Aryl-and heteroaryl-substituted tetrahydrobenzazepines and use thereof to block reuptake of norepinephrine, dopamine, and serotonin
A compound of formulae I(A-E) having the following structure: R5* R 4 N, I(A-E) wherein: the carbon atom designated * is in the R or S configuration; X is phenyl, optionally substituted from 1 to 4 times with substituents as defined in R1 4 ; R' is H, methyl, ethyl, or isopropyl; R2 is H, methy...
Saved in:
Main Authors | , , , , , , , , , , , |
---|---|
Format | Patent |
Language | English |
Published |
16.01.2014
|
Subjects | |
Online Access | Get full text |
Cover
Loading…
Abstract | A compound of formulae I(A-E) having the following structure: R5* R 4 N, I(A-E) wherein: the carbon atom designated * is in the R or S configuration; X is phenyl, optionally substituted from 1 to 4 times with substituents as defined in R1 4 ; R' is H, methyl, ethyl, or isopropyl; R2 is H, methyl, or gem-dimethyl; R3 is H, methyl, hydroxy, methoxy, fluoro, chloro, cyano, trifluoromethyl, or trifluoromethoxy; R4 is pyrimidinyl, optionally substituted from 1 to 4 times with substituents as defined below in R5 is H, fluoro, chloro, methyl, trifluoromethyl, trifluoromethoxy, cyano, hydroxy or methoxy; R 6 is H, fluoro, chloro, methyl, trifluoromethyl, trifluoromethoxy, cyano, hydroxy or methoxy; R7 is H, gem-dimethyl, or CI-C 4 alkyl, wherein each of the CI-C 4 alkyl is optionally substituted from 1 to 3 times with substituents as defined in R'5 ; R is H; R9 is H; R10 and R" are each independently selected from the group consisting of H, -C(O)R, CI-C 4 alkyl, C3 -C6 cycloalkyl, and C4-C7 cycloalkylalkyl, where each of CI-C 6 allyl, C3-C6 cycloalkyl, and C4 -C7 cycloalkylalkyl is optionally substituted from I to 3 times with substituents as defined below in R15; R' 0 and R" are each independently selected from the group consisting of phenyl, benzyl, and other 5- or 6-membered monocyclic heterocycles, where each of the phenyl, benzyl, and 5- or 6-membered monocyclic heterocycle is optionally substituted from 1 to 3 times with substituents as defined below in R14; R'0 and R" are taken together with the nitrogen to which they are attached to form a saturated or partially saturated monocyclic or fused bicyclic heterocycle selected from the group consisting of piperidine, pyrrolidine, morpholine, thiomorpholine, [1,2]oxazinane, isoxazolidine, 2-oxopiperidinyl, 2-oxopyrrolidinyl, 3-oxomorpholino, 3-oxothiomorpholino, 5,6,7,8-tetrahydroimidazo[1,2-a]pyrazine, 5,6,7,8-tetrahydro-[1,2,4]triazolc[4,3-a]pyrazine, and other monocyclic or fused bicyclic heterocycles containing 1-4 heteroatoms selected from oxygen, nitrogen and sulfur, wherein the heterocycle is attached to the benzazepine core via the nitrogen atom, and is optionally substituted from I to 3 times with a substituent selected 12 independently at each occurrence thereof from the group consisting of halogen, cyano, -OR -NR 2 R1D, -S(O),R' 3 , -C(O)R 3, and Ci-C 4 alkyl, where each of CI-C 4 alkyl is optionally substituted from 1 to 3 times with substituents as defined below in R15; R' 0 and R1 are taken together with the nitrogen to which they are attached to form a