1. A compound of formula (I),
or a pharmaceutically suitable salt or prodrug thereof wherein
– – – is absent or is a bond;
m, n are each independently 0, 1 or 2;
p is 1 or 2;
q and r are each independently 0 or 1;
s is 0, 1, 2, 3, or 4;
R1 is selected from the group consisting of alkyl, alkoxyalkyl, alkylcarbonyl, cyano, cyanoalkyl, halo, haloalkyl, R4O2C\u2014, RcRdNC(O)\u2014, and RcRdNS(O)2\u2014;
R2 is selected from the group consisting of aryl, cycloalkyl, heteroaryl, heterocycle, \u2014O(Rh), and ReRfN\u2014;
R3 is selected from the group consisting of alkyl, alkoxyalkyl, haloalkyl, hydroxyalkyl, R5\u2014C(O)\u2014, R5\u2014C(\u2550N\u2014ORp)\u2014, R6OC(O)\u2014, RgRjNC(O)\u2014, R5\u2014S(O)2\u2014, and RgRjNS(O)2\u2014;
R4 is selected from the group consisting of alkyl, arylalkyl, haloalkyl, heteroarylalkyl, and heterocyclealkyl;
R5, at each occurrence, is selected from the group consisting of alkyl, alkoxyalkyl, aryl, cycloalkyl, haloalkyl, heteroaryl, and heterocycle;
R6 is selected from the group consisting of alkyl, arylalkyl, haloalkyl, cycloalkyl, cycloalkylalkyl, heterocyclealkyl, and heteroarylalkyl;
Rc and Rd, at each occurrence, are each independently selected from the group consisting of hydrogen and alkyl, or Rc and Rd together with the nitrogen atom to which they are attached form a heterocyclic ring;
Re is selected from the group consisting of hydrogen, alkyl, cycloalkyl, and alkylcarbonyl;
Rf is selected from the group consisting of hydrogen and alkyl;
Rg, at each occurrence, is independently selected from the group consisting of hydrogen, alkyl, arylalkyl, cycloalkyl, cycloalkylalkyl, haloalkyl, hydroxyalkyl, alkoxyalkyl, haloalkoxyalkyl, heteroarylalkyl, heterocyclealkyl, and heterocyclealkyl;
Rj, at each occurrence, is independently selected from the group consisting of hydrogen, alkyl, and haloalkyl;
Rh is a cycloalkyl ring optionally substituted with 1, 2, 3, 4, 5, or 6 substituents independently selected from the group consisting of alkyl, alkenyl, alkynyl, halogen, hydroxy, alkoxy, haloalkyl, arylalkyl, heteroarylalkyl, cycloalkyl, and heterocyclealkyl; and
Rp is selected from the group consisting of hydrogen and alkyl.
2. The compound according to claim 1, or a pharmaceutically acceptable salt or prodrug thereof, wherein
m is 0;
n is 1;
p is 1;
q is ;
r is 0; and
– – – is absent.
3. The compound according to claim 2, or a pharmaceutically acceptable salt or prodrug thereof, wherein R3 is R5\u2014C(O)\u2014.
4. The compound according to claim 3, or a pharmaceutically acceptable salt or prodrug thereof, wherein R2 is selected from the group consisting of aryl, cycloalkyl, and heteroaryl.
5. The compound according to claim 3, or a pharmaceutically acceptable salt or prodrug thereof, wherein R2 is selected from the group consisting of \u2014O(Rh) and ReRfN\u2014.
6. The compound according to claim 2, or a pharmaceutically acceptable salt or prodrug thereof, wherein R3 is R6OC(O)\u2014.
7. The compound according to claim 6, or a pharmaceutically acceptable salt or prodrug thereof, wherein R2 is selected from the group consisting of aryl, cycloalkyl, and heteroaryl.
8. The compound according to claim 6, or a pharmaceutically acceptable salt or prodrug thereof, wherein R2 is selected from the group consisting of \u2014O(Rh) and ReRfN\u2014.
9. The compound according to claim 2, or a pharmaceutically acceptable salt or prodrug thereof, wherein R3 is RgRjNC(O)\u2014.
10. The compound according to claim 9, or a pharmaceutically acceptable salt or prodrug thereof, wherein R2 is selected from the group consisting of aryl, cycloalkyl, and heteroaryl.
11. The compound according to claim 9, or a pharmaceutically acceptable salt or prodrug thereof, wherein R2 is selected from the group consisting of \u2014O(Rh) and ReRfN\u2014.
