ARYL SULTAM DERIVATIVES AS RORc MODULATORS

Abstract

Compounds of the formula I: or pharmaceutically acceptable salts thereof, wherein m, n, p, q, r, A, W, X 1 , X 2 , X 3 , X 4 , Y, Z, R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , R 10 , R 11 and R 12 are as defined herein. Also disclosed are methods of making the compounds and using the compounds for treatment of inflammatory diseases such as arthritis.

What is claimed is: 
     
         1 . A compound of formula I: 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt thereof, 
         wherein:
 m is 0 or 1; 
 n is 0 or 1; 
 p is from 0 to 3; 
 q is 0, 1 or 2; 
 r is from 1 to 3; 
 A is: a bond; —(CR j R k ) t —; —C(O)—(CR j R k ) t —; —(CR j R k ) t —C(O)—; —NR a —(CR j R k ) t —; —(CR j R k ) t —NR a —; —C(O)NR a —(CR j R k ) t —; —(CR j R k ) t —NR a C(O)—; —O—(CR j R k ) t —; —(CR j R k ) t —O—; —S—(CR j R k ) t —; —(CR j R k ) t —S—; —SO 2 —(CR j R k ) t —; or —(CR j R k )—SO 2 —; 
 t is from 0 to 4; 
 W is: —CR b R c —; —O—; —S—; —SO 2 —; or —NR d —; 
 one of X 1 , X 2 , X 3  and X 4  is N and the others are CR e ; or two of X 1 , X 2 , X 3  and X 4  are N and the others are CR e ; or three of X 1 , X 2 , X 3  and X 4  are N and the other is CR e ; or each of X 1 , X 2 , X 3  and X 4  is CR e ; 
 Y is: —O—; —S—; SO 2 —; —CR f R g —; or —NR h —; 
 Z is: CH; or N wherein N may be oxidized; 
 R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7  and R 8  each independently is: hydrogen; or C 1-6 alkyl which may be unsubstituted or substituted one or more times with halo; 
 or R 3  and R 4  together with the atom to which they are attached may form an ethylene group; 
 or R 3  and R 4  together with the atoms to which they are attached may form a three, four, five, six or seven membered saturated or partially saturated ring that may optionally include one or two heteroatoms selected from —O—, —NR a — or —S—, and which may be optionally substituted one or more times with R i ; 
 or R 5  and R 6  together with the atoms to which they are attached may form a three, four, five, six or seven membered saturated or partially saturated ring that may optionally include one or two heteroatoms selected from —O—, —NR a — or —S—, and which may be optionally substituted one or more times with R i ; 
 or R 7  and R 8  together with the atoms to which they are attached may form a three, four, five, six or seven membered saturated or partially saturated ring that may optionally include one or two heteroatoms selected from —O—, —NR a — or —S—, and which may be optionally substituted one or more times with R i ; 
 or one of R 3  and R 4  together with one of R 5  and R 6  and the atoms to which they are attached may form a three, four, five, six or seven membered saturated or partially saturated ring that may optionally include one or two heteroatoms selected from —O—, —NR a — or —S—, and which may be optionally substituted one or more times with R i ; 
 or one of R 5  and R 6  together with one of R 7  and R 8  and the atoms to which they are attached may form a three, four, five, six or seven membered saturated or partially saturated ring that may optionally include one or two heteroatoms selected from —O—, —NR a — or —S—, and which may be optionally substituted one or more times with R i ; 
 each R 9  is independently: C 1-6 alkyl; halo; C 1-6 alkoxy; or cyano; wherein the C 1-6 alkyl moieties may be unsubstituted or substituted one or more times with halo; 
 R 10  is: hydrogen; carboxy; C 1-6 alkyl-carbonyl; C 1-6 alkoxy-carbonyl; oxo; hydroxy; aminocarbonyl; N—C 1-6 alkyl-aminocarbonyl; N,N-di-C 1-6 alkyl-aminocarbonyl; cyano; hydroxy-C 1-6 alkyl; N—C 1-6 alkoxy-C 1-6 alkyl-aminocarbonyl; N-hydroxy-C 1-6 alkyl-aminocarbonyl; N—C 1-6 alkoxy-aminocarbonyl; halo; or C 1-6 alkyl which may be unsubstituted or substituted one or more times with halo or oxo; 
 R 11  is: hydrogen; halo; carboxy; C 1-6 alkyl-carbonyl; C 1-6 alkoxy-carbonyl; oxo; hydroxy; aminocarbonyl; N—C 1-6 alkyl-aminocarbonyl; N,N-di-C 1-6 alkyl-aminocarbonyl; C 1-6 alkyl-sulfonylamino; C 1-6 alkyl-sulfonylamino-C 1-6 alkyl; cyano; hydroxy-C 1-6 alkyl; N—C 1-6 alkoxy-C 1-6 alkyl-aminocarbonyl; N-hydroxy-C 1-6 alkyl-aminocarbonyl; N—C 1-6 alkoxy-aminocarbonyl; or C 1-6  alkyl which may be unsubstituted or substituted one or more times with halo or oxo; 
 or R 10  and R 11  together with the atoms to which they are attached may form a three, four, five, six or seven membered saturated or partially saturated ring that may optionally include one or two heteroatoms selected from —O—, —NR a — or —S—, and which may be optionally substituted one or more times with R i ; 
 or R 10  and R 11  together with the atoms to which they are attached may form a double bond; 
 R 12  is: hydrogen; halo; carboxy; C 1-6 alkyl-carbonyl; C 1-6 alkoxy-carbonyl; oxo; hydroxy; aminocarbonyl; N—C 1-6 alkyl-aminocarbonyl; N,N-di-C 1-6 alkyl-aminocarbonyl; cyano; hydroxy-C 1-6 alkyl; N—C 1-6 alkoxy-C 1-6 alkyl-aminocarbonyl; N-hydroxy-C 1-6 alkyl-aminocarbonyl; N—C 1-6 alkoxy-aminocarbonyl; or C 1-6 alkyl which may be unsubstituted or substituted one or more times with halo or oxo; 
 R 13  is: hydrogen; or C 1-6 alkyl which may be unsubstituted or substituted one or more times with halo; 
 R a , R b , R c  and R d  each independent is: hydrogen; or C 1-6 alkyl which may be unsubstituted or substituted one or more times with halo; 
 or R b  and R c  together with the atoms to which they are attached may form a three, four, five, six or seven membered saturated or partially saturated ring that may optionally include one or two heteroatoms selected from —O—, —NR a — or —S—, and which may be optionally substituted one or more times with R i ; 
 or one of R b  and R c  together with one of R 7  and R 8  and the atoms to which they are attached may form a three, four, five, six or seven membered saturated or partially saturated ring that may optionally include one or two heteroatoms selected from —O—, —NR a — or —S—, and which may be optionally substituted one or more times with R i ; 
