1,3-thiazol-2-yl substituted benzamides

Abstract

The present invention relates to 1,3-thiazol-2-yl substituted benzamide compounds of general formula (I) as described and defined herein, to pharmaceutical compositions and combinations comprising said compounds and to the use of said compounds for manufacturing a pharmaceutical composition for the treatment or prophylaxis of a disease, in particular of neurogenic disorder, as a sole agent or in combination with other active ingredients.

1 : A compound of general formula (I): 
       
         
           
           
               
               
           
         
         in which 
         R 1  represents a halogen atom, C 1 -C 4 -alkyl or C 3 -C 6 -cycloalkyl, wherein C 1 -C 4 -alkyl is optionally substituted with 1-5 halogen atoms which are the same or different; 
         R 2  represents —C 2 -C 6 -alkyl-OR 4 , —(CH 2 ) q -(C 3 -C 7 -cycloalkyl), —(CH 2 ) q -(6- to 12-membered heterobicycloalkyl), —(CH 2 ) q -(4- to 7-membered heterocycloalkyl), —(CH 2 ) q -(5- to 10-membered heteroaryl) or —C 2 -C 6 -alkynyl; and
 wherein said —(CH 2 ) q -(C 3 -C 7 -cycloalkyl), —(CH 2 ) q -(6- to 12-membered heterobicycloalkyl) and —(CH 2 ) q -(4- to 7-membered heterocycloalkyl) are optionally substituted with one or more substituents which are the same or different, at any ring carbon atom and selected from the group consisting of C 1 -C 4  alkyl, optionally substituted with 1-5 halogen atoms which are the same or different, a halogen atom, —NR a R b , COOR 5  and oxo (═O); and 
 wherein independently any ring nitrogen atom, if present in said —(CH 2 ) q -(6- to 12-membered heterobicycloalkyl) and —(CH 2 ) q -(4- to 7-membered heterocycloalkyl) is substituted with R c ; and 
 wherein said —(CH 2 ) q -(5- to 10-membered heteroaryl) is optionally substituted with one or more substituents which are the same or different, and selected from the group consisting of C 1 -C 4 -alkyl, optionally substituted with 1-5 halogen atoms which are the same or different, a halogen atom, —NR a R b  and —COOR 5 ; 
 
         R 3  represents hydrogen or C 1 -C 4 -alkyl, which is optionally substituted with 1-5 halogen atoms which are the same or different; 
         R 4  and R 5  represent hydrogen or C 1 -C 4 -alkyl; 
         R a  and R b  represent hydrogen or C 1 -C 4 -alkyl; 
         R c  represents hydrogen, C 1 -C 4 -alkyl, optionally substituted with 1-5 halogen atoms which are the same or different, —C(O)O—C 1 -C 4 -alkyl, or —C(O)—C 1 -C 4 -alkyl; 
         A represents 5- to 10-membered heteroaryl which is optionally substituted with one or more substituents, which are the same or different, and selected from the group consisting of a halogen atom, C 1 -C 3 -alkyl, and C 1 -C 3 -alkoxy, wherein C 1 -C 3 -alkyl and C 1 -C 3 -alkoxy are optionally substituted with 1-5 halogen atoms which are the same or different; 
         q represents an integer of 0, 1, or 2; 
         or an isomer, enantiomer, diastereomer, racemate, hydrate, solvate, or a salt thereof, or a mixture of same. 
       
     
     
         2 : A compound according to  claim 1  having general formula (Ia): 
       
         
           
           
               
               
           
         
         in which A, R 1 , R 2  and R 3  have the meanings as defined in  claim 1 , and R 3  preferably represents C 1 -C 4 -alkyl, more preferably methyl. 
       
     
     
         3 : A compound according to  claim 1 , wherein
 A represents an optionally substituted 5- or 6-membered heteroaryl, preferably an optionally substituted 6-membered heteroaryl.   
     
     
         4 : A compound according to  claim 1 , wherein
 R 1  represents C 1 -C 4 -alkyl, preferably methyl or ethyl.   
     
