US 2023/0053411 A1 · 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.

Claims38

Dependent claims

A compound of general formula (I):
in which
R1 represents a halogen atom, C1-C4-alkyl or C3-C6-cycloalkyl, wherein C1-C4-alkyl is optionally substituted with 1-5 halogen atoms which are the same or different;
R2 represents —C2-C6-alkyl-OR4, —(CH2)q-(C3-C7-cycloalkyl), —(CH2)q-(6- to 12-membered heterobicycloalkyl), —(CH2)q-(4- to 7-membered heterocycloalkyl), —(CH2)q-(5- to 10-membered heteroaryl) or —C2-C6-alkynyl;
and
wherein said —(CH2)q-(C3-C7-cycloalkyl), —(CH2)q-(6- to 12-membered heterobicycloalkyl) and —(CH2)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 C1-C4 alkyl, optionally substituted with 1-5 halogen atoms which are the same or different, a halogen atom, —NRaRb, COOR5 and oxo (═O);
and
wherein independently any ring nitrogen atom, if present in said —(CH2)q-(6- to 12-membered heterobicycloalkyl) and —(CH2)q-(4- to 7-membered heterocycloalkyl) is substituted with Rc;
and
wherein said —(CH2)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 C1-C4-alkyl, optionally substituted with 1-5 halogen atoms which are the same or different, a halogen atom, —NRaRb and —COOR5;
R3 represents hydrogen or C1-C4-alkyl, which is optionally substituted with 1-5 halogen atoms which are the same or different;
R4 and R5 represent hydrogen or C1-C4-alkyl;
Ra and Rb represent hydrogen or C1-C4-alkyl;
Rc represents hydrogen, C1-C4-alkyl, optionally substituted with 1-5 halogen atoms which are the same or different, —C(O)O—C1-C4-alkyl, or —C(O)—C1-C4-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, C1-C3-alkyl, and C1-C3-alkoxy, wherein C1-C3-alkyl and C1-C3-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.

14 more elements

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.

23 more elements

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.

23 more elements

1,3-thiazol-2-yl substituted benzamides

Life of this patent

1,3-thiazol-2-yl substituted benzamides

Life of this patent

Abstract

Claims38