 or one of R b  and R c  together with one of R 5  and R 6  and the atoms to which they are attached may form a three, four, five, six or seven membered saturated or partially saturated ring that may optionally include one or two heteroatoms selected from —O—, —NR a — or —S—, and which may be optionally substituted one or more times with R i ; 
 each R e  is independently: hydrogen; C 1-6 alkyl; halo; C 1-6 alkoxy; or cyano; wherein the C 1-6 alkyl moieties may be unsubstituted or substituted one or more times with halo, hydroxy or C 1-6 alkoxy; 
 R f  is: hydrogen; halo; or C 1-6 alkyl which may be unsubstituted or substituted one or more times with halo, hydroxy, or C 1-6 alkoxy; 
 R g  is: hydrogen; C 1-6 alkyl; C 3-6 cycloalkyl; C 3-6 cycloalkenyl; C 3-6 cycloalkyl-C 1-6 alkyl; halo; C 1-6  alkyl-carbonyl; C 1-6 cycloalkyl-carbonyl; C 3-6 cycloalkyl-C 1-6 alkyl-carbonyl; cyano-C 1-6 alkyl-carbonyl; hydroxy-C 1-6 alkyl-carbonyl; C 1-6 alkoxy-C 1-6 alkyl-carbonyl; carboxy; N-cyano-aminocarbonyl; N-cyano-N—C 1-6 alkyl-aminocarbonyl; N—C 1-6 alkyl-acetimidamidyl; N,N′-di-C 1-6 alkyl-acetimidamidyl; N′-cyano-N—C 1-6 alkyl-acetimidamidyl; N′-hydroxy-acetimidamidyl; N′—C 1-6 alkoxy-acetimidamidyl; N′-hydroxy-N—C 1-6 alkyl-acetimidamidyl; N′—C 1-6 alkoxy-N—C 1-6 alkyl-acetimidamidyl; 2-nitro-1-N—C 1-6 alkylamino-vinyl; formyl; C 1-6 alkyl-sulfonyl; C 3-6 cycloalkyl-sulfonyl; C 3-6 cycloalkyl-C 1-6 alkyl-sulfonyl; C 1-6 alkyl-sulfonyl-C 1-6 alkyl; aminocarbonyl; N-hydroxy-aminocarbonyl; N—C 1-6 alkoxy-aminocarbonyl; N—C 1-6 alkyl-aminocarbonyl; aminocarbonyl-C 1-6 alkyl; N—C 1-6 alkyl-aminocarbonyl-C 1-6 alkyl; N,N-di-C 1-6 alkyl-aminocarbonyl-C 1-6 alkyl; C 1-6 alkoxy-carbonyl; N-hydroxy-N—C 1-6 alkyl-aminocarbonyl; N—C 1-6 alkoxy-N—C 1-6 alkyl-aminocarbonyl; N,N-di-C 1-6 alkyl-aminocarbonyl; aminosulfonyl; N—C 1-6 alkyl-aminosulfonyl; N,N-di-C 1-6 alkyl-aminosulfonyl; cyano; C 1-6 alkoxy; C 1-6 alkyl-sulfonylamino; N—C 1-6 alkyl-sulfonylaminocarbonyl; N—(C 1-6 alkyl-sulfonyl)-N—C 1-6 alkyl-aminocarbonyl; N—(C 1-6 alkyl-sulfonyl)-amino-C 1-6 alkyl; amino; N—C 1-6 alkyl-amino; N,N-di-C 1-6 alkyl-amino; halo-C 1-6 alkyl; phenyl; heterocyclyl; heteroaryl; C 1-6 alkyl-carbonylamino; carbonylamino; or hydroxyl; wherein the C 1-6 alkyl moieties may be unsubstituted or substituted one or more times with halo; and wherein the phenyl, heterocyclyl, heteroaryl, C 3-6 cycloalkyl, C 1-6 cycloalkenyl and C 3-6 cycloalkyl-C 1-6 alkyl moieties may be unsubstituted or substituted one or more times with R i ; 
 or R f  and R g  together with the atoms to which they are attached may form a four, five, six or seven membered saturated or partially saturated ring that may optionally include one or two heteroatoms selected from —O—, —NR a — or —S—, and which may be optionally substituted one or more times with R i ; 
 R h  is: hydrogen; C 1-6 alkyl; C 3-6 cycloalkyl; C 3-6 cycloalkenyl; C 3-6 cycloalkyl-C 1-6 alkyl; C 1-6 alkyl-carbonyl; C 3-6 cycloalkyl-carbonyl; C 3-6 cycloalkyl-C 1-6 alkyl-carbonyl; cyano-C 1-6 alkyl-carbonyl; hydroxy-C 1-6 alkyl-carbonyl; C 1-6 alkoxy-C 1-6 alkyl-carbonyl; N-cyano-aminocarbonyl; N-cyano-N—C 1-6 alkyl-aminocarbonyl; N—C 1-6 alkyl-acetimidamidyl; N,N′-di-C 1-6 alkyl-acetimidamidyl; N′-cyano-N—C 1-6 alkyl-acetimidamidyl; N′-hydroxy-acetimidamidyl; N′—C 1-6 alkoxy-acetimidamidyl; N′-hydroxy-N—C 1-6 alkyl-acetimidamidyl; N′—C 1-6 alkoxy-N—C 1-6 alkyl-acetimidamidyl; 2-nitro-1-N—C 1-6 alkylamino-vinyl; formyl; C 1-6 alkyl-sulfonyl; C 3-6 cycloalkyl-sulfonyl; C 3-6 cycloalkyl-C 1-6 alkyl-sulfonyl; C 1-6 alkyl-sulfonyl-C 1-6 alkyl; aminocarbonyl; N-hydroxy-aminocarbonyl; N—C 1-6 alkoxy-aminocarbonyl; N—C 1-6 alkyl-aminocarbonyl; N-hydroxy-N—C 1-6 alkyl-aminocarbonyl; N—C 1-6 alkoxy-N—C 1-6 alkyl-aminocarbonyl; N,N-di-C 1-6 alkyl-aminocarbonyl; aminosulfonyl; N—C 1-6 alkyl-aminosulfonyl; N,N-di-C 1-6 alkyl-aminosulfonyl; cyano; C 1-6  alkyl-sulfonylamino; C 1-6 alkyl-sulfonylamino-C 1-6 alkyl; N—(C 1-6 alkyl-sulfonyl)aminocarbonyl; N—(C 1-6 alkyl-sulfonyl)-N—C 1-6 alkyl-aminocarbonyl; N—(C 1-6 alkyl-sulfonyl)-amino-C 1-6 alkyl; aminocarbonyl-C 1-6 alkyl; N—C 1-6 alkyl-aminocarbonyl-C 1-6 alkyl; N,N-di-C 1-6 alkyl-aminocarbonyl-C 1-6 alkyl; C 1-6 alkoxy-carbonyl; halo-C 1-6 alkyl; phenyl; heterocyclyl; or heteroaryl; wherein the C 1-6 alkyl moieties may be unsubstituted or substituted one or more times with halo; and wherein the phenyl, heterocyclyl, heteroaryl, C 3-6 cycloalkyl, C 1-6 cycloalkenyl and C 3-6 cycloalkyl-C 1-6 alkyl moieties may be unsubstituted or substituted one or more times with R i ; 
 or R h  and one of R 10  and R 11  together with the atoms to which they are attached may form a four, five, six or seven membered aromatic, partially saturated or unsaturated ring that may optionally include one or two additional heteroatom selected from —O—, —NR a — or —S—, and which may be optionally substituted one or more times with R i —; 
 or one of R f  and R g  and one of R 10  and R 11  together with the atoms to which they are attached may form a three, four, five, six or seven membered aromatic, partially saturated or unsaturated ring that may optionally include an additional heteroatom selected from —O—, —NR a — or —S—, and which may be optionally substituted one or more times with R i ; 
 R i  is: C 1-6 alkyl; halo; oxo; hydroxy; acetyl; C 1-6 alkyl-carbonyl; amino-carbonyl; hydroxy-C 1-6  alkyl; cyano; heteroaryl; cyano-C 1-6 alkyl; C 1-6 alkoxy-C 1-6 alkyl; carboxy; or C 1-6 alkoxy; wherein the C 1-6  alkyl moieties may be unsubstituted or substituted one or more times with halo; 
 R j  and R k  each independent is: hydrogen; or C 1-6 alkyl which may be unsubstituted or substituted one or more times with halo; 
 wherein the compound is selected from: 
 wherein the compound is selected from: 
 