     
         5 : A compound according to  claim 1 , wherein
 R 3  represents C 1 -C 4 -alkyl, preferably methyl.   
     
     
         6 : A compound according to  claim 1 , wherein
 R 2  represents —C 2 -C 3 -alkyl-OR 4 , —CH 2 -(C 3 -C 4 -cycloalkyl), C 3 -C 4 -cycloalkyl, —(CH 2 ) q -(4- to 6-membered heterocycloalkyl), or —C 2 -C 4 -alkynyl; and
 wherein said —CH 2 -(C 3 -C 4 -cycloalkyl), C 3 -C 4 -cycloalkyl and —(CH 2 ) q -(4- to 6-membered heterocycloalkyl) are optionally substituted with one or more substituents which are the same or different, at any ring carbon atom; and 
 wherein independently any ring nitrogen atom, if present in said —(CH 2 ) q -(4- to 6-membered heterocycloalkyl) is substituted with R c ; and 
   q represents an integer of 0.   
     
     
         7 : A compound according to  claim 1 , wherein
 A represents an optionally substituted 5- or 6-membered heteroaryl, preferably an optionally substituted 6-membered heteroaryl; and   R 1  represents C 1 -C 4 -alkyl, preferably methyl or ethyl.   
     
     
         8 : A compound according to  claim 1 , wherein
 A represents an optionally substituted 5- or 6-membered heteroaryl, preferably an optionally substituted 6-membered heteroaryl; and   R 3  represents C 1 -C 4 -alkyl, preferably methyl.   
     
     
         9 : A compound according to  claim 1 , wherein
 A represents an optionally substituted 5- or 6-membered heteroaryl, preferably an optionally substituted 6-membered heteroaryl;   R 1  represents C 1 -C 4 -alkyl, preferably methyl or ethyl; and   R 3  represents C 1 -C 4 -alkyl, preferably methyl.   
     
     
         10 : A compound according to  claim 1 , wherein
 A represents an optionally substituted 5- or 6-membered heteroaryl, preferably an optionally substituted 6-membered heteroaryl;   R 1  represents C 1 -C 4 -alkyl, preferably methyl or ethyl;   R 2  represents —C 2 -C 3 -alkyl-OR 4 , —CH 2 -(C 3 -C 4 -cycloalkyl), C 3 -C 4 -cycloalkyl, —(CH 2 ) q -(4- to 6-membered heterocycloalkyl), or —C 2 -C 4 -alkynyl; and
 wherein said —CH 2 -(C 3 -C 4 -cycloalkyl), C 3 -C 4 -cycloalkyl and —(CH 2 ) q -(4- to 6-membered heterocycloalkyl) are optionally substituted with one or more substituents which are the same or different, at any ring carbon atom; and 
 wherein independently any ring nitrogen atom, if present in said —(CH 2 ) q -(4- to 6-membered heterocycloalkyl) is substituted with R c ; 
   R 3  represents C 1 -C 4 -alkyl, preferably methyl; and   q represents an integer of 0.   
     
     
         11 : A compound according to  claim 1 , wherein
 A represents 5- or 6-membered heteroaryl at least containing one or two nitrogen atom(s), preferably a 6-membered heteroaryl with one or two nitrogen atom(s),   wherein said 5- or 6-membered heteroaryl is optionally substituted one or two times, identically or differently, with a substituent selected from a fluorine or chlorine atom, C 1 -C 2 -alkyl, optionally substituted with 1-5 fluorine atoms, or C 1 -C 2 -alkoxy, optionally substituted with 1-5 fluorine atoms;   R 1  represents methyl or ethyl;   R 2  represents —C 2 -C 3 -alkyl-OR 4 , unsubstituted —CH 2 -(C 3 -C 4 -cycloalkyl), unsubstituted C 3 -C 4 -cycloalkyl, unsubstituted (CH 2 ) q -(4- to 6-membered heterocycloalkyl), or —C 2 -C 4 -alkynyl;   q represents an integer of 0; and   R 3  represents methyl.   
     
