ZA200206665B - Novel Compounds. - Google Patents

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ZA200206665B
ZA200206665B ZA200206665A ZA200206665A ZA200206665B ZA 200206665 B ZA200206665 B ZA 200206665B ZA 200206665 A ZA200206665 A ZA 200206665A ZA 200206665 A ZA200206665 A ZA 200206665A ZA 200206665 B ZA200206665 B ZA 200206665B
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South Africa
Prior art keywords
phenoxy
phenyl
hydroxy
acetamide
propoxy
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ZA200206665A
Inventor
Michael Bodkin
Peter Hansen
Krister Henriksson
Lars Pettersson
Tomas Eriksson
Martin Hemmerling
Tomas Klingstedt
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Astrazeneca Ab
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Publication of ZA200206665B publication Critical patent/ZA200206665B/en

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Description

NOVEL COMPOUNDS
The present invention relates to novel compounds, processes for their preparation,
Co pharmaceutical compositions containing them and their use in therapy.
US 5789402 describes certain indole deriatives which are said to be useful for the treatment of diseases which are caused or affected by disorders of the serotonin-affected neurological systems, particularly those relating to the serotonin 1 4 receptor and those } relating to the uptake of serotonin.
Chemokines play an important role in immune and inflammatory responses in various diseases and disorders, including asthma and allergic diseases, as well as autoimmune pathologies such as rheumatoid arthritis and atherosclerosis. These small secreted molecules are a growing superfamily of 8-14 kDa proteins characterised by a conserved four cysteine motif. The chemokine superfamily can be divided into two main groups exhibiting characteristic structural motifs, the Cys-X-Cys (C-X-C) and Cys-Cys (C-C) families. These are distinguished on the basis of a single amino acid insertion between the
NH-proximal pair of cysteine residues and sequence similarity.
The C-X-C chemokines include several potent chemoattractants and activators of neutrophils such as interleukin-8 (IL-8) and neutrophil-activating peptide 2 (NAP-2).
The C-C chemokines include potent chemoattractants of monocytes and lymphocytes but not neutrophils such as human monocyte chemotactic proteins 1-3 (MCP-1, MCP-2 and 2s MCP-3), RANTES (Regulated on Activation, Normal T Expressed and Secreted), eotaxin ' and the macrophage inflammatory proteins la and 18 (MIP-1a and MIP-18).
Studies have demonstrated that the actions of the chemokines are mediated by subfamilies of G protein-coupled receptors, among which are the receptors designated CCR1, CCR2, CCR2A, CCR2B, CCR3, CCR4, CCRS5, CCR6, CCR7, CCR8, CCRY, CCR10, CXCR],
~~ WO 01/62728 PCT/SE01/00403 ['Y t
CXCR2, CXCR3 and CXCR4. These receptors represent good targets for drug - development since agents which modulate these receptors would be useful in the treatment of disorders and diseases such as those previously mentioned. s In accordance with the present invention, there is therefore provided a compound of general formula
RA OH a
OSE rR % 4 6
R R 0) wherein,
R represents either a group
R®
X< ~~ hn 1 Y z (R rol Lf 1- . z ~ or a group
H
N
1 (R ft
No mis 0,1,2o0r3; each R} independently represents halogen, cyano, nitro, carboxyl, hydroxyl,
C;-Cg cycloalkyl, C,-Cg alkoxy, C;-Cg¢ alkoxycarbonyl, C;-Cq haloalkyl,
C,-Cg haloalkoxy, -NR’R!®, C;-C; cycloalkylamino, C;-Cy alkylthio,
C;-Cg alkylcarbonyl, C;-Cg alkylcarbonylamino, sulphonamido (-SO,NH), 3 C,-Cg alkylsulphonyl, -C(O)NR''R'Z, -NR'*C(0)-(NH),R'*, phenyl, or C;-Cg alkyl optionally substituted by carboxyl or C;-C¢ alkoxycarbonyl; pisOorl;
«
X represents an oxygen or sulphur atom or a CH,, CH(CH3), OCH,, CH,0O, CH,NH, * NH or carbonyl group and Y represents a nitrogen atom or a CH or C(OH) group, provided that when X represents an oxygen or sulphur atom or a CH,0, CH,NH or NH group, then
Y represents a CH group; z! represents a bond or a group (CHp)q where q is 1 or 2; z? represents a bond or a group CH,, with the proviso that z! and Z* do not both simultaneously represent a bond;
Q represents an oxygen or sulphur atom or a group CH, or NH; 2
R” represents a group 0 ) mel
R HN \ \ 16
X
HN” TCH, I
HN CH, 0
JL or * HC N
H . nis 0, 1 or 2; each R’ independently represents a C-Cg alkyl, C;-Cg4 alkoxycarbonyl, -CH,OH or ’ 1s carboxyl group;
RY, Rr, RS and R’ each independently represent a hydrogen atom or a C;-Cg alkyl fs group, or RY, R’, R® and R’ together represent a C;-C, alkylene chain linking the two carbon atoms to which they are attached to form a 4- to 7-membered saturated carbocycle,
or RS, R® and R7 each represent a hydrogen atom and R* and R® together with the carbon . atoms to which they are attached form a 5- to 6-membered saturated carbocycle;
R® represents a hydrogen atom, a C,-Cg alkyl group or is linked to R* as defined above;
R’ and R'? each independently represent a hydrogen atom or a C;-Cg alkyl group, or
R’ and R" together with the nitrogen atom to which they are attached form a 4- to 7- membered saturated heterocycle;
R!! and R'? each independently represent a hydrogen atom or a C,-Cg alkyl group optionally substituted by C,-C¢ alkoxycarbonyl;
RY represents a hydrogen atom or a C;-Cg alkyl group;
RM represents a hydrogen atom, or a C;-Cg4 alkyl group optionally substituted by carboxyl, C;-Cg¢ alkoxy or C;-Cg¢ alkoxycarbonyl; : RY represents carboxyl, C;-Cg¢ alkylcarbonyl, C;-Cg4 alkoxycarbonyl,
C,-C¢ alkoxycarbonylC;-Cg alkyl or a group NRUR', -NHSO,CH3, -NHC(O)CH3, is -C(ONRIR'®, -NHC(O)NR''R'®, -OC(O)NR''R®, -OCH,C(O)NR''R",
NHC(O)OR!” or -OR'; tis 0, 1,2 or 3; each R'S independently represents halogen, cyano, nitro, carboxyl, hydroxyl,
C;-Cg cycloalkyl, C;-Cg alkoxy, C;-C¢ alkoxycarbonyl, C;-Cgq haloalkyl,
C;-Cg haloalkoxy, -NR'R*’, C;-Cj cycloalkylamino, C,-Cg alkylthio,
C,-C¢ alkylcarbonyl, C;-Cg alkylcarbonylamino, sulphonamide (-SO,NH,),
C;-Cg alkylsulphonyl, -C(O)NR*'R%, NRZBcoyNH),R*, phenyl, or C;-Cg alkyl optionally substituted by carboxyl or C,-Cg¢ alkoxycarbonyl;
R!” and R'® each independently represent (i) a hydrogen atom, (ii) a 5- to 6- 2s membered saturated or unsaturated ring which may comprise at least one heteroatom chosen from nitrogen, oxygen and sulphur, the ring being optionally substituted with at . least one substituent selected from halogen, methyl and trifluoromethyl, or (iii) a C,-Cg alkyl group optionally substituted by at least one substituent selected from halogen, trifluoromethyl, carboxyl, C;-Cgq alkoxycarbonyl and a 5- to 6-membered saturated or unsaturated ring which may comprise at least one heteroatom chosen from nitrogen, oxygen and sulphur, the ring being optionally substituted with at least one , substituent selected from halogen, methyl and trifluoromethyl, or
R'7 and R'® together with the nitrogen atom to which they are attached form a 4- to 7-
Y membered saturated heterocycle; 5 rR! represents a hydrogen atom, or a C,-Cg4 alkyl group optionally substituted by carboxyl or C;-Cg alkoxycarbonyl;
R'7" is defined as for R'” above except that R'7" does not represent a hydrogen atom;
R'? and R?? each independently represent a hydrogen atom or a C,-Cg alkyl group, or
R" and R® together with the nitrogen atom to which they are attached form a 4- to 7- membered saturated heterocycle;
R?! and R?? each independently represent a hydrogen atom or a C;-Cg alkyl group optionally substituted by C;-Cg alkoxycarbonyl; visOor 1; rR> represents a hydrogen atom or a C;-Cg alkyl group; and
R* represents a hydrogen atom, or a C,-Cg alkyl group optionally substituted by carboxyl, C;-Cg alkoxy or C;-Cg4 alkoxycarbonyl; provided that when X is an oxygen atom or a group CH,, Y is CH, 7! and 72 each represent a group CH, and Q is an oxygen atom, then R? is other than an unsubstituted indolyl group; or a pharmaceutically acceptable salt or solvate thereof.
In the context of the present specification, an alkyl substituent group or an alkyl moiety in a substituent group may be linear or branched. 2s In one aspect of the present invention, there is provided a compound of general formula
RA OH q . Rs SR?
ROR m wherein,
R represents a group ‘ py RY). ®t) 1§ 7
ANN mis0, 1,2 o0r3; each R' independently represents halogen, cyano, nitro, carboxyl, hydroxyl,
C3-C; cycloalkyl, C;-Cg alkoxy, C;-Cg4 alkoxycarbonyl, C;-Cg¢ haloalkyl,
C,-Cg haloalkoxy, NRR!?, C;-C4 cycloalkylamino, C;-Cg alkylthio,
C,-Cg alkylcarbonyl, C;-Cg4 alkylcarbonylamino, sulphonamido, C;-Cs alkylsulphonyl, o -CONR'R', NRPC(0)-(NH),R', phenyl, or C;-Cg alkyl optionally substituted by carboxyl or C;-Cg alkoxycarbonyl; pisOorl;
X represents an oxygen or sulphur atom or a CH,, CH(CH;), OCHj, CH,O, CH,NH,
NH or carbonyl group and Y represents a nitrogen atom or a CH or C(OH) group, provided 1s that when X represents an oxygen or sulphur atom or a CH,0O, CH,NH or NH group, then
Y represents a CH group;
Zz! represents a bond or a group (CHy), where q is 1 or 2; 7° represents a bond or a group CH,, with the proviso that Zz! and Z2 do not both simultaneously represent a bond;
Q represents an oxygen or sulphur atom or a group CH, or NH; ] R* represents a group
N rR" .
