C8)alkyl-, and the radicals set forth in the definition of R12; R16 is NH(C&boxH;O)R18, NHCH2R18, SO2R18, GR20 CO2H or one of the radicals set forth in any of the definitions of R12, R14 and R15; R17 is oximino (&boxH;NOH) or one of the radicals set forth in any of the definitions of R12, R14 and R15; and R18 is (C1-C6)alkyl, hydrogen, phenyl or phenyl (C1-C6)alkyl; G is selected from the group consisting of CH2, nitrogen, oxygen, sulfur and carbonyl; R20 is a monocyclic or bicyclic heterocycle selected from the group consisting of pyrimidinyl, benzoxazolyl, 2,3-dihydro-3-oxobenzisosulfonazol-2-yl, morpholin-1-yl, thiomorpholin-1-yl, benzofuranyl, benzothienyl, indolyl, isoindolyl, isoquinolinyl, furyl, pyridyl, isothiazolyl, oxazolyl, triazolyl, tetrazolyl, quinolyl, thiazolyi, thienyl, and groups of the formulae â€ƒwherein B and D are selected from carbon, oxygen, and nitrogen, and at least one of B and D is other than carbon; E is carbon or nitrogen; n is an integer from 1 to 5; and any one of the carbons of the (CH2)n or (CH2)n+1 may be optionally substituted with (C1-C6)alkyl or (C2-C6)spiroalkyl, and either any two of the carbon atoms of said (CH2)n and (CH2)n+1 may be bridged by a one or two carbon atom linkage, or any one pair of adjacent carbons of said (CH2)n and (CH2)n+1 may form, together with from one to three carbon atoms that are not members of the carbonyl containing ring, a (C3-C5) fused carbocyclic ring; with the proviso that (a) when m is 0, one of R16 and R17 is absent and the other is hydrogen, (b) when R3 is a group of the formula Vil, R14 and R15 cannot be attached to the same carbon atom, (c) when R14 and R15 are attached to the same carbon atom, then either each of R14 and R15 is independently selected from hydrogen, fluoro, (C1-C6)alkyl, hydroxy-(C1-C6)alkyl and (C1-C6)alkoxy-(C1-C6)alkyl, or R14 and R15, together with the carbon to which they are attached, form a (C3-C6) saturated carbocyclic ring that forms a spiro compound with the nitrogen-containing ring to which they are attached; (d) R12 and R13 cannot both be hydrogen; (e) when R14 or R15 is attached to a carbon atom of X4 or (CH2)y that is adjacent to the ring nitrogen, then R14 or R15, respectively, must be a substituent wherein the point of attachment is a carbon atom; and (f) neither R14, R15, R16 nor R17 can form a ring with R13; or a pharmaceutically acceptable salt thereof, that is effective in treating or preventing such disorder; or (b) an amount of a compound having the formula â€ƒwherein W is Y or X(CH2)n; Y is optionally substituted (C1-C6)alkyl, optionally substituted (C2-C6)alkenyl or optionally substituted (C3-C8)cycloalkyl; X is optionally substituted (C1-C6)alkoxy, hydroxy, CONR1R2 CO2R1, CHR1OR2, CHR1NR2R3, COR1, CONR1OR2 or optionally substituted aryl or heteroaryl, wherein said aryl is selected from phenyl, naphthyl, and phenoxyphenyl, and wherein said heteroaryl is selected from pyridyl, quinolyl, thienyl, furyl, oxazolyl, tetrazolyl, thiazolyl, imidazolyl and pyrazolyl; and n is an integer from zero to six; Ar1, Ar2 and Ar3 are each, independently, optionally aryl or heteroaryl, wherein said aryl is selected from phenyl, naphthyl, and phenoxyphenyl, and wherein said heteroaryl is selected from pyridyl, quinolyl, thienyl, furyl, oxazolyl, tetrazolyl, thiazolyl, imidazolyl and pyrazolyl; and R1, R2 and R3 are independently selected from hydrogen, optionally substituted (C1-C6)alkyl, optionally substituted (C1-C6)alkoxy, optionally substituted (C3-C8)cycloalkyl, optionally substituted aryl or heteroaryl, wherein said aryl is selected from phenyl, naphthyl, and phenoxyphenyl, and wherein said heteroaryl is selected from pyridyl, quinolyl, thienyl, furyl, oxazolyl, tetrazolyl, thiazolyl, imidazolyl and pyrazolyl; and optionally substituted (C1-C5)heterocyclic groups, wherein said heterocyclic groups are selected from pyrrolidino, piperidino, morpholino, piperazinyl and thiamorpholino; and wherein the substituents on the foregoing substituted alkyl, alkenyl, cycloalkyl and alkoxy groups are independently selected from halo, nitro, amino, (C1-C4)alkyl, (C1-C4)alkoxy, trifluoromethyl and trifluoromethoxy; and wherein the substituents on the foregoing substituted (C1-C5)heterocyclic groups are attached to a sulfur or nitrogen atom on the ring and are independently selected from oxygen, di-oxygen and (C1-C4)alkyl when attached to a ring sulfur atom, and are independently selected from oxygen and (C1-C4)alkyl when attached to a ring nitrogen atom; and wherein the substituents on