The invention relates to heterocyclic derivatives, to the use of said derivatives in treating a range of metabolic diseases and other conditions mediated by agonism of the G-protein coupled bile acid GPBAR1/TGR5 receptor, to compositions and formulations containing said derivatives, processes for their preparation and methods of delivery.
C07D 231/12 - Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
C07D 233/56 - Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, attached to ring carbon atoms
C07D 233/64 - Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with substituted hydrocarbon radicals attached to ring carbon atoms, e.g. histidine
C07D 401/04 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring- member bond
C07D 413/04 - Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring- member bond
C07D 249/06 - 1,2,3-TriazolesHydrogenated 1,2,3-triazoles with aryl radicals directly attached to ring atoms
C07D 261/08 - Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings not condensed with other rings having two or more double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
C07D 263/32 - Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
A61K 31/4439 - Non-condensed pyridinesHydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
The present invention relates to piperidine derivatives of formula (I) and (II), their pharmaceutical compositions and methods of treatment of metabolic syndrome disorders such as obesity, diabetes, hypertension and hyperlipidemia using the said compounds. Formula (I) Formula (II) In formula (I), X and Y represent optionally substituted aryl or heteroaryl; R1 represents H or optionally substituted lower alkyl; R2 represents H, optionally substituted lower alkyl, ester, optionally substituted alkoxycarbonyl, acyl, thioester, thioacyl, thioether, optionally substituted alkoxyl, amino, optionally substituted aminoalkyl, amido or acylamino; and R3 represents H or OH. In formula (II), X represents optionally substituted aryl or heteroaryl; R4 represents H or optionally substituted lower alkyl; and R5 represents optionally substituted lower alkyl.
C07D 211/22 - Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms with hydrocarbon radicals, substituted by singly bound oxygen or sulfur atoms by oxygen atoms
A61K 31/165 - Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide
A61K 31/445 - Non-condensed piperidines, e.g. piperocaine
The present invention relates to the treatment of metabolic syndrome or disorders associated with metabolic syndrome including administering a compound of the invention.
C07D 211/22 - Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms with hydrocarbon radicals, substituted by singly bound oxygen or sulfur atoms by oxygen atoms
A61K 31/454 - Non-condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. pimozide, domperidone
A61K 31/445 - Non-condensed piperidines, e.g. piperocaine
A61P 3/10 - Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
The present invention relates to the treatment of metabolic syndrome and associated disorders such as obesity, diabetes, hypertension and hyperlipidemia by administering a suitably substituted 2,3-dihydropyrrolizine compound represented by general formula (I) or a suitably substituted l-benzoyl-2-methylindole represent by general formula (II) as shown: (I) (II)
A61K 31/407 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil condensed with heterocyclic ring systems, e.g. ketorolac, physostigmine
A61P 3/10 - Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
5.
TREATMENT OF METABOLIC SYNDROME WITH CYCLIC AMIDES
The present application relates to a compound of formula (I) or a pharmaceutically acceptable salt thereof, wherein the variables are'as defined in the claims. The present application also relates to the treatment of metabolic syndrome or disorders associated with metabolic syndrome in an affected mammal by administering a compound of formula (I) or a pharmaceutically acceptable salt thereof.
C07D 211/22 - Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms with hydrocarbon radicals, substituted by singly bound oxygen or sulfur atoms by oxygen atoms
A61K 31/4525 - Non-condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a five-membered ring with oxygen as a ring hetero atom
A61P 5/50 - Drugs for disorders of the endocrine system of the pancreatic hormones for increasing or potentiating the activity of insulin
A61K 31/445 - Non-condensed piperidines, e.g. piperocaine
C07D 265/30 - 1,4-OxazinesHydrogenated 1,4-oxazines not condensed with other rings
A61K 31/451 - Non-condensed piperidines, e.g. piperocaine having a carbocyclic ring directly attached to the heterocyclic ring, e.g. glutethimide, meperidine, loperamide, phencyclidine, piminodine
A61P 5/48 - Drugs for disorders of the endocrine system of the pancreatic hormones
The present invention relates to the treatment of metabolic syndrome or disorders associated with metabolic syndrome comprising administering a compound of the invention.
C07C 233/22 - Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by singly-bound oxygen atoms with the substituted hydrocarbon radical bound to the nitrogen atom of the carboxamide group by an acyclic carbon atom having the carbon atom of the carboxamide group bound to an acyclic carbon atom of a carbon skeleton containing six-membered aromatic rings
A61K 31/165 - Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide
The present invention relates to methods of treating obesity, anorexia nervosa, or bulimia nervosa comprising administering a compound of the invention conjointly with zonisamide, naltrexone, or a pharmaceutically acceptable salt thereof. The present invention further relates to the treatment of metabolic syndrome comprising administering a compound of the invention conjointly with zonisamide, naltrexone, or a pharmaceutically acceptable salt thereof.
The invention relates to methods of treating metabolic syndrome, or the specific disorders associated with metabolic syndrome, comprising the administration of norfluoxetine enriched for the (R) or (S) enantiomer conjointly with a statin, a calcium channel blocker, halofenate, captopril, or an imidazoline receptor agonist (e.g., an I1, I2, or I3 receptor agonist).
A61K 31/138 - Aryloxyalkylamines, e.g. propranolol, tamoxifen, phenoxybenzamine
A61K 31/216 - Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acids having aromatic rings, e.g. benactizyne, clofibrate
A61K 31/366 - Lactones having six-membered rings, e.g. delta-lactones
A61K 31/40 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
A61K 31/401 - ProlineDerivatives thereof, e.g. captopril
A61K 31/4422 - 1,4-Dihydropyridines, e.g. nifedipine, nicardipine
A61P 3/10 - Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
9.
PIPERIDINE AND PIPERAZINE COMPOUNDS FOR USE IN THE TREATMENT OF OBESITY, EATING DISORDERS AND SEXUAL DYSFUNCTION BY POTENTIATION OF MC4 RECEPTOR ACTIVITY
The present invention provides methods of treating obesity, eating disorders, and sexual dysfunction. The methods comprise administering to a mammalian host suffering from obesity, an eating disorder, or sexual dysfunction an effective dose of a compound of the invention. Also provided are methods of potentiating the effect of an MC4 receptor agonist in a mammalian host. In some cases the methods comprise administering to the host a compound that lowers the EC50 of the agonist. In other cases the methods comprise administering to the host a compound that increases the maximum effect of the agonist.
A61K 31/454 - Non-condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. pimozide, domperidone
A61K 31/4545 - Non-condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a six-membered ring with nitrogen as a ring hetero atom, e.g. pipamperone, anabasine
A61K 31/496 - Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
The present invention relates to methods of treating obesity, anorexia nervosa, or bulimia nervosa comprising administering a compound of the invention. The present invention further relates to the treatment of metabolic syndrome comprising administering a compound of the invention.
A61K 31/381 - Heterocyclic compounds having sulfur as a ring hetero atom having five-membered rings
A61K 31/4174 - Arylalkylimidazoles, e.g. oxymetazolin, naphazoline, miconazole
A61K 31/138 - Aryloxyalkylamines, e.g. propranolol, tamoxifen, phenoxybenzamine
C07D 233/54 - Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
C07D 333/56 - Radicals substituted by oxygen atoms
C07D 333/58 - Radicals substituted by nitrogen atoms
patents