     
         12 : A compound according to  claim 1 , wherein A represents pyrimidinyl, pyridazinyl, pyridinyl, pyrazinyl, thiazolyl or thiadiazolyl, preferably pyrimidinyl, pyridazinyl, thiazolyl or thiadiazolyl, more preferably pyrimidinyl, pyridazinyl or thiadiazolyl, wherein said pyrimidinyl, pyridazinyl, pyridinyl, pyrazinyl, thiazolyl and thiadiazolyl are optionally substituted. 
     
     
         13 : A compound according to  claim 1 , wherein A represents CF 3 -pyrimidinyl, preferably 2-CF 3 -pyrimidin-5-yl. 
     
     
         14 : A compound according to  claim 1 , wherein R 2  represents cyclopropylmethyl, tetrahydrofuran-3-yl, tetrahydrofuran-2-ylmethyl, tetrahydrofuran-3-ylmethyl, prop-2-yn-1-yl, but-2-yn-1-yl, oxetan-3-yl, tetrahydropyran-4-yl, tetrahydro-2H-pyran-4-ylmethyl, pyridin-4-yl, pyridin-3-yl, 1,3,4-thiadiazol-2-yl, 1,3-thiazol-2-yl, 2,2-dimethyl-2-methoxyethyl, methoxyethyl, piperidin-4-yl, pyrrolidin-3-yl or azetidin-3-yl which are optionally substituted, preferably unsubstituted cyclopropylmethyl, unsubstituted oxetan-3-yl or unsubstituted tetrahydrofuran-3-yl. 
     
     
         15 : A compound according to  claim 1 , wherein R 2  represents unsubstituted tetrahydrofuran-3-yl or unsubstituted oxetan-3-yl. 
     
     
         16 : A compound according to  claim 1 , wherein
 R 2  represents —(CH 2 ) q -(4- to 6-membered heterocycloalkyl); and wherein (CH 2 ) q -(4- to 6-membered heterocycloalkyl) is optionally substituted with one or more substituents which are the same or different, at any ring carbon atom; and
 wherein independently any ring nitrogen atom, if present in said —(CH 2 ) q -(4- to 6-membered heterocycloalkyl) is substituted with R c ; and wherein —(CH 2 ) q -(4- to 6-membered heterocycloalkyl) is preferably 
 —(CH 2 ) q -morpholinyl; and 
   q represents an integer of 1.   
     
     
         17 : A compound according to  claim 16 , wherein R 2  represents —(CH 2 ) q -morpholinyl substituted with R c , and wherein R c  preferably represents methyl. 
     
     
         18 : A compound according to  claim 17 , wherein
 R 2  represents (4-methylmorpholin-2-yl)methyl, preferably [(2R)-4-methylmorpholin-2-yl]methyl or [(2S)-4-methylmorpholin-2-yl]methyl, more preferably [(2R)-4-methyl-morpholin-2-yl]methyl.   
     
     
         19 : A compound according to  claim 1 , wherein
 R 2  represents —C 2 -C 4 -alkyl-OH and   R 1  represents halogen, preferably chloro.   
     
     
         20 : A compound according to  claim 1 , wherein
 R 2  represents 3-hydroxybutan-2-yl, preferably (2R,3R)-3-hydroxybutan-2-yl, (2S,3S)-3-hydroxybutan-2-yl, (2S,3R)-3-hydroxybutan-2-yl or (2R,3 S)-3-hydroxybutan-2-yl, more preferably (2R,3R)-3-hydroxybutan-2-yl or (2S,3S)-3-hydroxybutan-2-yl.   
     
     
         21 : A compound according to  claim 1 , wherein
 A represents an optionally substituted pyrimidinyl or pyridazinyl, wherein said pyrimidinyl or pyridazinyl are optionally substituted with one or two substituents which are the same or different, and selected from a fluorine or chlorine atom, C 1 -C 2 -alkyl, optionally substituted with 1 to 5 fluorine atoms, or C 1 -C 2 -alkoxy, optionally substituted with 1 to 5 fluorine atoms; preferably CF 3 -pyrimidinyl or 6-CF 3 -pyridazinyl, more preferably 2-CF 3 -pyrimidin-5-yl or 6-CF 3 -pyridazin-3-yl.   
     