said substituted aryl or heteroaryl in said Ar1 groups are independently selected from (C1-C6)alkyl optionally substituted with from one to three halo groups; (C1-C6)alkoxy optionally substituted with from one to three halo groups; (C1-C6)alkylsulfinyl; (C2-C6)alkenyl; (C1-C6)alkylthio; (C1-C6)alkylsulfonyl; (C1-C6)alkylsulfonylamino; and di-(C1-C6)alkylamino wherein one or both of the alkyl groups may be optionally substituted with a (C1-C6)alkylsulfonyl, or (C1-C6)alkylsulfinyl group; and wherein the substituents on said substituted aryl or heteroaryl in said Ar2 and Ar3 groups are independently selected from (C1-C4)alkyl, (C1-C4)alkoxy, (C1-C4)alkylthio, (C1-C4)alkylsulfinyl, di-(C1-C4)alkylamino, trifluoromethyl and trifluoromethoxy; with the proviso that when Y is unsubstituted or is substituted with (C1-C4)alkyl, it is attached to the 4- or 6-position of the quinuclidine ring; or a pharmaceutically acceptable salt thereof, that is effective in treating or preventing such disorder; or (c) A method of treating or preventing emesis in a mammal, comprising administering to said mammal an amount of a compound having the formula â€ƒwherein R1 is selected from hydrogen, (C1-C6) straight or branched alkyl, (C3-C7)cycloalkyl wherein one of the carbon atoms may optionally be replaced by nitrogen, oxygen or sulfur; aryl selected from phenyl, biphenyl, indanyl and naphthyl; heteroaryl selected from thienyl, furyl, pyridyl, thiazolyl, isothiazolyl, oxazolyl, isoxazolyl, triazolyl, tetrazolyl and quinolyl; phenyl (C2-C6)alkyl, benzhydryl and benzyl, wherein each of said aryl and heteroaryl groups and the phenyl moieties of said benzyl, phenyl (C2-C6)alkyl and benzhydryl may optionally be substituted with one or more substituents independently selected from halo, nitro, (C1-C6)alkyl optionally substituted with from one to three fluorine atoms, (C1-C6)alkoxy, amino, trihaloalkoxy, (C1-C6)alkylamino, (C1-C6)alkyl-Oâ€”(C&boxH;O)â€”, (C1-C6)alkyl-Oâ€”(C&boxH;O)â€”(C1-C6)alkyl, (C1-C6)alkyl-(C&boxH;O)â€”, (C1-C6)alkyl-(C&boxH;O)â€”, (C1-C6)alkyl-Oâ€”, (C1-C6)alkyl-(C&boxH;O)â€”, (C1-C6)alkyl-(C&boxH;O)â€”, (C1-C6)alkyl-, di-(C1-C6)alkylamino, â€”(C&boxH;O)NHâ€”(C1-C6)alkyl, (C1-C6)alkyl-(C&boxH;O)â€”NHâ€”(C1-C6)alkyl-, â€”NH(C&boxH;O)H and â€”NH(C&boxH;O)â€”(C1-C6)alkyl; and wherein one of the phenyl moieties of said benzhydryl may optionally be replaced by naphthyl, thienyl, furyl or pyridyl; R3 is aryl selected from phenyl and naphthyl; heteroaryl selected from indanyl, thienyl, furyl, pyridyl, thiazolyl, isothiazolyl, oxazolyl, isoxazolyl, triazolyl, tetrazolyl and quinolyl; and cycloalkyl having 3 to 7 carbon atoms wherein one of said carbon atoms may optionally be replaced by nitrogen, oxygen or sulfur; wherein each of said aryl and heteroaryl groups may optionally be substituted with one or more substituents, and said (C3-C7)cycloalkyl may optionally be substituted with one or two substituents, each of said substituents being independently selected from halo, nitro, (C1-C6)alkyl optionally substituted with from one to three fluorine atoms, (C1-C6)alkoxy substituted with from one to three fluorine atoms, amino, phenyl, trihaloalkoxy, (C1-C6)alkylamino, â€”(C&boxH;O)â€”NHâ€”(C1-C6)alkyl, (C1-C6)alkyl-(C&boxH;O), â€”(C&boxH;O)â€”(C1-C6)alkyl, â€”(C&boxH;O)H, â€”CH2OR13, NH(C1-C6)alkyl-, â€”NH(C&boxH;O)H, â€”NR24(C&boxH;O)â€”(C1-C6)alkyl and â€”NH(C&boxH;O)â€”(C1-C6)alkyl; one of R5 and R6 is hydrogen and the other is selected from hydroxymethyl, hydrogen, (C1-C3)alkyl, (C1-C8)acyloxy(C1-C3)alkyl, (C1-C8)alkoxymethyl and benzyloxymethyl; R7 and R8 are independently selected from hydrogen, (C1-C3)alkyl and phenyl; R9 is selected from methyl, hydroxymethyl, H(C&boxH;O)â€”, R14R15NCO2CH2â€”, R16OCO2CH2â€”, (C1-C4)alkyl-CO2CH2â€”, â€”CONR17 R18, R17R18NCO2â€”, R19OCO2â€”, C6H5CH2, (C1-C4)alkyl-CH(OH)â€”, C6H5CH(OH)â€”, C6H5CH2CH(OH)â€”, CH2halo, R20SO2OCH2, â€”CO2R16 and R21CO2â€”, R10 and R11 are independently selected from hydrogen, (C1-C3)alkyl and phenyl; R12 is hydrogen, benzyl or a group of the formula â€ƒwherein m is an integer from zero to twelve, and any one of the carbon-carbon single bonds of (CH2)m, wherein both carbon atoms of such bond are bonded to each other and to another carbon atom of the (CH2)m chain, may optionally be replaced by a carbon-carbon double or triple bond, and any one of the carbon atoms of (CH2)m may optionally be substituted with R23; R13, R14, R15, R16, R17, R18, R19, R20, R21 and R24 are independently selected from hydrogen, (C1-C3)alkyl and phenyl; R2 