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Claims for Patent: 6,586,430

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Claims for Patent: 6,586,430

Title: CCR5 modulators
Abstract:Compounds of Formula 1 which are useful as modulators of chemokine activity. The invention also provides pharmaceutical formulations and methods of treatment using these compounds.
Inventor(s): Armour; Duncan Robert (Kent, GB), Price; David Anthony (Kent, GB), Stammen; Blanda Luzia Christa (Kent, GB), Wood; Anthony (Kent, GB), Perros; Manoussos (Kent, GB), Edwards; Martin Paul (Kent, GB)
Assignee: Pfizer Inc. (New York, NY)
Application Number:09/452,578
Patent Claims: 1. A compound of the formula

or a pharmaceutically acceptable salt thereof, wherein [Region .alpha.] is a moiety of the formula ##STR260## wherein the symbol `*` indicates the point of attachment of the moiety of the formula (2.0.0) to Region .beta.; R.sup.4 is H or C.sub.1 -C.sub.2 alkyl; R.sup.6 is H, C.sub.1 -C.sub.2 alkyl, C.sub.1 -C.sub.2 alkoxy, --CN, --OH, or --CONH.sub.2 ; A is phenyl optionally substituted by up to 4 substituents independently selected from fluoro, chloro, --CO.sub.2 R.sup.4, --OH, --CN, --CONR.sup.4.sub.a R.sup.4.sub.b, --NR.sup.4.sub.a R.sup.4.sub.b, --NR.sup.4.sub.a COR.sup.4.sub.b, --NR.sup.4.sub.a CO.sub.2 R.sup.4.sub.b, --NR.sup.4.sub.a S(O).sub.p R.sup.4.sub.b, --S(O).sub.p NR.sup.4.sub.a R.sup.4.sub.b, C.sub.1 -C.sub.4 alkyl, C.sub.1 -C.sub.4 alkoxy, C.sub.1 -C.sub.2 alkoxycarbonyl, C.sub.1 -C.sub.2 alkylcarbonyl and C.sub.1 -C.sub.2 alkylcarbonyloxy, said C.sub.1 -C.sub.4 alkyl and C.sub.1 -C.sub.4 alkoxy being optionally substituted by up to 3 substituents independently selected from fluoro and chloro; p is 0, 1 or 2; R.sup.4.sub.a and R.sup.4.sub.b are each independently H or C.sub.1 -C.sub.2 alkyl; R.sup.5.sub.a is a direct bond, --CO-- or --SO.sub.2 --; W.sup.1 is (i) a direct bond, or (ii) in the case where R.sup.5.sub.a is --CO-- or --SO.sub.2 --, C.sub.1 -C.sub.3 alkylene optionally substituted by up to 2 substituents R.sup.23, or (iii) a moiety independently selected from formulas (2.0.6) through (2.0.16) inclusive; ##STR261## wherein the symbol `.fwdarw.` indicates the point of attachment of the moiety W.sub.1 to the nitrogen atom in partial formula (2.0.0) and the symbol `*` indicates the point of attachment of the moiety W.sup.1 to the other, remaining portions of partial formula (2.0.0); R.sup.23 is fluoro, chloro, --CO.sub.2 R.sup.4, --OH, --CN, C.sub.2 -C.sub.4 alkoxy, C.sub.3 -C.sub.7 cycloalkyl or phenyl, said C.sub.1 -C.sub.4 alkoxy, C.sub.3 -C.sub.7 cycloalkyl and phenyl being optionally substituted by up to two substituents R.sup.11 ; R.sup.11 is fluoro, chloro, --CO.sub.2 R.sup.4, --OH, --CN, --CONR.sup.4.sub.a R.sup.4.sub.b, --NR.sup.4.sub.a R.sup.4.sub.b, --NR.sup.4.sub.a COR.sup.4.sub.b, --NR.sup.4.sub.a CO.sub.2 R.sup.4.sub.b, --NR.sup.4.sub.a S(O).sub.p R.sup.4.sub.b, --S(O).sub.p NR.sup.4.sub.a R.sup.4.sub.b, C.sub.1 -C.sub.4 alkyl including dimethyl, C.sub.1 -C.sub.4 alkoxy, C.sub.1 -C.sub.2 alkoxycarbonyl, C.sub.1 -C.sub.2 alkylcarbonyl or C.sub.1 -C.sub.2 alkylcarbonyloxy, said C.sub.1 -C.sub.4 alkyl and C.sub.1 -C.sub.4 alkoxy each being optionally substituted by up to 3 substituents independently selected from fluoro and chloro; R.sup.24 is H or C.sub.1 -C.sub.4 alkyl; R.sup.25 and R.sup.26 are each independently --OH, C.sub.1 -C.sub.2 alkyl or C.sub.1 -C.sub.2 alkoxy, said C.sub.1 -C.sub.2 alkyl being optionally substituted by up to 3 substituents selected from fluoro and --OH; R.sup.27 is (i) C.sub.2 -C.sub.6 alkyl, C.sub.2 -C.sub.6 alkenyl or C.sub.2 -C.sub.6 alkynyl, each optionally substituted by up to 3 substituents R.sup.28 ; or (ii) --(CH.sub.2).sub.n --(C.sub.3 -C.sub.7 cycloalkyl) wherein (a) said C.sub.3 -C.sub.7 cycloalkyl is optionally substituted by up to 3 substituents R.sup.28, (b) n is 0, 1 or 2, (c) in the event that n is 0, the .alpha.-carbon of said C.sub.3 -C.sub.7 cycloalkyl is optionally substituted by one substituent selected from C.sub.1 -C.sub.4 alkyl and phenyl wherein said C.sub.1 -C.sub.4 alkyl and phenyl are optionally substituted by 1 or 2 substituents selected from --CH.sub.3, --OCH.sub.3, --OH or --NH.sub.2, and (d) in the event that n is 1 or 2, the resulting methylene or ethylene is optionally substituted by 1 substituent selected from fluoro, --NH.sub.2, --N(CH.sub.3).sub.2, --OH, --OCH.sub.3, C.sub.1 -C.sub.4 alkyl or phenyl, said C.sub.1 -C.sub.4 alkyl and phenyl being optionally substituted by 1 or 2 substituents selected from --CH.sub.3, --OCH.sub.3, --OH and --NH.sub.2 ; or (iii) phenyl, furyl, tetrahydrofuranyl, tetrahydropyranyl, oxetanyl, thienyl, pyrrolyl, pyrrolidinyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, imidazolyl, pyrazolyl, oxadiazolyl, thiadiazolyl, triazolyl, pyridyl, pyrazinyl, pyridazinyl, piperazinyl, pyrimidinyl, pyranyl, azetidinyl, morpholinyl, thiomorpholino, indolyl, indolinyl, benzo[b]furanyl, 2,3-dihydrobenzofuranyl, benzothienyl, 1H-indazolyl, benzimidazolyl, benzoxazolyl, benzisoxazolyl, benzthiazolyl, quinolinyl, isoquinolinyl, phthalazinyl, quinazolinyl or quinoxalinyl, each optionally substituted (a) on any one or more carbon atoms by up to 3 substituents R.sup.28, or (b) on any one or more nitrogen atoms that is not a point of attachment of said heterocyclic moiety by up to 3 substituents R.sup.13.sub.b, or (c) on any sulphur atom that is not a point of attachment of said heterocyclic moiety by up to 2 oxygen atoms; R.sup.28 is phenyl, fluoro, chloro, oxo, --OH, C.sub.1 -C.sub.2 alkyl, C.sub.1 -C.sub.3 alkoxy, --CO.sub.2 R.sup.29, --CO(C.sub.1 -C.sub.4)alkyl, --SO.sub.2 (C.sub.1 -C.sub.4)alkyl, --CONR.sup.29 R.sup.30, --NR.sup.29 R.sup.30, --NR.sup.29 COR.sup.30, --NR.sup.29 CO.sub.2 R.sup.30, --NR.sup.29 S(O).sub.p R.sup.30 or --SO.sub.2 NR .sup.29 R.sup.30 ; R.sup.29 and R.sup.30 are each independently H or C.sub.1 -C.sub.4 alkyl optionally substituted by up to 3 substituents selected from fluoro and chloro; R.sup.13.sub.b is H, C.sub.1 -C.sub.4 alkyl, C.sub.2 -C.sub.4 alkenyl, C.sub.1 -C.sub.2 alkoxy, C.sub.3 -C.sub.7 cycloalkyl, --CO(C.sub.1 -C.sub.4) alkyl, --SO.sub.2 (C.sub.1 -C.sub.4)alkyl or phenyl wherein said C.sub.1 -C.sub.4 alkyl, C.sub.2 -C.sub.4 alkenyl, C.sub.1 -C.sub.2 alkoxy, C.sub.3 -C.sub.7 cycloalkyl and phenyl are optionally substituted by up to 2 substituents R.sup.11 ; [Region .beta.] is an alkyl bridging element of partial Formula (3.0.0): ##STR262## wherein: "*" is a symbol which represents the point of attachment of the moiety of partial Formula (3.0.0) to R.sub.egion .alpha.; ".fwdarw." is a symbol which represents the point of attachment of the moiety of partial Formula (3.0.0) to R.sub.egion .gamma.; R.sup.40 and R.sup.41 are independently selected from the group consisting of hydrogen; (C.sub.1 -C.sub.2) alkyl including dimethyl; hydroxy; and (C.sub.1 -C.sub.3) alkoxy; [R.sub.egion .gamma.] is an aza-bicyclic moiety of partial Formula (4.2.0): ##STR263## wherein "*" is a symbol which represents the point of attachment of the moiety of partial Formula (4.2.0) to R.sub.egion .beta.; ".fwdarw." is a symbol representing a covalent bond from any of the carbon atoms of the moiety of partial Formula (4.2.0) to R.sub.egion .delta.; W.sup.4 is a direct bond; or is a member independently selected from the group consisting of partial Formulas (4.2.1) through (4.2.6): ##STR264## where: R.sup.52 is a member selected from the group consisting of hydrogen; phenyl; (C.sub.1 -C.sub.4)alkyl substituted by 0 or 1 substituent independently selected from (C.sub.1 -C.sub.2)alkoxy and --CO.sub.2 R.sup.4 ; (C.sub.3 -C.sub.6)cycloalkyl; --CO.sub.2 R.sup.4 ; .fwdarw.O; C(.dbd.O) (C.sub.1 -C.sub.3)alkyl; --C(.dbd.O)NR.sup.4.sub.a R.sup.4.sub.b ; --S(.dbd.O) (C.sub.1 -C.sub.4)alkyl; and (C.sub.1 -C.sub.2)alkylcarbonyl; where R.sup.4, R.sup.4.sub.a, and R.sup.4.sub.b ; are as defined above, but selected on an independent basis; R.sup.51 is absent or is a member selected from the group consisting of (C.sub.1 -C.sub.4)alkyl substituted by 0 or 1 substituent independently selected from (C.sub.1 -C.sub.2) alkoxy and --CO.sub.2 R.sup.4 where R.sup.4 is as defined above; and .fwdarw.O; it being understood that in the case where substituent R.sup.51 is present, the nitrogen atom is in quaternary form; and k, l and m are each an integer selected from 0, 1, 2, and 3; [R.sub.egion .delta.] is a member selected from the group consisting of: A. a two-nitrogen-atom-containing five-membered heterocyclic moiety of partial Formulas (5.0.0) through (5.0.10): ##STR265## ##STR266## wherein: the symbol: "*" indicates the point of attachment of each of the moieties of partial Formulas (5.0.0) through (5.0.10), inclusive, to R.sub.egion .gamma.; R.sup.60.sub.b through R.sup.60.sub.g, inclusive, R.sup.60.sub.k, and R.sup.60.sub.l are each a member selected from the group consisting of hydrogen; --CO.sub.2 R.sup.4 ; --C(.dbd.O)NR.sup.4.sub.a R.sup.4.sub.b ; --S(.dbd.O).sub.p NR.sup.4.sub.a R.sup.4.sub.b ; where: R.sup.4 ; R.sup.4.sub.a ; and R.sup.4.sub.b are as defined above but selected on an independent basis; .fwdarw.O; (C.sub.1 -C.sub.2)alkylcarbonyl; --(C.sub.1 -C.sub.4)alkyl; --(CH.sub.2).sub.n --(C.sub.3 -C.sub.7)cycloalkyl; --(C.sub.2 -C.sub.3)alkenyl; --(CH.sub.2).sub.n -(phenyl); and --(CH.sub.2).sub.n -(HET.sub.1), where n is an integer independently selected from 0, 1, and 2; wherein said (C.sub.1 -C.sub.4)alkyl, alkenyl, cycloalkyl, phenyl and HET.sub.1 (heterocyclyl) groups are independently substituted with 0 to 3 substituents R.sup.66, where: HET.sub.1 is a heterocyclyl group selected from the group consisting of thienyl; oxazolyl; isoxazolyl; thiazolyl; isothiazolyl; pyrazolyl; oxadiazolyl; thiadiazolyl; triazolyl; pyridyl; pyrazinyl; pyridazinyl; pyrimidinyl; thiomorpholino; and morpholinyl; where: R.sup.66 is a member selected from the group consisting of --F; --Cl; --OH; cyano; --C(.dbd.O)OR.sub.68 ; --C(.dbd.O)NR.sup.68 R.sup.69 ; --NR.sup.68 R.sup.69 ; --NR.sup.68 C(.dbd.O)R.sup.69 ; --NR.sup.68 C(.dbd.O)OR.sup.69 ; --NR.sup.68 S(.dbd.O).sub.2 R.sup.69 ; --S(.dbd.O).sub.2 NR.sup.68 R.sup.69 ; (C.sub.1 -C.sub.4)alkyl including dimethyl, and (C.sub.1 -C.sub.4)alkoxy wherein said alkyl and alkoxy are each independently substituted with 0 to 3 substituents independently selected from F and Cl; (C.sub.1 -C.sub.2)alkoxycarbonyl; (C.sub.1 -C.sub.2)alkylcarbonyl; and (C.sub.1 -C.sub.2)alkylcarbonyloxy, where: R.sup.68 and R.sup.69 are each a member selected from the group consisting of hydrogen; and (C.sub.1 -C.sub.2)alkyl; and where said: R.sup.61.sub.a ; R.sup.61.sub.d ; R.sup.61.sub.e ; and R.sup.61.sub.h through R.sup.61.sub.l inclusive; R.sup.64.sub.a through R.sup.64.sub.l inclusive; R.sup.65.sub.a through R.sup.65.sub.c inclusive; and R.sup.65.sub.g through R.sup.65.sub.i inclusive are each a member selected from the group consisting of hydrogen; --OH; --CF.sub.3 ; cyano; --(C.sub.1 -C.sub.3)alkoxy; --C(.dbd.O)OR.sup.4 ; --C(.dbd.O)NR.sup.4.sub.a R.sup.4.sub.b ; --NR.sup.4.sub.a R.sup.4.sub.b ; --NR.sup.4.sub.a C(.dbd.O)R.sup.4.sub.b ; --NR.sup.4.sub.a C(.dbd.O)OR.sup.4.sub.b ; --NR.sup.4.sub.a S(.dbd.O).sub.p R.sup.4.sub.b ; --S(.dbd.O).sub.p NR.sup.4.sub.a R.sup.4.sub.b ; where: R.sup.4 ; R.sup.4.sub.a ; and R.sup.4.sub.b are as defined further above but selected on an independent basis; --(C.sub.1 -C.sub.4)alkyl; --(CH.sub.2).sub.n -(C.sub.3 -C.sub.7)cycloalkyl; --(C.sub.2 -C.sub.3)alkenyl; --(CH.sub.2).sub.n -(phenyl); and --(CH.sub.2).sub.n -(HET.sub.1), where n is an integer selected from 0, 1, and 2; wherein said (C.sub.1 -C.sub.4)alkyl, alkenyl, cycloalkyl, phenyl, and HET.sub.1 (heterocyclyl) groups where HET.sub.1 (heterocyclyl) groups is as defined above, are independently substituted with 0 to 3 substituents R.sup.66 where: R.sup.66 is as defined above, or: R.sup.64.sub.a through R.sup.64.sub.c inclusive; R.sup.64.sub.g through R.sup.64.sub.i inclusive; R.sup.65.sub.a through R.sup.65.sub.c inclusive; and R.sup.65.sub.g through R.sup.65.sub.l inclusive may be taken together in their same subscript denominated pairs along with the remaining portions of the moieties of partial Formulas (5.0.0) through (5.0.2), and (5.0.6) through (5.0.8), to form a fused bicyclic ring system comprising a member independently selected from the group consisting of benzimidazolyl; purinyl, i.e., imidazopyrimidinyl; and imidazopyridinyl; wherein said fused bicyclic ring system is independently substituted with 0 to 3 substituents R.sup.66, where R.sup.66 has the same meaning as set out further above, except that it is independently selected therefrom; B. a (substituted)-amide, carbamate, or urea moiety selected from the group consisting of: 1, alkyl-, cycloalkyl-, and alkenyl-(substituted)-amide, carbamate, or urea moieties of partial Formula (5.1.0): ##STR267## wherein: the symbol "*" as defined above; R.sup.73 is a member selected from the group consisting of hydrogen and (C.sub.1 -C.sub.2)alkyl; W.sup.5 is selected from the group consisting the moieties of partial Formulas (5.1.1) through (5.1.12): ##STR268## wherein: the symbol: ".fwdarw." indicates the point of attachment of the moiety W.sup.5 represented by partial Formulas (5.1.1) through (5.1.12), inclusive, to the nitrogen atom in partial Formula (5.1.0), and the symbol: "*" indicates the point of attachment of the moiety W.sup.5 to R.sup.77 as defined further below; R.sup.74 and R.sup.75 are each selected from the group consisting of hydrogen; (C.sub.1 -C.sub.2)alkyl substituted by 0 or 1 substituent independently selected from OH; and (C.sub.1 -C.sub.2)alkoxy; and R.sup.77 is a member selected from the group consisting of (C.sub.1 -C.sub.6)alkyl; (C.sub.2 -C.sub.6)alkenyl; and --(CH.sub.2).sub.n -(C.sub.3 -C.sub.7)cycloalkyl, where n is an integer selected from 0, 1, and 2; and wherein said alkyl, alkenyl, and cycloalkyl groups comprising R.sup.77 are substituted with 0 to 3 substituents R.sup.78, where: R.sup.78 is a member selected from the group consisting of oxo; --OH; --(C.sub.1 -C.sub.2)alkyl; --(C.sub.1 -C.sub.3)alkoxy; --CF.sub.3 ; --C(.dbd.O)OR.sup.79 ; --C(.dbd.O)NR.sup.79 R.sup.80 ; --NR.sup.79 R.sup.80 ; --NR.sup.79 C(.dbd.O)R.sup.80 ; --NR.sup.79 C(.dbd.O)OR.sup.80 ; --NR.sup.79 S(.dbd.O).sub.2 R.sup.80 ; and --S(.dbd.O).sub.2 NR.sup.79 R.sup.80, where: R.sup.79 and R.sup.80 are each a member independently selected from the group consisting of hydrogen; and (C.sub.1 -C.sub.4)alkyl; and 2. aryl and heterocyclyl-(substituted)-amide, carbamate, or urea moieties of partial Formula (5.2.0): ##STR269## wherein: the symbol: "*"; R.sup.73 ; and W.sup.5 have the same meanings as under the definitions of partial Formula (5.1.0) above, except that they are independently selected therefrom; and under W.sup.5 the symbols: ".fwdarw." and "*" are as defined under partial Formula (5.1.0); and R.sup.82 is a member selected from the group consisting of phenyl; cinnolinyl; furyl; thienyl; pyrrolyl; oxazolyl; isoxazolyl; thiazolyl; isothiazolyl; imidazolyl; imidazolinyl; pyrazolyl; pyrazolinyl; oxadiazolyl; thiadiazolyl; triazolyl; pyridyl; pyrazinyl; pyridazinyl; pyrimidinyl; thiomorpholino; indolyl; isoindolyl; indolinyl; benzo[b]furanyl; 2;3-dihydrobenzofuranyl; benzo[b]thiophenyl; 1H-indazolyl; benzimidazolyl; benzthiazolyl; quinolinyl; isoquinolinyl; phthalazinyl; quinazolinyl; quinoxalinyl; wherein: the aryl or heterocyclyl moiety is substituted by 0 to 3 substituents R.sup.78 where R.sup.78 is as defined above, but selected on an independent basis; or C. a (substituted)-heterocyclyl moiety independently selected from the group consisting of:

1. a heterocyclyl moiety of partial Formula (5.3.0): ##STR270## wherein: the symbol: "*" indicates the point of attachment of partial Formula (5.3.0) to R.sub.egion .gamma.; Q is N, O or S and partial Formula (5.3.0) represents: a. a monocyclic heterocyclic group containing a total of 5- members of which one said member is nitrogen and a second said member is selected from O and S where said S may optionally be in the sulfonate form, wherein said heterocyclic group is selected from the group consisting of oxazolyl; isoxazolyl; thiazolyl; and iso-thiazolyl; or b. a monocyclic heterocyclic group containing a total of 5- members of which two said members are nitrogen and a third or fourth said member is independently selected from N, O, and S where said S may optionally be in the sulfonate form, --S(.dbd.O).sub.2 ; wherein said heterocyclic group is independently selected from the group consisting of triazolyl; tetrazolyl; oxadiazolyl; and thiadiazolyl; and R.sup.90.sub.a and R.sup.90.sub.b are each a member independently selected from the group consisting of hydrogen, --(C.sub.1 -C.sub.2)alkylcarbonyl; --(C.sub.1 -C.sub.4)alkyl; --(CH.sub.2).sub.n -(C.sub.3 -C.sub.7)cycloalkyl; --(C.sub.2 -C.sub.3)alkenyl; --(CH.sub.2).sub.n -(phenyl); and --(CH.sub.2).sub.n -(HET.sub.2), where n is an integer independently selected from 0, 1, and 2; wherein said (C.sub.1 -C.sub.4)alkyl, alkenyl, cycloalkyl, phenyl, and HET.sub.2 groups are independently substituted with 0 to 3 substituents R.sup.91, where: j is 0, 1 or 2; HET.sub.2 is a heterocyclyl group selected from the group consisting of thienyl; oxazolyl; isoxazolyl; thiazolyl; isothiazolyl; pyrazolyl; oxadiazolyl; thiadiazolyl; triazolyl; pyridyl; pyrazinyl; pyridazinyl; pyrimidinyl; thiomorpholino; and morpholinyl; where: R.sup.91 is selected from the group consisting of --F; --Cl; --CO.sub.2 R.sup.4 ; --OH; --CN; --CONR.sup.93 R.sup.94 ; --NR.sup.93 R.sup.94 ; C(.dbd.O)(C.sub.1 -C.sub.4)alkyl; --NR.sup.93 C(.dbd.O)R.sup.94 ; --NR.sup.93 C(.dbd.O)OR.sup.94 ; --NR.sup.93 S(.dbd.O)R.sup.94 ; --S(.dbd.O)NR.sup.93 R.sup.94 ; (C.sub.1 -C.sub.4)alkyl including dimethyl, and (C.sub.1 -C.sub.4)alkoxy wherein said alkyl and alkoxy are each independently substituted with 0 to 3 substituents independently selected from F and Cl; (C.sub.1 -C.sub.2)alkoxycarbonyl; (C.sub.1 -C.sub.2)alkylcarbonyl; and (C.sub.1 -C.sub.2)alkylcarbonyloxy; wherein: R.sup.93 and R.sup.94 are each a member independently selected from the group consisting of hydrogen; and (C.sub.1 -C.sub.2)alkyl; and 2. a heterocyclyl moiety of partial Formula (5.4.0): ##STR271## wherein: R.sup.90a, R.sup.90b and j have the same meanings as set out above and Q is N, O or S.

2. A compound of the formula (I), as claimed in claimed in claim 1, in which R.sup.6 is hydrogen.

3. A compound of the formula (I), as claimed in claims 1, in which A is phenyl.

4. A compound of the formula (I), as clamed in claim 1, in which R.sup.5.sub.a is a direct bond.

5. A compound of the formula (I), as claimed in claim 1, in which W.sup.1 is --CO--.

6. A compound of the formula (I), as claimed in claim 1, in which R.sup.27 is (i) methyl, ethyl, isopropyl, tert-butyl or allyl, each optionally substituted by one substituent selected from fluoro, chloro, --OH, --CF.sub.3, --CH.sub.3, --OCH.sub.3, --CN, --NH.sub.2, --NHCH.sub.3, --N(CH.sub.3).sub.2, --NHCOCH.sub.3 and --NCH.sub.3 (COCH.sub.3), or (ii) cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cyclopropylmethyl, cyclobutylethyl, cyclopentylpropmethyl or cyclopentylmethyl, each optionally substituted as defined in claim 1 or (iii) tetrahydropyranyl, oxetanyl, azetidinyl or tetrahydrofuranyl optionally substituted by up to 3 R.sup.28.

7. A compound of the formula (I), as claimed in claim 1, in which Region .alpha. is selected from the moieties of formulas (2.0.30) through (2.0.36) inclusive, formulas (2.1.3) through (2.1.10) inclusive or formulas (2.2.3) through (2.2.14) inclusive: ##STR272## ##STR273## ##STR274## ##STR275## ##STR276## ##STR277##

8. A compound of the formula (I), as claimed in claim 1, which R.sup.40 and R.sup.41 are H.

9. A compound of the formula (I), as claimed in claim 1, in which Region .gamma. comprises two carbon atoms between the point of attachment to Region .delta. and the nitrogen atom point of attachment of the moiety of formula (4.2.0) to Region .beta..