OO (R™),
. nis 0, 1 or 2; each R> independently represents a C-Cg alkyl, C;-C¢ alkoxycarbonyl, -CH,OH or carboxyl group;
RY, R’, R® and R” each independently represent a hydrogen atom or a C,-Cg alkyl group, or rR? R’, R® and R’ together represent a C;-C, alkylene chain linking the two carbon atoms to which they are attached to form a 4- to 7-membered saturated carbocycle, or RS, R® and R7 each represent a hydrogen atom and R* and R® together with the carbon atoms to which they are attached form a S- to 6-membered saturated carbocycle;
RS represents a hydrogen atom, a C,-Cg alkyl group or is linked to R* as defined above;
R> and R'° each independently represent a hydrogen atom or a C;-Cg alkyl group, or
R® and R'? together with the nitrogen atom to which they are attached form a 4- to 7- membered saturated heterocycle; .
R'! and R'? each independently represent a hydrogen atom or a C;-Cg alkyl group optionally substituted by C,-Cg4 alkoxycarbonyl;
RE represents a hydrogen atom or a C;-Cg¢ alkyl group; rR" represents a hydrogen atom, or a C,-Cg4 alkyl group optionally substituted by carboxyl, C,-Cg alkoxy or C;-C¢ alkoxycarbonyl;
RY represents carboxyl, C;-C¢ alkylcarbonyl, C,-Cg4 alkoxycarbonyl,
C,-Cg alkoxycarbonylC,-Cg alkyl or a group -NR' 'R'®, -NHS0,CH,, -NHC(O)CH;, -C(ONR'R!®, NHC(ONR!'R!®, -OC(O)NR'"R!®, -OCH,C(O)NR''R?,
NHC(O)OR!7 or -OR!; tis 0, 1,2 or 3; each R'® independently represents halogen, cyano, nitro, carboxyl, hydroxyl,
C;-C¢ cycloalkyl, C,-Cg alkoxy, Cy-Cgq alkoxycarbonyl, C;-Cg4 haloalkyl,
C,-Cg haloalkoxy, -NR'’R?®, C;-C¢ cycloalkylamino, C;-Cj alkylthio,
C;-Cg alkylcarbonyl, C;-C4 alkylcarbonylamino, sulphonamido (-SO,NH,),
C,-C¢ alkylsulphonyl, -C(O)NR*'R?, -NR**C(O)(NH),R**, phenyl, or C;-Cg alkyl optionally substituted by carboxyl or C-Cg¢ alkoxycarbonyl; ]
R'7 and R'® each independently represent (i) a hydrogen atom, (ii) a 5- to 6- . membered saturated or unsaturated ring which may comprise at least one heteroatom chosen from nitrogen, oxygen and sulphur, the ring being optionally substituted with at least one substituent selected from halogen, methyl and trifluoromethyl, or 5° (iii) a C;-Cq4 alkyl group optionally substituted by at least one substituent selected from halogen, trifluoromethyl, carboxyl, C;-Cg¢ alkoxycarbony! and a 5- to 6-membered saturated or unsaturated ring which may comprise at least one heteroatom chosen from nitrogen, oxygen and sulphur, the ring being optionally substituted with at least one substituent selected from halogen, methyl and trifluoromethyl, or 10 . R7andR% to gether with the nitrogen atom to which they are attached form a 4- to 7- membered saturated heterocycle;
RY represents a hydrogen atom, or a C;-Cg alkyl group optionally substituted by - carboxyl or C,-Cg4 alkoxycarbonyl; Co
R'7" is defined as for R'7 above except that R'”" does not represent a hydrogen atom;
R'? and R® each independently represent a hydrogen atom or a C;-Cq alkyl group, or
R'® and R® together with the nitrogen atom to which they are attached form a 4- to 7- membered saturated heterocycle;
R?! and R?? each independently represent a hydrogen atom or a C;-Cg alkyl group optionally substituted by C;-C¢ alkoxycarbonyl, visOorl; rR? represents a hydrogen atom or a C,-Cg alkyl group; and
R* represents a hydrogen atom, or a C;-Cg alkyl group optionally substituted by carboxyl, C;-Cg alkoxy or C;-Cq4 alkoxycarbonyl; or a pharmaceutically acceptable salt or solvate thereof.
In another aspect of the invention, there is provided a compound of general formula
RA OH a : J NR?
RR a)
wherein, : - R represents a group
Xo ~~ (R%), uf) 1§ i : ZN : mis 0, 1,2 or 3; ) each R' independently represents halogen, cyano, nitro, carboxyl, hydroxyl,
C5-Cg cycloalkyl, C;-Cg alkoxy, C;-Cg alkoxycarbonyl, C,-Cg4 haloalkyl,
C,-Cy haloalkoxy, -NR’R?, C;-C4 cycloalkylamino, C,-Cj alkylthio,
C,-C¢ alkylcarbonyl, C;-Cg4 alkylcarbonylamino, sulphonamido, Cy-Cg alkylsulphonyl, -C(ONR''R", -NR"C(0)-(NH),R'*, phenyl, or C,-C alkyl optionally substituted by carboxyl or C;-C¢ alkoxycarbonyl; pisOor 1;
X represents an oxygen or sulphur atom or a CH,, CH(CHj3), OCH), CH,O0, CH,NH,
NH or carbonyl group and Y represents a nitrogen atom or a CH or C(OH) group, provided that when X represents an oxygen or sulphur atom or a CH,O, CH,NH or NH group, then
Y represents a CH group; z! represents a bond or a group (CHa) where q is 1 or 2; z° represents a bond or a group CH, with the proviso that Zz! and Z* do not both simultaneously represent a bond;
Q represents an oxygen or sulphur atom or a group CH, or NH;
Rr? represents a group oO , HN me \
ACI ot 0 cn > @ on, or A : nis 0,1 or2; each R’ independently represents a C;-Cg alkyl, C,-Cg alkoxycarbonyl, -CH,OH or s carboxyl group;
RY, R®, R® and R” each independently represent a hydrogen atom or a C;-Cg alkyl group, or RY, R’, R® and R’ together represent a C,-C, alkylene chain linking the two carbon atoms to which they are attached to form a 4- to 7-membered saturated carbocycle, or rR’, R® and R” each represent a hydrogen atom and R* and R® together with the carbon 10 atoms to which they are attached form a 5- to 6-membered saturated carbocycle;
R® represents a hydrogen atom, a C;-Cg¢ alkyl group or is linked to R” as defined above;
R® and R'? each independently represent a hydrogen atom or a C{-Cg alkyl group, or
R® and RY together with the nitrogen atom to which they are attached form a 4- to 7- . 1s membered saturated heterocycle;
R'! and R'? each independently represent a hydrogen atom or a C-Cg alkyl group : optionally substituted by C,;-Cg4 alkoxycarbonyl;
Rr represents a hydrogen atom or a C,-Cg alkyl group; and rR" represents a hydrogen atom. or a C-Cg alkyl group optionally substituted by : carboxyl, C,~Cg4 alkoxy or C,-Cg¢ alkoxycarbonyl; provided that when X is an oxygen atom or a group CH,, Y is CH, z! and 7? each } represent a group CH, and Q is an oxygen atom, then R? is other than an unsubstituted 5s indolyl group; or a pharmaceutically acceptable salt or solvate thereof.
In a further aspect of the invention, there is provided a compound of general formula
RA OH
Le QA 2
XR CR
RR a wherein,
R represents a group
N
(R"),. £0) ~ ; mis0, 1,2 or 3; each R' independently represents halogen, cyano, nitro, carboxyl, hydroxyl,
C;-Cg cycloalkyl, C1-Cg alkoxy, C;-Cg alkoxycarbonyl, C;-Cgq haloalkyl, +. C;-Cg haloalkoxy, NRR!C, C5-Cg cycloalkylamino, C;-Cg alkylthio,
C;-Cg alkylcarbonyl, C;-Cg alkylcarbonylamino, sulphonamido, C;-Cg alkylsulphonyl, » -CONR'RY, NR"C(0)-(NH),R', phenyl, or C;-Cg alkyl optionally substituted by carboxyl or C;-Cg4 alkoxycarbonyl; pisOorl; . Q represents an oxygen or sulphur atom or a group CH, or NH;
Rr represents a group
0 .
H A
. 3
R" HN NT i 16
X
HN” “CH, JY
HN CH,
O -
JIL or * HC N
H .
RY, R’, RS and R” each independently represent a hydrogen atom or a C;-Cg alkyl group, or RY, rR’, RS and R’ together represent a C,~C, alkylene chain linking the two carbon atoms to which they are attached to form a 4- to 7-membered saturated carbocycle, or Rr’, R® and R each represent a hydrogen atom and R* and R® together with the carbon atoms to which they are attached form a 5- to 6-membered saturated carbocycle;
R® represents a hydrogen atom, a C~Cg alkyl group or is linked to R* as defined above;
R® and R1? each independently represent a hydrogen atom or a C;-Cg alkyl group, or
R’ and R'% to gether with the nitrogen atom to which they are attached form a 4- to 7- membered saturated heterocycle;
R!'! and R!? each independently represent a hydrogen atom or a C,-Cg alkyl group optionally substituted by C,-Cg4 alkoxycarbonyl; - 15 rR" represents a hydrogen atom or a C-Cg alkyl group; rR" represents a hydrogen atom, or a C,-Cg alkyl group optionally substituted by carboxyl, C,-Cg alkoxy or C-Cg¢ alkoxycarbonyl;
RY represents carboxyl, C;-Cg alkylcarbonyl, C,-Cg4 alkoxycarbonyl,
C,-Cj alkoxycarbonylC,-Cg alkyl or a group -NR''R'®, -NHS0,CH;, -NHC(O)CH;,
_ Wo o01/62728 PCT/SE01/00403 -CONR'R!8 NHC(O)NR!'R'S, -OC(O)NR!R'®, -OCH,C(O)NR!R'?, , -NHC(0)OR!” or Or!" ‘ tis 0,1, 2 or 3; ) each R'® independently represents halogen, cyano, nitro, carboxyl, hydroxyl, 5s C3-Cg cycloalkyl, C,-Cg¢ alkoxy, C;-Cg alkoxycarbonyl, C-C¢ haloalkyl,
C,-Cq haloalkoxy, -NR'R*®, C;-C; cycloalkylamino, C,-C alkylthio,
C,-Cg alkylcarbonyl, C;-C¢ alkylcarbonylamino, sulphonamido (-SO,NH,),
C,-Cg alkylsulphonyl, -C(O)NR>'R?, -NRZC(0)(NH),R**, phenyl, or C,-C alkyl optionally substituted by carboxyl or C,-Cg¢ alkoxycarbonyl;
R'7 and R'® each independently represent (i) a hydrogen atom, (ii) a 5- to 6- membered saturated or unsaturated ring which may comprise at least one heteroatom chosen from nitrogen, oxygen and sulphur, the ring being optionally substituted with at least one substituent selected from halogen, methyl and trifluoromethyl, or (iti) a C;-Cg alkyl group optionally substituted by at least one substituent selected from halogen, trifluoromethyl, carboxyl, C;-C¢ alkoxycarbonyl and a 5- to 6-membered saturated or unsaturated ring which may comprise at least one heteroatom chosen from nitrogen, oxygen and sulphur, the ring being optionally substituted with at least one substituent selected from halogen, methyl and trifluoromethyl, or
R!7 and R'® together with the nitrogen atom to which they are attached form a 4- to 7- membered saturated heterocycle; rR! represents a hydrogen atom, or a C;-Cg alkyl group optionally substituted by carboxyl or C;-Cg4 alkoxycarbonyl; - R17" is defined as for R'7 above except that R'7" does not represent a hydrogen atom;
R'® and R® each independently represent a hydrogen atom or a C;-C¢ alkyl group, or »s RY and R% together with the nitrogen atom to which they are attached form a 4- to 7- ’ membered saturated heterocycle; :
R*! and R* each independently represent a hydrogen atom or a C;-Cg alkyl group optionally substituted by C,-Cg¢ alkoxycarbonyl; visOorl; rR? represents a hydrogen atom or a C;-Cg alkyl group; and
R* represents a hydrogen atom, or a C-Cg alkyl group optionally substituted by . carboxyl, C;-Cg4 alkoxy or C;-Cg4 alkoxycarbonyl; or a pharmaceutically acceptable salt or solvate thereof.
