Spiro-substituted azacycles as modulators of chemokine receptor activity

A compound which is selected from the group consisting of:

• 1'-(3-((S)-(3-Chlorophenyl))-4-(N-(phenylsulfonyl)(methylamino))butyl)-spir o(2,3-dihydrobenzothiophene-3,4'-piperidine);
• 1'-(3-((S)-(3-Chlorophenyl))-4-(N-(phenylsulfonyl)(methylamino))butyl)-spir o(2,3-dihydrobenzothiophene-3,4'-piperidine)-1-oxide;
• 1'-(3-((S)-(3-Chlorophenyl))-4-(N-(phenylsulfonyl)(methylamino))butyl)-spir o(2,3-dihydrobenzothiophene-3,4'-piperidine)-1,1-dioxide;
• ' -(3-((R,S)-(Phenyl))-4-(N-(phenylsulfonyl)(methylamino))butyl)-spiro(2,3- dihydrobenzothiophene-3,4'-piperidine);
• 1'-(3-((R,S)-(3-Thienyl))-4-(N-(phenylsulfonyl)(methylamino))butyl)-spiro(2 ,3-dihydrobenzothiophene-3,4'-piperidine);
• 1'-(3-((R,S)-(2-Thienyl))-4-(N-(phenylsulfonyl)(methylamino))butyl)-spiro(2 ,3-dihydrobenzothiophene-3,4'-piperidine);
• 1'-(3-((S)-(4-Fluorophenyl))-4-(N-(phenylsulfonyl)(methylamino))butyl)-spir o(2,3-dihydrobenzothiophene-3,4'-piperidine);
• 1'-(3-((1R,S)-(3, 5-Dichlorophenyl))-4-(N-(phenylsulfonyl)(methylamino))butyl)-spiro(2,3-dih ydrobenzothiophene-3,4'-piperidine);
• 1'-(3-((S)-(3,4-Dichlorophenyl))-4-(N-(phenylsulfonyl)(ethylamino))butyl)-s piro(2,3-dihydrobenzothiophene-3,4'-piperidine);
• 1'-(3-((R,S)-(Phenyl))-4-(N-(phenylsulfonyl)(methylamino))butyl)-spiro(2,3- dihydrobenzothiophene-3,4'-piperidine)1-oxide;
• 1'-(3-((R,S)-(3-Thienyl))-4-(N-(phenylsulfonyl)(methylamino))butyl)-spiro(2 ,3-dihydrobenzothiophene-3 4'-piperidine)-1-oxide;
• 1'-(3-((R,S)-(2-Thienyl))-4-(N-(phenylsulfonyl)(methylamino))butyl)-spiro(2 ,3-dihydrobenzothiophene-3,4'-piperidine)-1-oxide;
• 1'-(3-((S)-(4-Fluorophenyl))-4-(N-(phenylsulfonyl)(methylamino))butyl)-spir o(2,3-dihydrobenzothiophene-3,4'-piperidine)-1-oxide;
• 1'-(3-((R,S)-(3,5-Dichlorophenyl))-4-(N-(phenylsulfonyl)(methylamino))butyl )-spiro(2,3-dihydrobenzothiophene-3,4'-piperidine)-1-oxide;
• 1'-(3-((S)-(3,4-Dichlorophenyl))-4-(N-(phenylsulfonyl)(ethylamino))butyl)-s piro(2,3-dihydrobenzothiophene-3,4'-piperidine)-1-oxide;
• ' -(3-((R,S)-(Phenyl))-4-(N-(phenylsulfonyl)(methylamino))butyl)-spiro(2,3- dihydrobenzothiophene-3,4'-piperidine)-l, 1-dioxide;
• 1'-(3-((R,S)-(2-Chlorophenyl))-4-(N-(phenylsulfonyl)(methylamino))butyl)-sp iro(2,3-dihydrobenzothiophene-3,4'-piperidine)-1,1-dioxide;
• 1'-(3-((R,S)-(3-Thienyl))-4-(N-(phenylsulfonyl)(methylamino))butyl)-spiro(2 ,3-dihydrobenzothiophene-3,4'-piperidine)-1,1-dioxide;