10. A compound of the formula (I), as claimed in claim 1, in which R.sup.52 is hydrogen.

11. A compound of the formula (I), as claimed in claim 1, in which R.sup.51 is absent.

12. A compound of the formula (I), as claimed in claim 1, in which Region .delta. is selected from the moieties of formulas (5.0.15) through (5.0.30) inclusive, formulas (5.0.35) through (5.0.47) inclusive, formulas (5.1.15) through (5.1.22) inclusive, formulas (5.2.1) through (5.2.10) inclusive, formulas (5.3.15) through (5.3.26) inclusive or formulas (5.4.10) through (5.4.17) inclusive: ##STR278## ##STR279## ##STR280## ##STR281## ##STR282## ##STR283## ##STR284## ##STR285## ##STR286## ##STR287## ##STR288## ##STR289##

13. A compound of the formula (I), as claimed in claim 1, wherein region .delta. is selected from the moieties of formulas (5.4.5) through (5.4.8) ##STR290##

14. A compound of the formula (I), as claimed in claim 1, which is selected from N-{3-[3-exo-(2-Methyl-1H-benzimidazol-1-yl)-8-azabicyclo[3.2. 1]oct-8-yl]-1-phenylpropyl}cyclobutanecarboxamide N-{(1S)-3-[3-exo-(2-Methyl-1H-benzimidazol-1-yl)-8-azabicyclo[3.2. 1]oct-8-yl]-1-phenylpropyl}cyclobutanecarboxamide N-{(1S)-3-[3-endo-(2-Methyl-1H-benzimidazol-1-yl)-8-azabicyclo[3.2. 1]oct-8-yl]-1-phenylpropyl}cyclobutanecarboxamide N-{(1S)-3-[3-exo-(2-Methyl-1H-benzimidazol-1-yl)-8-azabicyclo[3.2. 1]oct-8-yl]-1-phenylpropyl}tetrahydro-2H-pyran-4-carboxamide 1-Acetyl-N-{(1S)-3-[3-exo-(2-methyl-1H-benzimidazol-1-yl)-8-azabicyclo[3.2. 1]oct-8-yl]-1-phenylpropyl}3-azetidine carboxamide 1-Hydroxy-N-{(1S)-3-[3-exo-(2-methyl-1H-benzimidazol-1-yl)-8-azabicyclo[3. 2.1]oct-8-yl]-1-phenylpropyl}cyclopentanecarboxamide 2-Methyl-N-{(1S)-3-[3-exo-(2-methyl-1H-benzimidazol-1-yl)-8-azabicyclo[3.2. 1]oct-8-yl]-1-phenylpropyl}cyclopropanecarboxamide 2-Cyclopropyl-N-{1S)-3-[3-exo-(2-methyl-1H-benzimidazol-1-yl)-8-azabicyclo [3.2.1]oct-8-yl]-1-phenylpropyl}acetamide N-{(1S)-3-[3-exo-(2-methyl-1H-benzimidazol-1-yl)-8-azabicyclo[3.2. 1]oct-8-yl]-1-phenylpropyl}tetrahydro-3-furancarboxamide 3,3,3-Trifluoro-N-{(1S)-3-[3-exo-(2-methyl-1H-benzimidazol-1-yl)-8-azabicyc lo[3.2.1]oct-8-yl]-1-phenylpropyl}propanamide N-{(1S)-3-[3-exo-(2-Methyl-1H-benzimidazol-1-yl)-8-azabicyclo[3.2. 1]oct-8-yl]-1-phenylpropyl}tetrahydro-2-furancarboxamide 1-(Acetylamino)-N-{(1S)-3-[3-exo-(2-methyl-1H-benzimidazol-1-yl)-8-azabicyc lo[3.2.1]oct-8-yl]-1-phenylpropyl}cyclopentanecarboxamide N-{(1S)-3-[3-exo-(2-Methyl-1H-benzimidazol-1-yl)-8-azabicyclo[3.2. 1]oct-8-yl]-1-phenylpropyl}acetamide 1-Methoxy-N-{(1S)-3-[3-exo-(2-methyl-1H-benzimidazol-1-yl)-8-azabicyclo[3. 2.1]oct-8-yl]-1-phenylpropyl}cyclopentanecarboxamide 1-Amino-N-{(1S)-3-[3-exo-(2-methyl-1H-benzimidazol-1-yl)-8-azabicyclo[3.2. 1]oct-8-yl]-1-phenylpropyl}cyclopentanecarboxamide 1-Methyl-N-{(1S)-3-[3-exo-(2-methyl-1H-benzimidazol-1-yl)-8-azabicyclo[3.2. 1]oct-8-yl]-1-phenylpropyl}-2-oxo-4-pyrrolidinecarboxamide 1-Acetyl-N-{(1S)-3-[3-endo-(2-methyl-1H-benzimidazol-1-yl)-8-azabicyclo[3. 2.1]oct-8-yl]-1-phenylpropyl)3-azetidinecarboxamide N-{(1S)-3-[3-endo-(2-Methyl-1H-benzimidazol-1-yl)-8-azabicyclo[3.2. 1]oct-8-yl]-1-phenylpropyl}acetamide N-{(1S)-3-[6-(2-Methyl-1H-benzimidazol-1-yl)-3-azabicyclo[3.1. 0]hex-3-yl]-1-phenylpropyl}cyclobutanecarboxamide 2-Cyclopropyl-N-{(1S)-3-[3-exo-(3-{4-[(methylsulfonyl)amino]benzyl}-1,2,4-o xadiazol-5-yl)-8-azabicyclo[3.2.1]oct-8-yl]-1-phenylpropyl}acetamide N-{(1S)-3-[7-exo-(2-Methyl-1H-benzimidazol-1-yl)-3-oxa-9-azabicyclo[3.3. 1]non-9-yl]-1-phenylpropyl}cyclobutanecarboxamide 2-Cyclopropyl-N-{(1S)-3-[7-exo-(2-methyl-1H-benzimidazol-1-yl)-3-oxa-9-azab icyclo[3.3.1]non-9-yl]-1-phenylpropyl}acetamide 3,3,3-Trifluoro-N-{(1S)-3-[7-exo-(2-methyl-1H-benzimidazol-1-yl)-3-oxa-9-az abicyclo[3.3.1]non-9-yl]-1-phenylpropyl}propanamide N-{(1S)-3-[7-endo-(2-Methyl-1H-benzimidazol-1-yl)-3-oxa-9-azabicyclo[3.3. 1]non-9-yl]-1-phenylpropyl}cyclobutanecarboxamide 2-Cyclopropyl-N-{(1S)-3-[7-endo-(2-methyl-1H-benzimidazol-1-yl)-3-oxa-9-aza bicyclo[3.3.1]non-9-yl]-1-phenylpropyl}acetamide N-{(1S)-3-[7-exo-(2-Methyl-1H-benzimidazol-1-yl)-3-thia-9-azabicyclo[3.3. 1]non-9-yl]-1-phenylpropyl}cyclobutanecarboxamide 2-Cyclopropyl-N-[(1S)-3-(3-endo-{[2-(4-fluorophenyl)acetyl]amino}-8-azabicy clo[3.2.1]oct-8-yl)-1-phenylpropyl]acetamide N-[(1S)-3-(3-{[3-endo-(4-Fluorophenyl)ppropanoyl]amino}-8-azabicyclo[3.2. 1]oct-8-yl)-1-phenylpropyl]cyclobutanecarboxamide N-[(1S)-3-(3-{[3-exo-(4-Fluorophenyl)prpropanoyl]amino}-8-azabicyclo[3.2. 1]oct-8-yl)-1-phenylpropyl]cyclobutanecarboxamide 2-Cyclopropyl-N-[(1S)-3-(3-exo-{[2-(4-fluorophenyl)acetyl]amino}-8-azabicyc lo[3.2.1]oct-8-yl)-1-phenylpropyl]acetamide N-{(1S)-3-[3-exo-(2-Methyl-1H-benzimidazol-1-yl)-8-azabicyclo[3.2. 1]oct-8-yl]-1-phenylpropyl)}1-propionyl-3-azetidinecarboxamide N-{(1S)-3-[3-endo-(2-Methyl-1H-benzimidazol-1-yl)-8-azabicyclo[3.2. 1]oct-8-yl]-1-phenylpropyl}tetrahydro-3-furancarboxamide N-{(1S)-3-[3-endo-(2-Methyl-1H-benzimidazol-1-yl)-8-azabicyclo[3.2. 1]oct-8-yl]-1-phenylpropyl}tetrahydro-2H-pyran4-carboxamide N-{(1S)-3-[3-endo-(2-Methyl-1H-benzimidazol-1-yl)-8-azabicyclo[3.2. 1]oct-8-yl]-1-phenylpropyl}tetrahydro-2-furancarboxamide 1-Acetyl-N-{(1S)-3-[3-endo-(1H-benzimidazol-1-yl)-8-azabicyclo[3.2. 1]oct-8-yl]-1-phenylpropyl}-3-azetidinecarboxamide N-{(1S)-3-[3-endo-(1H-Benzimidazol-1-yl)-8-azabicyclo[3.2. 1]oct-8-yl]-1-phenylpropyl}-1-propionyl-3-azetidinecarboxamide Methyl 3-[({(1S)-3-[3-exo-(2-methyl-1H-benzimidazol-1-yl)-8-azabicyclo[3.2. 1]oct-8-yl]-1-phenylpropyl}amino)carbonyl]-1-azetidinecarboxylate N-{(1S)-3-[3-endo-(2-Methyl-1H-benzimidazol-1-yl)-8-azabicyclo[3.2. 1]oct-8-yl]-1-phenylpropyl}-1-propionyl-3-azetidinecarboxamide 1-Acetyl-N-{(1S)-3-[3-endo-(2-methyl-1H-benzimidazol-1-yl)-8-azabicyclo[3. 2.1]oct-8-yl]-1-phenylpropyl}-2-azetidinecarboxamide 2-[Acetyl(methyl)amino]-N-{(1S)-3-[3-endo-(2-methyl-1H-benzimidazol-1-yl)-8 -azabicyclo[3.2.1]oct-8-yl]-1-phenylpropyl}acetamide 3-[Acetyl(methyl)amino]-N-{(1S)-3-[3-endo-(2-methyl-1H-benzimidazol-1-yl)-8 -azabicyclo[3.2.1]oct-8-yl]-1-phenylpropyl}propanamide 2-Methoxy-N-{(1S)-3-[3-endo-(2-methyl-1H-benzimidazol-1-yl)-8-azabicyclo[3. 2.1]oct-8-yl]-1-phenylpropyl}acetamide 3-Methoxy-N-{(1S)-3-[3-endo-(2-methyl-1H-benzimidazol-1-yl)-8-azabicyclo[3. 