The integer m is preferably 0, 1 or 2.
Each R! independently represents halogen (e.g. chlorine, fluorine, bromine or iodine), cyano, nitro, carboxyl, hydroxyl, C;-C¢ cycloalkyl! (cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl), C;-Cg, preferably C,-C,, alkoxy (e.g. methoxy, ethoxy, n-propoxy or n-butoxy), C;-Cg, preferably C;-Cy, alkoxycarbonyl (e.g methoxycarbonyl or ethoxycarbonyl), C,-Cg, preferably C,-Cy, haloalkyl (e.g. trifluoromethyl),
C,-C, preferably C;-C,, haloalkoxy (e.g. trifluoromethoxy), NRR!,
C1-C¢ cycloalkylamino (e.g. cyclopropylamino, cyclobutylamino, cyclopentylamino or cyclohexylamino), C;-Cq, preferably C;-Cy, alkylthio (e.g. methylthio or ethylthio),
Cy-Cq, preferably C;-Cy, alkylcarbonyl (e.g. methylcarbonyl, ethylcarbonyl, n-propylcarbonyl, isopropylcarbonyl, n-butylcarbonyl, n-pentylcarbonyl or n-hexylcarbonyl), C;-Cg, preferably C;-C,, alkylcarbonylamino (e.g. methylcarbonylamino or ethylcarbonylamino), sulphonamido,
C,;-Cg, preferably C,-C,, alkylsulphonyl (e.g. methylsulphonyl, ethylsulphonyl, n-propylsulphonyl, isopropylsulphonyl, n-butylsulphonyl, n-pentylsulphonyl or n-hexylsulphonyl), -C(O)NR! IR", NRPC(0)-NH),R 4, phenyl, or
C;-C, preferably C,-C,, alkyl (e.g. methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert-butyl, n-pentyl or n-hexyl) optionally substituted by carboxyl or C;-Cg, preferably
C;-Cy, alkoxycarbonyl (e.g. methoxycarbonyl or ethoxycarbonyl). ) Most preferably, each Rr! independently represents halogen (particularly chlorine or } fluorine), cyano, nitro, C{-Cg4 alkoxy (especially methoxy), C;-Cg alkylcarbonyl (especially methylcarbonyl) or C,;-Cg4 alkylcarbonylamino (particularly methylcarbonylamino).

Claims (1)

  1. I. A compound of general formula RA OH Le Ig? R R S R® R oO wherein, R represents a group Xe ~~ (RY), ®t J [7% ~ NL mis0, 1,2 o0r3; ] each R' independently represents halogen, cyano, nitro, carboxyl, hydroxyl, " ~ C4-Cg cycloalkyl, C;-Cg4 alkoxy, C,-Cg¢ alkoxycarbonyl, C,;-Cg haloalkyl,
    C.-C haloalkoxy, -NRR'®, C;-C; cycloalkylamino, C;-Cg alkylthio, C-Cg alkylcarbonyl, C,-Cg alkylcarbonylamino, sulphonamido, C,-Cg alkylsulphonyl, -CONR'R?, -NRPC(0)-(NH),R"*, phenyl, or C,-Cj alkyl optionally substituted by carboxyl or C;-Cg alkoxycarbonyl; pisOorl; X represents an oxygen or sulphur atom or a CH,, CH(CHj3), OCH,, CH,0, CH;NH, NH or carbonyl group and Y represents a nitrogen atom or a CH or C(OH) group, provided that when X represents an oxygen or sulphur atom or a CH,0, CH,NH or NH group, then Y represents a CH group; . z! represents a bond or a group (CHp)q where q is 1 or 2; 7? represents a bond or a group CH, with the proviso that 7! and Z? do not both ) simultaneously represent a bond; Q represents an oxygen or sulphur atom or a group CH; or NH; R> represents a group
    ) R'S Ces nis 0, 1 or2; each R® independently represents a C,-Cg alkyl, C;-Cg¢ alkoxycarbonyl, -CH,OH or carboxyl group; RY, R, R® and R” each independently represent a hydrogen atom or a C;-Cg alkyl group, or RY, Rr’, R® and R’ together represent a C,-C, alkylene chain linking the two carbon atoms to which they are attached to form a 4- to 7-membered saturated carbocycle, or R, R® and R each represent a hydrogen atom and R* and R® together with the carbon atoms to which they are attached form a 5- to 6-membered saturated carbocycle; R® represents a hydrogen atom, a C-Cg alkyl group or is linked to R* as defined above; : R” and R'® each independently represent a hydrogen atom or a C|-Cg alkyl group, or is Rand R' together with the nitrogen atom to which they are attached forma 4- to 7- membered saturated heterocycle; R!! and R'? each independently represent a hydrogen atom or a C,-Cg alkyl group optionally substituted by C,-Cg4 alkoxycarbonyl; rR" represents a hydrogen atom or a C;-Cg alkyl group; RM represents a hydrogen atom, or a C;-Cg alkyl group optionally substituted by carboxyl, C;-Cg4 alkoxy or C;-C¢ alkoxycarbonyl; rR" represents carboxyl, C;-Cg alkylcarbonyl, C,-Cg4 alkoxycarbonyl, C,-Cy alkoxycarbonylC,-Cg alkyl or a group -NR!'R'®, -NHSO,CH;, -NHC(O)CH;, -C(O)NR!R!®, .NHC(O)NR'R'S, -OC(O)NR!'R'3, -OCH,C(O)NR!'RS, ’ 25 NHC(O)OR” or -OR' 7. tis 0,1,2 or 3;
    each R'® independently represents halogen, cyano, nitro, carboxyl, hydroxyl, - : C;3-Cg cycloalkyl, C;-Cg4 alkoxy, C;-Cg4 alkoxycarbonyl, C;-Cg haloalkyl, C,-C¢ haloalkoxy, NRPR®, C5-Cg cycloalkylamino, C,-Cg alkylthio, C,-Cg alkylcarbonyl, C;-Cg4 alkylcarbonylamino, sulphonamido (-SO,NH»), C,-Cg alkylsulphonyl, -C(O)NR*'R??, -NR**C(O)(NH),R**, phenyl, or C;-Cg alkyl optionally substituted by carboxyl or C,-C¢ alkoxycarbonyl;
    R'7 and R'8 each independently represent (i) a hydrogen atom, (ii) a 5-to 6- membered saturated or unsaturated ring which may comprise at least one heteroatom chosen from nitrogen, oxygen and sulphur, the ring being optionally substituted with at least one substituent selected from halogen, methyl and trifluoromethyl, or + (iii) a C,-Cg4 alkyl group optionally substituted by at least one substituent selected from halogen, trifluoromethyl, carboxyl, C,-C4 alkoxycarbonyl and a 5- to 6-membered saturated or unsaturated ring which may comprise at least cne heteroatom chosen from nitrogen, oxygen and sulphur, the ring being optionally substituted with at least one substituent selected from halogen, methyl and trifluoromethyl, or
    R' and R'® together with the nitrogen atom to which they are attached form a 4- to 7- membered saturated heterocycle; RY represents a hydrogen atom, ora C,-Cg alkyl group optionally substituted by carboxyl or C;-Cg4 alkoxycarbonyl,
    rR” is defined as for R!7 above except that R'”" does not represent a hydrogen atom;
    R" and R¥ each independently represent a hydrogen atom or a C;-Cg alkyl group, or R'? and R¥ together with the nitrogen atom to which they are attached form a 4- to 7- membered saturated heterocycle;
    R%! and R? each independently represent a hydrogen atom or a C;-Cg alkyl group
    2s optionally substituted by C,-C¢ alkoxycarbonyl; visOorl; . rR* represents a hydrogen atom or a C;-Cg4 alkyl group; and rR* represents a hydrogen atom, or a C;-Cg alkyl group optionally substituted by carboxyl, C;-C¢ alkoxy or C;-Cg4 alkoxycarbonyl; or a pharmaceutically acceptable salt or solvate thereof.
    . 2. A compound according to claim 1, wherein X represents an oxygen atom or a CH, OCH,, CH,0, NH or carbonyl group. 5s 3. A compound according to claim | or 2, wherein Y represents a nitrogen atom or CH group.
    4. A compound according to any one of claims 1 to 3, wherein Q represents an oxygen atom.
    J 5. A compound according to any one of claims 1 to 4, wherein RY represents C;-C, alkoxy, C,-C, alkylcarbonyl, C,;-C, alkoxycarbonylC,-C, alkyl, -NHC(O)CHj, C(O)NR''R'®, .NHSO,CH; or -NHC(O)NR''R"®.