heterocycle selected from the group consisting of piperazine, 2-oxopiperazinyl, 2-oxo-1,4 diazepanyl, 5-oxo-1,4-diazepanyl, 1,4-diazepane, and other heterocycles containing one additional nitrogen atom in the ring, where the heterocycle is optionally substituted on a ring carbon with from 1 to 3 times with a substituent selected independently at each occurrence thereof from the group consisting of halogen, cyano, -OR , -NR12 R 3 , -S(O),R' 3 , -C(O)R 3 , and CI-C 4 alkyl, or on the additional nitrogen atom from 1 to 3 times with a substituent selected independently at each occurrence thereof from the group consisting of S(O)nR'3 , C(O)R 3 , and CI-C 4 alkyl, wherein each of CI-C 4 alkyl is optionally substituted from I to 3 times with substituents as defined below in R15; R'0 and R" are taken together with the nitrogen to which they are attached to form a heterocycle selected from the group consisting of piperazine, 2-oxopiperazinyl, 2-oxo-1,4 diazepanyl, 5-oxo-1,4-diazepanyl, 1,4-diazepane, and other heterocycles containing one additional nitrogen atom in the ring, where the heterocycle is optionally substituted on the additional nitrogen atom with a substituent selected independently at each occurrence thereof from the group consisting of phenyl, benzyl, and 5- or 6-membered aromatic heterocycles containing 1-3 heteroatoms selected from the group consisting of oxygen, nitrogen, and sulfur, where each of the phenyl, benzyl, and 5- and 6-membered heterocycle is optionally substituted from 1 to 3 times with substituents as defined below in R' 4; R 2 is selected from the group consisting of H, CI-C 4 alkyl, C3-C6 cycloalkyl, C4 -C7 cycloalkylalkyl, and -C(O)R 1 3 , where each of CI-C 6 alkyl, C3 -C6 cycloalkyl, and C4-C7 cycloalkylalkyl is optionally substituted from I to 3 times with substituents as defined below in R"; R 3 is CI-C 4 alkyl; R' 4 is independently selected at each occurrence from a substituent in the group consisting of halogen, -NO 2, -OR 2 , -NR"R", -NR C(O)2R 3, -NR'2 C(O)NR 2R , -S(O)n R 3, -CN, C(O)R 3 , CI-C 6 alkyl, C2-C6 alkenyl, C2 -C6 alkynyl, C3-C6 cycloalkyl, and C4-C7 cycloalkylalkyl, wherein each of Ci-C 6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, and C4-C7 cycloalkylalkyl is optionally substituted from 1 to 3 times with substituents as defined below in R15; and R 5 is independently selected at each occurrence from a substituent in the group consisting of CN, halogen, C(O)R 3 , CI-C 3 alkyl, -OR 2 , -NR' 0R", -S(O)nR13 , aryl, and heteroaryl, wherein each of the aryl or heteroaryl groups is optionally substituted from I to 4 times with substituents as defined above in R1 4; and n is 0, 1, or 2. |
---|---|
AbstractList | A compound of formulae I(A-E) having the following structure: R5* R 4 N, I(A-E) wherein: the carbon atom designated * is in the R or S configuration; X is phenyl, optionally substituted from 1 to 4 times with substituents as defined in R1 4 ; R' is H, methyl, ethyl, or isopropyl; R2 is H, methyl, or gem-dimethyl; R3 is H, methyl, hydroxy, methoxy, fluoro, chloro, cyano, trifluoromethyl, or trifluoromethoxy; R4 is pyrimidinyl, optionally substituted from 1 to 4 times with substituents