         {1-[3-Fluoro-4-((3S,6R)-3-methyl-1,1-dioxo-6-phenyl-[1,2]thiazinan-2-ylmethyl)-phenyl]-4-[1,2,4]triazol-4-yl-piperidin-4-yl}-methanol; 
         {1-[3-Fluoro-4-((3S,6S)-3-methyl-1,1-dioxo-6-phenyl-[1,2]thiazinan-2-ylmethyl)-phenyl]-4-[1,2,4]triazol-4-yl-piperidin-4-yl}-methanol; 
         (3S,6R)-2-[2-Fluoro-4-(tetrahydro-pyran-4-ylmethoxy)-benzyl]-3-methyl-6-phenyl-[1,2]thiazinane 1,1-dioxide; 
         (3S,6S)-2-[2-Fluoro-4-(4-[1,2,4]triazol-4-yl-piperidin-1-yl)-benzyl]-3,6-dimethyl-6-phenyl-[1,2]thiazinane 1,1-dioxide; 
         (3S,6S)-2-{2-Fluoro-4-[4-(3-methyl-[1,2,4]triazol-4-yl)-piperidin-1-yl]-benzyl}-3-methyl-6-phenyl-[1,2]thiazinane 1,1-dioxide; 
         (3S,6R)-2-[2-Fluoro-4-((2S,4R)-2-methyl-4-[1,2,4]triazol-4-yl-piperidin-1-yl)-benzyl]-3-methyl-6-phenyl-[1,2]thiazinane 1,1-dioxide; 
         1-{(R)-4-[3-Fluoro-4-((3S,6R)-3-methyl-1,1-dioxo-6-phenyl-[1,2]thiazinan-2-ylmethyl)-phenyl]-3-hydroxymethyl-piperazin-1-yl}-ethanone; 
         (3S,6R)-2-{2-Fluoro-4-[4-(3-methyl-[1,2,4]triazol-4-yl)-piperidin-1-yl]-benzyl}-3-methyl-6-phenyl-[1,2]thiazinane 1,1-dioxide; 
         (3S,6R)-2-[2-Fluoro-4-((2S,4S)-2-methyl-4-[1,2,4]triazol-4-yl-piperidin-1-yl)-benzyl]-3-methyl-6-phenyl-[1,2]thiazinane 1,1-dioxide; 
         (4-{1-[3-Fluoro-4-((3S,6R)-3-methyl-1,1-dioxo-6-phenyl-[1,2]thiazinan-2-ylmethyl)-phenyl]-piperidin-4-yl}-4H-[1,2,4]triazol-3-yl)-acetonitrile; 
         (3R,4R)-1-[3-Fluoro-4-((3S,6R)-3-methyl-1,1-dioxo-6-phenyl-[1,2]thiazinan-2-ylmethyl)-phenyl]-4-[1,2,4]triazol-4-yl-piperidine-3-carboxylic acid methyl ester; 
         (3S,6R)-2-[2,5-Difluoro-4-(4-[1,2,4]triazol-4-yl-piperidin-1-yl)-benzyl]-3-methyl-6-phenyl-[1,2]thiazinane 1,1-dioxide; 
         (3S,6R)-2-{2-Fluoro-4-[4-(3-methoxymethyl-[1,2,4]triazol-4-yl)-piperidin-1-yl]-benzyl}-3-methyl-6-phenyl-[1,2]thiazinane 1,1-dioxide; 
         (3S,4R)-1-[3-Fluoro-4-((3S,6R)-3-methyl-1,1-dioxo-6-phenyl-[1,2]thiazinan-2-ylmethyl)-phenyl]-4-[1,2,4]triazol-4-yl-piperidine-3-carboxylic acid methyl ester; 
         (3S,6R)-2-[2-Fluoro-4-((3S,4R)-3-methyl-4-[1,2,4]triazol-4-yl-piperidin-1-yl)-benzyl]-3-methyl-6-phenyl-[1,2]thiazinane 1,1-dioxide; 
         (3S,6R)-2-[2-Fluoro-4-((3R,4S)-3-methyl-4-[1,2,4]triazol-4-yl-piperidin-1-yl)-benzyl]-3-methyl-6-phenyl-[1,2]thiazinane 1,1-dioxide; 
         (1S,5R,6S)-3-[2,3-Difluoro-4-((3S,6R)-3-methyl-1,1-dioxo-6-phenyl-[1,2]thiazinan-2-ylmethyl)-phenyl]-6-[1,2,4]triazol-4-yl-3-aza-bicyclo[3.1.0]hexane; 
         (1S,5R,6S)-3-[2,3-Difluoro-4-((3S,6S)-3-methyl-1,1-dioxo-6-phenyl-[1,2]thiazinan-2-ylmethyl)-phenyl]-6-[1,2,4]triazol-4-yl-3-aza-bicyclo[3.1.0]hexane; 
         (3S,6R)-2-[2,3-Difluoro-4-(4-[1,2,4]triazol-4-yl-piperidin-1-yl)-benzyl]-3-methyl-6-phenyl-[1,2]thiazinane 1,1-dioxide; 
         (1R,5S,6S)-3-[2,5-Difluoro-4-((3S,6R)-3-methyl-1,1-dioxo-6-phenyl-[1,2]thiazinan-2-ylmethyl)-phenyl]-6-[1,2,4]triazol-4-yl-3-aza-bicyclo[3.1.0]hexane; 
         (1S,5R,6S)-3-[2,5-Difluoro-4-((3S,6S)-3-methyl-1,1-dioxo-6-phenyl-[1,2]thiazinan-2-ylmethyl)-phenyl]-6-[1,2,4]triazol-4-yl-3-aza-bicyclo[3.1.0]hexane; 
         (1R,5S,6S)-3-[2,6-Difluoro-4-((3S,6S)-3-methyl-1,1-dioxo-6-phenyl-[1,2]thiazinan-2-ylmethyl)-phenyl]-6-[1,2,4]triazol-4-yl-3-aza-bicyclo[3.1.0]hexane; 
         (1R,5S,6S)-3-[2,6-Difluoro-4-((3S,6R)-3-methyl-1,1-dioxo-6-phenyl-[1,2]thiazinan-2-ylmethyl)-phenyl]-6-[1,2,4]triazol-4-yl-3-aza-bicyclo[3.1.0]hexane; 
         (3S,6R)-2-[2-Fluoro-4-((3R,4R)-3-methyl-4-[1,2,4]triazol-4-yl-piperidin-1-yl)-benzyl]-3-methyl-6-phenyl-[1,2]thiazinane 1,1-dioxide; 
         (3S,6R)-2-[2-Fluoro-4-((3S,4S)-3-methyl-4-[1,2,4]triazol-4-yl-piperidin-1-yl)-benzyl]-3-methyl-6-phenyl-[1,2]thiazinane 1,1-dioxide; 
         3-[3-Fluoro-4-((3S,6R)-3-methyl-1,1-dioxo-6-phenyl-[1,2]thiazinan-2-ylmethyl)-phenyl]-5-[1,2,4]triazol-4-yl-3-aza-bicyclo[4.1.0]heptane; 
         3-[3-Fluoro-4-((3S,6R)-3-methyl-1,1-dioxo-6-phenyl-[1,2]thiazinan-2-ylmethyl)-phenyl]-5-[1,2,4]triazol-4-yl-3-aza-bicyclo[4.1.0]heptane; 
         3-[3-Fluoro-4-((3S,6R)-3-methyl-1,1-dioxo-6-phenyl-[1,2]thiazinan-2-ylmethyl)-phenyl]-5-[1,2,4]triazol-4-yl-3-aza-bicyclo[4.1.0]heptane; 
         3-[3-Fluoro-4-((3S,6R)-3-methyl-1,1-dioxo-6-phenyl-[1,2]thiazinan-2-ylmethyl)-phenyl]-5-[1,2,4]triazol-4-yl-3-aza-bicyclo[4.1.0]heptane; 
         (3S,6R)-2-[3-Fluoro-4-(4-[1,2,4]triazol-4-yl-piperidin-1-yl)-benzyl]-3-methyl-6-phenyl-[1,2]thiazinane 1,1-dioxide; 
         Carbamic acid 1-acetyl-4-[3-fluoro-4-((3S,6R)-3-methyl-1,1-dioxo-6-phenyl-[1,2]thiazinan-2-ylmethyl)-phenyl]-piperidin-4-yl ester, 
         (3S,6S)-2-[3-Fluoro-4-(4-[1,2,4]triazol-4-yl-piperidin-1-yl)-benzyl]-3-methyl-6-phenyl-[1,2]thiazinane 1,1-dioxide; 
         (1R,3S,5S)-8-[3-Fluoro-4-((3S,6R)-3-methyl-1,1-dioxo-6-phenyl-[1,2]thiazinan-2-ylmethyl)-phenyl]-3-[1,2,4]triazol-4-yl-8-aza-bicyclo[3.2.1]octane; 
         (1R,5S,8R)-3-[3-Fluoro-4-((3S,6R)-3-methyl-1,1-dioxo-6-phenyl-[1,2]thiazinan-2-ylmethyl)-phenyl]-8-[1,2,4]triazol-4-yl-3-aza-bicyclo[3.2.1]octane; 
         (1R,5S,8R)-3-[3-Fluoro-4-((3S,6S)-3-methyl-1,1-dioxo-6-phenyl-[1,2]thiazinan-2-ylmethyl)-phenyl]-8-[1,2,4]triazol-4-yl-3-aza-bicyclo[3.2.1]octane; 
         (2S,4R)-1-[3-Fluoro-4-((3S,6R)-3-methyl-1,1-dioxo-6-phenyl-[1,2]thiazinan-2-ylmethyl)-phenyl]-4-[1,2,4]triazol-4-yl-piperidine-2-carboxylic acid methyl ester; 
         (3S,6R)-2-(2-fluoro-4-((1-(S-methylsulfonimidoyl)piperidin-4-yl)oxy)benzyl)-3-methyl-6-phenyl-1,2-thiazinane 1,1-dioxide; 
         (3S,6R)-2-(2-fluoro-4-((1-(S-methylsulfonimidoyl)piperidin-4-yl)oxy)benzyl)-3-methyl-6-phenyl-1,2-thiazinane 1,1-dioxide; 
         (1S,5R,6S)-3-[2-Fluoro-4-((3S,6R)-3-methyl-1,1-dioxo-6-phenyl-[1,2]thiazinan-2-ylmethyl)-phenyl]-6-[1,2,4]triazol-4-yl-3-aza-bicyclo[3.1.0]hexane; 
         (1S,5R,6S)-3-[2-Fluoro-4-((3S,6S)-3-methyl-1,1-dioxo-6-phenyl-[1,2]thiazinan-2-ylmethyl)-phenyl]-6-[1,2,4]triazol-4-yl-3-aza-bicyclo[3.1.0]hexane; 
         {(3R,4R)-1-[3-Fluoro-4-((3S,6R)-3-methyl-1,1-dioxo-6-phenyl-[1,2]thiazinan-2-ylmethyl)-phenyl]-4-[1,2,4]triazol-4-yl-piperidin-3-yl}-methanol; 
         4-[4-((S)-3-Methyl-1,1-dioxo-6-phenyl-[1,2]thiazinan-2-ylmethyl)-phenyl]-2-aza-bicyclo[2.2.2]octan-3-one; 