and R23 are independently selected from hydrogen, hydroxy, halo, amino, carboxy, carboxy(C1-C6)alkyl, (C1-C6)alkylamino, di-(C1-C6)alkylamino, (C1-C6)alkoxy, (C1-C6)-alkyl-Oâ€”(C&boxH;O)â€”, (C1-C6)alkyl-Oâ€”(C&boxH;O)â€”(C1-C6)alkyl, (C1-C6)alkyl-(C&boxH;O)â€”, (C1-C6)alkyl-(C&boxH;O)â€”(C1-C6)alkyll-Oâ€”, (C1â€”C6)alkyl-(C&boxH;O)â€”, (C1-C6)-alkyl-(C&boxH;O)â€”(C1-C6)alkyl, (C1-C6)straight or branched alkyl, (C3-C7)cycloalkyl wherein one of the carbon atoms may optionally be replaced by nitrogen, oxygen or sulfur; aryl selected from phenyl and naphthyl; heteroaryl selected from indanyl, thienyl, furyl, pyridyl, thiazolyl, isothiazolyl, oxazolyl, isoxazolyl, triazolyl, tetrazolyl and quinolyl; phenyl-(C2-C6)alkyl, benzhydryl and benzyl, wherein each of said aryl and heteroaryl groups and the phenyl moieties of said benzyl, phenyl-(C2-C6)alkyl and benzhydryl may optionally be substituted with one or two substituents independently selected from halo, nitro, (C1-C6)alkyl optionally substituted with from one to three fluorine atoms, (C1-C6)alkoxy optionally substituted with from one to three fluorine atoms, trifluoromethyl, amino, (C1-C6)-alkylamino, (C1-C6)alkyl-Oâ€”(C&boxH;O), (C1-C6)alkyl-Oâ€”(C&boxH;O)â€”(C1-C6)alkyl, (C1-C6)alkyl C6)alkyl-(C&boxH;O)â€”(C1-C6)alkyl-Oâ€”, (C1-C6)alkyl-(C&boxH;O)â€”, (C1-C6)alkyl-(C&boxH;O)â€”(C1-C6)alkyl-, di-(C1-C6)alkylamino, â€”(C&boxH;O)NHâ€”(C1-C6)alkyl, (C1-C6yalkyl-(C&boxH;O)â€”NHâ€”(C1-C6)alkyl, â€”NH(C&boxH;O)H and â€”NH(C&boxH;O)â€”(C1-C6)alkyl; and wherein one of the phenyl moieties of said benzhydryl may optionally be replaced by naphthyl, thienyl, furyl or pyridyl; or R9, together with the carbon to which it is attached, the nitrogen of the pyrrolidine ring, the carbon to which R7 is attached and the carbon to which R5 and R6 are attached form a second pyrrolidine ring; with the proviso that when R9, together with the carbon to which it is attached, the nitrogen of the pyrrolidine ring, the carbon to which R7 is attached and the carbon to which R5 and R6 are attached, form a second pyrrolidine ring (thus forming a bicyclic structure containing a bridgehead nitrogen), either R12 is absent or R12 is present and the nitrogen of the second pyrrolidine ring is positively charged; or a pharmaceutically acceptable salt thereof, that is effective in treating or preventing such disorder; or (d) an amount of a compound of the formula â€ƒwherein R1 is hydrogen, (C1-C8)alkyl, a saturated (C6-C10)carbocyclic ring system containing two fused rings, a saturated (C6-C10)carbocyclic bridged ring system containing two rings, or benzyl wherein the phenyl moiety of said benzyl may optionally be substituted with one or more substituents independently selected from halo, (C1-C6)alkyl optionally substituted with from one to three fluorine atoms and (C1-C8)alkoxy optionally substituted with from one to three fluorine atoms; R2 is hydrogen, benzyl or a group of the formula â€ƒwherein m is an integer from zero to twelve, and any one of the carbon-carbon single bonds of (CH2)m, wherein both carbon atoms of such bond are bonded to each other and to another carbon atom of the (CH2)m chain, may optionally be replaced by a carbon-carbon double or triple bond, and any one of the carbon atoms of (CH2)m may optionally be substituted with R9; R8 and R9 are independently selected from hydrogen, hydroxy, halo, amino, carboxy, carboxy(C1-C6)alkyl, (C1-C6)alkylamino, di-(C1-C6)alkytamino, (C1-C6)alkoxy, (C1-C6)alkyl-Oâ€”(C&boxH;O)â€”, (C1-C6)alkyl-Oâ€”(C&boxH;O)â€”(C1-C6)alkyl-Oâ€”(C1-C6)alkyl-(C&boxH;O)â€”Oâ€”, (C1-C6)alkyl-(C&boxH;O)â€”(C1-C6)alkyl-Oâ€”, (C1-C6)alkyl-(C&boxH;O)â€”, (C1-C6) straight or branched alkyl, (C3-C7)cycloalkyl wherein one of the carbon atoms may optionally be replaced by nitrogen, oxygen or sulfur; aryl selected from phenyl and naphthyl; heteroaryl selected from indanyl, thienyl, furyl, pyridyl, thiazolyl, isothiazolyl, oxazolyl, isoxazolyl, triazolyl, tetrazolyl and quinolyl; phenyl-(C2-Cr)alkyl, benzhydryl and benzyl, wherein each of said aryl and heteroaryl groups and the phenyl moieties of said benzyl, phenyl-(C2-C6)alkyl and benzhydryl may optionally be substituted with one or two substituents independently selected from halo, nitro, (C1-C6)alkyl optionally substituted with from one to three fluorine atoms, (C1-C6)alkoxy optionally substituted with from one to three fluorine atoms, trifluoromethyl, amino, (C1-C6)-alkylamino, (C1-C6)alkyl-Oâ€”(C&boxH;O)â€”, (C1-C6)alkyl-Oâ€”(C&boxH;O)â€”(C1-C6)alkyl-, (C1-C6)alkyl-(C&boxH;O)â€”Oâ€”, (C1-C6)alkyl-(C&boxH;O)â€”(C1-C6)alkyl-O (C1-C6)alkyl-(C&boxH;O)â€”, (C1-C6)alkyl-(C&boxH;O)â€”(C1-C6)alkyl-, di-(C1-C6)alkylamino, â€”(C&boxH;O)NHâ€”(C1-C6)-, alkyl-(C&boxH;O)â€”NH(C1-C6)alkyl, â€”NH(C&boxH;O)H and â€”NH(C&boxH;O)â€”(C1-C6)alkyl; and wherein one of the phenyl moieties of said benzhydryl may optionally be replaced by naphthyl, thienyl, furyl or pyridyl; or R1 and R2, together with the nitrogen to which they are attached, form a saturated or unsaturated monocyclic ring containing from three to eight carbon atoms, a fused bicyclic ring containing from six to ten carbon atoms, or a saturated bridged ring system containing from six to ten carbon atoms; R4 is aryl selected from phenyl and naphthyl; heteroaryl selected from indanyl, thienyl, furyl, pyridyl, thiazolyl, isothiazolyl, oxazolyl, isoxazolyl, triazolyl, tetrazolyl and quinolyl; and cycloalkyl having from three to seven carbon atoms wherein one of said carbon atoms may optionally be replaced by nitrogen, oxygen or sulfur; wherein each of said aryl and heteroaryl groups may optionally be substituted with one or more substituents, and said (C3-C7)cycloalkyl may optionally be substituted with one, two or three substituents, each of said substituents being independently selected from halo, nitro, (C1-C6)alkyl optionally substituted with from one to three fluorine atoms, (C1-C6)alkoxy optionally substituted with from one to three fluorine atoms, phenyl, amino, (C1-C6)alkylamino, â€”(C&boxH;O)â€”NHâ€”(C1-C6)alkyl, (C1-C6)alkyl-(C&boxH;O)â€”, â€”(C&boxH;O)â€”Oâ€”(C1-C6)alkyl, â€”(C&boxH;O)H, â€”CH2OR12, NH2(C1-C6)alkyl-, â€”NH(C&boxH;O)H, â€”NH(C&boxH;OY(C1-C6)alkyl, â€”NHâ€”(S&boxH;O)â€”(C1-C6)alkyl and (C1-C6)alkylâ€”Nâ€”(SO2)â€”(C1-C6)alkyl-, R3 is hydrogen, (C3-C8)cycloalkyl, (C1-C6) straight or branched alkyl or phenyl optionally substituted with one or more substituents independently selected from halo, (C1-C6)alkyl optionally substituted with from one to three fluorine atoms, and (C1-C6)alkoxy optionally substituted with from one to three fluorine atoms; R5 is hydrogen, (C1-C6)alkyl, or phenyl optionally substituted with one or more substituents independently selected from halo, (C1-C6)alkyl optionally substituted with from one to three fluorine atoms and (C1-C6)alkoxy optionally substituted with from one to three fluorine atoms; R6 is selected from hydrogen, (C1-C6) straight or branched alkyl, (C3-C7)cycloalkyl wherein one of the carbon atoms may optionally be replaced by nitrogen, oxygen or sulfur; aryl selected from phenyl, biphenyl, indanyl and naphthyl; heteroaryl selected from thienyl, furyl, pyridyl, thiazolyl, isothiazolyl, oxazolyl, isoxazolyl, triazolyl, tetrazolyl and quinolyl; phenyl (C2-C6)alkyl, benzhydryl and benzyl, wherein each of said aryl and heteroaryl groups and the phenyl moieties of said benzyl, phenyl (C2-C6)alkyl and benzhydryl may optionally be substituted with one or more substituents independently selected from halo, nitro, (C1-C6)alkyl optionally substituted with from one to three fluorine atoms, (C1-C6)alkoxy, trifluoromethyl, amino, trihaloalkoxy (e.g., trifluoromethoxy), (C1-C6)alkylamino, (C1-C6)alkyl-Oâ€”(C&boxH;O)â€”, (C1-C6)alkyl-Oâ€”(C&boxH;O)â€”(C1-C6)alkyl, (C1-C6)alkyl-(C&boxH;O)â€”Oâ€”, (C1-C6)alkyl-(C&boxH;O)(C1-C6)alkyl-Oâ€”, (C1-C6)alkyl-(C&boxH;O)â€”, (C1-C6)alkyl-(C&boxH;OY(C1-C6)alkyl-, di-(C1-C6)alkylamino, â€”(C&boxH;O)NHâ€”(C1-C6)alkyl, (C1-C6)alkyl-(C&boxH;O)â€”NHâ€”(C1-C6)alkyl-, â€”NH(C&boxH;O)H and â€”NH(C&boxH;O)â€”(C1-C6)alkyl; and wherein one of the phenyl moieties of said benzhydryl may optionally be replaced by naphthyl, thienyl, furyl or pyridyl; and R12 is hydrogen, (C1-C3)alkyl or phenyl; or a pharmaceutically acceptable salt thereof, that is effective in treating or preventing such disorder; (e) an amount of a compound of the formula â€ƒwherein R1 is cycloalkyl having from five to seven carbon atoms, pyrrolyl, thienyl, pyridyl, phenyl or substituted phenyl, wherein said substituted phenyl is substituted with from one to three substituents independently selected from fluorine, chlorine, bromine, trifluoromethyl, alkyl having from one to three carbon atoms, alkoxy having from one to three carbon atoms, carboxy, alkoxycarbonyl having from one to three carbon atoms in the alkoxy moiety and benzyloxycarbonyl; R2 is furyl, thienyl, pyridyl, indolyl, biphenyl, phenyl or substituted phenyl, wherein said substituted phenyt is substituted with one or two substituents independently selected from fluorine, chlorine, bromine, trifluoromethyl, alkyl having