as defined below in R5 is H, fluoro, chloro, methyl, trifluoromethyl, trifluoromethoxy, cyano, hydroxy or methoxy; R 6 is H, fluoro, chloro, methyl, trifluoromethyl, trifluoromethoxy, cyano, hydroxy or methoxy; R7 is H, gem-dimethyl, or CI-C 4 alkyl, wherein each of the CI-C 4 alkyl is optionally substituted from 1 to 3 times with substituents as defined in R'5 ; R is H; R9 is H; R10 and R" are each independently selected from the group consisting of H, -C(O)R, CI-C 4 alkyl, C3 -C6 cycloalkyl, and C4-C7 cycloalkylalkyl, where each of CI-C 6 allyl, C3-C6 cycloalkyl, and C4 -C7 cycloalkylalkyl is optionally substituted from I to 3 times with substituents as defined below in R15; R' 0 and R" are each independently selected from the group consisting of phenyl, benzyl, and other 5- or 6-membered monocyclic heterocycles, where each of the phenyl, benzyl, and 5- or 6-membered monocyclic heterocycle is optionally substituted from 1 to 3 times with substituents as defined below in R14; R'0 and R" are taken together with the nitrogen to which they are attached to form a saturated or partially saturated monocyclic or fused bicyclic heterocycle selected from the group consisting of piperidine, pyrrolidine, morpholine, thiomorpholine, [1,2]oxazinane, isoxazolidine, 2-oxopiperidinyl, 2-oxopyrrolidinyl, 3-oxomorpholino, 3-oxothiomorpholino, 5,6,7,8-tetrahydroimidazo[1,2-a]pyrazine, 5,6,7,8-tetrahydro-[1,2,4]triazolc[4,3-a]pyrazine, and other monocyclic or fused bicyclic heterocycles containing 1-4 heteroatoms selected from oxygen, nitrogen and sulfur, wherein the heterocycle is attached to the benzazepine core via the nitrogen atom, and is optionally substituted from I to 3 times with a substituent selected 12 independently at each occurrence thereof from the group consisting of halogen, cyano, -OR -NR 2 R1D, -S(O),R' 3 , -C(O)R 3, and Ci-C 4 alkyl, where each of CI-C 4 alkyl is optionally substituted from 1 to 3 times with substituents as defined below in R15; R' 0 and R1 are taken together with the nitrogen to which they are attached to form a heterocycle selected from the group consisting of piperazine, 2-oxopiperazinyl, 2-oxo-1,4 diazepanyl, 5-oxo-1,4-diazepanyl, 1,4-diazepane, and other heterocycles containing one additional nitrogen atom in the ring, where the heterocycle is optionally substituted on a ring carbon with from 1 to 3 times with a substituent selected independently at each occurrence thereof from the group consisting of halogen, cyano, -OR , -NR12 R 3 , -S(O),R' 3 , -C(O)R 3 , and CI-C 4 alkyl, or on the additional nitrogen atom from 1 to 3 times with a substituent selected independently at each occurrence thereof from the group consisting of S(O)nR'3 , C(O)R 3 , and CI-C 4 alkyl, wherein each of CI-C 4 alkyl is optionally substituted from I to 3 times with substituents as defined below in R15; R'0 and R" are taken together with the nitrogen to which they are attached to form a heterocycle selected from the group consisting of piperazine, 2-oxopiperazinyl, 2-oxo-1,4 diazepanyl, 5-oxo-1,4-diazepanyl, 1,4-diazepane, and other heterocycles containing one additional nitrogen atom in the ring, where the heterocycle is