    6. A compound according to any one of claims 1 to 5, wherein each R!6 independently represents halogen, cyano, hydroxyl, C,-C, alkoxy, C;-C4 alkoxycarbonyl, C1-Cy haloalkyl, C,-C, alkylcarbonyl, phenyl or C,-Cy alkyl.
    7. A compound of formula (I'), or a pharmaceutically acceptable salt or solvate thereof, 2 as defined in claim 1 being selected from: N-(2-{3-[3R,S-(4-Chloro-phenoxy)-pyrrolidin-1-yl]-2R,S-hydroxy-propoxy} -phenyl)- acetamide hydrochloride, N-(5-Chloro-2-{3-[3R,S-(4-Chloro-phenoxy)-pyrrolidin-1-yl]-2R,S-hydroxy- propoxy}-phenyl)-acetamide hydrochloride, N-(2-{3-[4-(3,4-dichlorophenoxy)-1-piperidinyl]-2-hydroxypropoxy} phenyl)- acetamide, ] 1-(2-aminophenoxy)-3-[4-(3,4-dichlorophenoxy)-1-piperidinyl]-2-propanol dihydrochloride, N-(2-{3-[3-(3,4-dichlorophenoxy)-1-pyrrolidiny!)-2-hydroxypropoxy} phenyl)- acetamide hydrochloride,
    2-{3-[4-(4-Fluoro-phenoxy)-piperidin- 1-yl]-2-hydroxy-propoxy} -benzoic acid methyl ester, 2-(2-{3-[4-(3,4-Difluoro-phenoxy)-piperidin- | -yl]-2-hydroxy-propoxy } - benzoylamino)-2-methyl-propionic acid methyl ester, N-[2-({(1R,2S,3R)*-3-[4-(3,4-dichlorophenoxy)- | -piperidinyl)-2- hydroxycyclopentyl} oxy)phenyl]acetamide, N-[2-({(1S5,25,3R)*-3-[4-(3,4-dichlorophenoxy)-1-piperidinyl)-2- hydroxycyclopentyl}oxy)phenyl]acetamide, N-[2-({(2,3-trans)-3-[4-(3 ,4-dichlorophenoxy)- 1 -piperidinyl]-2- hydroxycyclohexyl}oxy)phenyl]acetamide, N-(5-Chloro-2-{3-[3-(3,4-dichloro-phenoxy)-pyrrolidin- 1-yl}-2-hydroxy-propoxy}- phenyl)-acetamide, : N-(3-Acetyl-2-{3-[3-(3 4-dichloro-phenoxy)-pyrrolidin- 1-yl]-2-hydroxy-propoxy}-5- methyl-phenyl)-acetamide, N-(2-{3-[3-(3,4-Dichloro-phenoxy)-pyrrolidin-1-yl]-2-hydroxy-propoxy} -4-methyl- phenyl)-acetamide, N-(2-{3-[3-(3,4-Dichloro-phenoxy)-pyrrolidin-1-yl}-2-hydroxy-propoxy} -5-fluoro- phenyl)-acetamide, N-(4-{3-[3-(3,4-Dichloro-phenoxy)-pyrrolidin-1-y}} 2-hydroxy-propoxy} -biphenyl-3- yl)-acetamide, N-(2-{3-[3-(3,4-Dichloro-phenoxy)-pyrrolidin-1-yl}-2-hydroxy-propoxy} -4-fluoro- phenyl)-acetamide, N-(2-{3-[3-(3,4-Dichloro-phenoxy)-pyrrolidin-1-yl}-2-hydroxy-propoxy}-5-methyl- phenyl)-acetamide, N-(2-{3-[3-(3,4-Dichloro-phenoxy)-pyrrolidin- 1-y1]-2-hydroxy-propoxy} -phenyl)- acetamide, . N-(5-Chloro-2-{3-[3-(4-chloro-phenoxy)-pyrrolidin-1 -yl]-2-hydroxy-propoxy} - phenyl)-acetamide, N-(3-Acetyl-2-{3-[3-(4-chloro-phenoxy)-pyrrolidin-1-yl}-2-hydroxy-propoxy} -5- so methyl-phenyl)-acetamide,
    N-(2-{3-[3-(4-Chloro-phenoxy)-pyrrolidin-1-yl]-2-hydroxy-propoxy } -4-methyl- ~ : phenyl)-acetamide, N-(2-{3-[3-(4-Chloro-phenoxy)-pyrrolidin-1-yl}-2-hydroxy-propoxy} -5-fluoro- } phenyl)-acetamide, N-(4-{3-[3-(4-Chloro-phenoxy)-pyrrolidin-1-y1]-2-hydroxy-propoxy } -biphenyi-3-yl)- acetamide, N-(2-{3-[3-(4-Chloro-phenoxy)-pyrrolidin-1-yl]-2-hydroxy-propoxy } -4-fluoro- phenyl)-acetamide, N-(2-{3-[3-(4-Chloro-phenoxy)-pyrrolidin-1-yl]-2-hydroxy-propoxy} -5-methyl- to phenyl)-acetamide, N-(2-{3-[3-(4-Chloro-phenoxy)-pyrrolidin-1-yl]-2-hydroxy-propoxy} -phenyl)- acetamide ~~ N-(5-Chloro-2- {3-[3-(4-fluoro-phenoxy)-pyrrolidin- 1 _y1]-2-hydroxy-propoxy }- phenyl)-acetamide, N-(3-Acetyl-2-{3-[3-(4-fluoro-phenoxy)-pyrrolidin-1-yl]-2-hydroxy-propoxy }-5- methyl-phenyl)-acetamide, N-(2-{3-[3~(4-Fluoro-phenoxy)-pyrrolidin-1-yi]-2-hydroxy-propoxy} -4-methyl- phenyl)-acetamide, N-(5-Fluoro-2-{3-[3~(4-fluoro-phenoxy)-pyrrolidin-1-yl]-2-hydroxy-propoxy} - phenyl)-acetamide, N-(4-{3-[3-(4-Fluoro-phenoxy)-pyrrolidin-1-yi]-2-hydroxy-propoxy} -biphenyl-3-yl)- acetamide, N-(4-Fluoro-2- {3-[3-(4-fluoro-phenoxy)-pyrrolidin-1-yl]-2-hydroxy-propoxy}- phenyl)-acetamide, N-(2-{3-[3~(4-Fluoro-phenoxy)-pyrrolidin-1-yl}-2-hydroxy-propoxy} -5-methyl- phenyl)-acetamide, . N-(2- {3-[3-(4-Fluoro-phenoxy)-pyrrolidin- 1-yl]-2-hydroxy-propoxy} -phenyl)- acetamide, N-(5-Chloro-2- {3-[3-(3,4-difluoro-phenoxy)-pyrrolidin-1-yl]-2-hydroxy-propoxy} - phenyl)-acetamide,
    N-(3-Acetyl-2-{3-[3-(3 ,4-difluoro-phenoxy)-pyrrolidin- 1-y1}-2-hydroxy-propoxy}-3- : methyl-phenyl)-acetamide, N-(2- {3-[3-(3,4-Difluoro-phenoxy)-pyrrolidin- 1 -yl]-2-hydroxy-propoxy} -4-methyl- ) phenyl)-acetamide, N-(2-{3-[3-(3,4-Difluoro-phenoxy)-pyrrolidin- 1-yl]-2-hydroxy-propoxy} -5-fluoro- phenyl)-acetamide, N-(4-{3-[3-(3,4-Difluoro-phenoxy)-pyrrolidin- 1-yl]-2-hydroxy-propoxy} -biphenyl-3- yl)-acetamide, N-(2-{3-[3-(3,4-Difluoro-phenoxy)-pyrrolidin- 1 -y1}-2-hydroxy-propoxy } -4-fluoro- phenyl)-acetamide, N-(2-{3-[3-(3,4-Difluoro-phenoxy)-pyrrolidin-1-yl]-2-hydroxy-propoxy}-5-methyl- phenyl)-acetamide, N-(2- {3-[3-(3,4-Difluoro-phenoxy)-pyrrolidin- 1 -yl}-2-hydroxy-propoxy} -phenyl)- . acetamide, N-(5-Chloro-2-{3-[4-(3 4-dichloro-phenoxy)-piperidin- 1-yl]-2-hydroxy-propoxy}- phenyl)-acetamide, N-(3-Acetyl-2- {3-[4-(3,4-dichloro-phenoxy)-piperidin- 1 -yl]-2-hydroxy-propoxy} -5- methyl-phenyl)-acetamide, N-(2- {3-[4-(3,4-Dichloro-phenoxy)-piperidin-1-yl]-2-hydroxy-propoxy} -4-methyl- phenyl)-acetamide, N-(2-{3-[4-(3,4-Dichloro-phenoxy)-piperidin-1-yl]-2-hydroxy-propoxy} -5-fluoro- phenyl)-acetamide, N-(4-{3-[4-(3,4-Dichloro-phenoxy)-piperidin-1-yl]-2-hydroxy-propoxy} -biphenyl-3- yl)-acetamide, 2s N-(2-{3-[4-(3,4-Dichloro-phenoxy)-piperidin- 1-yi]-2-hydroxy-propoxy}-4-fluoro- phenyl)-acetamide, N-(2-{3-[4-(3,4-Dichloro-phenoxy)-piperidin- 1 -yl]}-2-hydroxy-propoxy}-5-methyl- phenyl)-acetamide, N-(2-{3-[4-(3,4-Dichloro-phenoxy)-piperidin- 1-y1]-2-hydroxy-propoxy} -phenyl)- acetamide,
    N-(5-Chloro-2-{3-[4-(4~chloro-phenoxy)-piperidin-1-yl]-2-hydroxy-propoxy}- ~ : phenyl)-acetamide, N-(3-Acetyl-2-{3-[4-(4-chloro-phenoxy)-piperidin-1-yl}-2-hydroxy-propoxy}-5- methyl-phenyl)-acetamide, N-(2-{3-[4-(4-Chloro-phenoxy)-piperidin-1-yl]-2-hydroxy-propoxy} -4-methyl- phenyl)-acetamide, N-(2- {3-[4-(4-Chloro-phenoxy)-piperidin-1-yl]-2-hydroxy-propoxy} -3-fluoro- phenyl)-acetamide, N-(4-{3-[4-(4-Chloro-phenoxy)-piperidin- 1-y1]-2-hydroxy-propoxy}-biphenyi-3-yl)- acetamide, N-(2-{3-[4-(4-Chloro-phenoxy)-piperidin-1-yl}-2-hydroxy-propoxy }-4-fluoro- phenyl)-acetamide, Co N-(2-{3-[4-(4-Chloro-phenoxy)-piperidin- 1-yl]-2-hydroxy-propoxy}-5-methyl- phenyl)-acetamide, N-(2-{3-]4-(4-Chloro-phenoxy)-piperidin-1-ylJ-2-hydroxy-propoxy} -phenyl)- acetamide, N-(2- {3-[4-(3,4-Dichloro-phenoxy)-piperidin-1-yl}-2-hydroxy-propoxy} -phenyl)- acetamide, . 3-(2-{3-[4-(3,4-Dichloro-phenoxy)-piperidin-1-yl]-2-hydroxy-propoxy}-phenyl)- propionic acid methyl ester, 1-[4-(3,4-Dichloro-phenoxy)-piperidin-1-y1]-3-(2,6-dimethoxy-phenoxy)-propan-2-ol, 1-[4-(3,4-Dichloro-phenoxy)-piperidin-1-yl]-3-(2-methoxy-phenoxy)-propan-2-ol, : 2-{3-[4~(3,4-Dichloro-phenoxy)-piperidin-1-yl]-2-hydroxy-propoxy}-N,N-dimethyl- benzamide, 1-(2-{3-[4-(3,4-Dichloro-phenoxy)-piperidin- 1 -yl]-2-hydroxy-propoxy} -phenyl)- propan-1-one, i 1-(2-{3-[4-(3,4-Dichloro-phenoxy)-piperidin-1 -yl]-2-hydroxy-propoxy}-phenyl)- ethanone, 3-(2-{3-[3-(4-Fluoro-phenoxy)-pyrrolidin- 1 -y1]-2-hydroxy-propoxy}-phenyl)- propionic acid methyl ester,