• 1'-(3-((R,S)-(2-Thienyl))-4-(N-(phenylsulfonyl)(methylamino))butyl)-spiro(2 ,3-dihydrobenzothiophene-3,4'-piperidine)-1,1-dioxide;
• 1'-(3-((S)-(4-Fluorophenyl))-4-(N-(phenylsulfonyl)(methylamino))butyl)-spir o(2,3-dihydrobenzothiophene-3,4'-piperidine)-1,1-dioxide;
• 1'-(3-((R,S)-(3,5-Dichlorophenyl))-4-(N-(phenylsulfonyl)(methylamino))butyl )-spiro(2,3-dihydrobenzothiophene-3,4'-piperidine)-1,1-dioxide;
• 1'-(3-((S)-(3,4-Dichlorophenyl))-4-(N-(phenylsulfonyl)(ethylamino))butyl)-s piro(2,3-dihydrobenzothiophene-3,4'-piperidine)-1,1-dioxide;
• 1'-(3-((R,S)-Phenyl)-4-(N-(phenylacetyl)(methylamino))butyl)-spiro(2,3-dihy drobenzothiophene-3,4'-piperidine);
• 1'-(3-((R,S)-Phenyl)-4-(N-(phenylacetyl)(methylamino))butyl)-spiro(2,3-dihy drobenzothiophene-3,4'-piperidine)-1-oxide;
• 1'-(3-((R,S)-Phenyl)-4-(N-(phenylacetyl)(methylamino))butyl)-spiro(2,3-dihy drobenzothiophene-3,4'-piperidine)-1,1-dioxide;
• 1'-(3-((R,S)-Phenyl)-4-(N-((R)-.alpha.-methyl phenylacetyl)(methylamino))butyl)-spiro(2,3-dihydrobenzothiophene-3,4'-pip eridine);
• ' -(3-((R,S)-Phenyl)-4-(N-((R)-.alpha.-methylphenylacetyl)(methylamino))but yl)-spiro(2,3-dihydrobenzothiophene-3,4'-piperidine)-1-oxide;
• 1'-(3-((R,S)-Phenyl)-4-(N-((R)-.alpha.-methyl phenylacetyl)(methylamino))butyl)-spiro(2,3-dihydrobenzothiophene-3,4'-pip eridine)-1,1-dioxide;
• 1'-(3-((R,S)-Phenyl)-4-(N-((S)-.alpha.-methyl phenylacetyl)(methylamino))butyl)-spiro(2,3-dihydrobenzothiophene-3,4'-pip eridine);
• 1'-(3-((R,S)-Phenyl)-4-(N-((S)-.alpha.-methylphenylacetyl)(methylamino))but yl)-spiro(2,3-dihydrobenzothiophene-3,4'-piperidine)-1,1-oxide;
• 1'-(3-((R,S)-Phenyl)-4-(N-((S)-.alpha.-methyl phenylacetyl)(methylamino))butyl)-spiro(2,3-dihydrobenzothiophene-3,4'-pip eridine)-1,1-dioxide;
• 1'-(3-((S)-(3-Chlorophenyl))-4-(N-(phenylsulfonyl)(methylamino))butyl)-spir o(indoline-3,4'-piperidine);
• 1'-(3-((S)-(3-Chlorophenyl))-4-(N-(phenylsulfonyl)(methylamino))butyl)-spir o(1-oxoisoindoline-3,4'-piperidine);
• 1'-(3-((S)-(3-Chlorophenyl))-4-(N-(phenylsulfonyl)(methylamino))butyl)-spir o(1-oxo-2-methylisoindoline-3,4'-piperidine);
• 1'-(3-((R,S)-Phenyl)-4-(N-(benzyl)(methylamino))butyl)-spiro(2,3-dihydroben zothiophene-3,4'-piperidine);
• 1'-(3-((R,S)-Phenyl)-4-(N-(benzyl)(methylamino))butyl)-spiro(2,3-dihydroben zothiophene-3,4'-piperidine)-1-oxide;