2.1]oct-8-yl]-1-phenylpropyl}propanamide 1-Acetyl-N-{(1S)-3-[3-endo-(2-methyl-1H-benzimidazol-1-yl)-8-azabicyclo[3. 2.1]oct-8-yl]-1-phenylpropyl}-3-pyrrolidinecarboxamide 1-Methyl-N-{(1S)-3-[3-endo-(2-methyl-1H-benzimidazol-1-yl)-8-azabicyclo[3. 2.1]oct-8-yl]-1-phenylpropyl}-2-oxo-4-pyrrolidinecarboxamide 1-Acetyl-N-{(1S)-3-[3-exo-(2-ethyl-1H-benzimidazol-1-yl)-8-azabicyclo[3.2. 1]oct-8-yl]-1-phenylpropyl}-3-azetidinecarboxamide N-{(1S)-3-[3-exo-(2-Ethyl-1H-benzimidazol-1-yl)-8-azabicyclo[3.2. 1]oct-8-yl]-1-phenylpropyl}-1-propionyl-3-azetidinecarboxamide 1-Acetyl-N-((1S)-1-phenyl-3-{3-exo-[2-(trifluoromethyl)-1H-benzimidazol-1-y l]-8-azabicyclo[3.2.1]oct-8-yl}propyl)-3-azetidinecarboxamide N-((1S)-1-Phenyl-3-{3-exo-[2-(trifluoromethyl)-1H-benzimidazol-1-yl]-8-azab icyclo[3.2.1]oct-8-yl}propyl)-1-propionyl-3-azetidinecarboxamide N-((1S)-1-Phenyl-3-{3-exo[2-(trifluoromethyl)-1H-benzimidazol-1-yl]-8-azabi cyclo[3.2.1]oct-8-yl}propyl)acetamide 2-[Acetyl(methyl)amino]-N-((1S)-1-phenyl-3-{3-exo-[2-(trifluoromethyl)-1H-b enzimidazol-1-yl]-8-azabicyclo[3.2.1]oct-8-yl}propyl)acetamide 1-Acetyl-N-{(1S)-3-[3-exo-(1H-benzimidazol-1-yl)-8-azabicyclo[3.2. 1]oct-8-yl]-1-phenylpropyl}-3-azetidinecarboxamide N(1S)-3-[3-exo-(1H-Benzimidazol-1-yl)-8-azabicyclo[3.2. 1]oct-8-yl]-1-phenylpropyl}-1-propionyl-3-azetidinecarboxamide 1-acetyl-N(1S)-3-[3-exo-(5-fluoro-1H-benzimidazol-1-yl)-8-azabicyclo[3.2. 1]oct-8-yl]-1-phenylpropyl)3-azetidinecarboxamide N-{(1S)-3-[3-exo-(5-Fluoro-1H-benzimidazol-1-yl)-8-azabicyclo[3.2. 1]oct-8-yl]-1-phenylpropyl}-1-propionyl-3-azetidinecarboxamide 1-Acetyl-N-{(1S)-3-[3-exo-(5-fluoro-2-methyl-1H-benzimidazol-1-yl)-8-azabic yclo[3.2.1]oct-8-yl]-1-phenylpropyl}3-azetidinecarboxamide N-{(1S)-3-[3-exo-(5-Fluoro-2-methyl-1H-benzimidazol-1-yl)-8-azabicyclo[3.2. 1]oct-8-yl]-1-phenylpropyl}-1-propionyl-3-azetidinecarboxamide N-{(1S)-3-[3-exo-(2-methyl-1H-benzimidazol-1-yl)-8-azabicyclo[3.2. 1]oct-8-yl]-1-phenylpropyl}-3-azetidinecarboxamide 1-methyl-N-{(1S)-3-[3-exo-(2-methyl-1H-benzimidazol-1-yl)-8-azabicyclo[3.2. 1]oct-8-yl]-1-phenylpropyl}-3-azetidinecarboxamide (2S)-1-acetyl-N-{(1S)-3-[3-exo-(2-methyl-1H-benzimidazol-1-yl)-8-azabicyclo [3.2.1]oct-8-yl]-1-phenylpropyl}-2-azetidinecarboxamide (2R)-1-acetyl-N-{(1S)-3-[3-exo-(2-methyl-1H-benzimidazol-1-yl)-8-azabicyclo [3.2.1]oct-8-yl]-1-phenylpropyl}-2-azetidinecarboxamide 2-[acetyl(methyl)amino]-N-{(1S)-3-[3-exo-(2-methyl-1H-benzimidazol-1-yl)-8- azabicyclo[3.2.1]oct-8-yl]-1-phenylpropyl}acetamide 3-[acetyl(methyl)amino]-N-{(1S)-3-[3-exo-(2-methyl-1H-benzimidazol-1-yl)-8- azabicyclo[3.2.1]oct-8-yl]-1-phenylpropyl}propanamide 1-acetyl-N-{(1S)-3-[3-exo-(2-methyl-1H-benzimidazol-1-yl)-8-azabicyclo[3.2. 1]oct-8-yl]-1-phenylpropyl}-3-pyrrolidinecarboxamide N-{(1S)-3-[3-exo-(2-methyl-1H-benzimidazol-1-yl)-8-azabicyclo[3.2. 1]oct-8-yl]-1-phenylpropyl}-1-(trifluoromethyl)cyclopropanecarboxamide 2-methoxy-N-{(1S)-3-[3-exo-(2-methyl-1H-benzimidazol-1-yl)-8-azabicyclo[3. 2.1]oct-8-yl]-1-phenylpropyl}acetamide 3-methoxy-N-{(1S)-3-[3-exo-(2-methyl-1H-benzimidazol-1-yl)-8-azabicyclo[3. 2.1]oct-8-yl]-1-phenylpropyl}propanamide 1-Acetyl-N-{(1S)-3-[3-exo-(4-fluoro-2-methyl-1H-benzimidazol-1-yl)-8-azabic yclo[3.2.1]oct-8-yl]-1-phenylpropyl}-3-azetidinecarboxamide N-{(1S)-3-[3-exo-(4-Fluoro-2-methyl-1H-benzimidazol-1-yl)-8-azabicyclo[3.2. 1]oct-8-yl]-1-phenylpropyl}-3-azetidinecarboxamide 1-Methyl-N-{(1S)-3-[3-exo-(4-fluoro-2-methyl-1H-benzimidazol-1-yl)-8-azabic yclo[3.2.1]oct-8-yl]-1-phenylpropyl}-3-azetidinecarboxamide N-{(1S)-3-[3-exo-(4-Fluoro-2-methyl-1H-benzimidazol-1-yl)-8-azabicyclo[3.2. 1]oct-8-yl]-1-phenylpropyl}-1-propionyl-3-azetidinecarboxamide 2-Methoxy-N-{(1S)-3-[3-exo-(4-Fluoro-2-methyl-1H-benzimidazol-1-yl)-8-azabi cyclo[3.2.1]oct-8-yl]-1-phenylpropyl}acetamide N-{(1S)-3-[3-exo-(4-Fluoro-2-Methyl-1H-benzimidazol-1-yl)-8-azabicyclo[3.2. 1]oct-8-yl]-1-phenylpropyl}acetamide 3-Methoxy-N-{(1S)-3-[3-exo-(4-fluoro-2-methyl-1H-benzimidazol-1-yl)-8-azabi cyclo[3.2.1]oct-8-yl]-1-phenylpropyl}propanamide 2-[Acetyl(methyl)amino]-N-{(1S)-3-[3-exo-(4-fluoro-2-methyl-1H-benzimidazol -1-yl)-8-azabicyclo[3.2.1]oct-8-yl]-1-phenylpropyl}acetamide 3-[Acetyl(methyl)amino]-N-{(1S)-3-[3-exo-(4-fluoro-2-methyl-1H-benzimidazol -1-yl)-8-azabicyclo[3.2.1]oct-8-yl]-l -phenylpropyl}propanamide N-{(1S)-3-[3-exo-(4-fluoro-2-methyl-1H-benzimidazol-1-yl)-8-azabicyclo[3.2. 1]oct-8-yl]-1-phenylpropyl}-3-methyl-3-oxetanecarboxamide 3-Ethyl-N-{(1S)-3-[3-exo-(4-fluoro-2-methyl-1H-benzimidazol-1-yl)-8-azabicy clo[3.2.1]oct-8-yl]-1-phenylpropyl}-3-oxetanecarboxamide N-{(1S)-3-[3-exo-(4-Fluoro-2-methyl-1H-benzimidazol-1-yl)-8-azabicyclo[3.2. 1]oct-8-yl]-1-phenylpropyl}-3-oxetanecarboxamide 3-Ethyl-N-{(1S)-3-[3-exo-(4-fluoro-1H-benzimidazol-1-yl)-8-azabicyclo[3.2. 1]oct-8-yl]-1-phenylpropyl}-3-oxetanecarboxamide N-{(1S)-3-[3-exo-(4-Fluoro-1H-benzimidazol-1-yl)-8-azabicyclo[3.2. 1]oct-8-yl]-1-phenylpropyl}-3-methyl-3-oxetanecarboxamide N-{(1S)-3-[3-exo-(4-Fluoro-1H-benzimidazol-1-yl)-8-azabicyclo[3.2. 1]oct-8-yl]-1-phenylpropyl}-3-oxetanecarboxamide N-{(1S)-3-[3-exo-(4-Fluoro-1H-benzimidazol-1-yl)-8-azabicyclo[3.2. 1]oct-8-yl]-1-phenylpropyl}-3-azetidinecarboxamide N-{(1S)-3-[3-exo-(4-Fluoro-1H-benzimidazol-1-yl)-8-azabicyclo[3.2. 1]oct-8-yl]-1-phenylpropyl}-1-methyl-3-azetidinecarboxamide 1-Acetyl-N-{(1S)-3-[3-exo-(4-fluoro-1H-benzimidazol-1-yl)-8-azabicyclo[3.2. 1]oct-8-yl]-1-phenylpropyl}-3-azetidinecarboxamide N-{(1S)-3-[3-exo-(4-Fluoro-1H-benzimidazol-1-yl)-8-azabicyclo[3.2. 1]oct-8-yl]-1-phenylpropyl}-1-propionyl-3-azetidinecarboxamide N-{(1S)-3-[3-exo-(4-Fluoro-1H-benzimidazol-1-yl)-8-azabicyclo[3.2. 1]oct-8-yl]-1-phenylpropyl}-2-methoxyacetamide N-{(1S)-3-[3-exo-(4-Fluoro-1H-benzimidazol-1-yl)-8-azabicyclo[3.2. 1]oct-8-yl]-1-phenylpropyl}acetamide N{-1S)-3-[3-exo-(4-fluoro-1H-benzimidazol-1-yl)-8-azabicyclo[3.2. 1]oct-8-yl]-1-phenylpropyl}-3-methoxypropanamide 2-[Acetyl(methyl)amino]-N-{(1S)-3-[3-exo-(4-fluoro-1H-benzimidazol-1-yl)-8- azabicyclo[3.2.1]oct-8-yl]-1-phenylpropyl}acetamide 3-[Acetyl(methyl)amino]-N-{(1S)-3-[3-exo-(4-fluoro-1H-benzimidazol-1-yl)-8- azabicyclo[3.2.1]oct-8-yl]-1-phenylpropyl}propanamide