    1-(2,6-Dimethoxy-phenoxy)-3-[3-(4-fluoro-phenoxy)-pyrrolidin- 1 -yl}-propan-2-l, : 1-[3-(4-Fluoro-phenoxy)-pyrrolidin- 1 -yl}-3-(2-methoxy-phenoxy)-propan-2-ol, (2-{3-[3-(4-Fluoro-phenoxy)-pyrrolidin- 1-yl]-2-hydroxy-propoxy}-benzoylamine)- acetic acid methyl ester, (2-{3-[3-(4-Chloro-phenoxymethyl)-piperidin- 1-y1}-2-hydroxy-propoxy} - benzoylamino)-acetic acid methyl ester, 2-(2-{3-[3-(4-Fluoro-phenoxy)-pyrrolidin- 1-yl}-2-hydroxy-propoxy} -benzoylamino)- 2-methyl-propionic acid methyl ester, 2-{3-[3-(4-Fluoro-phenoxy)-pyrrolidin-1-yl]}-2-hydroxy-propoxy}-N,N-dimethyl- benzamide, 1-(2-{3-[3-(4-Fluoro-phenoxy)-pymolidin-1-yl]-2-hydroxy-propoxy } -6~-methoxy- phenyl)-ethanone, 1-(2-{3-[3-(4-Fluoro-phenoxy)-pyrrolidin-1-yl]-2-hydroxy-propoxy } -phenyl)-propan- 1-one, 5 1-(2-{3-[3-(4-Fluoro-phenoxy)-pyrrolidin-1-yl]-2-hydroxy-propoxy } -phenyl)- ethanone, N-[2-(3-{[1-(3,4-dichlorobenzy!)-4-piperidinylJamino } -2-hydroxypropoxy)-4- methylphenyl]acetamide, 3-(2-{3-[3~(3,4-Difluoro-phenoxy)-pyrrolidin- 1-yl]-2-hydroxy-propoxy}-phenyl)- propionic acid methyl ester, 1-[3-(3,4-Difluoro-phenoxy)-pyrrolidin- 1-yl]-3-(2-methoxy-phenoxy)-propan-2-0l, (2-{3-[3-(3,4-Difluoro-phenoxy)-pyrrolidin-1-yl}-2-hydroxy-propoxy}- benzoylamino)-acetic acid methyl ester, 2-{3-[3-(3,4-Difluoro-phenoxy)-pyrrolidin-1-yl]-2-hydroxy-propoxy} -N,N-dimethyl- benzamide, 1-(2-{3-[3-(3,4-Difluoro-phenoxy)-pyrrolidin- 1-yl}-2-hydroxy-propoxy} -6-methoxy- . phenyl)-ethanone, 1-(2-{3-[3~(3,4-Difluoro-phenoxy)-pyrrolidin- 1 -yl}-2-hydroxy-propoxy} -phenyl)}- propan-1-one, :
    1-(2-{3-[3-(3,4-Difluoro-phenoxy)-pyrrolidin-1-yl]-2-hydroxy-propoxy } -phenyl)- : ethanone, : N-(2-{3-[4-(3,4-dichloroanilino)- 1 -piperidinyl]-2-hydroxypropoxy } phenyl)acetamide, 3-(2-{3-[3-(4-Chloro-phenoxy)-pyrrolidin- [ -yl]-2-hydroxy-propoxy} -phenyl)-
    5s propionic acid methyl ester,
    1-[3-(4-Chloro-phenoxy)-pyrrolidin- 1 -yl]-3-(2,6-dimethoxy-phenoxy)-propan-2-ol, 1-[3-(4-Chloro-phenoxy)-pyrrolidin-1-yl]-3-(2-methoxy-phenoxy)-propan-2-ol, (2-{3-[3-(4-Chloro-phenoxy)-pyrrolidin-1-yi]-2-hydroxy-propoxy} -benzoylamino)-
    acetic acid, methyl ester, 2-(2-{3-[3-(4-Chloro-phenoxy)-pyrrolidin-1 -y1]-2-hydroxy-propoxy} -benzoylamino)-
    2-methyl-propionic acid methyl ester, BR 2-{3-[3-(4-Chloro-phenoxy)-pyrrolidin-1-yl]-2-hydroxy-propoxy}-N,N-dimethyl-
    benzamide,
    _ 1-+(2-{3-[3-~(4-Chloro-phenoxy)-pyrrolidin- 1-y1]-2-hydroxy-propoxy}-6-methoxy-
    ts phenyl)-ethanone,
    1-(2- {3-[3-(4-Chloro-phenoxy)-pyrrolidin-1-yl}-2-hydroxy-propoxy}-phenyl)-propan- 1-one,
    1-(2-{3-[3-(4-Chloro-phenoxy)-pyrrolidin-1-yl}-2-hydroxy-propoxy} -phenyl)- ethanone,
    N-(2-{3-[3-(4-Cyano-phenoxy)-pyrrolidin-1-y1}-2-hydroxy-propoxy} -phenyl)-
    acetamide, 3-(2-{3-[3-(4-Cyano-phenoxy)-pyrrolidin-1-yl]-2-hydroxy-propoxy}-phenyl)- propionic acid methyl ester, (2- {3-[3-(4-Cyano-phenoxy)-pyrrolidin-1-y1}-2-hydroxy-propoxy} -benzoylamino)-
    acetic acid methyl ester, 2-{3-[3-(4-Cyano-phenoxy)-pyrrolidin-1-y1}-2-hydroxy-propoxy} -N,N-dimethyl- benzamide,
    4-{1-[2-Hydroxy-3-(2-propionyl-phenoxy)-propyl]-pyrrolidin-3-yloxy} -benzonitrile, N-(2-{2-Hydroxy-3-{3-(4-methoxy-phenoxy)-pyrrolidin-1-yl]-propoxy}-phenyl)- acetamide,
    N-(4-chloro-2-{3-[4-(3,4-dichloroanilino)-1-piperidinyl]-2- ‘ hydroxypropoxy} phenyl)acetamide, 3-(2-{3-[3-(3,4-Dichloro-phenoxy)-pyrrolidin- 1 -yl}-2-hydroxy-propoxy} -phenyl)- propionic acid methyl ester, 1-[3-(3,4-Dichloro-phenoxy)-pyrrolidin-1-y1]-3-(2-methoxy-phenoxy)-propan-2-ol, (2-{3-[3-(3,4-Dichloro-phenoxy)-pyrrolidin-1-y1}-2-hydroxy-propoxy} - benzoylamino)-acetic acid methyl ester, 2-(2-{3-[3-(3,4-Dichloro-phenoxy)-pyrrolidin-1-yl]-2-hydroxy-propoxy}- benzoylamino)-2-methyl-propionic acid methyl ester,
    10. 2-{3-[3-(3 4-Dichloro-phenoxy)-pyrrolidin- 1-y1]-2-hydroxy-propoxy }-N,N-dimethyl- benzamide, 1-(2-{3-[3-(3,4-Dichloro-phenoxy)-pyrrolidin- 1 -y1}-2-hydroxy-propoxy} -6-methoxy- phenyl)-ethanone, 1-(2-{3-[3-(3,4-Dichloro-phenoxy)-pyrrolidin- 1 -yl]-2-hydroxy-propoxy } -phenyl)- propan-l-one, : © 1-(2-{3-[3-(3,4-Dichloro-phenoxy)-pyrrolidin- 1-yl]-2-hydroxy-propoxy} -phenyl)- ethanone, Sh N-(2-{3-[4-(3,4-Difluoro-phenoxy)-piperidin-1-yl]-2-hydroxy-propoxy}-phenyl)- acetamide, 3-(2-{3-[4~(3,4-Difluoro-phenoxy)-piperidin-1 -yl}-2-hydroxy-propoxy}-phenyl)- propionic acid methyl ester, 2-{3-[4-(3 4-Difluoro-phenoxy)-piperidin-1-yl}-2-hydroxy-propoxy} -N,N-dimethyl- benzamide, 1-(2-{3-[4~(3,4-Difluoro-phenoxy)-piperidin-1-yl]-2-hydroxy-propoxy} -phenyl)- propan-l-one, (2-{3-[4-(3,4-Difluoro-phenoxy)-piperidin-1-yl}-2-hydroxy-propoxy }-benzoylamino)- . acetic acid methyl ester, N-(2-{3-[3-(3,4-Difluoro-phenoxymethyl)-piperidin-1-yl]-2-hydroxy-propoxy} - phenyl)-acetamide,
    N-(2-{3-[4-(4-Fluoro-phenoxy)-piperidin-1-yl]-2-hydroxy-propoxy}-phenyl)- : acetamide, 3-(2-{3-[4-(4-Fluoro-phenoxy)-piperidin-1-yl]-2-hydroxy-propoxy} -phenyl)-propionic acid methyl ester, 1-(2,6-Dimethoxy-phenoxy)-3-{4-(4-fluoro-phenoxy)-piperidin- 1 -yl]-propan-2-ol, 1-[4-(4-Fluoro-phenoxy)-piperidin- 1-yl]-3-(2-methoxy-phenoxy)-propan-2-ol, 1-(2-{3-[4-(4-Fluoro-phenoxy)-piperidin- 1 -yl}-2-hydroxy-propoxy } -phenyl)-ethanone, 2-{3-[4-(4-Fluoro-phenoxy)-piperidin- 1-yl]-2-hydroxy-propoxy } -N,N-dimethyl- benzamide,
    10 . 1-2-{3 _[4-(4-Fluoro-phenoxy)-piperidin- 1-y1]-2-hydroxy-propoxy}-phenyl)-propan- 1-one, (2-{3-[4-(4-Fluoro-phenoxy)-piperidin- 1-y1]-2-hydroxy-propoxy }-benzoylamino)- acetic acid methyl ester, N-(2-{3-[3-(4-Fluoro-phenoxymethyl)-piperidin-1-yl]-2-hydroxy-propoxy} -phenyl)- acetamide,
    : . 3-(2-{3-[3-(4-Fluoro-phenoxymethyl)-piperidin-1-yl]-2-hydroxy-propoxy} -phenyl)- propionic acid methyl ester, 1-[3-(4-Fluoro-phenoxymethyl)-piperidin-1-yl]-3-(2-methoxy-phenoxy)-propan-2-ol, 1-(2-{3-[3-(4-Fluoro-phenoxymethyl)-piperidin-1-yl]-2-hydroxy-propoxy } -phenyl)- ethanone, 2-(2-{3-[3-(4-Fluoro-phenoxymethyl)-piperidin-1-yl]-2-hydroxy-propoxy} - benzoylamino)-2-methyl-propionic acid methyl ester, 2-{3-[3-(4-Fluoro-phenoxymethyl)-piperidin-1-yl]-2-hydroxy-propoxy}-N,N- dimethyl-benzamide, 1-(2- {3-[3-(4-Fluoro-phenoxymethyl)-piperidin- 1-y1}-2-hydroxy-propoxy }-6- methoxy-phenyl)-ethanone, . N-(2-{3-[4-(4-Acetylamino-phenoxy)-piperidin-1 -yl]-2-hydroxy-propoxy} -phenyl)- acetamide, N-(4-{1-[3-(2-Acetyl-phenoxy)-2-hydroxy-propyl]-piperidin-4-yloxy} -phenyl)- acetamide,
