http://rdf.ncbi.nlm.nih.gov/pubchem/patent/AR-040397-A1
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| Predicate | Object |
|---|---|
| assignee | http://rdf.ncbi.nlm.nih.gov/pubchem/patentassignee/MD5_40a92325286ca98dbffa06d2c67ed064 |
| classificationIPCInventive | http://rdf.ncbi.nlm.nih.gov/pubchem/patentipc/A61K- http://rdf.ncbi.nlm.nih.gov/pubchem/patentipc/C07D- |
| filingDate | 2000-08-31-04:00^^<http://www.w3.org/2001/XMLSchema#date> |
| publicationDate | 2005-04-06-04:00^^<http://www.w3.org/2001/XMLSchema#date> |
| publicationNumber | AR-040397-A1 |
| titleOfInvention | FUSIONATED PIRROLCARBOXAMIDS; PHARMACEUTICAL COMPOSITION THAT INCLUDES THEM, THE USE OF THE SAME FOR THE MANUFACTURE OF A MEDICINAL PRODUCT, A METHOD FOR LOCATING GABAA RECEPTORS, A METHOD FOR INHIBITING THE SETTING OF A BENZODIAZEPIN TO A GABAA RECEPTOR AND A METHOD FOR ALTERATING |
| abstract | These are fused pyrrolcarboxamide compounds (formula (1)). These compounds are highly selective inverse agonists or antagonists of GABAA brain receptors or prodrugs of agonists, antagonists or inverse agonists of GABAA brain receptors. Therefore, they are useful in the diagnosis and treatment of anxiety, depression, dementia caused by Alzheimer's disease, sleep and seizure disorders, overdose with benzodiazepines and to improve memory. There are also pharmaceutical compounds, including packaged pharmaceutical compounds. The compounds are also useful as tests for the localization of GABAA receptors in tissue samples. The uses of said compounds for the manufacture of medicaments for the treatment of a disease or disorder associated with pathogenic agonism, inverse agonism or GABAA receptor antagonism are also described. Claim 1: A compound of the formula (1) or a pharmaceutically acceptable salt thereof wherein: T is halogen, hydrogen, hydroxyl, amino, alkyl or alkoxy; X is hydrogen, hydroxy, amino, benzyl, t-butoxycarbonyl, benzyloxycarbonyl, alkyl, or alkoxy; G has the structure (2) wherein Q is an optionally substituted aryl or an optionally substituted heteroaryl group having 1 to 3 rings, 3 to 8 members in each ring and 1 to 3 heteroatoms; W is selected from hydrogen, -O-, -NH-, -NR7-, -S (O) 0-2-, -C (= O) -, -OC (= O) -, -C (= O) O-, -C (= O) NH-, -NHC (= O) -, -NR7C (= O) -, -NHS (O) 0-2-, -NR7S (O) 0-2-, -S (O) 0-2NH-, -S (O) 0-2NR7-, and CR7R8 where R7 and R8 are the same or different and represent hydrogen, alkyl, or R7-R8 taken together represent a cyclic half that has 3-7 carbon atoms, wherein W cannot be hydrogen when Q is phenyl, 2- or 3-thienyl, or 2-, 3-, or 4 pyridyl, indolyl, imidazolyl, or pyridazinyl; Z is hydrogen, hydroxy, cycloalkyl (alkoxy), amino, mono or di (alkyl1) amino, azacycloalkyl, -O (alkyl1), -S (O) 0-2 (alkyl1), -C (= O) (alkyl1) , -OC (= O) (alkyl1), -OC (= O) H, -C (= O) O (alkyl1), -C (= O) OH, -C (= O) NH (alkyl1), - C (= O) N (alkyl1) 2, -C (= O) NH2, -NHC (= O) (alkyl1), -NHC (= O) H, -N (alkyl1) C (= O) (alkyl1) , -NHS (O) 0-2 (alkyl1), -N (alkyl1) S (O) 0-2 (alkyl1), -S (O) 0-2NH (alkyl1), -S (O) 0-2 ( alkyl1) N (alkyl1), wherein each alkyl1 is independently straight, branched, or cyclic, may contain one or two double or triple bonds or combinations thereof, and is unsubstituted or substituted with one or more substituents independently selected from hydroxy , oxo, halogen, amino, cyano, nitro, and alkoxy, or Z is -N (RN) 2S (O) 0-2 (RS) where each RN is independently hydrogen or alkyl where the alkyl is straight, branched, or cyclic, may contain one or two double or triple bonds, and is unsubstituted or substituted with one or more independent substituents Selected from hydroxy, oxo, halogen, amino, cyano, nitro, and alkoxy, RS is hydroxy, alkoxy, heteroaryl, aryl, or alkyl wherein each aryl and heteroaryl is optionally substituted with one or two of alkyl, hydroxy, alkoxy, trifluoromethyl, halogen, amino, or mono- or dialkylamino; and each alkyl is optionally substituted with hydroxy, alkoxy, trifluoromethyl, halogen, amino, mono- or di-alkylamino, aryl, or heteroaryl; or Z is phenyl or phenylalkyl where the phenyl portion is optionally substituted with alkyl, hydroxy, alkoxy, trifluoromethyl, halogen, amino, or mono- or di-alkylamino, or Z is 2-, 3-, or 4-pyridyl, 1- or 2-imidazolyl, 1-, 2-, or 3-pyrrolyl, azeditinyl, norborn-2-yl, or adamantan-2-yl; each of which can be substituted on a tertiary carbon or a secondary nitrogen with C1-6 alkyl, or Z is NR9COR10 where R9 and R10 are the same or different and represent hydrogen or alkyl or cycloalkyl, or Z is optionally connected by W , to Q from a ring of 1-6 members; or Z represents a group of the formula (3) where p is 1, 2, or 3; D and D 'independently represent oxygen, NRy or CHRy provided that only D or D' can be NRy, where each Ry is hydrogen or alkyl; and Rz is hydrogen or alkyl, or Z represents a group of the formula (4) wherein p is 1, 2, or 3; q is 0, 1, or 2; each Rz is independently hydrogen or alkyl; or Z represents a group of the formula (5) where s is 0, 1, 2 or 3, and the sum of s and m is not less than 1; Ro is hydroxy, C1-6 alkoxy, amino, mono- or dialkylamino wherein each alkyl is independently and optionally substituted with amino, or mono- or dialkylamino, or Ro is a group of the formula (3) wherein p, D, D ', and Rz are as defined above; structures (6) and (7) independently represent a carbon chain optionally substituted with halogen, oxo, cyano, nitro, amino, mono or dialkylamino, alkyl, alkenyl, alkynyl, trifluoromethyl, trifluoromethoxy, or cycloalkyl; where k is 0, 1, 2, or 3; m is 0, 1, 2, or 3; and structure (8) represents a carbon chain optionally substituted with RS and R6 and n is 0, 1, 2, or 3; and R3, R4, R5, and R6 are the same or different and are independently selected in each case from hydrogen, alkyl, -COR11 or -CO2R11 wherein R11 is C3-7 alkyl or cycloalkyl; or -CONR12R13 wherein R12 and R13 are independently selected from hydrogen, alkyl, C3-7 cycloalkyl, phenyl, 2-, 3-, or 4-pyridyl, or NR12R13 forms a heterocyclic group of morpholinyl, piperidinyl, pyrrolidinyl, or N- piperazinyl alkyl; or R3 and R4 can be taken together to form a cyclic half having 3-7 carbon atoms; or R5 and R6 can be taken together to form a cyclic half having 3-7 carbon atoms; wherein each alkyl group forming R3, R4, R5, or R6 substituent or half thereof can be independently substituted with hydroxy or mono or dialkylamino where each alkyl is independently alkyl or cycloalkyl. |
| priorityDate | 1999-08-31-04:00^^<http://www.w3.org/2001/XMLSchema#date> |
| type | http://data.epo.org/linked-data/def/patent/Publication |
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Total number of triples: 45.