12. The compound according to claim 1, or a pharmaceutically acceptable salt or prodrug thereof, wherein
m is 1;
n is 0;
p is 1;
q is 0;
r is 0; and
– – – is absent.
13. The compound according to claim 12, or a pharmaceutically acceptable salt or prodrug thereof, wherein R3 is R5\u2014C(O)\u2014.
14. The compound according to claim 13, or a pharmaceutically acceptable salt or prodrug thereof, wherein R2 is selected from the group consisting of aryl, cycloalkyl, and heteroaryl.
15. The compound according to claim 13, or a pharmaceutically acceptable salt or prodrug thereof, wherein R2 is selected from the group consisting of \u2014O(Rh) and ReRfN\u2014.
16. The compound according to claim 12, or a pharmaceutically acceptable salt or prodrug thereof, wherein R3 is R6OC(O)\u2014.
17. The compound according to claim 16, or a pharmaceutically acceptable salt or prodrug thereof, wherein R2 is selected from the group consisting of aryl, cycloalkyl, and heteroaryl.
18. The compound according to claim 16, or a pharmaceutically acceptable salt or prodrug thereof, wherein R2 is selected from the group consisting of \u2014O(Rh) and ReRfN\u2014.
19. The compound according to claim 12, or a pharmaceutically acceptable salt or prodrug thereof, wherein R3 is RgRjNC(O)\u2014.
20. The compound according to claim 19, or a pharmaceutically acceptable salt or prodrug thereof, wherein R2 is selected from the group consisting of aryl, cycloalkyl, and heteroaryl.
21. The compound according to claim 19, or a pharmaceutically acceptable salt or prodrug thereof, wherein R2 is selected from the group consisting of \u2014O(Rh) and ReRfN\u2014.
22. The compound according to claim 1 or a pharmaceutically acceptable salt or prodrug thereof, selected from the group consisting of
ethyl 2-{(2,2,3,3-tetramethylcyclopropyl)carbonylamino}-5,6,7,8-tetrahydro-4H-5,8-epoxycycloheptabthiophene-3-carboxylate;
ethyl 2-{2-fluoro-6-(trifluoromethyl)benzoylamino}-5,6,7,8-tetrahydro-4H-5,8-epoxycycloheptabthiophene-3-carboxylate;
ethyl 2-(hexahydro-2,5-methanopentalen-3a(1H)-ylcarbonyl)amino-5,6,7,8-tetrahydro-4H-5,8-epoxycycloheptabthiophene-3-carboxylate;
N-{3-(3,3-difluoroazetidin-1-yl)carbonyl-5,6,7,8-tetrahydro-4H-5,8-epoxycycloheptabthien-2-yl}-2-fluoro-6-(trifluoromethyl)benzamide;
N-3-(azetidin-1-ylcarbonyl)-5,6,7,8-tetrahydro-4H-5,8-epoxycycloheptabthien-2-yl-2-fluoro-6-(trifluoromethyl)benzamide;
2-fluoro-N-{3-(3-methoxyazetidin-1-yl)carbonyl-5,6,7,8-tetrahydro-4H-5,8-epoxycycloheptabthien-2-yl}-6-(trifluoromethyl)benzamide;
2-{2-fluoro-6-(trifluoromethyl)benzoyl amino}-N-propyl-5,6,7,8-tetrahydro-4H-5,8-epoxycycloheptabthiophene-3-carboxamide;
N-3-(cyclobutylcarbonyl)-5,6,7,8-tetrahydro-4H-5,8-epoxycycloheptabthien-2-yl-2-fluoro-6-(trifluoromethyl)benzamide;
N-cyclobutyl-2-{2-fluoro-6-(trifluoromethyl)benzoylamino}-5,6,7,8-tetrahydro-4H-5,8-epoxycycloheptabthiophene-3-carboxamide;
N-cyclopentyl-2-{2-fluoro-6-(trifluoromethyl)benzoylamino}-5,6,7,8-tetrahydro-4H-5,8-epoxycycloheptabthiophene-3-carboxamide;
2-{2-fluoro-6-(trifluoromethyl)benzoylamino}-N-(2-methoxyethyl)-5,6,7,8-tetrahydro-4H-5,8-epoxycycloheptabthiophene-3-carboxamide;
2-{2-fluoro-6-(trifluoromethyl)benzoylamino}-N-(2,2,2-trifluoroethyl)-5,6,7,8-tetrahydro-4H-5,8-epoxycycloheptabthiophene-3-carboxamide;
2-{2-fluoro-6-(trifluoromethyl)benzoylamino}-N-(2R)-tetrahydro furan-2-ylmethyl-5,6,7,8-tetrahydro-4H-5,8-epoxycycloheptabthiophene-3-carboxamide;