    N-(4-cyano-2-{3-[4-(3,4-dichloroanilino)-1-piperidinyl]-2- i . hydroxypropoxy } phenyl)acetamide, 3-(2-{3-[4-(4-Chloro-phenoxy)-piperidin-1-yl]-2-hydroxy-propoxy} -phenyl)- propionic acid methyl ester, 1-[4-(4-Chloro-phenoxy)-piperidin-1-yl}-3-(2-methoxy-phenoxy)-propan-2-ol, 1-(2-{3-[4-(4-Chloro-phenoxy)-piperidin-1-y1]-2-hydroxy-propoxy} -phenyl)- ethanone, 2-(2-{3-[4-(4-Chloro-phenoxy)-piperidin-1-y1}-2-hydroxy-propoxy} -benzoylamino)-2- methyl-propionic acid methyl ester, 2-{3-[4-(4-Chloro-phenoxy)-piperidin- 1-yl}-2-hydroxy-propoxy}-N N-dimethyl- benzamide, - 1+(2-{3-[4-(4-Chloro-phenoxy)-piperidin-1-yl]-2-hydroxy-propoxy} -6-methoxy- phenyl)-ethanone, : +1-(2-{3-[4-(4-Chloro-phenoxy)-piperidin-1-y1]-2-hydroxy-propoxy} -phenyl)-propan- l-one, : (2-{3-[4-(4-Chloro-phenoxy)-piperidin-1-yl]-2-hydroxy-propoxy} -benzoylamino)- acetic acid methyl ester, N-(2-{3-[3-(4-Chloro-phenoxymethyl)-piperidin-1-yl]-2-hydroxy-propoxy } -phenyl)- acetamide, 3-(2-{3-[3-(4- Chloro-phenoxymethyl)-piperidin- 1-y1]-2-hydroxy-propoxy } -phenyl)- propionic acid methyl ester, 1-(2-{3 -[3~(4-Chloro-phenoxymethyl)-piperidin- 1-yl]-2-hydroxy-propoxy }-phenyl)- ethanone, 2-{3-[3-(4-Chloro-phenoxymethyl)-piperidin-1-y1]-2-hydroxy-propoxy}-N,N- dimethyl-benzamide, ) 1-(2-{3-[3-(4-Chloro-phenoxymethyl)-piperidin-1-yl}-2-hydroxy-propoxy} -phenyl)- . propan-1-one, N-[2-({(1R,2R)-2-[4-(3,4-dichlorophenoxy)-1-piperidinyl]-1- hydroxycyclopentyl} methoxy)phenyl]acetamide,
    Methyl (25,4R)-1-{3-[2-(acetylamino)phenoxy]-2-hydroxypropyl}-4-[(4- - chlorobenzyl)oxy]-2-pyrrolidinecarboxylate hydrochloride, N-(2-{3-[4-(3,4-Dichloroanilino)- | -piperidinyl]-2-hydroxypropoxy } -4- ) methylphenyl)acetamide, : N-(2-{3-[4-(4-Chloroanilino)- 1 -piperidinyl}-2-hydroxypropoxy} phenyl)acetamide, N-(4-Chloro-2- {3-[4-(4-chloroanilino)- 1 -piperidinyl}-2-hydroxypropoxy} phenyl)- acetamide, N-(2-{3-[4-(4-Chloroanilino)-1-piperidinyl]-2-hydroxypropoxy} -4- cyanophenyl)acetamide, N-(2-{3-[4-(4-Chloroanilino)-1-piperidinyl]-2-hydroxypropoxy } -4- methylphenyl)acetamide, N-(5-Chioro-2- {3-[4-(4-fluoroanilino)- 1 -piperidinyl}-2- : hydroxypropoxy} phenyl)acetamide, N-(5-Chloro-2-{3-[4~(3,4-difluoroanilino)- 1 -piperidinyl]-2- ts hydroxypropoxy}phenyl)acetamide, N-(5-Cyano-2- {3-[4-(4-fluoroanilino)-1-piperidinyl}-2-hydroxypropoxy}- - phenyl)acetamide, N-(5-Cyano-2-{3-[4-(3,4-difluoroanilino)-1-piperidinyl}-2- hydroxypropoxy} phenyl)acetamide, N-(2- {3-[4-(4-Fluoroanilino)-1-piperidinyl]-2-hydroxypropoxy } -4- methylphenyl)acetamide, N-(2- {3-[4~(3,4-Difluoroanilino)-1-piperidinyl]-2-hydroxypropoxy } -4- methylphenyl)acetamide, N-(2-{3-[3(S)-(4-Chloro-phenoxy)-pyrrolidin-1-yl]-2-(R)-hydroxy-propoxy- phenyl)acetamide, ’ N-(2- {3-[3S-(4-Chloro-phenoxy)-pyrrolidin- 1-yl]-2S-hydroxy-propoxy } -phenyl)- ] acetamide hydrochloride, N-(2-{3-[3(R)-(4-Chloro-phenoxy)-pyrrolidin-1-yl]-2-(S)-hydroxy-propoxy- phenyl)acetamide,
    N-[5-Chloro-2-({(2S)-3-[(3S)-3-(4-chloro-phenoxy)pyrrolidinyl]-2- . hydroxypropyl} oxy)phenyllacetamide, N-[5-Chloro-2-({(2R)-3-[(3R)-3-(4-chloro-phenoxy)pyrrolidinyl]}-2- ’ | hydroxypropyl} oxy)phenyljacetamide, N-{5-Chloro-2-({(2S)-3-[(3R)-3-(4-chloro-phenoxy)pyrrolidinyl]-2- hydroxypropyl} oxy)phenyl]acetamide, N-[5-Chloro-2-({(2R)-3-{(3S)-3-(4-chloro-phenoxy)pyrrolidinyl]-2- hydroxypropyl} oxy)phenyllacetamide, N-(2-{3-[3-(4-Chloro-phenoxy)-pyrrolidin-1-yl]-2-hydroxy-propoxy}-4,5-difluoro- phenyl)-acetamide, N-{5-Chloro-2-[2-hydroxy-3-(3-phenoxy-pyrrolidin-1-yl)-propoxy]-phenyl }- acetamide, N-(5-Chloro-2-{2-hydroxy-3-[3-(4-nitro-phenoxy)-pyrrolidin- 1-yl]-propoxy} -phenyl)- acetamide, N-(5-Acetyl-2-{3-[3-(3,4-dichloro-phenoxy)-pyrrolidin-1-yl]-2-hydroxy-propoxy} - phenyl)-acetamide, : : : 4-Acetylamino-3-{3-[3-(3,4-dichloro-phenoxy)-pyrrolidin- 1-yl}-2-hydroxy-propoxy} - benzoic acid methyl ester, N-(2~{3-[3-(4-Chloro-phenoxy)-pyrrolidin-1-yl}-2-hydroxy-propoxy} -3-cyano- phenyl)-acetamide, 4-Acetylamino-3-{3-[3-(4-chloro-phenoxy)-pyrrolidin-1-yl]-2-hydroxy-propoxy)}- benzoic acid methyl ester, N-(5-Cyano-2-{3-[4-(3,4-dichloro-phenoxy)-piperidin-1-yl]-2-hydroxy-propoxy}- phenyl)-acetamide, N-(2-{3-[4-(3,4-Dichloro-phenoxy)-piperidin-1-yi]-2-hydroxy-propoxy}-5- ) trifluoromethyl-phenyl)-acetamide, } N-(5-Chloro-2- {3-[3-(4-fluoro-phenoxy)-pyrrolidin-1-yl}-2-hydroxy-propoxy} - phenyl)-acetamide trifluoroacetate, N-(5-Acetyl-2-{3-[3-(4-chloro-phenoxy)-pyrrolidin-1-yl}-2-hydroxy-propoxy}- phenyl)-acetamide trifluoroacetate,
    N-(2-{3-[3-(4-Chlorophenoxy)-1-pyrrolidinyl]}-2-hydroxypropoxy} phenyl)- . methanesulfonamide, N-(5-Chloro-2-[3-[3,4-dichlorophenoxy)-1-pyrrodinyl}-2-hydroxypropoxy}- phenylurea, 1-(3-{2-[(Aminocarbonyl)amino]phenoxy}-2-hydroxypropyl)-3-(4- chlorophenoxy)pyrrolidinium 2,2,2-trifluoroacetate, 1-(3-{2-[(Aminocarbonyl)amino]phenoxy}-2-hydroxypropyl)-3-(3,4- dichlorophenoxy)pyrrolidinium 2,2,2-trifluoroacetate, 1-(3-{2-[(Aminocarbonyl)amino]-4-chlorophenoxy}-2-hydroxypropyl)-3-(4- chlorophenoxy)pyrrolidinium 2,2,2-trifluoroacetate, N-(2-{3-[3-(4-Chlorophenoxy)-1-pyrrolidinyl]}-2-hydroxypropoxy} phenyl)-N'- ethylurea hydrochloride, N-(2-{3-[3-(4-Chlorophenoxy)-1-pyrrolidinyl]-2-hydroxypropoxy } phenyl)-V'- methylurea hydrochloride, (25,45)- 1-{3-[2-(Acetylamino)phenoxy]-2-hydroxypropyl } -4-(4-chlorophenoxy)-2- pyrrolidinecarboxylic acid; compound with trifluoroacetic acid, Ethyl (25,45)-1-{3-[2-(acetylamino)phenoxy]-2-hydroxypropy!}-4-(3,4- dichlorophenoxy)-2-pyrrolidinecarboxylate; trifluoroacetic acid salt, N-[2-({(25)-3-[(2S,4S)-4-(4-Chlorophenoxy)-2-(hydroxymethyl)pyrmrolidinyl]-2- hydroxypropyl}oxy)phenyl]acetamide; trifluoroacetic acid salt, N-[2-({(2R)-3-[(2S,45)-4-(4-Chlorophenoxy)-2-(hydroxymethyl)pyrrolidinyl]-2- hydroxypropyl} oxy)phenyl]acetamide; trifluoroacetic acid salt, N-(2-{3-[3-(4-Chlorophenoxy)-1-pyrrolidinyl]-2-hydroxy-2- methylpropoxy} phenyl)acetamide hydrochloride, N-(2-{(1S5",2R’,35")~3-[3~(4-Chloro-phenoxy)-pyrrolidin-1-yl]-2-hydroxy- ’ cyclopentyloxy}-phenyl)-acetamide, N-(2-{(1R",2R",3S")-3-[3-(4-Chloro-phenoxy)-pyrrolidin-1-y1]-2-hydroxy- cyclopentyloxy}-phenyl)-acetamide, N-(2-{(2R’,3R")-3-[4-(3,4-Dichloro-phenoxy)-piperidin-1-yl]-2-hydroxy-butoxy}- phenyl)-acetamide,
    WwWQ 01/62728 PCT/SE01/00403