• 1'-(3-((R,S)-Phenyl)-4-(N-(benzyl)(methylamino))butyl)-spiro(2,3-dihydroben zothiophene-3,4'-piperidine)-1,1-dioxide;
• N-(2-(3-Chlorophenyl)-5-(spiro(benzo›b!thiophene-3(2H),4'-piperidin)-1'-yl) pentyl)-N-methylbenzenesulfonamide;
• N-(2-(3-Chlorophenyl)-5-(spiro(benzo›b!thiophene-3(2H),4'-piperidin)-1-oxid e-1'-yl)pentyl)-N-methylbenzenesulfonamide;
• N-(2-(3-Chlorophenyl)-5-(spiro(benzo›b!thiophene-3(2H), 4'-piperidin)-1,1-dioxide-1'-yl)pentyl)-N-methylbenzenesulfonamide;
• N-Methyl-N-(2-phenyl-2-(spiro(benzo›b!thiophene-3(2H),4'-piperidin)-1,1-yl) ethyl)benzenesulfonamide;
• N-Methyl-N-(2-phenyl-2-(spiro(benzo›b!thiophene-3(2H),4'-piperidin)-1-oxide -1'-yl)ethyl)benzenesulfonamide;
• N-Methyl-N-(2-(phenyl-2-(spiro(benzo›b!thiophene-3(2H),4'-piperidin)-1,1-di oxide-1'-yl)ethyl)benzenesulfonamide;
• N-Methyl-N-(3-phenyl-5-(spiro(benzo›b!thiophene-3(2H),4'-piperidin)-1'-yl)p entyl)benzenesulfonamide;
• N-Methyl-N-(3-phenyl-5-spiro(benzo›b!thiophene-3(2H),4'-piperidin)-1-oxide- 1'-yl)pentyl)benzenesulfonamide;
• N-Methyl-N-(3-phenyl-5-spiro(benzo›b!thiophene-3(2H),4'-piperidin)-1,1-diox ide-1'-yl)pentyl)benzenesulfonamide;
• N-Methyl-N-(3-phenyl-5-(spiro(benzo›b!thiophene-3(2H),4'-piperidin)-1'-yl)p entyl)benzamide;
• N-Methyl-N-(3-phenyl-5-(spiro(benzo›b!thiophene-3(2H),4-piperidin)-1-oxide- 1'-yl)pentyl)benzamide;
• N-Methyl-N-(3-phenyl-5-spiro(benzo›b!thiophene-3(2H),4'-piperidin)-1-oxide- 1'-yl)pentyl)benzenesulfonamide;
• N-Methyl-N-(3-phenyl-5-spiro(benzo›b!thiophene-3(2H),4'-piperidin)-1,1-diox ide-1'-yl)pentyl)benzenesulfonamide;
• N-Methyl-N-(3-phenyl-5-(spiro(benzo›b!thiophene-3(2H),4'-piperidin)1'-yl)pe ntyl)benzamide;
• N-Methyl-N-(3-phenyl-5-(spiro(benzo›b!thiophene-3(2H),4'-piperidin)-1-oxide -1'-yl)pentyl)benzamide;
• N-Methyl-N-(3-phenyl-5-(spiro(benzo›b!thiophene-3(2H),4'-piperidin)-1,1-dio xide-1'-yl)pentyl)benzamide;
• N-Methyl-N-(2-phenyl-3-(spiro(benzo›b!thiophene-3(2H),4'-piperidin)-1-oxide -1'-yl)propyl)benzenesulfonamide;
• N-Methyl-N-(2-phenyl-3-(spiro(benzo›b!thiophene-3(2H),4'-piperidin)-1,1-dio xide-1'-yl)propyl)benzenesulfonamide;
• N-(2-Benzyl-3-(spiro(benzo›b!thiophene-3(2H),4'-piperidin)-1'-yl)propyl)-N- methylbenzenesulfonamide;
• N-(2-Benzyl-3-(spiro(benzo›b!thiophene-3(2H), 4'-piperidin)-1-oxide-1'-yl)propyl)-N-methylbenzenesulfonamide;
• N-(2-Benzyl-3-(spiro(benzo›b!thiophene-3(2H),4'-piperidin)-1,1-dioxide-1'-y l)propyl)-N-methylbenzenesulfonamide;