and the pharmaceutically acceptable salts thereof.

15. The compound of claim 1 wherein group Y has the structure ##STR291##

16. A compound of the formula

or a pharmaceutically acceptable salt thereof, wherein [Region .alpha.] is a moiety of the formula ##STR292## wherein the symbol `*` indicates the point of attachment of the moiety of the formula (2.0.0) to Region .beta.; R.sup.4 is H or C.sub.1 -C.sub.2 alkyl; R.sup.6 is H, C.sub.1 -C.sub.2 alkyl, C.sub.1 -C.sub.2 alkoxy, --CN, --OH, or --CONH.sub.2 ; A is phenyl optionally substituted by up to 4 substituents independently selected from fluoro, chloro, --CO.sub.2 R.sup.4, --OH, --CN, --CONR.sup.4.sub.a R.sup.4.sub.b, --NR.sup.4.sub.a R.sup.4.sub.b, --NR.sup.4.sub.a COR.sup.4.sub.b, --NR.sup.4.sub.a CO.sub.2 R.sup.4.sub.b, --NR.sup.4.sub.a S(O).sub.p R.sup.4.sub.b, --S(O).sub.p NR.sup.4.sub.a R.sup.4.sub.b, C.sub.1 -C.sub.4 alkyl, C.sub.1 -C.sub.4 alkoxy, C.sub.1 -C.sub.2 alkoxycarbonyl, C.sub.1 -C.sub.2 alkylcarbonyl and C.sub.1 -C.sub.2 alkylcarbonyloxy, said C.sub.1 -C.sub.4 alkyl and C.sub.1 -C.sub.4 alkoxy being optionally substituted by up to 3 substituents independently selected from fluoro and chloro; p is 0, 1 or2; R.sup.4.sub.a and R.sup.4.sub.b are each independently H or C.sub.1 -C.sub.2 alkyl; R.sup.5.sub.a is a direct bond, --CO-- or --SO.sub.2 --; W.sup.1 is (i) a direct bond, or (ii) in the case where R.sup.5.sub.a is --CO-- or --SO.sub.2 --, C.sub.1 -C.sub.3 alkylene optionally substituted by up to 2 substituents R.sup.23, or (iii) a moiety independently selected from formulas (2.0.6) through (2.0.16) inclusive; ##STR293## wherein the symbol `.fwdarw.` indicates the point of attachment of the moiety W.sup.1 to the nitrogen atom in partial formula (2.0.0) and the symbol `*` indicates the point of attachment of the moiety W.sup.1 to the other, remaining portions of partial formula (2.0.0); R.sup.23 is fluoro, chloro, --CO.sub.2 R.sup.4, --OH, --CN, C.sub.1 -C.sub.4 alkoxy, C.sub.3 -C.sub.7 cycloalkyl or phenyl, said C.sub.1 -C.sub.4 alkoxy, C.sub.3 -C.sub.7 cycloalkyl and phenyl being optionally substituted by up to two substituents R.sup.11 ; R.sup.11 is fluoro, chloro, --CO.sub.2 R.sup.4, --OH, --CN, --CONR.sup.4.sub.a R.sup.4.sub.b, --NR.sup.4.sub.a R.sup.4.sub.b, --NR.sup.4.sub.a COR.sup.4.sub.b, NR.sup.4.sub.a CO.sub.2 R.sup.4.sub.b, --NR.sup.4.sub.a S(O).sub.p R.sup.4.sub.b, --S(O).sub.p NR.sup.4.sub.a R.sup.4.sub.b, C.sub.1 -C.sub.4 alkyl including dimethyl, C.sub.1 -C.sub.4 alkoxy, C.sub.1 -C.sub.2 alkoxycarbonyl, C.sub.1 -C.sub.2 alkylcarbonyl or C.sub.1 -C.sub.2 alkylcarbonyloxy, said C.sub.1 -C.sub.4 alkyl and C.sub.1 -C.sub.4 alkoxy each being optionally substituted by up to 3 substituents independently selected from fluoro and chloro; R.sup.24 is H or C.sub.1 -C.sub.4 alkyl; R.sup.25 and R.sup.26 are each independently --OH, C.sub.1 -C.sub.2 alkyl or C.sub.1 -C.sub.2 alkoxy, said C.sub.1 -C.sub.2 alkyl being optionally substituted by up to 3 substituents selected from fluoro and --OH; R.sup.27 is (i) C.sub.1 -C.sub.6 alkyl, C.sub.2 -C.sub.6 alkenyl or C.sub.2 -C.sub.6 alkynyl, each optionally substituted by up to 3 substituents R.sup.28 ; or (ii) --(CH.sub.2).sub.n -(C.sub.3 -C.sub.7 cycloalkyl) wherein (a) said C.sub.3 -C.sub.7 cycloalkyl is optionally substituted by up to 3 substituents R.sup.28, (b) n is0, 1 or 2, (c) in the event that n is 0, the .alpha.-carbon of said C.sub.3 -C.sub.7 cycloalkyl is optionally substituted by one substituent selected from C.sub.1 -C.sub.4 alkyl and phenyl wherein said C.sub.1 -C.sub.4 alkyl and phenyl are optionally substituted by 1 or 2 substituents selected from --CH.sub.3, --OCH.sub.3, --OH or --NH.sub.2, and (d) in the event that n is 1 or 2, the resulting methylene or ethylene is optionally substituted by 1 substituent selected from fluoro, --NH.sub.2, --N(CH.sub.3).sub.2, --OH, --OCH.sub.3, C.sub.1 -C.sub.4 alkyl or phenyl, said C.sub.1 -C.sub.4 alkyl and phenyl being optionally substituted by 1 or 2 substituents selected from --CH.sub.3, --OCH.sub.3, --OH and --NH.sub.2 ; or (iii) phenyl, furyl, tetrahydrofuranyl, tetrahydropyranyl, oxetanyl, thienyl, pyrrolyl, pyrrolidinyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, imidazolyl, pyrazolyl, oxadiazolyl, thiadiazolyl, triazolyl, pyridyl, pyrazinyl, pyridazinyl, piperazinyl, pyrimidinyl, pyranyl, azetidinyl, morpholinyl, thiomorpholino, indolyl, indolinyl, benzo[b]furanyl, 2,3-dihydrobenzofuranyl, benzothienyl, 1H-indazolyl, benzimidazolyl, benzoxazolyl, benzisoxazolyl, benzthiazolyl, quinolinyl, isoquinolinyl, phthalazinyl, quinazolinyl or quinoxalinyl, each optionally substituted (a) on any one or more carbon atoms by up to 3 substituents R.sup.28, or (b) on any one or more nitrogen atoms that is not a point of attachment of said heterocyclic moiety by up to 3 substituents R.sup.13.sub.b, or (c) on any sulphur atom that is not a point of attachment of said heterocyclic moiety by up to 2 oxygen atoms; R.sup.28 is phenyl, fluoro, chloro, oxo, --OH, C.sub.1 -C.sub.2 alkyl, C.sub.1 -C.sub.3 alkoxy, --CO.sub.2 R.sup.29, --CO(C.sub.1 -C.sub.4)alkyl, --SO.sub.2 (C.sub.1 -C.sub.4)alkyl, --CONR.sup.29 R.sup.30, --NR.sup.29 R.sup.30, --NR.sup.29 COR.sup.30, --NR.sup.29 CO.sub.2 R.sup.30, --NR.sup.29 S(O).sub.p R.sup.30 or --SO.sub.2 NR.sup.29 R.sup.30 ; R.sup.29 and R.sup.30 are each independently H or C.sub.1 -C.sub.4 alkyl optionally substituted by up to 3 substituents selected from fluoro and chloro; R.sup.13.sub.b is H, C.sub.1 -C.sub.4 alkyl, C.sub.2 -C.sub.4 alkenyl, C.sub.1 -C.sub.2 alkoxy, C.sub.3 -C.sub.7 cycloalkyl, --CO(C.sub.1 -C.sub.4)alkyl, --SO.sub.2 (C.sub.1 -C.sub.4)alkyl or phenyl wherein said C.sub.1 -C.sub.4 alkyl, C.sub.2 -C.sub.4 alkenyl, C.sub.1 -C.sub.2 alkoxy, C.sub.3 -C.sub.7 cycloalkyl and phenyl are optionally substituted by up to 2 substituents R.sup.11 ; [R.sub.egion .beta.] is an alkyl bridging element of partial Formula (3.0.0): ##STR294## wherein: "*" is a symbol which represents the point of attachment of the moiety of partial Formula (3.0.0) to R.sub.egion .alpha.; ".fwdarw." is a symbol which represents the point of attachment of the moiety of partial Formula (3.0.0) to R.sub.egion .gamma.; R.sup.40 and R.sup.41 are independently selected from the group consisting of hydrogen; (C.sub.1 -C.sub.2)alkyl including dimethyl; hydroxy; and (C.sub.1 -C.sub.3)alkoxy; [R.sub.egion .gamma.] is an aza-bicyclic moiety of partial Formula (4.2.0): ##STR295## wherein "*" is a symbol which represents the point of attachment of the moiety of partial Formula (4.2.0) to R.sub.egion .beta.; ".fwdarw." is a symbol representing a covalent bond from any of the carbon atoms of the moiety of partial Formula (4.2.0) to R.sub.egion .delta.; W.sup.4 is a direct bond; or is a member independently selected from the group consisting of partial Formulas (4.2.1) through (4.2.6): ##STR296## where: R.sup.52 is a member selected from the group consisting of hydrogen; phenyl; (C.sub.1 -C.sub.4)alkyl substituted by 0 or 1 substituent independently selected from (C.sub.1 -C.sub.2)alkoxy and --CO.sub.2 R.sup.4 ; (C.sub.3 -C.sub.6)cycloalkyl; --CO.sub.2 R.sup.4 ; .fwdarw.O; C(.dbd.O)(C.sub.1 -C.sub.3)alkyl; --C(.dbd.O)NR.sup.4.sub.a R.sup.4.sub.b ; --S(.dbd.O)(C.sub.1 -C.sub.4)alkyl; and (C.sub.1 -C.sub.2)alkylcarbonyl; where R.sup.4, R.sup.4.sub.a, and R.sup.4.sub.b ; are as defined above, but selected on an independent basis; R.sup.51 is absent or is a member selected from the group consisting of (C.sub.1-C.sub.4)alkyl