from one to three carbon atoms, alkoxy having from one to three carbon atoms, carboxy, alkoxycarbonyl having from one to three carbon atoms in the alkoxy moiety and benzyloxycarbonyl; and R3 is thienyl, phenyl, fluorophenyl, chlorophenyl or bromophenyl; or a pharmaceutically acceptable salt thereof, that is effective in treating or preventing such disorder; or (f) an amount of a compound of the formula â€ƒwherein m is an integer from 0 to 8, and any one of the carbon-carbon single bonds of (CH2)m, wherein both carbon atoms of such bond are bonded to each other and to another carbon in the (CH2)m chain, may optionally be replaced by a carbon-carbon double bond or a carbon-carbon triple bond, and any one of the carbon atoms of said (CH2)m may optionally be substituted with R8; w is an integer from 0 to 2; y is an integer from 1 to 4; z is an integer from 1 to 4, and wherein any one of the carbon atoms of said (CH2)z may optionally be substituted with R4; R1 is hydrogen or (C1-C8)alkyl optionally substituted with hydroxy, alkoxy or fluoro; R2 is a group selected from hydrogen, (C1-C6)straight or branched alkyl, (C3-C7)cycloalkyl wherein one of the carbon atoms may optionally be replaced by nitrogen, oxygen or sulfur; aryl selected from phenyl, indanyl, and naphthyl; heteroaryl selected from thienyl, furyl, pyridyl, thiazolyl, isothiazolyl, oxazolyl, isoxazolyl, triazolyl, tetrazolyl and quinolyl; phenyl(C2-C6)alkyl, benzhydryl and benzyl, wherein one of the phenyl moieties of said benzhydryl may optionally be replaced by naphthyl, thienyl, furyt or pyridyl and wherein each of said aryl and heteroaryl groups and the phenyl moieties of said benzyl, phenyl(C2-C6)alkyl and benzhydryl may optionally be substituted with one or more substituents independently selected from halo, nitro, (C1-C6)alkyl, (C1-C6)alkoxy, trifluoromethyl, amino, (C1-C6yalkylamino, (C1-C6)alkyl-Oâ€”(C&boxH;O)â€”, (C1-C6)alkyl-Oâ€”(C&boxH;O)â€”(C1-C6)alkyl, (C1-C6)-(C&boxH;O)â€”Oâ€”, (C1-C6)alkyl-(C&boxH;O)â€”(C1-C6)alkyl-Oâ€”, (C1-C6)alkyl-(C&boxH;O)â€”, (C1-C6)alkyl-(C&boxH;O)â€” (C1-C6)alkyl-, di-(C1-C6)alkylamino, â€”(C&boxH;O)NHâ€”(C1-C6)alkyl,(C1-C6)-alkyl-(C&boxH;O)â€”NHâ€”(C1-C6)alkyl, â€”NH(C&boxH;O)H and â€”NH(C&boxH;O)â€”(C1-C6)alkyl; R5 is hydrogen, phenyl or (C1-C6)alkyl; or R2 and R5, together with the carbon to which they are attached, form a saturated carbocyclic ring having from 3 to 7 carbon atoms wherein one of said carbon atoms may optionally be replaced by oxygen, nitrogen or sulfur; R3 is aryl selected from phenyl, indanyl, and naphthyl; heteroaryl selected from thienyl, furyl, pyridyl, thiazolyl, isothiazolyl, oxazolyl, isoxazolyl, triazolyl, tetrazolyl and quinolyl; and cycloalkyl having 3 to 7 carbon atoms wherein one of said carbon atoms may optionally be replaced by nitrogen, oxygen or sulfur; wherein each of said aryl and heteroaryl groups may optionally be substituted with one or more substituents, and said (C3-C7)cycloalkyl may optionally be substituted with one or two substituents, each of said substituents being independently selected from halo, nitro, (C1-C6)alkyl optionally substituted with from one to three fluorine atoms, (C1-C6)alkoxy optionally substituted with from one to three fluorine atoms, trifluoromethyl, phenyl, amino, (C1-C6)alkylamino, (C1-C6)dialkyl amino, â€”(C&boxH;O)â€”NHâ€”(C1-C6)alkyl, (C1-C6)alkyl-(C&boxH;O)â€”NHâ€”(C1-C6)alkyl, â€”NH(C&boxH;O)H and â€”NH(C&boxH;O)â€”(C1-C6)alkyl; R4 is independently selected from hydrogen, hydroxy, halo, amino, oxo (&boxH;O), nitrile, (C1-C6)alkylamino, di-(C1-C6)alkylamino, (C1-C6)alkoxy, (C1-C6)alkyl-Oâ€”(C&boxH;O)â€”, (C1-C6)alkyl-Oâ€”(C&boxH;O)â€”(C1-C6)alkyl, (C1-C6)alkyl-(C&boxH;O)â€”Oâ€”, (C1-C6)alkyl-(C&boxH;O)(C1-C6)alkyl-Oâ€”, hydroxy-(C1-C6)alkyl, (C1-C6)alkoxy(C1-C6)alkyl, (C1-C6)alkyl-(C&boxH;O)â€”, (C1-C6)alkyl-(C&boxH;O)â€”(C1-C6)alkyl-, and the groups set forth in the definition of R2; R6 is NH(C&boxH;O)R9, NHCH2R9, NHSO2R9 or one of the groups set forth in any of the definitions of R2, and R4; R8 is oximino (&boxH;NOH) or one of the groups set forth in any of the definitions of R2, and R4; R9 is (C1-C6)alkyl, hydrogen, phenyl or phenyl (C1-C6)alkyl; with the proviso that (a) when m is 0, R8 is absent and R6 is hydrogen, (b) neither R4, R6, nor R8 can form, together with the carbon to which it is attached, a ring with R5, and (c) the sum of y and z must be less than 7; or a pharmaceutically acceptable salt thereof, that is effective in treating or preventing such disorder; or (g) an amount of a compound of the