    N-(2-{(1S5",2R",35")-3-[4-(4-Chloro-phenoxy)-piperidin- 1 -y1]-2-hydroxy- v cyclopentyloxy}-phenyl)-acetamide, N-(2-{(2R",35")-3-[4-(3,4-Dichloro-phenoxy)-piperidin- 1 -yl]-2-hydroxy-butoxy} - phenyl)-acetamide, N-(2-{(2R" 3R")-3-[3-(4-Chloro-phenoxy)-pyrrolidin-1-yl]-2-hydroxy-butoxy } - phenyl)-acetamide, N-(2-{(2R’ 35")-3-[3-(4-Chloro-phenoxy)-pyrrolidin-1-yl]-2-hydroxy-butoxy } - phenyl)-acetamide, N-(2-{(15",2R",3S")-3-[4-(3-Chloro-phenoxy)-piperidin-1-yl]-2-hydroxy- cyclopentyloxy) -phenyl)-acetamide, N-[5-Chloro-2-({(1S,2R,35)"-3-[4-(3,4-dichlorophenoxy)-1-piperidinyl}-2- hydroxycyclopentyl} oxy)phenyljacetamide, : . N-[4-Fluoro-2-({(1S,2R,35)’-3-[4-(3,4-dichlorophenoxy)- i -piperidinyl]-2- hydroxycyclopentyl}oxy)phenyl]acetamide, 1s N-(2-{3-[4-(3,4-Dichlorobenzyl)- 1 -piperazinyl]-2-hydroxypropoxy } -phenyl)acetamide dihydrochloride, | . N-(2- {3-[4-(3,4-Dichlorobenzyl)-1-piperazinyi]-2-hydroxypropoxy } -4- fluorophenyl)acetamide, : N-(2-{3-[4~(3,4-Dichlorobenzyl)-2,5-dimethyl-1-piperazinyl]-2- hydroxypropoxy} phenyl)acetamide, N-(5-Chloro-2-{3-[4-(3,4-dichlorobenzyl)-1-piperazinyl}-2- hydroxypropoxy } phenyl)acetamide, N-(5-Chioro-2-{3-[4-(3,4-dichlorobenzyl)-2,5-dimethyl- 1 -piperazinyl]-2- hydroxypropoxy } phenyl)acetamide, N-(2-{3-[4-(3,4-Dichlorobenzyl)-2,5-dimethyl- 1-piperazinyl}-2-hydroxypropoxy } -4- ) methylphenyl)acetamide, . N-(2-{3-[4-(3,4-Dichlorobenzyl)-2,5-dimethyl- 1 -piperazinyl]-2-hydroxypropoxy } -4- fluorophenyl)acetamide, N-(2-{3 [(S*R*)-4-(3,4-Dichlorobenzyl)-2,5-dimethyl- 1 -piperazinyl]-2- s0 hydroxypropoxy}phenyl)acetamide,
    N-(2-{3 [(S*R*)-4-(4-Chlorobenzyl)-2,5-dimethyl-1-piperazinyl]-2- . hydroxypropoxy} phenyl)acetamide, N-(5-Chloro-2-{3-[(S*R *)-4-(3,4-dichlorobenzyl)-2,5-dimethylpiperazinyl}-2- hydroxypropoxy}phenyl)acetamide, ~ N-(5-Chloro-2-{3-[(S*R *)-4-(4-chlorobenzyl)-2,5-dimethylpiperazinyl]-2- : hydroxypropoxy} phenyl)acetamide, 1-(5-Chloro-2-{3-[4-(4-chlorobenzoyl)- 1-piperazinyl}-2-hydroxypropoxy} phenyl)-1- ethanone, N-(5-Cyano-2-{3-[(S*R*)-4-(3,4-dichlorobenzyl)-2,5-dimethylpiperazinyl]-2- hydroxypropoxy} phenyl)acetamide, . N=(2-{3-[(S*R *)-4-(4-Chlorobenzyl)-2,5-dimethylpiperazinyl}-2-hydroxypropoxy} -5- cyanophenyl)acetamide, - N-(5-Chloro-2-{3-[4-(4-chlorobenzyl)- 1 -piperazinyi]-2-hydroxypropoxy}- phenyl)acetamide, 5 N-(4-Chloro-2-{3-[4-(4-chlorobenzyl)-2,5-dimethyl- 1 -piperazinyl]-2- hydroxypropoxy}phenyl)acetamide, N-(2-{3-[4-(4-Chlorobenzoyl)-1-piperazinyl]-2-hydroxypropoxy} -5- cyanophenyl)acetamide, N-(2-{3-[4-(4-Chlorobenzoyl)-1-piperazinyl]-2-hydroxypropoxy}-4- methylphenyl)acetamide, N-[5-Chloro-2-({(1R,2S,3R)-3-[(3S)-3~(4-chlorophenoxy)pyrrolidinyl]-2- hydroxycyclopentyl}oxy)phenyljacetamide, N-{2-[(2S)~(3-{(3S)-3-[(4-Chlorophenyl)oxy]-1-pyrrolidinyl } -2-hydroxypropyl)oxy]- 4-fluorophenyl }acetamide, N-[2-({(2S5)-3-[(3S)-3-(4-Chlorobenzyl)pyrrolidinyl]-2- : ’ hydroxypropyl}oxy)phenyllacetamide hydrochloride, N~(5-Chloro-2- {3-[3-(4-chloro-benzyl)-pyrrolidin- 1 -yl]-2-hydroxy-propoxy} -phenyl)- acetamide trifluoroacetic acid salt, N=(2-{3-[3-(4~Chlorophenoxy)-1-pyrrolidiny1]-2-hydroxypropoxy } -4-methyl phenyl)- 1-pyrrolidinecarboxamide trifluoroacetate,
    N-(2-{3-[3-(4-Chlorophenoxy)-1-pyrrolidinyl}-2-hydroxypropoxy}-4- . hydroxyphenyl)acetamide trifluoroacetate, N-[2-({(28)-3-[4-(3,4-Dichlorophenoxy)-1 -piperidinyl}-2-hydroxypropyl} oxy)-4- ) fluorophenyl]acetamide trifluoroacetic acid salt, N-(2-(3~(4-Chloro-phenoxy)-pyrrolidin-1-yl)-2-hydroxy-propoxy)-4,6-difluoro- phenyl)-acetamide hydrochloride, N-[2-({(25)-3-[(2S,4S)-4-(4-Chlorophenoxy)-2-methylpyrrolidinyl]-2- hydroxypropyl} oxy)-4-fluorophenyljacetamide trifluoroacetic acid salt, N-[2-({(28)-3-[(3R)-3-(4-Chlorobenzyl)pyrrolidinyl]-2- hydroxypropyl}oxy)phenyl]acetamide hydrochloride, N-{2-[(2R)- (3-{(3S)-3-[(4-Chlorophenyl)oxy]-1-pyrrolidinyl}-2-hydroxypropyl)oxy]- 4-fluorophenyl} acetamide, N-[2+({(2S)-3-[(2R,4S)-4~(4-Chlorophenoxy)-2-methylpyrrolidinyl]-2- hydroxypropyl} oxy) phenyljacetamide trifluoroacetic acid salt, N-{2-[(28)~(3-{(3R)-3-[(4-Chlorophenyl)oxy]-1-pyrrolidinyl}-2-hydroxypropyl)oxy]- 4-fluorophenyl} acetamide, N'-(2-{3-[3-(4-Chlorophenoxy)- 1 -pyrrolidinyl]-2-hydroxypropoxy} -4-methylphenyl)- N,N-dimethylurea trifluoroacetate, N-(2- {3-[3~(4-Chloroanilino)-1-pyrrolidinyl]-2-hydroxypropoxy} phenyl)acetamide, N-{2-[(3-{3-[(4-Chlorophenyl)oxy]-1-pyrrolidinyl}-2-hydroxy-1- methylpropyl)oxy]phenyl} acetamide hydrochloride, N-(2-{3-[3-(4-Chlorophenoxy)-1-pyrrolidinyl}-2-hydroxypropoxy} -4- methoxyphenyl)acetamide hydrochloride, N-(2-[3-(4-Chloro-benzyloxy)-pyrrolidin-1 -yl]-2-hydroxy-propoxy)-phenyl)- 2s acetamide trifluoroacetic acid salt, ’ N-(2-{3-[3-(4-Chloro-phenoxy)-pyrrolidin-1-yl]-2-hydroxy-2-methyl-propoxy}- phenyl)-acetamide, N-(2-{(15,2R,38)"-3-[(3S)-3-(3,4-Difluoro-phenoxy)-pyrrolidin-1-yl]-2-hydroxy- cyclopentyloxy}-5-chloro-phenyl)-acetamide (diastereomeric mixture),
    N-[2-({(2R,38) *-3-[(3S)-3-(4-Chlorophenoxy)pyrrolidinyl]-2-hydroxybutyl} oxy)-+- . methylphenyl]acetamide (diastereomeric mixture), N-{2-[(3-{4-[(3,4-Dichlorophenyl)oxy]-1-piperidinyl}-2-hydroxy-2- methylpropyl)oxy]-4-fluorophenyl} acetamide hydrochloride, N-(2-{(1 S.2R 38)"-3-[(3S)- 3-(4-Chloro-phenoxy)-pyrrolidin- 1-y1]-2-hydroxy- cyclopentyloxy} _4-fluoro-phenyl)-acetamide (diastereomeric mixture), N-(5-Chloro-2- {3-[3-(3,4-difluoro-phenoxy)-pyrrolidin-1-yl}-2-hydroxy-propoxys}- phenyl)-acetamide, N-(5-Chloro-2-{3-[3-(4-fluoro-phenoxy)-pyrrolidin- 1 -yl}-2-hydroxy-propoxy}- phenyl)-acetamide, N-(4-Cyano-2-{3-[4-(3,4-dichloroanilino)- 1-piperidinyi]-2- hydroxypropoxy} phenyl)acetamide, N-(4-Hydroxy-2-{(1S,2R,35)"-3-[(3S)-3-(4-chloro-phenoxy)-pyrrolidin-1-yI]-2- hydroxy-cyclopentyloxy } -phenyl)-acetamide (diastereomeric mixture), I N-(4-Hydroxy-2-{(15,2R,35)-3-[(35)-3-(4-chloro-phenoxy)-pyrrolidin-1-yl]-2- hydroxy-cyclopentyloxy } -phenyl)-acetamide, N-(4-Hydroxy-2-{(1R,25,3R)-3-[(3S)-3-(4-chloro-phenoxy)-pyrrolidin-1-yl]-2- hydroxy-cyclopentyloxy} -phenyl)-acetamide, N-[2-({(15,2R,35)-3-[(35)-3 -(4-Chlorophenoxy)pyrrolidiny1]-2- hydroxycyclopentyl}oxy)phenyl]acetamide, N-12-({(1R,2S,3R)-3-[(35)-3-(4-Chlorophenoxy)pyrrolidiny1]-2- hydroxycyclopentyl}oxy)phenyl]acetamide, N-[5-Chloro-2-({(1S5,2R,38)-3-[(3S5)-3-(4-chlorophenoxy)pyrrolidinyl]-2- hydroxycyclopentyl} oxy)phenyljacetamide, N-{5-Chloro-2-[((15,2R,3S)"-3-{[1-(4-chlorobenzyl)-4-piperidinyl Jamino}-2- hydroxycyclopentyl)oxy]phenyl} acetamide (racemic mixture), and N-[2-({(2)-3-[(35)-3-(4-Chlorophenoxy)pyrrolidinyl]-2-hydroxypropyl } oxy)-4- hydroxyphenyl]acetamide.
    8. A process for the preparation of a compound of formula (I') as defined in claim . which comprises, (a) reacting a compound of general formula ) R-H (I wherein R is as defined in formula (I'), with a compound of general formula oR gq RY R° (IIr") wherein Q, R?, RY, R>, RS, rR’ and R® are as defined in formula (I'); or (b) reacting a compound of general formula RU o RW Raw .. wherein R, R*, R>, RS, R’ and RS are as defined in formula (I'), with a compound of general formula L'- Q- R? (Vv) wherein L' represents a hydrogen atom or an activating group and Q and R? are as defined in formula (I); and optionally thereafter converting the compound of formula (I') to a further compound of formula (I'); and, if desired, forming a pharmaceutically acceptable salt or solvate of the compound of formula (I').