substituted by 0 or 1 substituent independently selected from (C.sub.1 -C.sub.2)alkoxy and --CO.sub.2 R.sup.4 where R.sup.4 is as defined above; and .fwdarw.O; it being understood that in the case where substituent R.sup.51 is present, the nitrogen atom is in quaternary form; and k, l and m are each an integer selected from 0, 1, 2, and 3; [R.sub.egion .delta.] is a member selected from the group consisting of: A. a two-nitrogen-atom-containing five-membered heterocyclic moiety of partial Formulas (5.0.0) through (5.0.10): ##STR297## ##STR298## wherein: the symbol: "*" indicates the point of attachment of each of the moieties of partial Formulas (5.0.0) through (5.0.10), inclusive, to R.sub.egion .gamma.; R.sup.60.sub.b through R.sup.60.sub.g, inclusive, R.sup.60.sub.k, and R.sup.60.sub.l are each a member selected from the group consisting of hydrogen; --CO.sub.2 R.sup.4 ; --C(.dbd.O)NR.sup.4.sub.a R.sup.4.sub.b ; --S(.dbd.O).sub.p NR.sup.4.sub.a R.sup.4.sub.b ; where: R.sup.4 ; R.sup.4.sub.a ; and R.sup.4.sub.b are as defined above but selected on an independent basis; .fwdarw.O; (C.sub.1 -C.sub.2)alkylcarbonyl; --(C.sub.1 -C.sub.4)alkyl; --(CH.sub.2).sub.n -(C.sub.3 -C.sub.7)cycloalkyl; --(C.sub.2 -C.sub.3)alkenyl; --(CH.sub.2).sub.n -(phenyl); and --(CH.sub.2).sub.n -(HET.sub.1), where n is an integer independently selected from 0, 1, and 2; wherein said (C.sub.1 -C.sub.4)alkyl, alkenyl, cycloalkyl, phenyl and HET.sub.1 (heterocyclyl) groups are independently substituted with 0 to 3 substituents R.sup.66, where: HET.sub.1 is a heterocyclyl group selected from the group consisting of thienyl; oxazolyl; isoxazolyl; thiazolyl; isothiazolyl; pyrazolyl; oxadiazolyl; thiadiazolyl; triazolyl; pyridyl; pyrazinyl; pyridazinyl; pyrimidinyl; thiomorpholino; and morpholinyl; where: R.sup.66 is a member selected from the group consisting of --F; --Cl; --OH; cyano; --C(.dbd.O)OR.sup.68 ; --C(.dbd.O)NR.sup.68 R.sup.69 ; --NR.sup.68 R.sup.69 ; --NR.sup.68 C(.dbd.O)R.sup.69 ; --NR.sup.68 C(.dbd.O)OR.sup.69 ; --NR.sup.68 S(.dbd.O).sub.2 R.sup.69 ; --S(.dbd.O).sub.2 NR.sup.68 R.sup.69 ; (C.sub.1 -C.sub.4)alkyl including dimethyl, and (C.sub.1 -C.sub.4)alkoxy wherein said alkyl and alkoxy are each independently substituted with 0 to 3 substituents independently selected from F and Cl; (C.sub.1 -C.sub.2)alkoxycarbonyl; (C.sub.1 -C.sub.2)alkylcarbonyl; and (C.sub.1 -C.sub.2)alkylcarbonyloxy, where: R.sup.68 and R.sup.69 are each a member selected from the group consisting of hydrogen; and (C.sub.1 -C.sub.2)alkyl; and where said: R.sup.61 .sub.a ; R.sup.61.sub.d ; R.sup.61.sub.e ; and R.sup.61.sub.h through R.sup.61.sub.l inclusive; R.sup.64.sub.a through R.sup.64.sub.l inclusive; R.sup.65.sub.a through R.sup.65.sub.c inclusive; and R.sup.65.sub.g through R.sup.65.sub.i inclusive are each a member selected from the group consisting of hydrogen; --OH; --CF.sub.3 ; cyano; --(C.sub.1 -C.sub.3)alkoxy; --C(.dbd.O)OR.sup.4 ; --C(.dbd.O)NR.sup.4.sub.a R.sup.4.sub.b ; --NR.sup.4.sub.a R.sup.4.sub.b ; --NR.sup.4.sub.a C(.dbd.O)R.sup.4.sub.b ; --NR.sup.4.sub.a C(.dbd.O)OR.sup.4.sub.b ; --NR.sup.4.sub.a S(.dbd.O).sub.p R.sup.4.sub.b ; --S(.dbd.O).sub.p NR.sup.4.sub.a R.sup.4.sub.b ; where: R.sup.4 ; R.sup.4.sub.a ; and R.sup.4.sub.b are as defined further above but selected on an independent basis; --(C.sub.1 -C.sub.4)alkyl; --(CH.sub.2).sub.n -(C.sub.3 -C.sub.7)cycloalkyl; --(C.sub.2 -C.sub.3)alkenyl; --(CH.sub.2).sub.n -(phenyl); and --(CH.sub.2).sub.n -(HET.sub.1), where n is an integer selected from 0, 1, and 2; wherein said (C.sub.1 -C.sub.4)alkyl, alkenyl, cycloalkyl, phenyl, and HET.sub.1 (heterocyclyl) groups where HET.sub.1 (heterocyclyl) groups is as defined above, are independently substituted with 0 to 3 substituents R.sup.66 where: R.sup.66 is as defined above, or: R.sup.64.sub.a through R.sup.64.sub.c inclusive; R.sup.64.sub.g through R.sup.64.sub.i inclusive; R.sup.65.sub.a through R.sup.65.sub.c inclusive; and R.sup.65.sub.g through R.sup.65.sub.l inclusive may be taken together in their same subscript denominated pairs along with the remaining portions of the moieties of partial Formulas (5.0.0) through (5.0.2), and (5.0.6) through (5.0.8), to form a fused bicyclic ring system comprising a member independently selected from the group consisting of benzimidazolyl; purinyl, i.e., imidazopyrimidinyl; and imidazopyridinyl; wherein said fused bicyclic ring system is independently substituted with 0 to 3 substituents R.sup.66, where R.sup.66 has the same meaning as set out further above, except that it is independently selected therefrom; B. a (substituted)-amide, carbamate, or urea moiety selected from the group consisting of: 1. alkyl-, cycloalkyl-, and alkenyl-(substituted)-amide, carbamate, or urea moieties of partial Formula (5.1.0): ##STR299## wherein: the symbol "*" is as defined above; R.sup.73 is a member selected from the group consisting of hydrogen and (C.sub.1 -C.sub.2)alkyl; W.sup.5 is selected from the group consisting the moieties of partial Formulas (5.1.1) through (5.1.12): ##STR300## ##STR301## wherein: the symbol: ".fwdarw." indicates the point of attachment of the moiety W.sup.5 represented by partial Formulas (5.1.1) through (5.1.12), inclusive, to the nitrogen atom in partial Formula (5.1.0), and the symbol: "*" indicates the point of attachment of the moiety W.sup.5 to R.sup.77 as defined further below; R.sup.74 and R.sup.75 are each selected from the group consisting of hydrogen; (C.sub.1 -C.sub.2)alkyl substituted by 0 or 1 substituent independently selected from OH; and (C.sub.1 -C.sub.2)alkoxy; and R.sup.77 is a member selected from the group consisting of (C.sub.1 -C.sub.6)alkyl; (C.sub.2 -C.sub.6)alkenyl; and --(CH.sub.2).sub.n -(C.sub.3 -C.sub.7)cycloalkyl, where n is an integer selected from 0, 1, and 2; and wherein said alkyl, alkenyl, and cycloalkyl groups comprising R.sup.77 are substituted with 0 to 3 substituents R.sup.78, where: R.sup.78 is a member selected from the group consisting of oxo; --OH; --(C.sub.1 -C.sub.2)alkyl; --(C.sub.1 -C.sub.3)alkoxy; --CF.sub.3 ; --C(.dbd.O)OR.sup.79 ; --C(.dbd.O)NR.sup.79 R.sup.80 ; --NR.sup.79 R.sup.80 ; --NR.sup.79 C(.dbd.O)R.sup.80 ; --NR.sup.79 C(.dbd.O)OR.sup.80 ; --NR.sup.79 S(.dbd.O).sub.2 R.sup.80 ; and --S(.dbd.O).sub.2 NR.sup.79 R.sup.80, where: R.sup.79 and R.sup.80 are each a member independently selected from the group consisting of hydrogen; and (C.sub.1 -C.sub.4)alkyl; and 2. aryl and heterocyclyl-(substituted)-amide, carbamate, or urea moieties of partial Formula (5.2.0): ##STR302## wherein: the symbol: "*"; R.sup.73 ; and W.sup.5 have the same meanings as under the definitions of partial Formula (5.1.0) above, except that they are independently selected therefrom; and under W.sup.5 the symbols: ".fwdarw." and "*" are as defined under partial Formula (5.1.0); and R.sup.82 is a member selected from the group consisting of phenyl; cinnolinyl; furyl; thienyl; pyrrolyl; oxazolyl; isoxazolyl; thiazolyl; isothiazolyl; imidazolyl; imidazolinyl; pyrazolyl; pyrazolinyl; oxadiazolyl; thiadiazolyl; triazolyl; pyridyl; pyrazinyl; pyridazinyl; pyrimidinyl; thiomorpholino; indolyl; isoindolyl; indolinyl; benzo[b]furanyl; 2;3-dihydrobenzofuranyl; benzo[b]thiophenyl; 1H-indazolyl; benzimidazolyl; benzthiazolyl; quinolinyl; isoquinolinyl; phthalazinyl; quinazolinyl; quinoxalinyl; wherein: the aryl or heterocyclyl moiety is substituted by 0 to 3 substituents R.sup.78 where R.sup.78 is as defined above, but selected on an independent basis; or