     
         22 : A compound according to  claim 1 , namely
 3-(5-Methyl-1,3-thiazol-2-yl)-5-[(3R)-tetrahydrofuran-3-yloxy]-N-{(1R)-1-[2-(trifluoromethyl)pyrimidin-5-yl]ethyl}benzamide;   3-(5-Methyl-1,3-thiazol-2-yl)-5-[(3S)-tetrahydrofuran-3-yloxy]-N-{(1R)-1-[2-(trifluoromethyl)pyrimidin-5-yl]ethyl}benzamide;   3-(5-Methyl-1,3-thiazol-2-yl)-5-(oxetan-3-yloxy)-N-{(1R)-1-[2-(trifluoromethyl)pyrimidin-5-yl]ethyl}benzamide;   3-(5-Ethyl-1,3-thiazol-2-yl)-5-[(3R)-tetrahydrofuran-3-yloxy]-N-{(1R)-1-[2-(trifluoromethyl)pyrimidin-5-yl]ethyl}benzamide;   3-(5-Ethyl-1,3-thiazol-2-yl)-5-[(3S)-tetrahydrofuran-3-yloxy]-N-{(1R)-1-[2-(trifluoromethyl)pyrimidin-5-yl]ethyl}benzamide;   3-(5-Ethyl-1,3-thiazol-2-yl)-5-(oxetan-3-yloxy)-N-{(1R)-1-[2-(trifluoromethyl)pyrimidin-5-yl]ethyl}benzamide;   3-(5-Methyl-1,3-thiazol-2-yl)-5-[(3R)-tetrahydrofuran-3-yloxy]-N-{(1R)-1-[6-(trifluoromethyl)pyridazin-3-yl]ethyl}benzamide;   3-(5-Methyl-1,3-thiazol-2-yl)-5-[(3S)-tetrahydrofuran-3-yloxy]-N-{(1R)-1-[6-(trifluoromethyl)pyridazin-3-yl]ethyl}benzamide.   
     
     
         23 : A compound according to  claim 1 , namely
 3-(5-methyl-1,3-thiazol-2-yl)-5-[(3R)-tetrahydrofuran-3-yloxy]-N-{(1R)-1-[2-(trifluoromethyl)pyrimidin-5-yl]ethyl}benzamide;   3-(5-methyl-1,3-thiazol-2-yl)-5-[(3S)-tetrahydrofuran-3-yloxy]-N-{(1R)-1-[2-(trifluoromethyl)pyrimidin-5-yl]ethyl}benzamide.   
     
     
         24 : A compound according to  claim 23 , namely 3-(5-methyl-1,3-thiazol-2-yl)-5-[(3R)-tetrahydrofuran-3-yloxy]-N-{(1R)-1-[2-(trifluoromethyl)pyrimidin-5-yl]ethyl}benzamide. 
     
     
         25 : A compound according to  claim 1 , namely
 3-(5-ethyl-1,3-thiazol-2-yl)-5-{[(2R)-4-methylmorpholin-2-yl]methoxy}-N-{(1R)-1-[2-(trifluoromethyl)pyrimidin-5-yl]ethyl}benzamide;   3-{[(2R)-4-methylmorpholin-2-yl]methoxy}-5-(5-methyl-1,3-thiazol-2-yl)-N-{(1R)-1-[2-(trifluoromethyl)pyrimidin-5-yl]ethyl}benzamide;   3-(5-ethyl-1,3-thiazol-2-yl)-5-{[(2R)-4-methylmorpholin-2-yl]methoxy}-N-{(1R)-1-[6-(trifluoromethyl)pyridazin-3-yl]ethyl}benzamide.   
     
     
         26 : A compound according to  claim 25 , namely 3-{[(2R)-4-methylmorpholin-2-yl]methoxy}-5-(5-methyl-1,3-thiazol-2-yl)-N-{(1R)-1-[2-(trifluoromethyl)pyrimidin-5-yl]ethyl}-benzamide. 
     
