DK1954669T3 - Substituerede phenethylaminer med serotonerg og/eller norepinephrinerg aktivitet - Google Patents

Substituerede phenethylaminer med serotonerg og/eller norepinephrinerg aktivitet Download PDF

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Publication number
DK1954669T3
DK1954669T3 DK06844628.5T DK06844628T DK1954669T3 DK 1954669 T3 DK1954669 T3 DK 1954669T3 DK 06844628 T DK06844628 T DK 06844628T DK 1954669 T3 DK1954669 T3 DK 1954669T3
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compound
group
enantiomer
refers
compounds
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Thomas G Gant
Sepehr Sarshar
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Auspex Pharmaceuticals Inc
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    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/13—Amines
    • A61K31/135—Amines having aromatic rings, e.g. ketamine, nortriptyline
    • A61K31/137—Arylalkylamines, e.g. amphetamine, epinephrine, salbutamol, ephedrine or methadone
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    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/13—Amines
    • A61K31/135—Amines having aromatic rings, e.g. ketamine, nortriptyline
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    • C07C217/54—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having etherified hydroxy groups bound to carbon atoms of at least one six-membered aromatic ring and amino groups bound to acyclic carbon atoms or to carbon atoms of rings other than six-membered aromatic rings of the same carbon skeleton
    • C07C217/74—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having etherified hydroxy groups bound to carbon atoms of at least one six-membered aromatic ring and amino groups bound to acyclic carbon atoms or to carbon atoms of rings other than six-membered aromatic rings of the same carbon skeleton with rings other than six-membered aromatic rings being part of the carbon skeleton
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    • C07C235/00—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms
    • C07C235/02—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to acyclic carbon atoms and singly-bound oxygen atoms bound to the same carbon skeleton
    • C07C235/32—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to acyclic carbon atoms and singly-bound oxygen atoms bound to the same carbon skeleton the carbon skeleton containing six-membered aromatic rings
    • C07C235/34—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to acyclic carbon atoms and singly-bound oxygen atoms bound to the same carbon skeleton the carbon skeleton containing six-membered aromatic rings having the nitrogen atoms of the carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms
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    • C07C255/37—Carboxylic acid nitriles having cyano groups bound to acyclic carbon atoms having cyano groups bound to acyclic carbon atoms of a carbon skeleton containing at least one six-membered aromatic ring the carbon skeleton being further substituted by etherified hydroxy groups
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Claims (18)