    9. A pharmaceutical composition comprising a compound of formula (I'), or a pharmaceutically acceptable salt or solvate thereof, as claimed in any one of claims 1 to 7 2s in association with a pharmaceutically acceptable adjuvant, diluent or carrier.
    10. A process for the preparation of a pharmaceutical composition as claimed in claim 9 : which comprises mixing a compound of formula (I'), or a pharmaceutically acceptable salt or solvate thereof, as claimed in any one of claims 1 to 7 with a pharmaceutically acceptable adjuvant, diluent or carrier.
    11. A compound of formula (I), or a pharmaceutically-acceptable salt or solvate thereof, as claimed in any one of claims 1 to 7 for use in therapy.
    12. Use of a compound of formula (I'), or a pharmaceutically acceptable salt or solvate ‘10 thereof, as claimed in any one of claims 1 to 7 in the manufacture of a medicament for use in therapy.
    +. 13. Use of a compound of formula (I'), or a pharmaceutically acceptable salt or solvate thereof, as claimed in any one of claims 1 to 7 in the manufacture of a medicament for the 1s treatment of human diseases or conditions in which modulation of chemokine receptor activity is beneficial.
    14. Use of a compound of formula (I), or a pharmaceutically acceptable salt or solvate thereof, as claimed in any one of claims 1 to 7 in the manufacture of a medicament for use in treating rheumatoid arthritis.
    15. Use of a compound of formula (I'), or a pharmaceutically acceptable salt or solvate thereof, as claimed in any one of claims 1 to 7 in the manufacture of a medicament for use in treating chronic obstructive pulmonary disease.
    . 16. Use of a compound of formula (I'), or a pharmaceutically acceptable salt or solvate thereof, as claimed in any one of claims 1 to 7 in the manufacture of a medicament for use } in treating asthma.
    ] 184 PCT/SE01/00403
    17. Use of a compound of formula (I’), or a pharmaceutically acceptable salt or solvate thereof, as claimed in any one of claims 1 to 7 in the manufacture of a medicament for use in treating multiple sclerosis.
    18. © Use of a compound of formula (I’), or a pharmaceutically acceptable salt or solvate thereof, as claimed in any one of claims 1 to 7 in the manufacture of a medicament for treating an inflammatory disease in a patient suffering from, or at risk of, said disease.
    19. Use of a compound of formula (I’), or a pharmaceutically acceptable salt or solvate thereof, as claimed in any one of claims 1 to 7 in the manufacture of a medicament for treating an airways disease in a patient suffering from, or at risk of, said disease.
    20. A substance or composition for use in a method for the treatment of human diseases or conditions in which modulation of chemokine receptor activity is beneficial, said substance or composition comprising a compound of formula (I’), or a pharmaceutically acceptable salt or solvate thereof, as claimed in any one of claims 1 to 7, and said method comprising administering said substance or composition.
    21. A substance or composition for use in a method of treating rheumatoid arthritis, said substance or composition comprising a compound of formula I’), or a pharmaceutically acceptable salt or solvate thereof, as claimed in any one of claims 1 to 7, and said method comprising administering said substance or composition. © 22. A substance or composition for use in a method of treating chronic obstructive pulmonary disease, said substance or composition comprising a compound of formula (I’), or a pharmaceutically acceptable salt or solvate thereof, as claimed in any one of claims 1 to 7, and said method comprising administering said substance or composition. AMENDED SHEET
    ] 185 PCT/SE01/00403
    23. A substance or composition for use in a method of treating asthma, said substance or composition comprising a compound of formula (I’), or a pharmaceutically acceptable salt or solvate thereof, as claimed in any one of claims 1 to 7, and said method comprising administering said substance or composition.
    24. A substance or composition for use in a method of treating multiple sclerosis, said substance or composition comprising a compound of formula (I’), or a pharmaceutically acceptable salt or solvate thereof, as claimed in any one of claims 1 to 7, and said method comprising administering said substance or composition.
    25. A substance or composition for use in a method of treating an inflammatory disease in a patient suffering from, or at risk of, said disease, said substance or composition comprising a compound of formula (I’), or a pharmaceutically acceptable salt or solvate thereof, as claimed in any one of claims 1 to 7, and said method comprising administering a therapeutically effective amount of said substance or composition to the patient.
    26. A substance or composition for use in a method of treating an airways disease in a patient suffering from, or at risk of, said disease, said substance or composition comprising a compound of formula (I’), or a pharmaceutically acceptable salt or solvate thereof, as claimed in any one of claims 1 to 7, and said method comprising administering a therapeutically effective amount of said substance or composition to the patient.
    27. A compound according to any one of claims 1 to 7, or 11, substantially as herein described and illustrated.
    28. A process according to claim 8, substantially as herein described and illustrated.
    29. A composition according to claim 9, substantially as herein described and illustrated. AMENDED SHEET
    186 PCT/SE01/00403
    30. A process according to claim 10, substantially as herein described and illustrated.
    31. Use according to any one of claims 12 to 19, substantially as herein described and illustrated.
    32. A substance or composition for use in a method of treatment according to any one of claims 11 or 20 to 26, substantially as herein described and illustrated.
    33. A new compound, a new process for the preparation of a compound, a new composition, a new process for the preparation of a composition, a new use of a compound as claimed in any one of claims 1 to 7, or a substance or composition for a new use in a method of treatment, substantially as herein described. AMENDED SHEET
ZA200206665A 2000-02-25 2002-08-20 Novel Compounds. ZA200206665B (en)

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