ECSP18060864A - Derivados de 3-(carboximetil)-8-amino-2-oxo-1,3-diaza-espiro-[4.5]- decano - Google Patents

Derivados de 3-(carboximetil)-8-amino-2-oxo-1,3-diaza-espiro-[4.5]- decano

Info

Publication number
ECSP18060864A
ECSP18060864A ECSENADI201860864A ECDI201860864A ECSP18060864A EC SP18060864 A ECSP18060864 A EC SP18060864A EC SENADI201860864 A ECSENADI201860864 A EC SENADI201860864A EC DI201860864 A ECDI201860864 A EC DI201860864A EC SP18060864 A ECSP18060864 A EC SP18060864A
Authority
EC
Ecuador
Prior art keywords
diaza
decane
spiro
oxo
derivatives
Prior art date
Application number
ECSENADI201860864A
Other languages
English (en)
Inventor
Klaus Schiene
Thomas Koch
Achim Kless
Sven Kühnert
Florian Jakob
Anita Wegert
Wolfgang Schröder
Klaus Linz
Paul Ratcliffe
René Michael Koenigs
Ruth Jostock
Original Assignee
Gruenenthal Gmbh
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Gruenenthal Gmbh filed Critical Gruenenthal Gmbh
Publication of ECSP18060864A publication Critical patent/ECSP18060864A/es

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Classifications

    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/41Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A61K31/41641,3-Diazoles
    • A61K31/41841,3-Diazoles condensed with carbocyclic rings, e.g. benzimidazoles
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00Drugs for disorders of the nervous system
    • A61P25/04Centrally acting analgesics, e.g. opioids
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D235/00Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings
    • C07D235/02Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings condensed with carbocyclic rings or ring systems
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D401/00Heterocyclic 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
    • C07D401/02Heterocyclic 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
    • C07D401/06Heterocyclic 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 linked by a carbon chain containing only aliphatic carbon atoms
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D401/00Heterocyclic 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
    • C07D401/02Heterocyclic 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
    • C07D401/12Heterocyclic 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 linked by a chain containing hetero atoms as chain links
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D403/00Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
    • C07D403/02Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
    • C07D403/06Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D403/00Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
    • C07D403/02Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
    • C07D403/12Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D405/00Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
    • C07D405/02Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
    • C07D405/06Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D405/00Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
    • C07D405/02Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
    • C07D405/12Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D409/00Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
    • C07D409/02Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
    • C07D409/04Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring-member bond
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D409/00Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
    • C07D409/02Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
    • C07D409/12Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D413/00Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D413/02Heterocyclic 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
    • C07D413/06Heterocyclic 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 linked by a carbon chain containing only aliphatic carbon atoms
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D413/00Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D413/02Heterocyclic 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
    • C07D413/12Heterocyclic 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 linked by a chain containing hetero atoms as chain links
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D417/00Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
    • C07D417/02Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
    • C07D417/12Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D487/00Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
    • C07D487/02Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
    • C07D487/04Ortho-condensed systems
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K5/00Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
    • C07K5/04Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
    • C07K5/06Dipeptides
    • C07K5/06008Dipeptides with the first amino acid being neutral
    • C07K5/06017Dipeptides with the first amino acid being neutral and aliphatic
    • C07K5/06026Dipeptides with the first amino acid being neutral and aliphatic the side chain containing 0 or 1 carbon atom, i.e. Gly or Ala

Abstract

Derivados de 3-(carboximetil)-8-amino-2-oxo-1,3-diaza-espiro-[4.5]-decano, su preparación y su uso en medicamentos, en particular en el tratamiento del dolor.
ECSENADI201860864A 2016-01-13 2018-08-13 Derivados de 3-(carboximetil)-8-amino-2-oxo-1,3-diaza-espiro-[4.5]- decano ECSP18060864A (es)

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
EP16151014 2016-01-13

Publications (1)

Publication Number Publication Date
ECSP18060864A true ECSP18060864A (es) 2018-08-31

Family

ID=55129635

Family Applications (1)

Application Number Title Priority Date Filing Date
ECSENADI201860864A ECSP18060864A (es) 2016-01-13 2018-08-13 Derivados de 3-(carboximetil)-8-amino-2-oxo-1,3-diaza-espiro-[4.5]- decano

Country Status (29)

