1-58. (Cancelled)
59. A compound of formula
wherein,
A is selected from the group of H, halogen, CN, N3, NR12, NR1S(O)2R2, OR3, SR3, lower alkyl, C(O)N(R4)2, guanidine, amidine, R1NR2, NR1OR4, and perhaloalkyl;
Q is selected from the group of C1-C6 alkyl, C3-C10 cycloalkyl, arylalkyl, aryl, heteroaryl, and C2-C8 heterocyclic, all optionally substituted;
X is S, or S(O)2;
Y is selected from the group of C(O)R2, S(O)2R2, C(O)NR42, and C(O)OR2, optionally substituted C2-C8 alkyl, optionally substituted C2-C8 alkenyl, optionally substituted C2-C8 alkynyl, optionally substituted aryl, optionally substituted alicyclic, optionally substituted araalkyl, optionally substituted aryloxyalkyl, optionally substituted alkoxyalkyl, optionally substituted dioxolane, alkylaminoalkyl, optionally substituted alkylcarbonylaminoalkyl, (\u2014(CH2)n, \u2014C(O)\u2014NR4\u2014(CH2)N), optionally substituted alkylcarbonyloxylalkyl (\u2014(CH2)n\u2014C(O)\u2014O(CH2)n), C1-C6 hydroxyalkyl, C1-C6 haloalkyl and C1-C6 perhaloalkyl;
Z is selected from the group of H, halogen, CN, OR3 SR3, C1-C6 perhaloalkyl, optionally substituted C1-C6 alkyl, optionally substituted C2-C6 alkenyl, optionally substituted C2-C6 alkynyl, optionally substituted aryl, optionally substituted alicyclic, optionally substituted araalkyl, optionally substituted aryloxyalkyl, optionally substituted alkoxyalkyl, optionally substituted heterocyclic, C(O)R2, \u2014S(O)2R2, guanidine, amidine, and C(O)NR42;
R1 is independently selected from the group of H, optionally substituted C1-C6 alkyl, optionally substituted C3-C10 cycloalkyl, optionally substituted C1-C6 heteroalkyl, optionally substituted aryl, optionally substituted heterocyclic, C(O)R2, C(O)OR2, C(O)NR42, C(S)OR2, C(S)NR42, PO3R4, and SO2R2;
R2 is independently selected from the group of C1-C6 alkyl, heteroaryl, C3-C10 cycloalkyl, heterocyclic, heteroaryl, and aryl, all optionally substituted;
R3 is independently selected from the group of H, optionally substituted C1-C6 alkyl, optionally substituted C3-C10 cycloalkyl, optionally C1-C6 substituted heteroalkyl, optionally substituted aryl, optionally substituted heterocyclic and C(O)NR42;
R4 is independently selected from the group of H, optionally substituted C1-C6 alkyl, optionally substituted C3-C10 cycloalkyl, optionally substituted C1-C6 heteroalkyl, optionally substituted aryl, and optionally substituted heterocyclic;
n is 1, 2 or 3;
or a tautomer or pharmaceutically acceptable salt or ester thereof.
60. A compound according to claim 1 wherein Q is a member selected from the group of:
wherein:
L is O, S or NR1;
each R6 is independently selected from the group of H, optionally substitute C1-C6 alkyl, OR3, SR3, NHR3, C(O)N(R4)2, OR5, NO2, CN, halogen, and S(O)2R2;
R5 is selected from the group of H, OH, and optionally substituted C1-C6 alkyl;
n is from 1, 2 or 3;
or a tautomer or a pharmaceutically acceptable salt or ester thereof.
61. A compound according to claim 59, wherein A is selected from the group of H, halogen, NR12, OR3, SR3, optionally substituted C1-C6 alkyl, and C(O)N(R4)2.
62. A compound according to claim 59, wherein Z is selected from the group of H, halogen, CN, OR3, SR3, optionally substituted C1-C6 perhaloalkyl, optionally substituted C1-C6 alkyl, optionally substituted C2-C6 alkenyl, optionally substituted C2-C6 alkynyl, and optionally substituted aryl.
63. A compound according to claim 59, wherein X is selected from S and S(O).
64. A compound according to claim 59, wherein Y is selected from the group of optionally substituted C2-C6 alkyl, optionally substituted C2-C6 alkenyl, optionally substituted C2-C6 alkynyl, optionally substituted aryl, and optionally substituted C3-C8 carbocyclic.
65. A compound according to claim 59, wherein Q is further selected from optionally substituted aryl and optionally substituted heteroaryl.
66. A compound according to claim 60, wherein:
X is S;
A is selected from the group of Cl, NH2, and CH3;
Z is selected from the group of H, F, Cl, Br and CF3; and
Y is selected from the group of optionally substituted C3-C8 alkyl, optionally substituted C3-C8 alkenyl, optionally substituted C3-C8 alkynyl, optionally substituted C6-C10 aryl, and optionally substituted C3-C10 alicyclic.