C. a (substituted)-heterocyclyl moiety independently selected from the group consisting of: 1. a heterocyclyl moiety of partial Formula (5.3.0): ##STR303## wherein: the symbol: "*" indicates the point of attachment of partial Formula (5.3.0) to R.sub.egion .gamma.; Q is N, O or S and partial Formula (5.3.0) represents: a. a monocyclic heterocyclic group containing a total of 5- members of which one said member is nitrogen and a second said member is selected from 0 and S where said S may optionally be in the sulfonate form, wherein said heterocyclic group is selected from the group consisting of oxazolyl; isoxazolyl; thiazolyl; and iso-thiazolyl; or b. a monocyclic heterocyclic group containing a total of 5- members of which two said members are nitrogen and a third or fourth said member is independently selected from N, O, and S where said S may optionally be in the sulfonate form, --S(.dbd.O).sub.2 ; wherein said heterocyclic group is independently selected from the group consisting of triazolyl; tetrazolyl; oxadiazolyl; and thiadiazolyl; and R.sup.90.sub.a and R.sup.90.sub.b are each a member independently selected from the group consisting of hydrogen, --(C.sub.1 -C.sub.2)alkylcarbonyl; --(C.sub.1 -C.sub.4)alkyl; --(CH.sub.2).sub.n -(C.sub.3 -C.sub.7)cycloalkyl; --(C.sub.2 -C.sub.3)alkenyl; --(CH.sub.2).sub.n -(phenyl); and --(CH.sub.2).sub.n -(HET.sub.2), where n is an integer independently selected from 0, 1, and 2; wherein said (C.sub.1 -C.sub.4)alkyl, alkenyl, cycloalkyl, phenyl, and HET.sub.2 groups are independently substituted with 0 to 3 substituents R.sup.91, where: j is 0, 1 or 2; HET.sub.2 is a heterocyclyl group selected from the group consisting of thienyl; oxazolyl; isoxazolyl; thiazolyl; isothiazolyl; pyrazolyl; oxadiazolyl; thiadiazolyl; triazolyl; pyridyl; pyrazinyl; pyridazinyl; pyrimidinyl; thiomorpholino; and morpholinyl; where: R.sup.91 is selected from the group consisting of --F; --Cl; --CO.sub.2 R.sup.4 ; --OH; --CN; --CONR.sup.93 R.sup.94 ; --NR.sup.93 R.sup.94 ; C(.dbd.O)(C.sub.1 -C.sub.4)alkyl; --NR.sup.93 C(.dbd.O)R.sup.94 ; --NR.sup.93 C(.dbd.O)OR.sup.94 ; --NR.sup.93 S(.dbd.O)R.sup.94 ; --S(.dbd.O)NR.sup.93 R.sup.94 ; (C.sub.1 -C.sub.4)alkyl including dimethyl, and (C.sub.1 -C.sub.4)alkoxy wherein said alkyl and alkoxy are each independently substituted with 0 to 3 substituents independently selected from F and Cl; (C.sub.1 -C.sub.2)alkoxycarbonyl; (C.sub.1 -C.sub.2)alkylcarbonyl; and (C.sub.1 -C.sub.2)alkylcarbonyloxy; wherein: R.sup.93 and R.sup.94 are each a member independently selected from the group consisting of hydrogen; and (C.sub.1 -C.sub.2)alkyl.

17. A pharmaceutical composition comprising a compound of claim 1 or a pharmaceutically acceptable salt thereof together with a pharmaceutically acceptable excipient, diluent or carrier.

18. A pharmaceutical composition for treating or preventing infection by human immunodeficiency virus (HIV) comprising an amount of a compound as claimed in claim 1 which is therapeutically effective to treat or prevent said infection by HIV, together with a pharmaceutically acceptable carrier therefor.

19. A method of treating a disease ameliorated by CCR5 chemokine receptor antagonism in an individual comprising administering an effective amount of a compound of claim 1.

20. A method of treating or preventing infection by human immunodeficiency virus (HIV) in a patient, comprising administering to said patient an amount of a compound of claim 1 which is therapeutically effective to treat or prevent said infection by HIV.

21. A method of treating or preventing a respiratory disease comprising administering an effective amount of a compound of claim 1, wherein said disease is selected from the group consisting of adult respiratory distress syndrome, bronchitis, chronic bronchitis, chronic obstructive pulmonary disease, cystic fibrosis, asthma, emphysema, rhinitis and chronic sinusitis.
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