formula â€ƒwherein X1 is (C1-C5)alkoxy or halosubstituted (C1-C5)alkoxy; X2 is hydrogen, halogen, (C1-C5)alkyl, (C2-C5)alkenyl, (C2-C5)alkynyl, (C1-C5)alkoxy, (C1-C5)alkylthio, (C1-C5)alkylsulfinyl, (C1-C5)alkylsulfonyl, halosubstituted (C1-C5)alkyl, halosubstituted (C1-C5)alkoxy, (C1-C5)alkylamino, dialkylamino having from 1 to 5 carbon atoms in each alkyl moiety, (C1-C5)alkylsulfonylamino (which may be substituted by halogen), â€ƒ(which may be substituted by halogen in the alkylsulfonyl moiety), (C1-C5)alkanoylamino (which may be substituted by halogen) or â€ƒ(which may be substituted by halogen in the alkanoyl moiety); Ar1 and Ar2 are each, independently, thienyl, phenyl, fluorophenyt, chlorophenyl or bromophenyl; A is Yâ€”(CH2)mâ€”CH(R2)â€”(CH2)nâ€”NR1â€”; R1 is hydrogen, (C1-C5)alkyl, benzyl or â€”(CH2)pâ€”Y; R2 is hydrogen, (C1-C5)alkyl (which may be substituted by a substituent selected from the group consisting of hydroxy, amino, methylthio and mercapto), benzyl, 4-hydroxybenzyl, 3-indolylmethyl or â€”(CH2)pâ€”Y; Y is â€”CN, â€”CH2Z or â€”COZ; Z is hydroxy, amino, (C1-C5)alkoxy, (C1-C5)alkylamino or dialkylamino having from 1 to 5 carbon atoms in each alkyl moiety; m, n and p are each, independently, 0, 1, 2 or 3; and R1 and R2 may be connected to form a ring; or a pharmaceutically acceptable salt thereof, that is effective in treating or preventing such disorder; or (h) an amount of a compound of the formula â€ƒwherein R1 is phenyl optionally substituted with one or more substituents, preferably with from one to three substituents, independently selected from hydrogen, halo, nitro, (C1-C10)alkyl optionally substituted with from one to three fluorine atoms, (C1-C10)alkoxy optionally substituted with from one to three fluorine atoms, trifluoromethyl, hydroxy, phenyl, cyano, amino, (C1-C6)-alkylamino, di-(C1-C6)alkylamino, â€”(C&boxH;O)â€”NHâ€”(C1-C6)alkyl, (C1-C6)alkyl-(C&boxH;O)â€”NHâ€”(C1-C6)alkyl, hydroxy(C1-C4)alkyl, â€”NH(C&boxH;O)H, â€”NH(C&boxH;O)â€”(C1-C6)alkyl, (C1-C4)alkoxy(C1-C4)alkyl, â€”S(O)vâ€”(C1-C10)alkyl wherein v is zero, one or two, â€”S(O)v-aryl wherein v is zero, one or two, â€”O-aryl, â€”SO2NR4R5 wherein each of R4 and R5 is independently, (C1-C6)alkyl, or R4 and R5, together with the nitrogen to which they are attached, form a saturated ring containing one nitrogen and from 3 to 6 carbons, â€ƒwherein one or both of the alkyl moieties may optionally be substituted with from one to three fluorine atoms, â€”N(SO2â€”(C1-C10)alkyl)2 and â€ƒand wherein the aryl moieties of said â€”S(O)v-aryl, â€”O-aryl and â€ƒare independently selected from phenyl and benzyl and may optionally be substituted with from one to three substituents independently selected from (C1-C4)alkyl, (C1-C4)alkoxy and halo; or R1 is phenyl substituted with a group having the formula â€ƒwherein a is 0, 1 or 2 and the asterisk represents a position meta to the point of attachment of R1; R2 is selected from (C1-C6) straight or branched alkyl, (C3-C7)cycloalkyl wherein one of the carbon atoms may optionally be replaced by nitrogen, oxygen or sulfur; aryl selected from biphenyl, phenyl, indanyl and naphthyl; heteroaryl selected from thienyl, furyl, pyridyl, thiazolyl, isothiazolyl, oxazolyl, isoxazolyl, triazolyl, tetrazolyl and quinolyl; phenyl (C2-C6)alkyl, benzhydryl and benzyl, wherein each of said aryl and heteroaryl groups and the phenyl moieties of said benzyl, phenyl (C2-C6)alkyl and benzhydryl may optionally be substituted with one or more substituents, preferably with from one to three substituents, independently selected from halo, nitro, (C1-C10)alkyl optionally substituted with from one to three fluorine atoms, (C1-C10)alkoxy optionally substituted with from one to three fluorine atoms, amino, hydroxy-(C1-C6)alkyl, (C1-C6)alkoxy-(C1-C6)alkyl, (C1-C6)-alkylamino, (C1-C6)alkyl-Oâ€”(C&boxH;O)â€”, (C1-C6)alkyl-Oâ€”(C&boxH;O)â€”(C1-C6)alkyl, (C1-C6)alkyl-(C&boxH;O)â€”Oâ€”, (C1-C6)alkyl-(C&boxH;O)â€”(C1-C6)alkyl-Oâ€”, (C1-C6)alkyl-(C&boxH;O)â€”, (C1-C6)alkyl-(C&boxH;O)â€”(C1-C6)alkyl-, di-(C1-C6)alkylamino, â€”(C&boxH;O)NH(C1-C6)alkyl, (C1-C6)-alkyl-(C&boxH;O)â€”NHâ€”(C1-C6)alkyl, â€”NH(C&boxH;O)H and â€”NH(C&boxH;O)â€”(C1-C6)alkyl; and wherein one of the phenyl moieties of said benzhydryl may optionally be replaced by naphthyl, thienyl, furyl or pyridyl; m is an integer from 0 to 8, and any one of the carbon-carbon single bonds of (CH2)m, wherein both carbon atoms of such bond are bonded to each other and to another carbon atom in the (CH2)m chain, may optionally be replaced by