         (1S,5R,6S)-3-[3-Fluoro-4-((3S,6R)-3-methyl-1,1-dioxo-6-phenyl-[1,2]thiazinan-2-ylmethyl)-phenyl]-6-[1,2,4]triazol-4-yl-3-aza-bicyclo[3.1.1]heptane; 
         {(3S,4R)-1-[3-Fluoro-4-((3S,6R)-3-methyl-1,1-dioxo-6-phenyl-[1,2]thiazinan-2-ylmethyl)-phenyl]-4-[1,2,4]triazol-4-yl-piperidin-3-yl}-methanol; 
         (2R,4R)-1-[3-Fluoro-4-((3S,6R)-3-methyl-1,1-dioxo-6-phenyl-[1,2]thiazinan-2-ylmethyl)-phenyl]-4-[1,2,4]triazol-4-yl-piperidine-2-carboxylic acid methyl ester; 
         (4-{1-[3-Fluoro-4-((3S,6R)-3-methyl-1,1,1-dioxo-6-phenyl-[1,2]thiazinan-2-ylmethyl)-phenyl]-piperidin-4-yl}-4H-[1,2,4]triazol-3-yl)-methanol; 
         (4-{1-[3-Fluoro-4-((3S,6S)-3-methyl-1,1-dioxo-6-phenyl-[1,2]thiazinan-2-ylmethyl)-phenyl]-piperidin-4-yl}-4H-[1,2,4]triazol-3-yl)-methanol; 
         (2S,4S)-1-[3-Fluoro-4-((3S,6R)-3-methyl-1,1-dioxo-6-phenyl-[1,2]thiazinan-2-ylmethyl)-phenyl]-4-[1,2,4]triazol-4-yl-piperidine-2-carboxylic acid methyl ester; 
         4-{4-[3-Fluoro-4-((3S,6R)-3-methyl-1,1,1-dioxo-6-phenyl-[1,2]thiazinan-2-ylmethyl)-phenyl]-piperazin-1-yl}-benzoic acid; 
         (3S,6R)-2-[2-Fluoro-4-(1-oxy-4-[1,2,4]triazol-4-yl-piperidin-1-yl)-benzyl]-3-methyl-6-phenyl-[1,2]thiazinane 1,1-dioxide; 
         8-[3-Fluoro-4-((3S,6R)-3-methyl-1,1-dioxo-6-phenyl-[1,2]thiazinan-2-ylmethyl)-phenyl]-1,4-dioxa-8-aza-spiro[4.5]decane; 
         1-{4-[2-Hydroxymethyl-4-((3S,6R)-3-methyl-1-dioxo-6-phenyl-[1,2]thiazinan-2-ylmethyl)-phenyl]-piperazin-1-yl}-ethanone; 
         {(3S,4R)-1-[3-Fluoro-4-((3S,6R)-3-methyl-1,1-dioxo-6-phenyl-[1,2]thiazinan-2-ylmethyl)-phenyl]-4-[1,2,4]triazol-4-yl-piperidin-3-yl}-methanol; 
         {(3R,4S)-1-[3-Fluoro-4-((3S,6R)-3-methyl-1,1-dioxo-6-phenyl-[1,2]thiazinan-2-ylmethyl)-phenyl]-4-[1,2,4]triazol-4-yl-piperidin-3-yl}-methanol; 
         {(3S,4S)-1-[3-Fluoro-4-((3S,6R)-3-methyl-1,1-dioxo-6-phenyl-[1,2]thiazinan-2-ylmethyl)-phenyl]-4-[1,2,4]triazol-4-yl-piperidin-3-yl}-methanol; 
         (3S,6R)-2-[4-(3,6-Dihydro-2H-pyran-4-yl)-2-fluoro-benzyl]-3-methyl-6-phenyl-[1,2]thiazinane 1,1-dioxide; 
         (3S,6R)-2-[2-Fluoro-4-(tetrahydro-pyran-4-yl)-benzyl]-3-methyl-6-phenyl-[1,2]thiazinane 1,1-dioxide; 
         {(3S,4S)-1-[3-Fluoro-4-((3S,6R)-3-methyl-1,1-dioxo-6-phenyl-[1,2]thiazinan-2-ylmethyl)-phenyl]-4-[1,2,4]triazol-4-yl-piperidin-3-yl}-methanol; 
         (3S,6R)-2-[2-Fluoro-4-((R)-3-[1,2,4]triazol-4-yl-piperidin-1-yl)-benzyl]-3-methyl-6-phenyl-[1,2]thiazinane 1,1-dioxide 
         8-[3-Fluoro-4-((3S,6R)-3-methyl-1,1-dioxo-6-phenyl-[1,2]thiazinan-2-ylmethyl)-phenyl]-1-oxa-8-aza-spiro[4.5]decane; 
         9-[3-Fluoro-4-((3S,6R)-3-methyl-1,1-dioxo-6-phenyl-[1,2]thiazinan-2-ylmethyl)-phenyl]-1,5-dioxa-9-aza-spiro[5.5]undecane; 
         7-[3-Fluoro-4-((3S,6R)-3-methyl-1,1-dioxo-6-phenyl-[1,2]thiazinan-2-ylmethyl)-phenyl]-1-oxa-7-aza-spiro[3,5]nonane; 
         (S)-8-[3-Fluoro-4-((3S,6R)-3-methyl-1,1-dioxo-6-phenyl-[1,2]thiazinan-2-ylmethyl)-phenyl]-1,4-dioxa-8-aza-spiro[4.5]decane-7-carboxylic acid methyl ester, 
         4-[3-Fluoro-4-((3S,6R)-3-methyl-1,1-dioxo-6-phenyl-[1,2]thiazinan-2-ylmethyl)-phenyl]-morpholine; 
         (R)-8-[3-Fluoro-4-((3S,6R)-3-methyl-1,1-dioxo-6-phenyl-[1,2]thiazinan-2-ylmethyl)-phenyl]-1,4-dioxa-8-aza-spiro[4.5]decane-7-carboxylic acid methyl ester, 
         (3S,6R)-2-[2-Fluoro-4-((S)-3-[1,2,4]triazol-4-yl-piperidin-1-yl)-benzyl]-3-methyl-6-phenyl-[1,2]thiazinane 1,1-dioxide; 
         (3R,6R)-2-(4-(4-(4H-1,2,4-triazol-4-yl)piperidin-1-yl)-2-fluorobenzyl)-3-(difluoromethyl)-6-phenyl-1,2-thiazinane 1,1-dioxide 
         (3R,6S)-2-(4-(4-(4H-1,2,4-triazol-4-yl)piperidin-1-yl)-2-fluorobenzyl)-3-(difluoromethyl)-6-phenyl-1,2-thiazinane 1,1-dioxide; 
         (3R,6S)-2-(4-(4-(4H-1,2,4-triazol-4-yl)piperidin-1-yl)-2,5-difluorobenzyl)-3-(difluoromethyl)-6-phenyl-1,2-thiazinane 1,1-dioxide; 
         (3R,6R)-2-(4-(4-(4H-1,2,4-triazol-4-yl)piperidin-1-yl)-2,5-difluorobenzyl)-3-(difluoromethyl)-6-phenyl-1,2-thiazinane 1,1-dioxide; 
         (3R,6S)-2-(4-(4-(4H-1,2,4-triazol-4-yl)piperidin-1-yl)-2,5-difluorobenzyl)-6-phenyl-3-(trifluoromethyl)-1,2-thiazinane 1,1-dioxide; 
         (3R,6R)-2-(4-(4-(4H-1,2,4-triazol-4-yl)piperidin-1-yl)-2,5-difluorobenzyl)-6-phenyl-3-(trifluoromethyl)-1,2-thiazinane 1,1-dioxide; 
         (3R,6R)-2-(4-((1R,5S,6S)-6-(4H-1,2,4-triazol-4-yl)-3-azabicyclo[3.1.0]hexan-3-yl)-2,5-difluorobenzyl)-6-phenyl-3-(trifluoromethyl)-1,2-thiazinane 1,1-dioxide; 
         (3R,6S)-2-(4-((1R,5S,6S)-6-(4H-1,2,4-triazol-4-yl)-3-azabicyclo[3.1.0]hexan-3-yl)-2,5-difluorobenzyl)-6-phenyl-3-(trifluoromethyl)-1,2-thiazinane 1,1-dioxide; 
         (3R,6R)-2-(4-(4-(4H-1,2,4-triazol-4-yl)piperidin-1-yl)-2-fluorobenzyl)-6-phenyl-3-(trifluoromethyl)-1,2-thiazinane 1,1-dioxide; 
         (3R,6S)-2-(4-(4-(4H-1,2,4-triazol-4-yl)piperidin-1-yl)-2-fluorobenzyl)-6-phenyl-3-(trifluoromethyl)-1,2-thiazinane 1,1-dioxide; 
         (3R,6R)-2-(4-((1R,5S,6S)-6-(4H-1,2,4-triazol-4-yl)-3-azabicyclo[3.1.0]hexan-3-yl)-2-fluorobenzyl)-6-phenyl-3-(trifluoromethyl)-1,2-thiazinane 1,1-dioxide; 
         (3R,6S)-2-(4-((1R,5S,6S)-6-(4H-1,2,4-triazol-4-yl)-3-azabicyclo[3.1.0]hexan-3-yl)-2-fluorobenzyl)-6-phenyl-3-(trifluoromethyl)-1,2-thiazinane 1,1-dioxide; 
         (4R)-methyl 1-(2,5-difluoro-4-((3-methyl-1,1-dioxido-6-phenyl-1,2-thiazinan-2-yl)methyl)phenyl)-4-(4H-1,2,4-triazol-4-yl)piperidine-3-carboxylate; 
         2-(2-fluoro-4-((4R)-3-methoxy-4-(4H-1,2,4-triazol-4-yl)piperidin-1-yl)benzyl)-3-methyl-6-phenyl-1,2-thiazinane 1,1-dioxide; 
         2-(4-((5R)-5-(4H-1,2,4-triazol-4-yl)-2-azabicyclo[2.2.1]heptan-2-yl)-2,5-difluorobenzyl)-3-methyl-6-phenyl-1,2-thiazinane 1,1-dioxide 
         2-(4-((5R)-5-(4H-1,2,4-triazol-4-yl)-2-azabicyclo[2.2.1]heptan-2-yl)-2,5-difluorobenzyl)-3-methyl-6-phenyl-1,2-thiazinane 1,1-dioxide; 
         2-(2-fluoro-4-((4R)-3-fluoro-4-(4H-1,2,4-triazol-4-yl)piperidin-1-yl)benzyl)-3-methyl-6-phenyl-1,2-thiazinane 1,1-dioxide; and 
         8-(3-fluoro-4-(((3S,6R)-3-methyl-1,1-dioxido-6-phenyl-1,2-thiazinan-2-yl)methyl)phenyl)-3-methyl-1-oxa-8-azaspiro[4.5]decan-2-one. 
       