     
         27 : A compound according to  claim 1 , namely
 Trans Isomer 2; 3-{[3-hydroxybutan-2-yl]oxy}-5-(5-methyl-1,3-thiazol-2-yl)-N-{(1R)-1-[2-(trifluoromethyl)pyrimidin-5-yl]ethyl}benzamide;   Trans Isomer 1; 3-{[3-hydroxybutan-2-yl]oxy}-5-(5-methyl-1,3-thiazol-2-yl)-N-{(1R)-1-[6-(trifluoromethyl)pyridazin-3-yl]ethyl}benzamide;   Trans Isomer 1; 3-(5-chloro-1,3-thiazol-2-yl)-5-{[3-hydroxybutan-2-yl]oxy}-N-{(1R)-1-[2-(trifluoromethyl)pyrimidin-5-yl]ethyl}benzamide;   Cis Isomer 1; 3-(5-chloro-1,3-thiazol-2-yl)-5-{[3-hydroxybutan-2-yl]oxy}-N-{(1R)-1-[2-(trifluoromethyl)pyrimidin-5-yl]ethyl}benzamide;   Cis Isomer 2; 3-(5-chloro-1,3-thiazol-2-yl)-5-{[3-hydroxybutan-2-yl]oxy}-N-{(1R)-1-[2-(trifluoromethyl)pyrimidin-5-yl]ethyl}benzamide;   Trans Isomer 2; 3-(5-chloro-1,3-thiazol-2-yl)-5-{[3-hydroxybutan-2-yl]oxy}-N-{(1R)-1-[2-(trifluoromethyl)pyrimidin-5-yl]ethyl}benzamide;   Cis Isomer 1; 3-[(-3-hydroxybutan-2-yl)oxy]-5-(5-methyl-1,3-thiazol-2-yl)-N-{(1R)-1-[6-(trifluoromethyl)pyridazin-3-yl]ethyl}benzamide;   Cis Isomer 2; 3-[(-3-hydroxybutan-2-yl)oxy]-5-(5-methyl-1,3-thiazol-2-yl)-N-{(1R)-1-[6-(trifluoromethyl)pyridazin-3-yl]ethyl}benzamide;   Cis Isomer 1; 3-[(3-hydroxybutan-2-yl)oxy]-5-(5-methyl-1,3-thiazol-2-yl)-N-{(1R)-1-[2-(trifluoromethyl)pyrimidin-5-yl]ethyl}benzamide;   Cis Isomer 2; 3-[(3-hydroxybutan-2-yl)oxy]-5-(5-methyl-1,3-thiazol-2-yl)-N-{(1R)-1-[2-(trifluoromethyl)pyrimidin-5-yl]ethyl}benzamide.   
     
     
         28 : A compound according to  claim 27 , namely Cis Isomer 1; 3-(5-chloro-1,3-thiazol-2-yl)-5-{[3-hydroxybutan-2-yl]oxy}-N-{(1R)-1-[2-(trifluoromethyl)pyrimidin-5-yl]ethyl}-benzamide. 
     
     
         29 : A pharmaceutical composition comprising a compound according to  claim 1 , or an isomer, enantiomer, diastereomer, racemate, hydrate, solvate, or salt thereof, particularly a pharmaceutically acceptable salt thereof, or a mixture of same, and a pharmaceutically acceptable diluent or carrier. 
     
     
         30 : Use of a compound according to  claim 1 , or an isomer, enantiomer, diastereomer, racemate, hydrate, solvate, or salt thereof, particularly a pharmaceutically acceptable salt thereof, or a mixture of same, for the prophylaxis or treatment of a disease. 
     
     
         31 : Use of a compound according to  claim 1 , or an isomer, enantiomer, diastereomer, racemate, hydrate, solvate, or salt thereof, particularly a pharmaceutically acceptable salt thereof, or a mixture of same, for the preparation of a medicament for the prophylaxis or treatment of a disease. 
     