a carbon-carbon double bond or a carbon-carbon triple bond, and any one of the carbon atoms of said (CH2)m may optionally be substituted with R4; R3 is selected from NH(C&boxH;O)R8, NHCH2R8, SO2R8, AR9, CO2H and the radicals set forth in the definitions of R2, R6 and R7; A is CH2, nitrogen, oxygen, sulfur or carbonyl; R8 is (C1-C6)alkyl, hydrogen, phenyl or phenyl (C1-C6)alkyl; R4 is selected from oximino (&boxH;NOH) and the radicals set forth in the definitions of R2, R6 and R7; R9 is a monocyclic or bicyclic heterocycle selected from the group consisting of pyrimidinyl, benzoxazolyl, 2,3-dihydro-3-oxobenzisosulfonazol-2-yl, morpholin-1-yl, thiomorpholin-1-yl, benzofuranyl, benzothienyl, indolyl, isoindolyl, isoquinolinyl, furyl, pyridyl, isothiazolyl, oxazolyl, triazolyl, tetrazolyl, quinolyl, thiazolyl, thienyl, and groups of the formulae â€ƒwherein B and D are selected from carbon, oxygen and nitrogen, and at least one of B and D is other than carbon; E is carbon or nitrogen; n is an integer from 1 to 5; any one of the carbon atoms of said (CH2)n and (CH2)n+1 may be optionally substituted with (C1-C6)alkyl or (C2-C6)spiroalkyl; and either any and either any one pair of the carbon atoms of said (CH2)n and (CH2)n+1 may be bridged by a one or two carbon atom linkage, or any one pair of adjacent carbon atoms of said (CH2)n and (CH2)l+1 may form, together with from one to three carbon atoms that are not members of the carbonyl containing ring, a (C3-C5) fused carbocyclic ring; X is (CH2)q wherein q is two or three and wherein one of the carbon-carbon single bonds in said (CH2)q may optionally be replaced by a carbon-carbon double bond, and wherein any one of the carbon atoms of said (CH2)q may optionally be substituted with R6, and wherein any one of the carbon atoms of said (CH2)q may optionally be substituted with R7; R6 and R7 are independently selected from hydrogen, hydroxy, halo, amino, oxo (&boxH;O), cyano, hydroxy-(C1-C6)alkyl, (C1-C6)alkoxy-(C1-C6)alkyl, (C1-C6)alkylamino, di-(C1-C6)alkoxy, â€”(C&boxH;O)â€”OH, (C1-C6)alkyl-Oâ€”(C&boxH;O)â€”, (C1-C6)alkyl-Oâ€”(C&boxH;O)â€”(C1-C6)alkyl, (C1-C6)alkyl-(C&boxH;O)â€”Oâ€”, (C1-C6)alkyl-(C&boxH;O)â€”(C1-C6)alkyl-Oâ€”, (C1-C6)alkyl-(C&boxH;O)â€”, (C1-C6)alkyl-(C&boxH;O)â€”(C1-C6)alkyl- and the radicals set forth in the definition of R2; and Y is (CH2)z wherein z is zero or one; with the proviso that: (a) when A is â€”(CH2)â€” or carbonyl, R9 cannot be furyl, pyridyl, isothiazolyl, oxazolyl, triazolyl, tetrazolyl, quinolyl, thiazolyl or thienyl; (b) when m is zero, one of R3 and R4 is absent and the other is hydrogen; and (c) when R6 or R7 is attached to a carbon atom of X that is adjacent to the ring nitrogen, then R6 or R7, respectively, must be a substituent wherein the point of attachment is a carbon atom; or a pharmaceutically acceptable salt thereof, that is effective in treating or preventing such disorder; or (i) an amount of a compound of the formula â€ƒwherein Ar1 and Ar2 are each independently phenyl; R1 is alkyl having from 1 to 6 carbon atoms; R2 is hydrogen or alkyl having from 1 to 6 carbon atoms; and either X and Y are taken separately and they are each, independently, hydrogen, dialkylphosphoryl having from 2 to 12 carbon atoms, alkyl having from 1 to 6 carbon atoms; or X and Y are taken together and they represent a hydrocarbon chain having 3, 4, or 5 carbon atoms, optionally containing up to 2 double bonds and optionally having 1 or 2 substituents selected from oxo, hydroxy and alkyl having from 1 to 6 carbon atoms; provided that when X and Y are taken together they are attached to adjacent carbon atoms; and provided that if either X or Y is hydrogen, then the other one must be alkenyl or alkynyl; or a pharmaceutically acceptable salt thereof, that is effective in treating or preventing such disorder; or (j) an amount of a compound of the formula â€ƒwherein Ar1 and Ar2 are each, independently, thienyl, phenyl, fluorophenyl, chlorophenyl or bromophenyl; X is â€”CONR3R4, â€”CO2R3, CH2OR3, â€”CH2NR3R4 or â€”CONR3OR4; R1, R3 and R4 are each, independently, hydrogen or alkyl having 1 to 4 carbon atoms; R2 is alkyl having 1 to 4 carbon atoms; Y is alkylsulfonyl having 1 to 4 carbon atoms, N-alkyl-N-alkanoylamino (which may be substituted by halogen in the alkanoy moiety) having 1 to 4 carbon atoms in the alkyl and the alkanoyl moieties, N-alkyl-N-alkylsulfonylamino (which may be substituted by halogen in the alkylsulfonyl moiety) having 1 to 4 carbon atoms in the alkyl and the alkyl sulfonyl moieties, alkenyl having 