Country Link
US (7) US20170197971A1 (es)
EP (1) EP3402785B1 (es)
JP (1) JP6854823B2 (es)
KR (1) KR20180097733A (es)
CN (1) CN108779075B (es)
AR (1) AR107358A1 (es)
AU (1) AU2017206910B2 (es)
BR (1) BR112018014296B1 (es)
CA (1) CA3011180A1 (es)
CL (1) CL2018001910A1 (es)
CO (1) CO2018008449A2 (es)
CY (1) CY1122892T1 (es)
DK (1) DK3402785T3 (es)
EA (1) EA034904B1 (es)
EC (1) ECSP18060864A (es)
ES (1) ES2793384T3 (es)
HR (1) HRP20200809T1 (es)
HU (1) HUE049134T2 (es)
IL (1) IL260497B (es)
LT (1) LT3402785T (es)
MX (1) MX2018008646A (es)
NZ (1) NZ745184A (es)
PL (1) PL3402785T3 (es)
PT (1) PT3402785T (es)
RS (1) RS60224B1 (es)
SI (1) SI3402785T1 (es)
TW (1) TWI640514B (es)
WO (1) WO2017121649A1 (es)
ZA (1) ZA201805358B (es)

Families Citing this family (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2017121650A1 (en) 2016-01-13 2017-07-20 Grünenthal GmbH 8-amino-2-oxo-1,3-diaza-spiro-[4.5]-decane derivatives
CA3011180A1 (en) 2016-01-13 2017-07-20 Grunenthal Gmbh 3-(carboxymethyl)-8-amino-2-oxo-1,3-diaza-spiro-[4.5]-decane derivatives
RS60223B1 (sr) 2016-01-13 2020-06-30 Gruenenthal Gmbh Derivati 3-(karboksietil)-8-amino-2-okso-1,3-diaza-spiro-[4.5]-dekana
EP3402784B1 (en) 2016-01-13 2020-03-11 Grünenthal GmbH 3-((hetero-)aryl)-alkyl-8-amino-2-oxo-1,3-diaza-spiro-[4.5]-decane derivatives
EA037598B1 (ru) 2016-01-13 2021-04-20 Грюненталь Гмбх Производные 3-((гетеро-)арил)-8-амино-2-оксо-1,3-диазаспиро[4,5]декана
WO2019039855A2 (ko) 2017-08-22 2019-02-28 주식회사 엘지화학 방열 소재의 혼합 방법