1. Forbindelse valgt fra gruppen bestående af:
eller en enkelt enantiomer, en blanding af (+)-enantiomeren og (-)-enantiomeren, en individuel diastereomer, en blanding af diastereomerer, eller et farmaceutisk acceptabelt salt eller solvat deraf, hvor deuterium-berigelse i forbindelserne er mindst 1%.
2. Farmaceutisk sammensætning omfattende en terapeutisk effektiv mængde af en forbindelse ifølge krav 1, eller en enkelt enantiomer afen forbindelse ifølge krav 1, en blanding af (+)-enantiomeren, og (-)-enantiomeren afen forbindelse ifølge krav 1, en individuel diastereomer afen forbindelse ifølge krav 1, en blanding af diastereomerer af en forbindelse ifølge krav 1, eller et farmaceutisk acceptabelt salt eller solvat deraf, med en farmaceutisk acceptabel bærer.
3. Forbindelsen eller den farmaceutiske sammensætning ifølge krav 1 eller 2, hvor blandingen er på 90 vægtprocent eller mere af (-)-enantiomeren og 10 vægtprocent eller mindre af (+)-enantiomeren.
4. Forbindelsen eller den farmaceutiske sammensætning ifølge krav 1 eller 2, hvor blandingen er på 90 vægtprocent eller mere af (+)-enantiomeren og 10 vægtprocent eller mindre af (-)-enantiomeren.
5. Den farmaceutiske sammensætning ifølge krav 2, hvor sammensætningen er egnet til oral, parenteral, eller intravenøs infusionadministration.
6. Den farmaceutiske sammensætning ifølge krav 5, hvor den orale administration omfatter administrering af en tablet eller en kapsel.
7. Den farmaceutiske sammensætning ifølge krav 2, hvor forbindelsen ifølge krav 1 er administreret i en dosis på 0,5 milligram til 400 milligram total dagligt.
8. Forbindelsen ifølge krav 1 eller den farmaceutiske sammensætning ifølge et hvilket som helst af kravene 2 til 5 til anvendelse i behandling af et pattedyr som lider af en sygdom eller tilstand som involverer monoamin-genoptagelse eller monoaminreceptor-relateret sygdom.
9. Forbindelsen eller den farmaceutiske sammensætning ifølge krav 8, hvor monoaminsygdommen eller -tilstanden er valgt fra gruppen bestående af en psykotropisk sygdom, en angstsygdom, en generaliseret angstsygdom, depression, en post-traumatisk stresssygdom, en obsessiv-kompulsiv tilstand, en panikangst, hedeture, senildemens, migræne, hepatopulmonær syndrom, kronisk smerte, nociceptiv smerte, neuropatisk smerte, smertefuld retinopathia diabetica, bipolar depression, obstruktiv søvnapnø, en psykiatrisk lidelse, præmenstruel dysfori, socialfobi, social angstsygdom, urininkontinens, anoreksi, bulimia nervosa, fedme, iskæmi, hovedskade, calciumoverbelastning i hjerneceller, stofafhængighed, og præmatur ejakulation.
10. Forbindelsen af farmaceutisk sammensætning ifølge krav 8 eller 9, hvor forbindelsen ifølge formel 1 påvirker: mindsket inter-individuel variation i plasmaniveauer af forbindelsen eller en metabolit deraf sammenlignet med den ikke-isotopisk berigede forbindelse; øget gennemsnitlige plasmaniveauer af forbindelsen pr. dosisenhed deraf som sammenlignet med den ikke-isotopisk berigede forbindelse; mindsket gennemsnitlige plasmaniveauer af mindst en metabolit af forbindelsen pr. dosisenhed deraf som sammenlignet med den ikke-isotopisk berigede forbindelse; en mindsket inhibering af mindst en cytokrom P450 isoform i pattedyrsindivider pr. dosisenhed deraf som sammenlignet med den ikke-isotopisk berigede forbindelse; eller et mindsket stofskifte med mindst en polymorft udtrykt cytokrom P450 isoform i pattedyrsindivider pr. dosisenhed deraf som sammenlignet med den ikke-isotopisk berigede forbindelse.
11. Forbindelsen eller den farmaceutiske sammensætning ifølge krav 10 hvor forbindelsen ifølge formel I påvirker et mindsket stofskifte med mindst en polymorft-udtrykt cytokrom P450 isoform valgt fra gruppen bestående af CYP2C8, CYP2C9, CYP2C19, og CYP2D6 eller forbindelsen ifølge formel I påvirker en mindsket inhibition af mindst en cytokrom P450 isoform valgt fra gruppen bestående af CYP1A1, CYP1A2, CYP1B1, CYP2A6, CYP2A13, CYP2B6, CYP2C8, CYP2C9, CYP2C18, CYP2C19, CYP2D6, CYP2E1, CYP2G1, CYP2J2, CYP2R1, CYP2S1, CYP3A4, CYP3A5, CYP3A5P1, CYP3A5P2, CYP3A7, CYP4A11, CYP4B1, CYP4F2, CYP4F3, CYP4F8, CYP4F11, CYP4F12, CYP4X1, CYP4Z1, CYP5A1, CYP7A1, CYP7B1, CYP8A1, CYP8B1, CYP11A1, CYP11B1, CYP11B2, CYP17, CYP19, CYP21, CYP24, CYP26A1, CYP26B1, CYP27A1, CYP27B1, CYP39, CYP46, og CYP51.
12. Forbindelsen eller sammensætningen ifølge krav 8, hvor forbindelsen ifølge formel I fremkalder en forbedret klinisk virkning under behandlingen af pattedyret pr. dosisenhed deraf som sammenlignet med den ikke-isotopisk berigede forbindelse.
13. Forbindelsen eller sammensætningen ifølge krav 12, hvor den forbedrede kliniske virkning omfatter en virkning valgt fra gruppen bestående af fremmet helbredende hastighed, fremmet symptomlindringshastighed, forbedret patient compliance, og mindsket stofmisbrugsafvænnings-symptomatologi under behandlingen.
14. Forbindelsen ifølge krav 1 eller en farmaceutisk sammensætning ifølge et hvilket som helst af kravene 2 til 5 til anvendelse i behandling af et pattedyr til en stofafhængighed omfattende co-administrering af forbindelsen eller sammensætningen og en anden bestanddel, hvor den anden bestanddel omfatter en terapeutisk effektiv mængde afen opioidantagonist, som kan vælges fra gruppen bestående af nalmefen, naltrexon, og naloxon.
15. Forbindelsen eller sammensætningen ifølge krav 14, hvor stofafhængigheden er valgt fra gruppen bestående af tobaksafhængighed, alkoholisme, marihuanaafhængighed, og kokainafhængighed.
16. Forbindelsen eller sammensætningen ifølge krav 14 eller 15, hvor den første bestanddel er administreret: efterfølgende administrationen af den anden bestanddel; i alt væsentligt samtidigt med den anden bestanddel; eller før den anden bestanddel.
17. Forbindelsen eller sammensætningen ifølge et hvilket som helst af kravene 14 til 16, hvor forbindelsen eller sammensætningen fremkalder en forbedret klinisk virkning for behandlingen afen stofafhængighed, som sammenlignet med den ikke-isotopisk berigede analog deraf.
18. Forbindelsen eller sammensætningen ifølge krav 17, hvor den forbedrede kliniske virkning omfatter en virkning valgt fra gruppen bestående af fremmet helbredende hastighed, fremmet symptomlindringshastighed, forbedret patient compliance, og mindsket stofmisbrugsafvænningssymptomatologi under behandling.
DK06844628.5T 2005-12-01 2006-11-30 Substituerede phenethylaminer med serotonerg og/eller norepinephrinerg aktivitet DK1954669T3 (da)