     
     
         2 . The compound of  claim 1 , wherein the compound is selected from:
 (1R,5S,6S)-3-[2,5-Difluoro-4-((3S,6R)-3-methyl-1,1-dioxo-6-phenyl-[1,2]thiazinan-2-ylmethyl)-phenyl]-6-[1,2,4]triazol-4-yl-3-aza-bicyclo[3.1.0]hexane;   (3R,6R)-2-(4-((1R,5S,6S)-6-(4H-1,2,4-triazol-4-yl)-3-azabicyclo[3.1.0]hexan-3-yl)-2,5-difluorobenzyl)-6-phenyl-3-(trifluoromethyl)-1,2-thiazinane 1,1-dioxide;   (3S,6R)-2-[2,5-Difluoro-4-(4-[1,2,4]triazol-4-yl-piperidin-1-yl)-benzyl]-3-methyl-6-phenyl-[1,2]thiazinane 1,1-dioxide;   (3R,6R)-2-(4-(4-(4H-1,2,4-triazol-4-yl)piperidin-1-yl)-2,5-difluorobenzyl)-3-(difluoromethyl)-6-phenyl-1,2-thiazinane 1,1-dioxide; and   (3R,6R)-2-(4-(4-(4H-1,2,4-triazol-4-yl)piperidin-1-yl)-2,5-difluorobenzyl)-6-phenyl-3-(trifluoromethyl)-1,2-thiazinane 1,1-dioxide.   
     