67. A compound according to claim 66, wherein A is NH2; Z is selected from the group of H, Cl and F; Y is selected from the group of \u2014(CH2)2CH\u2550C(CH3)2, \u2014(CH2)3CCH; \u2014(CH2)4Br, \u2014(CH2)4Cl, \u2014(CH2)4OAc, \u2014(CH2)4NHEt, \u2014(CH2)4OH, \u2014(CH2)5Br, \u2014(CH2)5Cl, \u2014(CH2)5OAc, \u2014(CH2)2\u2014O(CH)(CH3)2, and \u2014(CH2)5OH; and Q is selected from the group of 2,5-dimethoxyphenyl, 2-iodo-5-methoxyphenyl, 4-iodo-5-methoxyphenyl, 2-iodo-4-fluoro-5-methoxyphenyl, 2-bromo-5-methoxyphenyl, 2-chloro-5-methoxyphenyl, 2,4-diiodo-5-methoxyphenyl, 2-iodo-4-bromo-5-methoxyphenyl, 2-iodo-4-chloro-5-methoxyphenyl, and 2-chloro-3,4,5-trimethoxyphenyl.
68. A compound according to claim 59, wherein said compound is selected from the group of:
69. A pharmaceutical composition comprising a compound according to any one of claims 59, 63, 66, 67 and 68, and a pharmaceutically acceptable carrier or excipient.
70. A method of inhibiting an HSP90 comprising contacting a cell having an HSP90 with a compound according to claim 66.
71. A method according to claim 70 wherein said cell is a mammalian cell.
72. A method according to claim 70 wherein said mammalian cell is human.
73. A method according to 70, wherein said method comprises chemotherapy.
74. A method according to claim 73, wherein said chemotherapy is directed against breast cancer cells and melanoma cells.
75. A method for treating an individual having cancer comprising administering to said individual a pharmaceutical composition comprising a compound according to any one of claims 59, 63, 66, 67 and 68.
76. A method according to claim 75, wherein said administration is oral administration.
77. A method according to claim 75, wherein said administration is topical administration.
78. A method according to claim 75, wherein said administration is parenteral administration.
79. A method for treating an individual having a disease or condition selected from the group of inflammation, an infectious disease, an autoimmune disease, ischemia, a fibrogenetic disorder and nerve degeneration comprising administering to said individual a pharmaceutical composition comprising a compound according to any one of claims 59, 63, 66, 67 and 68.
80. A method for treating an individual having cancer comprising administering to said individual a compound according to claim 66 and an antineoplastic agent.
81. A method according to claim 80, wherein said antineoplastic agent is selected from the group of a radioisotope, an antibody, a recombinant protein, Herceptin, taxol, taxane, gleevac, an alkylating agent, anti-metabolite, epidophyllotoxin, an antineoplastic enzyme, a topoisomerase inhibitor, procarbazine, mitoxantrone, a platinum coordination complex, a growth inhibitor, a hormonal therapeutic agent, an anti-hormonal therapeutic agent, a haematopoietic growth factor, an anthracycline drug, a vinca drug, a mitomycin, a bleomycin, a cytotoxic nucleoside, a tepothilone, a discodermolide, a pteridine drug, a diynesne, a podophyllotoxin, carminomycin, daunorubicin, an aminopterin, methotrexate, methopterin, dichloromethotrexate, mitomycin C, porfiromycin, 5-fluorouracil, 6-mercaptopurine, gemcitabine, cytosine arabinoside, podophyllotoxin, a podo-phyllotoxin, etoposide, etoposide phosphate, teniposide, melphalan, vinblastine, vincristine, leurosidine, vindesine, leurosine, paclitaxel, estramustine, carboplatin, cyclophosphamide, bleomycin, gemcitibine, ifosamide, melphalan, hexamethyl melamine, thiotepa, cytarabin, idatrexate, trimetrexate, dacarbazine, L-asparaginase, camptothecin, CPT-11, topotecan, ara-C, bicalutamide, flutamide, leuprolide, a pyrodobenzoindole, an interferon and an interleukin.
82. A method according to claim 80, wherein said administration of said compound is oral administration.
83. A method according to claim 80, wherein said administration of said compound is topical administration.
84. A method according to claim 80, wherein said administration of said compound is parenteral administration.
The claims below are in addition to those above.
All refrences to claim(s) which appear below refer to the numbering after this setence.
1. A coating zone, comprising:
part of a paint booth;
a conveyor for transporting an application object through the coating zone in a conveying direction,
at least one guide rail extending through the coating zone adjacent the conveyor, the at least one guide rail arranged above the conveyor at a height being at least at the level of the top of the object,
at least one robot configured to move along the conveyor on the guide rail, the robot being capable of being configured to perform a coating operation and having a first axis for joint rotation of at least one moving member of the robot in relation to a main body guided along the guide rail, and
a load-bearing structure supporting the at least one guide rail, the load-bearing structure including at least one load-bearing pillar extending substantially vertically downwards from the level of the guide rail,
wherein the guide rail and the main body of the robot are arranged in such a way that the first axis of the robot is inclined relative to a vertical plane parallel to the conveying direction.