Family Cites Families (26)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
FR2734265B1 (fr) 1995-05-17 1997-06-13 Adir Nouveaux composes spiro heterocycliques, leur procede de preparation et les compositions pharmaceutiques les contenant
KR100729242B1 (ko) 2001-04-18 2007-06-15 유로-셀티크 소시에떼 아노뉨 노시셉틴 유사체
DE10130020A1 (de) 2001-06-25 2003-12-04 Gruenenthal Gmbh Substituierte 1-Oxa-2,8-diaza-spiro[4.5]dec-2-en-derivate
DE10210195B4 (de) 2002-03-07 2005-12-15 Schwarz Pharma Ag Verwendung von 1,3-Diazaspiro-[4,5]decan-2,4-dithion zur Behandlung von Schmerz
DE60330456D1 (de) 2002-07-05 2010-01-21 Targacept Inc N-aryl diazaspirozyklische verbindungen, deren verwendung und das verfahren zu ihren herstellung
DE10252667A1 (de) * 2002-11-11 2004-05-27 Grünenthal GmbH Spirocyclische Cyclohexan-Derivate
EP1628978A2 (en) 2003-05-23 2006-03-01 Zealand Pharma A/S Triaza-spiro compounds as nociceptin analogues and uses thereof
JO2676B1 (en) 2004-04-06 2012-06-17 جانسين فارماسوتيكا ان. في Derivatives of second-aza-spiro- (5,4) -dikan and their use as antihistamines
DE102005023784A1 (de) 2005-05-19 2006-11-30 Grünenthal GmbH Substituierte Spiro-Verbindungen und deren Verwendung zur Herstellung von Arzneimitteln
DE102005044813A1 (de) 2005-05-19 2007-10-04 Grünenthal GmbH Substituierte Spiro-Verbindungen und deren Verwendung zur Herstellung von Arzneimitteln
DE102005030051A1 (de) 2005-06-27 2006-12-28 Grünenthal GmbH Substituierte 1-Oxa-3,8-diazaspiro[4,5]-decan-2-on-Verbindungen und deren Verwendung zur Herstellung von Arzneimitteln
DE102006019597A1 (de) 2006-04-27 2007-10-31 Grünenthal GmbH Spirocyclische Cyclohexan-Derivate
CA2666489C (en) 2006-10-19 2012-10-02 F. Hoffmann-La Roche Ag Imidazolone and imidazolidinone derivatives as 11b-hsd1 inhibitors for diabetes
WO2008124209A1 (en) 2007-04-09 2008-10-16 Janssen Pharmaceutica, N.V. 1,3,8-trisubstituted-1,3,8-triaza-spiro[4.5]decan-4-one derivatives as ligands of the orl-i receptor for the treatment of anxiety and depression
CN102046595B (zh) 2008-03-27 2014-03-05 格吕伦塔尔有限公司 取代的4-氨基环己烷衍生物
TW201038572A (en) 2009-03-25 2010-11-01 Gruenenthal Gmbh Substituted spiro-amide compounds
WO2010151815A2 (en) 2009-06-25 2010-12-29 Abbott Laboratories 3,9-diazaspiro[5,5]undecane amides and ureas and methods of use thereof
TWI582092B (zh) * 2010-07-28 2017-05-11 歌林達股份有限公司 順式-四氫-螺旋(環己烷-1,1’-吡啶[3,4-b]吲哚)-4-胺-衍生物
EP3154971A4 (en) * 2014-06-13 2017-11-01 Purdue Pharma L.P. Heterocyclic morphinan derivatives and use thereof
AR107354A1 (es) 2016-01-13 2018-04-18 Bristol Myers Squibb Co Salicilamidas espiroheptanos y compuestos relacionados como inhibidores de rock
RS60223B1 (sr) 2016-01-13 2020-06-30 Gruenenthal Gmbh Derivati 3-(karboksietil)-8-amino-2-okso-1,3-diaza-spiro-[4.5]-dekana
KR102417487B1 (ko) 2016-01-13 2022-07-06 노보 노르디스크 에이/에스 지방산 치환기를 가진 egf(a) 유사체
CA3011180A1 (en) 2016-01-13 2017-07-20 Grunenthal Gmbh 3-(carboxymethyl)-8-amino-2-oxo-1,3-diaza-spiro-[4.5]-decane derivatives
EP3402784B1 (en) 2016-01-13 2020-03-11 Grünenthal GmbH 3-((hetero-)aryl)-alkyl-8-amino-2-oxo-1,3-diaza-spiro-[4.5]-decane derivatives
WO2017121650A1 (en) 2016-01-13 2017-07-20 Grünenthal GmbH 8-amino-2-oxo-1,3-diaza-spiro-[4.5]-decane derivatives
EA037598B1 (ru) 2016-01-13 2021-04-20 Грюненталь Гмбх Производные 3-((гетеро-)арил)-8-амино-2-оксо-1,3-диазаспиро[4,5]декана

Also Published As

Publication number Publication date
BR112018014296A2 (pt) 2019-01-22
AU2017206910B2 (en) 2020-07-16
CN108779075A (zh) 2018-11-09
BR112018014296B1 (pt) 2023-10-31
US10807989B2 (en) 2020-10-20
PT3402785T (pt) 2020-05-15
US20200399280A1 (en) 2020-12-24
HRP20200809T1 (hr) 2020-08-07
HUE049134T2 (hu) 2020-08-28
ZA201805358B (en) 2024-03-27
KR20180097733A (ko) 2018-08-31
WO2017121649A1 (en) 2017-07-20
RS60224B1 (sr) 2020-06-30
US20230174540A1 (en) 2023-06-08
AR107358A1 (es) 2018-04-25
CO2018008449A2 (es) 2018-09-10
US20170197971A1 (en) 2017-07-13
CN108779075B (zh) 2022-01-11
SI3402785T1 (sl) 2020-07-31
US20180282341A1 (en) 2018-10-04
EA034904B1 (ru) 2020-04-03
CA3011180A1 (en) 2017-07-20
JP2019501940A (ja) 2019-01-24
CL2018001910A1 (es) 2018-10-19
PL3402785T3 (pl) 2020-07-27
TWI640514B (zh) 2018-11-11
US20210179627A1 (en) 2021-06-17
EP3402785B1 (en) 2020-02-26
ES2793384T3 (es) 2020-11-13
US20190382407A1 (en) 2019-12-19
DK3402785T3 (da) 2020-04-20
EP3402785A1 (en) 2018-11-21
CY1122892T1 (el) 2021-10-29
TW201731823A (zh) 2017-09-16
MX2018008646A (es) 2018-11-19
AU2017206910A1 (en) 2018-08-30
LT3402785T (lt) 2020-04-10
JP6854823B2 (ja) 2021-04-07
US20190106430A1 (en) 2019-04-11
IL260497B (en) 2020-08-31
EA201891612A1 (ru) 2019-01-31
NZ745184A (en) 2024-03-22

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