     
         32 : Use according to  claim 30 , wherein said disease is a genitourinary, gastrointestinal, respiratory or pain-related disease, condition or disorder; gynecological diseases including dysmenorrhea, dyspareunia, and endometriosis; endometriosis-associated pain; endometriosis-associated symptoms, wherein said symptoms are in particular dysmenorrhea, dyspareunia, dysuria, or dyschezia; urinary tract disease states associated with the bladder outlet obstruction; urinary incontinence conditions such as reduced bladder capacity, increased frequency of micturition, urge incontinence, stress incontinence, or bladder hyperreactivity; benign prostatic hypertrophy; prostatic hyperplasia; prostatitis; detrusor hyperreflexia; overactive bladder and symptoms related to overactive bladder wherein said symptoms are in particular increased urinary frequency, nocturia, urinary urgency or urge incontinence; pelvic hypersensitivity; urethritis; prostatitis; prostatodynia; cystitis; idiopathic bladder hypersensitivity; epilepsy; partial and generalized seizures; respiratory disorders including chronic obstructive pulmonary disorder (COPD), asthma, bronchospasm, chronic cough and the like; gastrointestinal disorders including irritable bowel syndrome (IBS), inflammatory bowel disease (IBD), biliary colic and other biliary disorders, renal colic, diarrhea-dominant IBS, gastroesophageal reflux, gastrointestinal distension, Crohn's disease and the like; Parkinson's disease; Alzheimer's disease; myocardial infarction; lipid disorders; and pain-associated diseases selected from the group consisting of hyperalgesia, allodynia, functional bowel disorders (such as irritable bowel syndrome), arthritis (such as osteoarthritis and rheumatoid arthritis), burns, migraine or cluster headaches, nerve injury, neuritis, neuralgias, poisoning, ischemic injury, interstitial cystitis, cancer, traumatic nerve-injury, post-traumatic injuries (including fractures and sport injuries), trigeminal neuralgia, small fiber neuropathy, diabetic neuropathy, chronic arthritis and related neuralgias, HIV and HIV treatment-induced neuropathy, pruritus. 
     
     
         33 : Use according to  claim 1 , wherein said disease is a gynecological disease, preferably dysmenorrhea, dyspareunia or endometriosis, endometriosis-associated pain, or other endometriosis-associated symptoms, wherein said symptoms are in particular dysmenorrhea, dyspareunia, dysuria, or dyschezia. 
     
     
         34 : Use according to  claim 1 , wherein said disease is associated with pain syndromes (including acute, chronic, inflammatory and neuropathic pain), preferably inflammatory pain, surgical pain, visceral pain, dental pain, premenstrual pain, endometriosis-associated pain, central pain, pain due to burning mouth syndrome, pain due to burns, pain due to migraine, cluster headaches, pain due to nerve injury, pain due to neuritis, neuralgias, pain due to poisoning, pain due to ischemic injury, pain due to interstitial cystitis, cancer pain, pain due to viral, parasitic or bacterial infections, pain due to traumatic nerve-injury, pain due to post-traumatic injuries (including fractures and sport injuries), pain due to trigeminal neuralgia, pain associated with small fiber neuropathy, pain associated with diabetic neuropathy, chronic lower back pain, phantom limb pain, pelvic pain syndrome, chronic pelvic pain, neuroma pain, complex regional pain syndrome, pain associated with gastrointestinal distension, chronic arthritic pain and related neuralgias, and pain associated with cancer, pain associated with chemotherapy, HIV and HIV treatment-induced neuropathy; and pain associated with diseases or disorders selected from the group consisting of hyperalgesia, allodynia, functional bowel disorders (such as irritable bowel syndrome) and arthritis (such as osteoarthritis and rheumatoid arthritis). 
     
     
         35 : A compound according to  claim 1 , or an isomer, enantiomer, diastereomer, racemate, hydrate, solvate, or salt thereof, particularly a pharmaceutically acceptable salt thereof, or a mixture of same, for the manufacture of a medicament. 
     