2 to 4 carbon atoms, alkynyl having 2 to 4 carbon atoms, halosubstituted alkyl having 1 to 4 carbon atoms, alkylamino having 1 to 4 carbon atoms, alkanoylamino (which may be substituted by halogen) having 1 to 4 carbon atoms or alkylsulfonylamino (which may be substituted by halogen) having 1 to 4 carbon atoms; or a pharmaceutically acceptable salt thereof that is effective in treating or preventing disorder; or (k) an amount of a compound of the formula â€ƒwherein R is C1-C6 alkyl; X is C1-C6 alkyl having one or more substituents bonded through a heteroatom selected from hydroxy, halogen, C1-C6 alkoxy, C2-C6 alkanoyl, C1-C6 alkanoyloxy, C1-C6 alkylthio, mono C1-C6 alkylamino, di C1-C6 alkylamino, amino, cyano and azido; Ar1 and Ar2 are each, independently, aryl optionally substituted by one C1-C6 alkyl, C1-C6 alkoxy, C1-C6 alkylthio, halogen, cyano, nitro, phenoxy, mono C1-C5 alkylamino, di C1-C6 alkylamino, halosubstituted C1-C6 alkyl, or halosubstituted C1-C6 alkoxy; Y is hydrogen, C1-C6 alkyl, C2-C6 alkenyl, C3-C8 cycloalkyl, Zâ€”(CH2)pâ€”, or Wâ€”(CH2)mâ€”CHR2â€”(CH2)nâ€”NR1COâ€” wherein Y is at the 4-, 5- or 6-position on the quinuclidine ring; R1 is hydrogen, C1-C6 alkyl, benzyl or â€”(CH2)râ€”W; R2 is hydrogen or C1-C6 alkyl which may be substituted by one hydroxy, amino, methylthio, mercapto, benzyl, 4-hydroxybenzyl, 3-indolylmethyl or â€”(CH2)râ€”W; Z is C1-C6 alkoxy, â€”CONR4R5, â€”CO2R4, â€”CHR4OR5, â€”CHR4NR5R6, â€”COR4, â€”CONR4OR5 or optionally substituted aryl; each W is independently cyano, hydroxymethyl, C2-C6 alkoxymethyl, aminomethyl, mono C1-C6 alkylaminomethyl, di C1-C6 alkylaminomethyl, carboxyl, carbamoyl or C1-C6 alkoxycarbonyl; R4, R5 and R6 are independently hydrogen, C1-C6 alkyl, C1-C6 alkoxy, C3-C8 cycloalkyl or optionally substituted aryl or heterocyclic group; p is 0 to 6; and m, n and r are each, independently, 0 to 3; or a pharmaceutically acceptable salt thereof, that is effective in treating or preventing such disorders; or (l) an amount of a compound of the formula â€ƒwherein X and Y are each hydrogen, halo, C1-C6 alkyl, halosubstituted C1-C6 alkyl, C1-C6 alkoxy, C1-C6 alkylthio, C1-C6 alkylsulfinyl, C1-C6 alkylsulfonyl or tri C1-C6 alkylsilyl; Ar1 and Ar2 are each aryl optionally substituted by halo; A is â€”COâ€” or â€”(CH2)â€”; Zâ€”Aâ€” is at the 2 or 3 position on the quinuclidine ring; Z is hydroxy, C1-C6 alkoxy, NR1R2 or W1â€”(CH2)mâ€”CHR4â€”(CH2)nâ€”NR3 wherein R1 and R2, when taken separately, are each hydrogen or C1-C6 alkyl; R1 and R2, when taken together with the nitrogen atom to which they are attached, represent piperidino, pyrrolidino, morpholino, thiomorpholino or piperazino; R3 is hydrogen, C1-C6 alkyl, benzyl or â€”(CH2)râ€”W2; R4 is hydrogen or C1-C6 alkyl which may be substituted by hydroxy, amino, methylthio, mercapto, benzyl, 4-hydroxylbenzyl, 3-indolylmethyl or â€”(CH2)sâ€”W3; R3 and R4, when taken together, represent CH2 or CH2CH2; W1, W2 and W3 are each cyano, hydroxymethyl, C2-C6 alkoxymethyl, aminomethyl, (C1-C6 alkylamino)methyl, (di C1-C6 alkylamino)methyl, carboxyl, (C1-C6 alkyl)carbamoyl, or (di C1-C6 alkyl)carbamoyl, carbamoyl or (C1-C6 alkoxy)carbonyl; and m, n, and s are each 0, 1, 2 or 3; or a pharmaceutically acceptable salt thereof that is effective in treating or preventing such disorder; or (m) an amount of a compound of the formula â€ƒwherein Y is C2-C4 alkylene; Z is a valence bond or C1-C6 alkylene; R1 is phenyl, biphenyl, indanyl, naphthyl, thienyl, furyl, pyridyl, thiazolyl, isothiazolyl, oxazolyl, soxazolyl, tetrazolyl, quinolyl, phenyl C1-C6 alkyl- or benzhydryl, wherein each of the ring moieties may ptionally be substituted by one or more substituents independently selected from halogen, C1-C6 alkyl, alosubstituted C1-C6 alkyl, C1-C6 alkoxy and halosubstituted C1-C6 alkoxy; R2 is hydrogen or C1-C6 alkyl; R3 is hydrogen, hydroxy, cyano, amino or carboxy; and R4 represents a group of the formula (II) or (III) â€ƒwherein X1, X2 and X3 are each halo, hydrogen, nitro, C1-C6 alkyl, halosubstituted C1-C6 alkoxy, losubstituted C1-C6 alkoxy, hydroxy, amino, C1-C6 alkylthio, C1-C6 alkylsulfinyl or C1-C6 alkylsulfonyl; Q1 and Q2 are each H2, oxygen or sulfur; A is valence bond, methylene, oxygen, sulfur or NH; R5 and R6 are each hydrogen or C1-C6 alkyl; and R6 is hydrogen, halogen, C1-C6 alkyl, halosubstituted C1-C6 alkyl or C1-C6 alkoxy; provided that when Z is a valence bond, R3 must be hydrogen; or a pharmaceutically acceptable salt thereof, that is effective in treating or preventing such disorder.