2-{2-fluoro-6-(trifluoromethyl)benzoylamino}-N-(2S)-tetrahydrofuran-2-ylmethyl-5,6,7,8-tetrahydro-4H-5,8-epoxycycloheptabthiophene-3-carboxamide;
2-fluoro-N-3-(2-furoyl)-5,6,7,8-tetrahydro-4H-5,8-epoxycycloheptabthien-2-yl-6-(trifluoromethyl)benzamide;
N-3-(cyclobutylcarbonyl)-5,6,7,8-tetrahydro-4H-5,8-epoxycycloheptabthien-2-yl-N\u2032-(1,1-dimethylpropyl)urea;
N-3-(cyclobutylcarbonyl)-5,6,7,8-tetrahydro-4H-5,8-epoxycycloheptabthien-2-yl-N\u2032-cyclopentylurea;
N-3-(cyclobutylcarbonyl)-5,6,7,8-tetrahydro-4H-5,8-epoxycycloheptabthien-2-yl-N\u2032-(1,2,2-trimethylpropyl)urea;
ethyl 2-{2-fluoro-6-(trifluoromethyl)benzoylamino}-5,6,7,8-tetrahydro-4H-4,7-epoxycycloheptabthiophene-3-carboxylate;
N-3-(cyclobutylcarbonyl)-5,6,7,8-tetrahydro-4H-5,8-epoxycycloheptabthien-2-yl-N\u2032-(1,2-dimethylpropyl)urea;
ethyl 2-(hexahydro-2,5-methanopentalen-3a(1H)-ylcarbonyl)amino-5,6,7,8-tetrahydro-4H-4,7-epoxycycloheptabthiophene-3-carboxylate;
N-{3-(3,3-difluoroazetidin-1-yl)carbonyl-5,6,7,8-tetrahydro-4H-4,7-epoxycycloheptabthien-2-yl}-2-fluoro-6-(trifluoromethyl)benzamide;
2-{2-fluoro-6-(trifluoromethyl)benzoylamino}-N-propyl-5,6,7,8-tetrahydro-4H-4,7-epoxycycloheptabthiophene-3-carboxamide;
N-{3-(3,3-difluoroazetidin-1-yl)carbonyl-5,6,7,8-tetrahydro-4H-4,7-epoxycycloheptabthien-2-yl}hexahydro-2,5-methanopentalene-3a(1H)-carboxamide;
ethyl 2-({(1R,2S,5R)-2-isopropyl-5-methylcyclohexyloxy}carbonyl)amino-5,6,7,8-tetrahydro-4H-5,8-epoxycycloheptabthiophene-3-carboxylate;
ethyl 2-{5-chloro-2-(trifluoromethyl)benzoylamino}-5,6,7,8-tetrahydro-4H-5,8-epoxycycloheptabthiophene-3-carboxylate;
ethyl 2-{3-chloro-2-fluoro-6-(trifluoromethyl)benzoylamino }-5,6,7,8-tetrahydro-4H-5,8-epoxycycloheptabthiophene-3-carboxylate;
2-(hexahydro-2,5-methanopentalen-3a(1H)-ylcarbonyl)amino-N-propyl-5,6,7,8-tetrahydro-4H-4,7-epoxycycloheptabthiophene-3-carboxamide;
2-(hexahydro-2,5-methanopentalen-3a(1H)-ylcarbonyl)amino-N-(3,3,3-trifluoropropyl)-5,6,7,8-tetrahydro-4H-4,7-epoxycycloheptabthiophene-3-carboxamide;
ethyl 2-(isoquinolin-1-ylcarbonyl)amino-5,6,7,8-tetrahydro-4H-5,8-epoxycycloheptabthiophene-3-carboxylate;
2-{2-fluoro-6-(trifluoromethyl)benzoylamino}-N-(3,3,3-trifluoropropyl)-5,6,7,8-tetrahydro-4H-5,8-epoxycycloheptabthiophene-3-carboxamide;
N-ethyl-2-{2-fluoro-6-(trifluoromethyl)benzoylamino}-5,6,7,8-tetrahydro-4H-5,8-epoxycycloheptabthiophene-3-carboxamide;
N-cyclopentyl-2-{2-fluoro-6-(trifluoromethyl)benzoylamino}-5,6,7,8-tetrahydro-4H-4,7-epoxycycloheptabthiophene-3-carboxamide;
propyl 2-{2-fluoro-6-(trifluoromethyl)benzoylamino}-5,6,7,8-tetrahydro-4H-5,8-epoxycycloheptabthiophene-3-carboxylate;
2-{2-fluoro-6-(trifluoromethyl)benzoylamino}-N,N-dimethyl-5,6,7,8-tetrahydro-4H-5,8-epoxycycloheptabthiophene-3-carboxamide;
N-{3-(3-methoxyazetidin-1-yl)carbonyl-5,6,7,8-tetrahydro-4H-4,7-epoxycycloheptabthien-2-yl}hexahydro-2,5-methanopentalene-3a(1H)-carboxamide;
ethyl 2-({(1R,2S,5R)-5-methyl-2-(1-methyl-1-phenylethyl)cyclohexyloxy}-carbonyl)amino-5,6,7,8-tetrahydro-4H-5,8-epoxycycloheptabthiophene-3-carboxylate;
propyl 2-{2-(trifluoromethyl)benzoylamino}-5,6,7,8-tetrahydro-4H-5,8-epoxycycloheptabthiophene-3-carboxylate; and
ethyl 2-{2-(trifluoromethyl)benzoylamino}-5,6,7,8-tetrahydro-4H-5,8-epoxycycloheptabthiophene-3-carboxylate.
23. A pharmaceutical composition comprising a therapeutically effective amount of a compound of formula (I) according to claim 1, or a pharmaceutically acceptable salt thereof, in combination with a pharmaceutically acceptable carrier.