     
         36 : A compound according to  claim 1 , or an isomer, enantiomer, diastereomer, racemate, hydrate, solvate, or salt thereof, particularly a pharmaceutically acceptable salt thereof, or a mixture of same, for use in the treatment of genitourinary, gastrointestinal, respiratory or pain-related disease, condition or disorder; gynecological diseases including dysmenorrhea, dyspareunia, and endometriosis; endometriosis-associated pain; endometriosis-associated symptoms, wherein said symptoms are in particular dysmenorrhea, dyspareunia, dysuria, or dyschezia; urinary tract disease states associated with the bladder outlet obstruction; urinary incontinence conditions such as reduced bladder capacity, increased frequency of micturition, urge incontinence, stress incontinence, or bladder hyperreactivity; benign prostatic hypertrophy; prostatic hyperplasia; prostatitis; detrusor hyperreflexia; overactive bladder and symptoms related to overactive bladder wherein said symptoms are in particular increased urinary frequency, nocturia, urinary urgency or urge incontinence; pelvic hypersensitivity; urethritis; prostatitis; prostatodynia; cystitis; idiopathic bladder hypersensitivity; epilepsy; partial and generalized seizures; respiratory disorders including chronic obstructive pulmonary disorder (COPD), asthma, bronchospasm, chronic cough and the like; gastrointestinal disorders including irritable bowel syndrome (IBS), inflammatory bowel disease (IBD), biliary colic and other biliary disorders, renal colic, diarrhea-dominant IBS, gastroesophageal reflux, gastrointestinal distension, Crohn's disease and the like; Parkinson's disease; Alzheimer's disease; myocardial infarction; lipid disorders; and pain-associated diseases selected from the group consisting of hyperalgesia, allodynia, functional bowel disorders (such as irritable bowel syndrome), arthritis (such as osteoarthritis and rheumatoid arthritis), burns, migraine or cluster headaches, nerve injury, neuritis, neuralgias, poisoning, ischemic injury, interstitial cystitis, traumatic nerve-injury, post-traumatic injuries (including fractures and sport injuries), trigeminal neuralgia, small fiber neuropathy, diabetic neuropathy, chronic arthritis and related neuralgias, HIV and HIV treatment-induced neuropathy, pruritus. 
     
     
         37 : A compound according to  claim 1 , or an isomer, enantiomer, diastereomer, racemate, hydrate, solvate, or salt thereof, particularly a pharmaceutically acceptable salt thereof, or a mixture of same, for use in the treatment of pain syndromes (including acute, chronic, inflammatory and neuropathic pain), preferably inflammatory pain, surgical pain, visceral pain, dental pain, premenstrual pain, endometriosis-associated pain, central pain, pain due to burning mouth syndrome, pain due to burns, pain due to migraine, cluster headaches, pain due to nerve injury, pain due to neuritis, neuralgias, pain due to poisoning, pain due to ischemic injury, pain due to interstitial cystitis, cancer pain, pain due to viral, parasitic or bacterial infections, pain due to traumatic nerve-injury, pain due to post-traumatic injuries (including fractures and sport injuries), pain due to trigeminal neuralgia, pain associated with small fiber neuropathy, pain associated with diabetic neuropathy, chronic lower back pain, phantom limb pain, pelvic pain syndrome, chronic pelvic pain, neuroma pain, complex regional pain syndrome, pain associated with gastrointestinal distension, chronic arthritic pain and related neuralgias, and pain associated with cancer, pain associated with chemotherapy, HIV and HIV treatment-induced neuropathy; and pain associated with diseases or disorders selected from the group consisting of hyperalgesia, allodynia, functional bowel disorders (such as irritable bowel syndrome) and arthritis (such as osteoarthritis and rheumatoid arthritis). 
     
     
         38 : A compound according to  claim 1  or an isomer, enantiomer, diastereomer, racemate, hydrate, solvate, or salt thereof, particularly a pharmaceutically acceptable salt thereof, or a mixture of same, for use in the treatment of a gynecological disease, preferably dysmenorrhea, dyspareunia or endometriosis, endometriosis-associated pain, or other endometriosis-associated symptoms, wherein said symptoms are in particular dysmenorrhea, dyspareunia, dysuria, or dyschezia.