optionally substituted on the additional nitrogen atom with a substituent selected independently at each occurrence thereof from the group consisting of phenyl, benzyl, and 5- or 6-membered aromatic heterocycles containing 1-3 heteroatoms selected from the group consisting of oxygen, nitrogen, and sulfur, where each of the phenyl, benzyl, and 5- and 6-membered heterocycle is optionally substituted from 1 to 3 times with substituents as defined below in R' 4; R 2 is selected from the group consisting of H, CI-C 4 alkyl, C3-C6 cycloalkyl, C4 -C7 cycloalkylalkyl, and -C(O)R 1 3 , where each of CI-C 6 alkyl, C3 -C6 cycloalkyl, and C4-C7 cycloalkylalkyl is optionally substituted from I to 3 times with substituents as defined below in R"; R 3 is CI-C 4 alkyl; R' 4 is independently selected at each occurrence from a substituent in the group consisting of halogen, -NO 2, -OR 2 , -NR"R", -NR C(O)2R 3, -NR'2 C(O)NR 2R , -S(O)n R 3, -CN, C(O)R 3 , CI-C 6 alkyl, C2-C6 alkenyl, C2 -C6 alkynyl, C3-C6 cycloalkyl, and C4-C7 cycloalkylalkyl, wherein each of Ci-C 6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, and C4-C7 cycloalkylalkyl is optionally substituted from 1 to 3 times with substituents as defined below in R15; and R 5 is independently selected at each occurrence from a substituent in the group consisting of CN, halogen, C(O)R 3 , CI-C 3 alkyl, -OR 2 , -NR' 0R", -S(O)nR13 , aryl, and heteroaryl, wherein each of the aryl or heteroaryl groups is optionally substituted from I to 4 times with substituents as defined above in R1 4; and n is 0, 1, or 2. |
Author | NACRO, KASSOUM ISHERWOOD, MATTHEW L FLEMING, KRISTEN N ZHA, CONGXIANG MANNING, DAVID D OLSON, RICHARD E HU, MIN GUZZO, PETER R MOLINO, BRUCE F LIU, SHUANG CUI, WENGE SAMBANDAM, ARUNA |
Author_xml | – fullname: OLSON, RICHARD E – fullname: ISHERWOOD, MATTHEW L – fullname: FLEMING, KRISTEN N – fullname: GUZZO, PETER R – fullname: HU, MIN – fullname: CUI, WENGE – fullname: ZHA, CONGXIANG – fullname: MANNING, DAVID D – fullname: NACRO, KASSOUM – fullname: MOLINO, BRUCE F – fullname: SAMBANDAM, ARUNA – fullname: LIU, SHUANG |
BookMark | eNqNTTsOgkAUpNDC3x1eYSkJrjHWajQeQGuzyBAI-N5m91FA68UF4gFs5peZzDyasDBm0efo2zq2nFEBhRc72NCkQUttFBkp1Nuizbyk4M52cCUj0LBoAkgLeEhOKpTW8qrIo3FqK1Afsvix7grf44YycfY9qmEe-jsVLnkZTXNbB6x-vIjW18v9fIvh5Ing7AsMfR4fJtkak5j9ITmdzO7P2hdxAE60 |
ContentType | Patent |
DBID | EVB |
DatabaseName | esp@cenet |
DatabaseTitleList | |
Database_xml | – sequence: 1 dbid: EVB name: esp@cenet url: http://worldwide.espacenet.com/singleLineSearch?locale=en_EP sourceTypes: Open Access Repository |
DeliveryMethod | fulltext_linktorsrc |
Discipline | Medicine Chemistry Sciences |
ExternalDocumentID | AU2012202570BB2 |
GroupedDBID | EVB |
ID | FETCH-epo_espacenet_AU2012202570BB23 |
IEDL.DBID | EVB |
IngestDate | Fri Jul 19 15:34:55 EDT 2024 |
IsOpenAccess | true |
IsPeerReviewed | false |
IsScholarly | false |
Language | English |
LinkModel | DirectLink |
MergedId | FETCHMERGED-epo_espacenet_AU2012202570BB23 |
Notes | Application Number: AU20120202570 |
OpenAccessLink | https://worldwide.espacenet.com/publicationDetails/biblio?FT=D&date=20140116&DB=EPODOC&CC=AU&NR=2012202570B2 |