     
         3 . A compound of formula XXIXa or XXIXb: 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt thereof, 
         wherein:
 p is from 0 to 3; 
 s is from 0 to 3; 
 R 1 , R 2  and R 3  each independently is: hydrogen; or C 1-6 alkyl which may be unsubstituted or substituted one or more times with halo; 
 each R 9  is independently: C 1-6 alkyl; halo; C 1-6 alkoxy; or cyano; wherein the C 1-6 alkyl moieties may be unsubstituted or substituted one or more times with halo; and 
 each R e  is independently: hydrogen; C 1-6 alkyl; halo; C 1-6 alkoxy; or cyano; wherein the C 1-6 alkyl moieties may be unsubstituted or substituted one or more times with halo, hydroxy or C 1-6 alkoxy; 
 provided that the compound is not (1R,5S,6S)-3-[3-fluoro-4-((3S)-methyl-1,1-dioxo-6-phenyl-[1,2]thiazinan-2-ylmethyl)-phenyl]-6-[1,2,4]triazol-4-yl-3-aza-bicyclo[3.1.0]hexane. 
 
       
     
     
         4 . A compound of formula XXXa or XXXb: 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt thereof, 
         wherein:
 p is from 0 to 3; 
 q is 0, 1 or 2; 
 r is from 1 to 3; 
 A is: a bond; —(CR j R k )—; —C(O)—(CR j R k ) t —; —(CR j R k ), —C(O)—; —NR a —(CR j R k ) t —; —(CR j R k ) t —NR a —; —C(O)NR a —(CR j R k ) t —; —(CR j R k ) t —NR a C(O)—; —O—(CR j R k ) t —; —(CR j R k ) t —O—; —S—(CR j R k ) t —; —(CR j R k ) t —S—; —SO 2 —(CR j R k ) t —; or —(CR j R k ) t —SO 2 —; 
 t is from 0 to 4; 
 Y is: —O—; —S—; SO 2 —; —CR f R g —; or —NR h —; 
 Z is: CR m ; or N wherein N may be oxidized; 
 R 1 , R 2 , and R 3  each independently is: hydrogen; or C 1-6 alkyl which may be unsubstituted or substituted one or more times with halo; 
 each R 9  is independently: C 1-6 alkyl; halo; C 1-6 alkoxy; or cyano; wherein the C 1-6 alkyl moieties may be unsubstituted or substituted one or more times with halo; 
 R 10  is: hydrogen; carboxy; C 1-6 alkyl-carbonyl; C 1-6 alkoxy-carbonyl; oxo; hydroxy; aminocarbonyl; N—C 1-6 alkyl-aminocarbonyl; N,N-di-C 1-6 alkyl-aminocarbonyl; cyano; hydroxy-C 1-6 alkyl; N—C 1-6 alkoxy-C 1-6 alkyl-aminocarbonyl; N-hydroxy-C 1-6 alkyl-aminocarbonyl; N—C 1-6 alkoxy-aminocarbonyl; halo; or C 1-6 alkyl which may be unsubstituted or substituted one or more times with halo or oxo; 
 R 11  is: hydrogen; halo; carboxy; C 1-6 alkyl-carbonyl; C 1-6 alkoxy-carbonyl; oxo; hydroxy; aminocarbonyl; N—C 1-6 alkyl-aminocarbonyl; N,N-di-C 1-6 alkyl-aminocarbonyl; C 1-6 alkyl-sulfonylamino; C 1-6 alkyl-sulfonylamino-C 1-6 alkyl; cyano; hydroxy-C 1-6 alkyl; N—C 1-6 alkoxy-C 1-6 alkyl-aminocarbonyl; N-hydroxy-C 1-6 alkyl-aminocarbonyl; N—C 1-6 alkoxy-aminocarbonyl; or C 1-6 alkyl which may be unsubstituted or substituted one or more times with halo or oxo; 
 or R 10  and R 11  together with the atoms to which they are attached may form a three, four, five, six or seven membered saturated or partially saturated ring that may optionally include one or two heteroatoms selected from —O—, —NR a — or —S—, and which may be optionally substituted one or more times with R i ; 
 or R 10  and R 11  together with the atoms to which they are attached may form a double bond; 
 R a  is: hydrogen; or C 1-6 alkyl which may be unsubstituted or substituted one or more times with halo; 
 R f  is: hydrogen; halo; or C 1-6 alkyl which may be unsubstituted or substituted one or more times with halo, hydroxy, or C 1-6 alkoxy; 
 R g  is: hydrogen; C 1-6 alkyl; C 3-6 cycloalkyl; C 3-6 cycloalkenyl; C 3-6 cycloalkyl-C 1-6 alkyl; halo; C 1-6  alkyl-carbonyl; C 1-6 cycloalkyl-carbonyl; C 3-6 cycloalkyl-C 1-6 alkyl-carbonyl; cyano-C 1-6 alkyl-carbonyl; hydroxy-C 1-6 alkyl-carbonyl; C 1-6 alkoxy-C 1-6 alkyl-carbonyl; carboxy; N-cyano-aminocarbonyl; N-cyano-N—C 1-6 alkyl-aminocarbonyl; N—C 1-6 alkyl-acetimidamidyl; N,N′-di-C 1-6 alkyl-acetimidamidyl; N′-cyano-N—C 1-6 alkyl-acetimidamidyl; N′-hydroxy-acetimidamidyl; N′—C 1-6 alkoxy-acetimidamidyl; N′-hydroxy-N—C 1-6 alkyl-acetimidamidyl; N′—C 1-6 alkoxy-N—C 1-6 alkyl-acetimidamidyl; 2-nitro-1-N—C 1-6 alkylamino-vinyl; formyl; C 1-6 alkyl-sulfonyl; C 3-6 cycloalkyl-sulfonyl; C 3-6 cycloalkyl-C 1-6 alkyl-sulfonyl; C 1-6 alkyl-sulfonyl-C 1-6 alkyl; aminocarbonyl; N-hydroxy-aminocarbonyl; N—C 1-6 alkoxy-aminocarbonyl; N—C 1-6 alkyl-aminocarbonyl; aminocarbonyl-C 1-6 alkyl; N—C 1-6 alkyl-aminocarbonyl-C 1-6 alkyl; N,N-di-C 1-6 alkyl-aminocarbonyl-C 1-6 alkyl; C 1-6 alkoxy-carbonyl; N-hydroxy-N—C 1-6 alkyl-aminocarbonyl; N—C 1-6 alkoxy-N—C 1-6 alkyl-aminocarbonyl; N,N-di-C 1-6 alkyl-aminocarbonyl; aminosulfonyl; N—C 1-6 alkyl-aminosulfonyl; N,N-di-C 1-6 alkyl-aminosulfonyl; cyano; C 1-6 alkoxy; C 1-6 alkyl-sulfonylamino; N—C 1-6 alkyl-sulfonylaminocarbonyl; N—(C 1-6 alkyl-sulfonyl)-N—C 1-6 alkyl-aminocarbonyl; N—(C 1-6 alkyl-sulfonyl)-amino-C 1-6 alkyl; amino; N—C 1-6 alkyl-amino; N,N-di-C 1-6 alkyl-amino; halo-C 1-6 alkyl; phenyl; heterocyclyl; heteroaryl; C 1-6 alkyl-carbonylamino; carbonylamino; or hydroxyl; wherein the C 1-6 alkyl moieties may be unsubstituted or substituted one or more times with halo; and wherein the phenyl, heterocyclyl, heteroaryl, C 3-6 cycloalkyl, C 1-6 cycloalkenyl and C 3-6 cycloalkyl-C 1-6 alkyl moieties may be unsubstituted or substituted one or more times with R i ; 
 or R f  and R g  together with the atoms to which they are attached may form a four, five, six or seven membered saturated or partially saturated ring that may optionally include one or two heteroatoms selected from —O—, —NR a — or —S—, and which may be optionally substituted one or more times with R i ; 
 R h  is: hydrogen; C 1-6 alkyl; C 3-6 cycloalkyl; C 3-6 cycloalkenyl; C 3-6 cycloalkyl-C 1-6 alkyl; C 1-6 alkyl-carbonyl; C 3-6 cycloalkyl-carbonyl; C 3-6 cycloalkyl-C 1-6 alkyl-carbonyl; cyano-C 1-6 alkyl-carbonyl; hydroxy-C 1-6 alkyl-carbonyl; C 1-6 alkoxy-C 1-6 alkyl-carbonyl; N-cyano-aminocarbonyl; N-cyano-N—C 1-6 alkyl-aminocarbonyl; N—C 1-6 alkyl-acetimidamidyl; N,N′-di-C 1-6 alkyl-acetimidamidyl; N′-cyano-N—C 1-6 alkyl-acetimidamidyl; N′-hydroxy-acetimidamidyl; N′—C 1-6 alkoxy-acetimidamidyl; N′-hydroxy-N—C 1-6 alkyl-acetimidamidyl; N′—C 1-6 alkoxy-N—C 1-6 alkyl-acetimidamidyl; 2-nitro-1-N—C 1-6 alkylamino-vinyl; formyl; C 1-6 alkyl-sulfonyl; C 3-6 cycloalkyl-sulfonyl; C 1-6 cycloalkyl-C 1-6 alkyl-sulfonyl; C 1-6 alkyl-sulfonyl-C 1-6 alkyl; aminocarbonyl; N-hydroxy-aminocarbonyl; N—C 1-6 alkoxy-aminocarbonyl; N—C 1-6 alkyl-aminocarbonyl; N-hydroxy-N—C 1-6 alkyl-aminocarbonyl; N—C 1-6 alkoxy-N—C 1-6 alkyl-aminocarbonyl; N,N-di-C 1-6 alkyl-aminocarbonyl; aminosulfonyl; N—C 1-6 alkyl-aminosulfonyl; N,N-di-C 1-6 alkyl-aminosulfonyl; cyano; C 1-6  alkyl-sulfonylamino; C 1-6 alkyl-sulfonylamino-C 1-6 alkyl; N—(C 1-6 alkyl-sulfonyl)aminocarbonyl; N—(C 1-6  alkyl-sulfonyl)-N—C 1-6 alkyl-aminocarbonyl; N—(C 1-6 alkyl-sulfonyl)-amino-C 1-6 alkyl; aminocarbonyl-C 1-6 alkyl; N—C 1-6 alkyl-aminocarbonyl-C 1-6 alkyl; N,N-di-C 1-6 alkyl-aminocarbonyl-C 1-6 alkyl; C 1-6 alkoxy-carbonyl; halo-C 1-6 alkyl; phenyl; heterocyclyl; or heteroaryl; wherein the C 1-6 alkyl moieties may be unsubstituted or substituted one or more times with halo; and wherein the phenyl, heterocyclyl, heteroaryl, C 3-6 cycloalkyl, C 1-6 cycloalkenyl and C 3-6 cycloalkyl-C 1-6 alkyl moieties may be unsubstituted or substituted one or more times with R i ; 
 or R h  and one of R 10  and R 11  together with the atoms to which they are attached may form a four, five, six or seven membered aromatic, partially saturated or unsaturated ring that may optionally include one or two additional heteroatom selected from —O—, —NR a — or —S—, and which may be optionally substituted one or more times with R i —; 
 or one of R f  and R g  and one of R 10  and R 11  together with the atoms to which they are attached may form a three, four, five, six or seven membered aromatic, partially saturated or unsaturated ring that may optionally include an additional heteroatom selected from —O—, —NR a — or —S—, and which may be optionally substituted one or more times with R i ; 
 R f  is: C 1-6 alkyl; halo; oxo; hydroxy; acetyl; C 1-6 alkyl-carbonyl; amino-carbonyl; hydroxy-C 1-6  alkyl; cyano; heteroaryl; cyano-C 1-6 alkyl; C 1-6 alkoxy-C 1-6 alkyl; carboxy; or C 1-6 alkoxy; wherein the C 1-6  alkyl moieties may be unsubstituted or substituted one or more times with halo; and 
 R j  and R k  each independent is: hydrogen; or C 1-6 alkyl which may be unsubstituted or substituted one or more times with halo. 
 
       
     
     
         5 . A compound of formula XXXIIa or XXXIIb: 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt thereof, 
         wherein:
 p is from 0 to 3; 
 s is from 0 to 3; 
 R 1 , R 2  and R 3  each independently is: hydrogen; or C 1-6 alkyl which may be unsubstituted or substituted one or more times with halo; 
 each R 9  is independently: C 1-6 alkyl; halo; C 1-6 alkoxy; or cyano; wherein the C 1-6 alkyl moieties may be unsubstituted or substituted one or more times with halo; and 
 each R e  is independently: hydrogen; C 1-6 alkyl; halo; C 1-6 alkoxy; or cyano; wherein the C 1-6 alkyl moieties may be unsubstituted or substituted one or more times with halo, hydroxy or C 1-6 alkoxy; 
 
       
     