• N-Methyl-N-(2-methyl-2-phenyl-4-(spiro(benzo›b!thiophene-3(2H),4'-piperidin )-1 '-yl)butyl)benzenesulfonamide;
• N-Methyl-N-(2-methyl-2-phenyl-4-(spiro(benzo›b!thiophene-3(2H), 4'-piperidin)-1-oxide-1'-yl)butyl)benzenesulfonamide;
• N-Methyl-N-(2-methyl-2-phenyl-4-(spiro(benzo›b!thiophene-3(2H),4'-piperidin )-1,i-dioxide-1'-yl)butyl)benzenesulfonamide;
• ' -(3-((S)-(3,4-Dichlorophenyl))-4-(N-(phenylmethylsulfonyl) (methylamino))-butyl)-spiro(2,3-dihydrobenzothiophene-3,4'-piperidine);
• 1'-(3-((S)-(3,4-Dichlorophenyl))-4-(N-(quinoline-8-sulfonyl) (methylamino))-butyl)-spiro(2,3-dihydrobenzothiophene-3,4'-piperidine);
• 1'-(3-((R)-(3,4-Dichlorophenyl))-4-(N-(benzenesulfonyl) (methylamino))butyl)-spiro(2,3-dihydrobenzothiophene-3,4'-piperidine);
• 1'-(3-((R)-(3,4-Dichlorophenyl))-4-(N-(thiophene-2-sulfonyl) (methylamino))-butyl)-spiro(2,3-dihydrobenzothiophene-3,4'-piperidine);
• 1'-(3-((S)-(3,4-Dichlorophenyl))-4-(N-(benzenesulfonyl)-(methylamino))butyl )-spiro(2,3-dihydrobenzothiophene-3,4'-piperidine)-1,1-dioxide;
• 1'-(3-((S)-(4-Chlorophenyl))-4-(N-(benzenesulfonyl)-(methylamino))butyl)-sp iro(2,3-dihydrobenzothiophene-3,4'-piperidine)-1-oxide;
• 1'-(3-((S)-(4-Chlorophenyl))-4-(N-(methanesulfonyl)-(methylamino))butyl)-sp iro(2,3-dihydrobenzothiophene-3,4'-piperidine)-1-oxide;
• 1'-(3-((S)-(4-Chlorophenyl))-4-(N-(phenylmethylsulfonyl)-(methylamino))buty l)-spiro(2,3-dihydrobenzothiophene-3,4'-piperidine)-1-oxide;
• 1'-(3-((S)-(4-Chlorophenyl))-4-(N-(quinoline-8-sulfonyl)-(methylamino))buty l)-spiro(2,3-dihydrobenzothiophene-3,4'-piperidine)-1-oxide;
• 1'-(3-((R)-(4-Chlorophenyl))-4-(N-(benzenesulfonyl)-(methylamino))butyl)-sp iro(2,3-dihydrobenzothiophene-3,4'-piperidine)-1-oxide;
• 1'-(3-((R)-(4-Chlorophenyl))-4-(N-(thiophene-2-sulfonyl)-(methylamino))buty l)-spiro(2,3-dihydrobenzothiophene-3,4'-piperidine)-1-oxide;
• 1'-(3-((S)-(4-Chlorophenyl))-4-(N-(quinoline-3-sulfonyl)-(methylamino))buty l)-spiro(2,3-dihydrobenzothiophene-3,4'-piperidine)-1-oxide;
• ' -(3-((S)-(4-Chlorophenyl))-4-(N-(phenoxycarbonyl)-(methylamino))butyl)-sp iro(2,3-dihydrobenzothiophene-3,4'-piperidine)-1-oxide;
• 1'-(3-((S)-(4-Chlorophenyl))-4-(N-(phenylaminocarbonyl)-(methylamino))butyl )-spiro(2,3-dihydrobenzothiophene-3,4'-piperidine)-1-oxide;
• 1'-(3-((S)-(4-Chlorophenyl))-4-(N-(benzoylformyl)-(methylamino))butyl)spiro (2,3-dihydrobenzothiophene-3,4'-piperidine)-1-oxide;