ParticipantIDs | epo_espacenet_AU2012202570BB2 |
PublicationCentury | 2000 |
PublicationDate | 20140116 |
PublicationDateYYYYMMDD | 2014-01-16 |
PublicationDate_xml | – month: 01 year: 2014 text: 20140116 day: 16 |
PublicationDecade | 2010 |
PublicationYear | 2014 |
RelatedCompanies | ALBANY MOLECULAR RESEARCH, INC |
RelatedCompanies_xml | – name: ALBANY MOLECULAR RESEARCH, INC |
Score | 2.9263182 |
Snippet | A compound of formulae I(A-E) having the following structure: R5* R 4 N, I(A-E) wherein: the carbon atom designated * is in the R or S configuration; X is... |
SourceID | epo |
SourceType | Open Access Repository |
SubjectTerms | CHEMISTRY HETEROCYCLIC COMPOUNDS HUMAN NECESSITIES HYGIENE MEDICAL OR VETERINARY SCIENCE METALLURGY ORGANIC CHEMISTRY PREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS ORMEDICINAL PREPARATIONS |
Title | Aryl-and heteroaryl-substituted tetrahydrobenzazepines and use thereof to block reuptake of norepinephrine, dopamine, and serotonin |
URI | https://worldwide.espacenet.com/publicationDetails/biblio?FT=D&date=20140116&DB=EPODOC&locale=&CC=AU&NR=2012202570B2 |
hasFullText | 1 |
inHoldings | 1 |
isFullTextHit | |
isPrint | |
link | http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwhV1LT8JAEN4QNOpNUeMLswfSk42wLS0eiKEthJjwiAHDjWzpNBqwbdolBq7-cWcqKCe9NNt9JfuYmf1mZ2YZq4Bp2wYEgd6YSaGbEma6HwrQhQwlylMhoUreyL2-1R2bT5P6pMAWW1-YPE7oRx4cESlqhvSucn6d_CqxvNy2Mrv33zArfuyMmp62QceEFmqW5jnN9nDgDVzNdRFJav1nKhOI8-t21UGGvUcHaYq0335xyC8l2RUqnWO2P8T-InXCChCV2KG7fXutxA56mytvTG6oLztln610tdAR-vNXMmKJJf1mSPnf1_0BV6CQd6wCcvGJ1nINCRm1c2qxzIDTWQ_ikKuY-yjD5jyFZaLkHDhmRnGaV8fFxe8dDxBNv-cpao4bNVakuT1jlU575HZ1HM30Z_KmrfHO0B1hnLNiFEdwwbiwfMMXEDxAEJrGTMigYVQlsgArBAPs8JKV_-zq6p_ya3ZEK0L6ipp1w4oqXUIZJbjyb_OJ_wJNAqRE |
link.rule.ids | 230,309,786,891,25594,76903 |
linkProvider | European Patent Office |
linkToHtml | http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwhV1LT8JAEN4QNOJNUeML3QPpyUbYlhYPxNAWgsorBgw3sm2n0YBt0y4xcPWPO1tBOells4_uJNvpzOw3O7MlpAy6aWrg-2rd40zVOXiqGzBQGQ842lPGoSKzkXt9ozPWHye1SY7MN7kw2T2hH9nliChRHsq7yPR1_OvEcrLYyvTWfcOu6L49ajjKGh1LtFA1FMdqtIYDZ2Arto1IUuk_yzGGOL9mVixU2DsmgsIMLL1YMi8l3jYq7QOyO0R6oTgkOQiLpGBv_r1WJHu99ZE3VtfSlx6Rz2aynKsI_emrDGKJuGymKPnfx_0-FSBQdyx9meITrvgKYhnUTuWMRQpU7vUgCqiIqIs2bEYTWMSCz4BiZxgl2ePIXCxvqI9o-j2ryen4oUZCem6PSbndGtkdFVcz_Xl50-Z4a-kW005IPoxCOCWUGa7mMvDvwA90zWPcr2sVjirACEADMzgjpT9Jnf8zfk0KnVGvO-0-9J8uyL7kjvRdVI1LkhfJAkpozYV7lTHhCyGSpy4 |
openUrl | ctx_ver=Z39.88-2004&ctx_enc=info%3Aofi%2Fenc%3AUTF-8&rfr_id=info%3Asid%2Fsummon.serialssolutions.com&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Apatent&rft.title=Aryl-and+heteroaryl-substituted+tetrahydrobenzazepines+and+use+thereof+to+block+reuptake+of+norepinephrine%2C+dopamine%2C+and+serotonin&rft.inventor=OLSON%2C+RICHARD+E&rft.inventor=ISHERWOOD%2C+MATTHEW+L&rft.inventor=FLEMING%2C+KRISTEN+N&rft.inventor=GUZZO%2C+PETER+R&rft.inventor=HU%2C+MIN&rft.inventor=CUI%2C+WENGE&rft.inventor=ZHA%2C+CONGXIANG&rft.inventor=MANNING%2C+DAVID+D&rft.inventor=NACRO%2C+KASSOUM&rft.inventor=MOLINO%2C+BRUCE+F&rft.inventor=SAMBANDAM%2C+ARUNA&rft.inventor=LIU%2C+SHUANG&rft.date=2014-01-16&rft.externalDBID=B2&rft.externalDocID=AU2012202570BB2 |