     
         6 . A compound selected from:
 (3S,6R)-2-[[2-fluoro-4-[(3R,4R)-3-fluoro-4-(1,2,4-triazol-4-yl)-1-piperidyl]phenyl]methyl]-3-methyl-6-phenyl-thiazinane 1,1-dioxide;   4-[4-[3-fluoro-4-[[(3S,6R)-3-methyl-1,1-dioxo-6-phenyl-thiazinan-2-yl]methyl]phenyl]piperazin-1-yl]benzoic acid;   (3S,6R)-2-[[2-fluoro-4-(1-oxa-6-azaspiro[3.3]heptan-6-yl)phenyl]methyl]-3-methyl-6-phenyl-thiazinane 1,1-dioxide;   8-[3-fluoro-4-[[(3S,6R)-3-methyl-1,1-dioxo-6-phenyl-thiazinan-2-yl]methyl]phenyl]-1,3-dimethyl-1,3,8-triazaspiro[4.5]decane-2,4-dione;   1-[4-[[3-fluoro-4-[[(3S,6R)-3-methyl-1,1-dioxo-6-phenyl-thiazinan-2-yl]methyl]phenyl]-hydroxy-methyl]-1-piperidyl]ethanone;   (3S,6R)-2-[[2-fluoro-4-[(3S,4R)-3-fluoro-4-(1,2,4-triazol-4-yl)-1-piperidyl]phenyl]methyl]-3-methyl-6-phenyl-thiazinane 1,1-dioxide;   (3S,6R)-2-[[2-fluoro-4-[(3R,4S)-3-fluoro-4-(1,2,4-triazol-4-yl)-1-piperidyl]phenyl]methyl]-3-methyl-6-phenyl-thiazinane 1,1-dioxide;   (3S,6R)-2-[[2-fluoro-4-[(3S,4R)-3-methoxy-4-(1,2,4-triazol-4-yl)-1-piperidyl]phenyl]methyl]-3-methyl-6-phenyl-thiazinane 1,1-dioxide;   (3S,6R)-2-[[2-fluoro-4-[(3R,4S)-3-methoxy-4-(1,2,4-triazol-4-yl)-1-piperidyl]phenyl]methyl]-3-methyl-6-phenyl-thiazinane 1,1-dioxide;   (3S,6R)-2-[[2-fluoro-4-[(3R,4R)-3-fluoro-4-(1,2,4-triazol-4-yl)-1-piperidyl]phenyl]methyl]-3-methyl-6-phenyl-thiazinane 1,1-dioxide   (3S,6R)-2-[[2-fluoro-4-[(3S,4S)-3-fluoro-4-(1,2,4-triazol-4-yl)-1-piperidyl]phenyl]methyl]-3-methyl-6-phenyl-thiazinane 1,1-dioxide;   4-[4-[3-fluoro-4-[[(3S,6R)-3-methyl-1,1-dioxo-6-phenyl-thiazinan-2-yl]methyl]phenyl]piperazin-1-yl]-2-hydroxy-benzoic acid;   4-[4-[3-fluoro-4-[[(3S,6R)-3-methyl-1,1-dioxo-6-phenyl-thiazinan-2-yl]methyl]phenyl]piperazin-1-yl]-2-hydroxy-benzoic acid;   (3S,6R)-2-[[2,5-difluoro-4-[(1S,4S,5S)-5-(1,2,4-triazol-4-yl)-2-azabicyclo[2.2.1]heptan-2-yl]phenyl]methyl]-3-methyl-6-phenyl-thiazinane 1,1-dioxide;   (3S,6R)-2-[[2,5-difluoro-4-[(1R,4R,5R)-5-(1,2,4-triazol-4-yl)-2-azabicyclo[2.2.1]heptan-2-yl]phenyl]methyl]-3-methyl-6-phenyl-thiazinane 1,1-dioxide;   (3S,6R)-2-[[4-(3,6-dihydro-2H-pyran-4-ylmethyl)-2-fluoro-phenyl]methyl]-3-methyl-6-phenyl-thiazinane 1,1-dioxide;   (3S,6R)-2-[[2-fluoro-4-(tetrahydropyran-4-ylidenemethyl)phenyl]methyl]-3-methyl-6-phenyl-thiazinane 1,1-dioxide;   methyl 4-[2,5-difluoro-4-[[(3S,6R)-3-methyl-1-dioxo-6-phenyl-thiazinan-2-yl]methyl]phenyl]tetrahydropyran-4-carboxylate;   methyl(3S,4S)-3-[2,5-difluoro-4-[[(3S,6R)-3-methyl-1,1-dioxo-6-phenyl-thiazinan-2-yl]methyl]phenyl]tetrahydropyran-4-carboxylate;   (3R,4R)-1-[2,5-difluoro-4-[[(3S,6R)-3-methyl-1,1-dioxo-6-phenyl-thiazinan-2-yl]methyl]phenyl]-4-(1,2,4-triazol-4-yl)piperidin-3-ol;   (3S,4S)-1-[2,5-difluoro-4-[[(3S,6R)-3-methyl-1,1-dioxo-6-phenyl-thiazinan-2-yl]methyl]phenyl]-4-(1,2,4-triazol-4-yl)piperidin-3-ol;   methyl 2-[2,5-difluoro-4-[[(3S,6R)-3-methyl-1-dioxo-6-phenyl-thiazinan-2-yl]methyl]phenyl]acetate;   methyl 4-[2,5-difluoro-4-[[(3S,6S)-3-methyl-1-dioxo-6-phenyl-thiazinan-2-yl]methyl]phenyl]tetrahydropyran-4-carboxylate;   (3R,4R)-3-[2,5-difluoro-4-[[(3S,6R)-3-methyl-1,1-dioxo-6-phenyl-thiazinan-2-yl]methyl]phenyl]tetrahydropyran-4-carboxylic acid,   methyl(3S,4S)-3-[2,5-difluoro-4-[[(3S,6R)-3-methyl-1,1-dioxo-6-phenyl-thiazinan-2-yl]methyl]phenyl]tetrahydropyran-4-carboxylate;   methyl(3R,4R)-3-[2,5-difluoro-4-[[(3S,6R)-3-methyl-1,1-dioxo-6-phenyl-thiazinan-2-yl]methyl]phenyl]tetrahydropyran-4-carboxylate;   (3S,6R)-2-[[2,5-difluoro-4-[(3S,4R)-3-fluoro-4-(1,2,4-triazol-4-yl)-1-piperidyl]phenyl]methyl]-3-methyl-6-phenyl-thiazinane 1,1-dioxide;   (3S,6R)-2-[[2,5-difluoro-4-[(3R,4S)-3-fluoro-4-(1,2,4-triazol-4-yl)-1-piperidyl]phenyl]methyl]-3-methyl-6-phenyl-thiazinane 1,1-dioxide   2-[2,5-difluoro-4-[[(3S,6R)-3-methy; 1,1,1-dioxo-6-phenyl-thiazinan-2-yl]methyl]phenyl]ethanol;   2-[2,5-difluoro-4-[[(3S,6R)-3-methyl-1,1-dioxo-6-phenyl-thiazinan-2-yl]methyl]phenyl]-N-(3-hydroxycyclobutyl)acetamide;   2-[2,5-difluoro-4-[[(3S,6R)-3-methyl-1,1-dioxo-6-phenyl-thiazinan-2-yl]methyl]phenyl]acetamide;   2-[2,5-difluoro-4-[[(3S,6R)-3-methyl-1,1-dioxo-6-phenyl-thiazinan-2-yl]methyl]phenyl]propan-1-ol;   2-[2,5-difluoro-4-[[(3S,6R)-3-methyl-1,1-dioxo-6-phenyl-thiazinan-2-yl]methyl]phenyl]propan-1-ol;   diethyl 2-[2,5-difluoro-4-[[(3S,6R)-3-methyl-1-dioxo-6-phenyl-thiazinan-2-yl]methyl]phenyl]propanedioate;   2-[2,5-difluoro-4-[[(3S,6R)-3-methyl-1,1-dioxo-6-phenyl-thiazinan-2-yl]methyl]phenyl]propane-1,3-diol;   tert-butyl 2-[2,5-difluoro-4-[[(3S,6R)-3-methyl-1,1-dioxo-6-phenyl-thiazinan-2-yl]methyl]phenyl]acetate;   4-[2,5-difluoro-4-[[(3S,6R)-3-methyl-1,1-dioxo-6-phenyl-thiazinan-2-yl]methyl]phenyl]-5-hydroxy-pentanenitrile;   1-[4-[4-[[(6S)-5,5-dioxo-6-phenyl-5$1̂{6}-thia-4-azaspiro[2,5]octan-4-yl]methyl]-3-fluoro-phenyl]piperazin-1-yl]ethanone;   1-[4-[4-[[(6S)-5,5-dioxo-6-phenyl-5$1̂{6}-thia-4-azaspiro[2,5]octan-4-yl]methyl]-3-fluoro-phenyl]piperazin-1-yl]ethanone;   2-[1-[2,5-difluoro-4-[[(3S,6R)-3-methyl-1,1-dioxo-6-phenyl-thiazinan-2-yl]methyl]phenyl]-1-methyl-ethoxy]acetic acid;   2-[1-[2,5-difluoro-4-[[(3S,6R)-3-methyl-1,1-dioxo-6-phenyl-thiazinan-2-yl]methyl]phenyl]-1-methyl-ethoxy]acetamide;   2-[2,5-difluoro-4-[[(3S,6R)-3-methyl-1,1-dioxo-6-phenyl-thiazinan-2-yl]methyl]phenyl]-3-(oxetan-3-yl)propan-1-ol;   2-[2,5-difluoro-4-[[(3S,6R)-3-methyl-1,1-dioxo-6-phenyl-thiazinan-2-yl]methyl]phenyl]-3-(oxetan-3-yl)propan-1-ol;   