2. The coating zone according to claim 1, wherein the angle of inclination of the first axis relative to the vertical plane is approximately 10\xb0.
3. The coating zone according to claim 1, wherein the guide rail is mounted on top of a horizontal support extending horizontally through a side wall of the coating zone and is set back with its end remote from the interior of the zone as far as the vicinity of the side wall.
4. The coating zone according to claim 1, wherein a maximum angle of rotation of the main body about the first axis is greater than 90\xb0.
5. The coating zone according to claim 1, wherein the guide rail is inclined in a vertical plane substantially parallel to the conveying direction relative to a horizontal plane.
6. The coating zone according to claim 5, wherein an angle of inclination of the guide rail and the robot is adjustable in relation to the horizontal plane.
7. The coating zone according to claim 1, comprising
an upper ceiling, through which feed air enters the coating zone, two side walls arranged on opposing sides of the conveyor, which extend from the ceiling downwards as far as a floor level,
a first walk-in control region, which is located at floor level on the outside remote from the conveyor of at least one of the two side walls, and
a second walk-in control region, which is located on the outside of at least one of the two side walls in the vicinity of the guide rail above the first walk-in control region and above the conveyor,
wherein the side wall extends obliquely upwards at the upper walk-in control region with a progressive reduction in the width of the interior of the coating zone.
8. The coating zone according to claim 7, wherein the at least one guide rail is positioned at a guide rail height, the guide rail height being at least as great as an upper end of the lower control region.
9. The coating zone according to claim 1, further comprising:
at least one mutually separate load-bearing structures at least one side of the conveyor configured to provide lateral support of the at least one guide rail,
an upper ceiling, and
two side walls arranged on opposing sides of the conveyor, the two side walls extending from the ceiling downwards to a floor level,
wherein one of the at least one load-bearing structures arranged laterally on a first one of the side wall next to the transport path of the conveyor, leaving the transport path open, is supported at one of on the floor level, under the floor level, and on the ceiling, with supporting elements of the one of the at least one load-bearing structures extending transversely of the transport path.
10. The coating zone according to claim 1, wherein two guide rails for robots are arranged one above the other on at least one side of the conveyor.
11. The coating zone according to claim 1, further comprising at least
one coating robot on at least one of the guide rails, and
at least one add-on unit is displaceable on at least one of the guide rails, the at least one add-on unit including one of a mobile dryer, a probe, and a measuring instrument.
12. The coating zone according to claim 11, wherein an add-on unit and an application device of the coating installation are each displaceable in the zone on one of a common guide rail and their own guide rails.
13. A coating installation having a plurality of coating zones according to claim 1, wherein the individual coating zones are arranged one of one after the other and parallel to one another along a transport path.
14. A coating zone, comprising:
part of a paint booth;
a conveyor for transporting an application object through the coating zone in a conveying direction,
two guide rails, each of the guide rails extending through the coating zone adjacent the conveyor, each of the guide rails arranged above the conveyor at a height being at least at the level of the top of the object,
at least one robot that is capable of being configured to perform a coating operation and that is configured to move along the conveyor on each of the guide rails, the robots each having a first axis for joint rotation of at least one moving member of the robot in relation to a main body guided along the respective guide rail, and
respective load-bearing structures supporting each of the guide rails, each of the load-bearing structures including at least one load-bearing pillar extending substantially vertically downwards from the level of a respective one of the guide rails,
wherein the guide rails and the main bodies of the robots are arranged in such a way that the first axis of each robot is inclined relative to a vertical plane parallel to the conveying direction.
15. The coating zone according to claim 14, wherein the angle of inclination of the first axis of each robot relative to the vertical plane is approximately 10\xb0.
16. The coating zone according to claim 14, wherein the guide rails are each mounted on top of a horizontal support extending horizontally through a side wall of the coating zone and is set back with its end remote from the interior of the zone as far as the vicinity of the side wall.
17. The coating zone according to claim 14, wherein a maximum angle of rotation of the main bodies of each of the robots about their respective first axes are greater than 90\xb0.
18. The coating zone according to claim 14, wherein at least one of the guide rails is inclined in a vertical plane substantially parallel to the conveying direction relative to a horizontal plane.
19. The coating zone according to claim 18, wherein an angle of inclination of the at least one guide rail and the robot associated with the at least one guide rail is adjustable in relation to the horizontal plane.
20. The coating zone according to claim 1, further comprising:
an upper ceiling, through which feed air enters the coating zone,
two side walls arranged on opposing sides of the conveyor, which extend from the ceiling downwards as far as a floor level,
a first walk-in control region, which is located at a floor level on the outside remote from the conveyor of at least one of the two side walls, and
a second walk-in control region, which is located on the outside of the at least one of the two side walls in the vicinity of the guide rail above the first walk-in control region and above the conveyor,
wherein the side wall extends obliquely upwards at the upper walk-in control region with a progressive reduction in the width of the interior of the coating zone.