• 1'-(3-((S)-(4-Chlorophenyl))-4-(N-(pyridine-3-sulfonyl)-(methylamino))butyl )-spiro(2,3-dihydrobenzothiophene-3,4'-piperidine)-1-oxide;
• 1'-(3-((S)-(3,4-Dichlorophenyl))-4-(N-(4-chlorobenzenesulfonyl)-(methylamin o))butyl)-spiro(2,3-dihydrobenzothiophene-3,4'-piperidine)-1-oxide;
• 1'-(3-((S)-(3,4-Dichlorophenyl))-4-(N-(3-nitrobenzenesulfonyl)-(methylamino ))butyl)-spiro(2,3-dihydrobenzothiophene-3,4'-piperidine)-1,1-dioxide;
• 1'-(3-((S)-(3,4-Dichlorophenyl))-4-(N-(4-nitrobenzenesulfonyl)-(methylamino ))butyl)-spiro(2,3-dihydrobenzothiophene-3,4'-piperidine)-1,1-dioxide;
• 1'-(3-((S)-(3,4-Dichlorophenyl))-4-(N-(2-chlorobenzenesulfonyl)-(methylamin o))butyl)-spiro(2,3-dihydrobenzothiophene-3,4'-piperidine)-1-oxide;
• 1'-(3-((S)-(3,4-Dichlorophenyl))-4-(N-(3-chlorobenzenesulfonyl)-(methylamin o))butyl)-spiro(2,3-dihydrobenzothiophene-3,4'-piperidine)1-oxide;
• 1'-(3-((S)-(3,4-Dichlorophenyl))-4-(N-(2,3,4,5,6-pentafluorobenzenesulfonyl )-(methylamino))butyl)-spiro(2,3-dihydrobenzothiophene-3,4'-piperidine)-1-o xide;
• ' -(3-((S)-(3,4-Dichlorophenyl))-4-(N-(4-biphenylsulfonyl)-(methylamino))bu tyl)-spiro(2,3-dihydrobenzothiophene-3,4'-piperidine)-1-oxide;
• 1'-(3-((S)-(3,4-Dichlorophenyl))-4-(N-(4-methoxybenzenesulfonyl)-(methylami no))butyl)-spiro(2,3-dihydrobenzothiophene-3,4'-piperidine)-1-oxide;
• (+/-) N-methyl-N-phenylsulfonyl-2-(3-chloro-4-benzyloxy)-4-(spiro›2,3-dihydroben zothiophene-3,4'-piperdin-1'-yl)butanamine;
• (+/-) N-methyl-N-phenylsulfonyl-2-(3-chloro-4-benzyloxy)-4-(spiro›2,3-dihydroben zothiophene-3,4'-piperdin-1'-yl)butamine, S-oxide;
• (+/-) N-methyl-N-phenylsulfonyl-2-(3-chloro-4-benzyloxy)-4-(spiro›2,3-dihydroben zothiophene-3'-piperdin-1'-yl)butamine, S-dioxide;
• (+/-) N-methyl-N-phenylsulfonyl-2-(3-chloro-4-hydroxy)-4-(spiro›2,3-dihydrobenzo thiophene-3,4'-piperdin-1'-yl)butanamine;
• (+/-) N-methyl-N-phenylsulfonyl-2-(3-chloro-4-hydroxy)-4-(spiro›2,3-dihydrobenzo thiophene-3,4'-piperdin-1'-yl)butanamine, S-oxide;
• (+/-) N-methyl-N-phenylsulfonyl-2-(3-chloro-4-hydroxy)-4-(spiro›2,3-dihydrobenzo thiophene-3,4'-piperdin-1'-yl)butanamine, S-dioxide;
• (+/-) N-methyl-N-phenylsulfonyl-2-(4-benzyloxy)-4-(spiro›2,3-dihydrobenzothiophe ne-3,4'-piperdin-1'-yl)butanamine;
• (+/-) N-methyl-N-phenylsulfonyl-2-(4-benzyloxy)-4-(spiro›2,3-dihydrobenzothiophe ne-3,4'-piperdin-1'-yl)butanamine, S-oxide;