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US74131505P 2005-12-01 2005-12-01
US84136606P 2006-08-30 2006-08-30
PCT/US2006/045673 WO2007064697A1 (en) 2005-12-01 2006-11-30 Substituted phenethylamines with serotoninergic and/or norepinephrinergic activity

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US (9) US7456317B2 (da)
EP (2) EP1954669B1 (da)
JP (1) JP5302005B2 (da)
KR (1) KR101068180B1 (da)
AU (1) AU2006320655A1 (da)
BR (1) BRPI0620587A2 (da)
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EA (1) EA200801488A1 (da)
ES (1) ES2549079T3 (da)
HK (1) HK1125626A1 (da)
HU (1) HUE027865T2 (da)
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PT (1) PT1954669E (da)
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US20100076087A1 (en) * 2005-10-06 2010-03-25 Auspex Pharmaceuticals, Inc. Methods of reduction of interpatient variability
EP1954669B1 (en) * 2005-12-01 2015-07-08 Auspex Pharmaceuticals, Inc. Substituted phenethylamines with serotoninergic and/or norepinephrinergic activity
KR101338343B1 (ko) * 2006-08-31 2013-12-06 신닛테츠 수미킨 가가쿠 가부시키가이샤 유기 전계발광 소자 재료 및 유기 전계발광 소자
PL2125698T3 (pl) 2007-03-15 2017-03-31 Auspex Pharmaceuticals, Inc. Deuterowana wenlafaksyna-d9
US7767860B2 (en) 2007-09-06 2010-08-03 Auspex Pharmaceuticals, Inc Substituted amino alcohols
US20110053968A1 (en) 2009-06-09 2011-03-03 Auspex Pharmaceuticals, Inc. Aminopyrimidine inhibitors of tyrosine kinase
WO2010147830A2 (en) * 2009-06-15 2010-12-23 Auspex Pharmaceuticals, Inc. Aminothiazole modulators of beta-3-adrenoreceptor
CN102869775A (zh) 2009-09-30 2013-01-09 哈佛大学校长及研究员协会 通过调节自噬抑制基因产物调节自噬的方法
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