24. A method for treating pain in a mammal in need thereof comprising administering to the mammal a therapeutically effective amount of a compound of formula (I) according to claim 1, or a pharmaceutically acceptable salt thereof.
25. A method for treating nociceptive pain in a mammal in need thereof comprising administering to the mammal a therapeutically effective amount of a compound of formula (I) according to claim 1, or a pharmaceutically acceptable salt thereof.
26. A method for treating neuropathic pain in a mammal in need thereof comprising administering to the mammal a therapeutically effective amount of a compound of formula (I) according to claim 1, or a pharmaceutically acceptable salt thereof.
27. A method for treating a disorder selected from the group consisting of inflammatory disorders, immune disorders, neurological disorders, cancers of the immune system, respiratory disorders, and cardiovascular disorders in a mammal in need thereof, comprising administering to the mammal a therapeutically effective amount of a compound of formula (I) according to claim 1, or a pharmaceutically acceptable salt thereof.
28. A method for providing neuroprotection in a mammal in need thereof comprising administering to the mammal a therapeutically effective amount of a compound of formula (I) according to claim 1, or a pharmaceutically acceptable salt thereof.
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 method for welding a steel pipe comprising:
introducing a forming body into an inner space of a steel pipe to be welded, wherein the forming body sealingly acts as a gas barrier for the temporary internal sealing of a flow cross section of the steel pipe,
welding the steel pipe under protective gas, wherein the steel pipe is sealed by the forming body during welding;
after welding, introducing a liquid into contact with the inner space of the steel pipe; and
dissolving the forming body as a result of contact with the liquid,
wherein the forming body is composed of a biologically degradable material the main constituent of which is corn starch andor corn semolina andor corn flakes and which has a water solubility of \u226790% and which yields an ash content of 0.29% during incineration according to DIN 51719 and a pH value of 6.6 when dissolved in fully demineralized water,
wherein the forming body, already in its initial state as produced, has a cylindrical shape and size that is adapted to the inner space of the steel pipe to ensure a reliable sealing of the inner space of the steel pipe during welding and has an edge region with a chamfer which is formed in the transitional region between an end face and a longitudinal side face of the forming body and wherein the forming body is dimensionally stable, pressure-stable, and temperature-stable so that its shape does not change when pressure and an increased temperature during welding are applied, and
when the forming body is introduced into the inner space of the steel pipe and is positioned at the desired location inside the steel pipe by means of an elongated, cylindrical introduction tool which presses onto an end face of the forming body when the forming body is pressed into the inner space of the steel pipe by means of the introduction tool, wherein the forming body is in contact with its outer circumferential face extensively against an inner circumferential face of the steel pipe.
2. The method of claim 1, wherein the steel pipe is in a membrane wall of a steam boiler of a power plant.