• (+/-) N-methyl-N-phenylsulfonyl-2-(4-hydroxy)-4-(spiro›2,3-dihydrobenzothiophene -3,4'-piperdin-1'-yl)butanamine;
• (+/-) N-methyl-N-phenylsulfonyl-2-(4-benzyloxy)-4-(spiro›2,3-dihydrobenzothiophe ne-3,4'-piperdin-1'-yl)butanamine,S-oxide;
• (+/-) N-methyl-N-phenylsulfonyl-2-(4-benzyloxy)-4-(spiro›2,3-dihydrobenzothiophe ne-3,4'-piperdin-1'-yl)butamine,S-dioxide;
• N-phenylsulfonyl-2(S)-(3,4-dichloro)-4-(spiro›2,3-dihydrobenzothiophene-3,4 '-piperdin-1'-yl)butanamine;
• N-phenylsulfonyl-2(S)-(3,4-dichloro)-4-(spiro›2,3-dihydrobenzothiophene-3,4 '-piperdin-1'-yl)butanamine, S-oxide;
• and pharmaceutically acceptable salts thereof.

A method for modulation of chemokine receptor activity in a mammal comprising the administration of an effective amount of a compound of Formula II:

• ##STR84## wherein the optional substitutents residing at the positions numbered #2, #2', #3', #4, #5, #6 or #7 on the above structures, are independently selected from the group consisting of:
• (a) hydroxy,
• (b) oxo,
• (c) cyano,
• (d) chloro,
• (e) fluoro,
• (f) -CF.sub.3,
• (g) -phenyl;
• R.sub.1 is:
• ##STR85## where B is phenyl, or mono di or trisubstituted phenyl, wherein the substitutents on phenyl are independently selected from:
• chloro fluoro, methyl, phenyl or CF.sub.3 ;
• R.sub.10 is selected from:
• hydrogen, C.sub.1-3 alkyl, and phenyl;
• R.sub.11 and R.sub.12 are independently selected from:
• hydrogen, halogen, methyl, phenyl or CF.sub.3.
• and pharmaceutically acceptable salts thereof.

A method for treating infection by HIV, delaying of the onset of AIDS, or treating AIDS comprising the administration to a patient of an effective amount of a compound of the Formula II:

• ##STR86## wherein the optional substitutents residing at the positions numbered #2, #2', #3', #4, #5, #6, or #7 on the above structures, are independently selected from the group consisting of:
• (a) hydroxy,
• (b) oxo,
• (c) cyano,
• (d) chloro,
• (e) fluoro
• (f) -CF.sub.3,
• (g) -phenyl;
• R.sub.1 is:
• ##STR87## where B is phenyl, or mono di or trisubstituted phenyl, wherein the substitutents on phenyl are independently selected from:
• chloro, fluoro, methyl, phenyl or CF.sub.3 ;
• R.sub.1 is selected from:
• hydrogen, C.sub.1-3 alkyl, and phenyl;
• R.sub.11 and R.sub.12 are independently selected from:
• hydrogen, halogen, methyl, phenyl or CF.sub.3 ;
• and pharmaceutically acceptable salts thereof.