3-[2,5-difluoro-4-[[(3S,6R)-3-methyl-1,1-dioxo-6-phenyl-thiazinan-2-yl]methyl]phenyl]-4-hydroxy-butanenitrile;   3-[2,5-difluoro-4-[[(3S,6R)-3-methyl-1,1-dioxo-6-phenyl-thiazinan-2-yl]methyl]phenyl]-4-hydroxy-butanenitrile;   3-[2,5-difluoro-4-[[(3S,6R)-3-methyl-1,1-dioxo-6-phenyl-thiazinan-2-yl]methyl]phenyl]-4-hydroxy-butanamide;   3-[2,5-difluoro-4-[[(3S,6R)-3-methyl-1,1-dioxo-6-phenyl-thiazinan-2-yl]methyl]phenyl]-4-hydroxy-butanamide;   2-[2,5-difluoro-4-[[(3S,6R)-3-methyl-1,1-dioxo-6-phenyl-thiazinan-2-yl]methyl]phenyl]-2-(oxetan-3-yl)ethanol;   2-[2,5-difluoro-4-[[(3S,6R)-3-methyl-1,1-dioxo-6-phenyl-thiazinan-2-yl]methyl]phenyl]-2-(oxetan-3-yl)ethanol;   3-[1-[2,5-difluoro-4-[[(3S,6R)-3-methyl-1,1-dioxo-6-phenyl-thiazinan-2-yl]methyl]phenyl]-1-methyl-ethoxy]propane-1,2-diol;   2-[2,5-difluoro-4-[[(3S,6R)-3-methyl-1,1-dioxo-6-phenyl-thiazinan-2-yl]methyl]phenyl]-2-phenyl-ethanol;   2-[2,5-difluoro-4-[[(3S,6R)-3-methyl-1,1-dioxo-6-phenyl-thiazinan-2-yl]methyl]phenyl]-2-phenyl-ethanol;   (2S)-3-[1-[2,5-difluoro-4-[[(3S,6R)-3-methyl-1,1-dioxo-6-phenyl-thiazinan-2-yl]methyl]phenyl]-1-methyl-ethoxy]propane-1,2-diol;   (2R)-3-[1-[2,5-difluoro-4-[[(3S,6R)-3-methyl-1,1-dioxo-6-phenyl-thiazinan-2-yl]methyl]phenyl]-1-methyl-ethoxy]propane-1,2-diol;   3-[1-[2,5-difluoro-4-[[(3S,6R)-3-methyl-1,1-dioxo-6-phenyl-thiazinan-2-yl]methyl]phenyl]-2-hydroxy-ethyl]-1-methyl-pyrrolidin-2-one;   3-[1-[2,5-difluoro-4-[[(3S,6R)-3-methyl-1,1-dioxo-6-phenyl-thiazinan-2-yl]methyl]phenyl]-2-hydroxy-ethyl]-1-methyl-pyrrolidin-2-one;   3-[1-[2,5-difluoro-4-[[(3S,6R)-3-methyl-1,1-dioxo-6-phenyl-thiazinan-2-yl]methyl]phenyl]-2-hydroxy-ethyl]-1-methyl-pyrrolidin-2-one;   3-[1-[2,5-difluoro-4-[[(3S,6R)-3-methyl-1,1-dioxo-6-phenyl-thiazinan-2-yl]methyl]phenyl]-2-hydroxy-ethyl]-1-methyl-pyrrolidin-2-one;   4-[2,5-difluoro-4-[[(3S,6R)-3-methyl-1,1-dioxo-6-phenyl-thiazinan-2-yl]methyl]phenyl]-5-hydroxy-pentanamide;   4-[2,5-difluoro-4-[[(3S,6R)-3-methyl-1,1-dioxo-6-phenyl-thiazinan-2-yl]methyl]phenyl]-5-hydroxy-pentanamide;   (3S,6R)-2-[[2,5-difluoro-4-[4-(1,2,4-triazol-4-yl)-1-piperidyl]phenyl]methyl]-3-ethyl-6-phenyl-thiazinane 1,1-dioxide;   (3S,6S)-2-[[2,5-difluoro-4-[(1R,5S)-6-(1,2,4-triazol-4-yl)-3-azabicyclo[3.1.0]hexan-3-yl]phenyl]methyl]-3-ethyl-6-phenyl-thiazinane 1,1-dioxide;   (3S,6R)-2-[[2,5-difluoro-4-[(1R,5S)-6-(1,2,4-triazol-4-yl)-3-azabicyclo[3.1.0]hexan-3-yl]phenyl]methyl]-3-ethyl-6-phenyl-thiazinane 1,1-dioxide;   (3S,6S)-2-[[2,5-difluoro-4-[4-(1,2,4-triazol-4-yl)-1-piperidyl]phenyl]methyl]-3-ethyl-6-phenyl-thiazinane 1,1-dioxide;   (3S,6R)-3-ethyl-2-[[2-fluoro-4-[(1R,5S)-6-(1,2,4-triazol-4-yl)-3-azabicyclo[3.1.0]hexan-3-yl]phenyl]methyl]-6-phenyl-thiazinane 1,1-dioxide;   (3S,6S)-3-ethyl-2-[[2-fluoro-4-[(1R,5S)-6-(1,2,4-triazol-4-yl)-3-azabicyclo[3.1.0]hexan-3-yl]phenyl]methyl]-6-phenyl-thiazinane 1,1-dioxide;   (7S)-2-[[2,5-difluoro-4-[(1R,5S)-6-(1,2,4-triazol-4-yl)-3-azabicyclo[3.1.0]hexan-3-yl]phenyl]methyl]-7-phenyl-thiazepane 1,1-dioxide;   (7S)-2-[[2,5-difluoro-4-[4-(1,2,4-triazol-4-yl)-1-piperidyl]phenyl]methyl]-7-phenyl-thiazepane 1,1-dioxide;   (7R)-2-[[2,5-difluoro-4-[4-(1,2,4-triazol-4-yl)-1-piperidyl]phenyl]methyl]-7-phenyl-thiazepane 1,1-dioxide;   (7R)-2-[[2,5-difluoro-4-[(1R,5S)-6-(1,2,4-triazol-4-yl)-3-azabicyclo[3.1.0]hexan-3-yl]phenyl]methyl]-7-phenyl-thiazepane 1,1-dioxide;   (7S)-2-[[2-fluoro-4-[(1R,5S)-6-(1,2,4-triazol-4-yl)-3-azabicyclo[3.1.0]hexan-3-yl]phenyl]methyl]-7-phenyl-thiazepane 1,1-dioxide;   (7R)-2-[[2-fluoro-4-[(1R,5S)-6-(1,2,4-triazol-4-yl)-3-azabicyclo[3.1.0]hexan-3-yl]phenyl]methyl]-7-phenyl-thiazepane 1,1-dioxide;   (7S)-2-[[2,5-difluoro-4-[(1R,5S)-6-(1,2,4-triazol-4-yl)-3-azabicyclo[3.1.0]hexan-3-yl]phenyl]methyl]-7-phenyl-thiazepane 1,1-dioxide;   (7S)-2-[[2,5-difluoro-4-[4-(1,2,4-triazol-4-yl)-1-piperidyl]phenyl]methyl]-7-phenyl-thiazepane 1,1-dioxide;   (3S,4S)-3-[2,5-difluoro-4-[[(3S,6R)-3-methyl-1,1-dioxo-6-phenyl-thiazinan-2-yl]methyl]phenyl]tetrahydropyran-4-carboxylic acid;   2-[2,5-difluoro-4-[[(3S,6R)-3-methyl-1,1-dioxo-6-phenyl-thiazinan-2-yl]methyl]phenyl]-N-(3-hydroxycyclobutyl)acetamide;   4-[4-[3-fluoro-4-[[(3S,6S)-3-methyl-1,1-dioxo-6-phenyl-thiazinan-2-yl]methyl]phenyl]piperazin-1-yl]benzoic acid; and   4-[4-[3-fluoro-4-[[(3S,6S)-3-methyl-1,1-dioxo-6-phenyl-thiazinan-2-yl]methyl]phenyl]piperazin-1-yl]-2-hydroxy-benzoic acid.   
     
     
         7 . The compound (1R,5S,6S)-3-[2,5-Difluoro-4-((3S,6R)-3-methyl-1,1-dioxo-6-phenyl-[1,2]thiazinan-2-ylmethyl)-phenyl]-6-[1,2,4]triazol-4-yl-3-aza-bicyclo[3.1.0]hexane;
 or a pharmaceutically acceptable salt thereof.   
     
     
         8 . The compound (3R,6R)-2-(4-((R,5S,6S)-6-(4H-1,2,4-triazol-4-yl)-3-azabicyclo[3.1.0]hexan-3-yl)-2,5-difluorobenzyl)-6-phenyl-3-(trifluoromethyl)-1,2-thiazinane 1,1-dioxide;
 or a pharmaceutically acceptable salt thereof.   
     
     
         9 . A composition comprising:
 (a) a pharmaceutically acceptable carrier; and   (b) a compound of  claim 1 .   
     
     
         10 . A method for treating arthritis, asthma, COPD, psoriasis, lupus (Lupus erythematosus), Sjogren's disease, irritable bowel disease, idiopathic pulmonary fibrosis or muscular sclerosis, said method comprising administering to a subject in need thereof an effective amount of a compound of  claim 1 .