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PE20140207A1 - Composiciones y metodos para modular el fxr - Google Patents

Composiciones y metodos para modular el fxr

Info

Publication number
PE20140207A1
PE20140207A1 PE2013001456A PE2013001456A PE20140207A1 PE 20140207 A1 PE20140207 A1 PE 20140207A1 PE 2013001456 A PE2013001456 A PE 2013001456A PE 2013001456 A PE2013001456 A PE 2013001456A PE 20140207 A1 PE20140207 A1 PE 20140207A1
Authority
PE
Peru
Prior art keywords
cyclopropyl
phenyl
fxr
compounds
hexanil
Prior art date
Application number
PE2013001456A
Other languages
English (en)
Inventor
David C Tully
Paul Vincent Rucker
Phillip B Alper
Daniel Mutnick
Donatella Chianelli
Original Assignee
Irm Llc
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 Irm Llc filed Critical Irm Llc
Publication of PE20140207A1 publication Critical patent/PE20140207A1/es

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    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/46—8-Azabicyclo [3.2.1] octane; Derivatives thereof, e.g. atropine, cocaine
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/47—Quinolines; Isoquinolines
    • A61K31/4709—Non-condensed quinolines and containing further heterocyclic rings
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/4965—Non-condensed pyrazines
    • A61K31/497—Non-condensed pyrazines containing further heterocyclic rings
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/50—Pyridazines; Hydrogenated pyridazines
    • A61K31/501—Pyridazines; Hydrogenated pyridazines not condensed and containing further heterocyclic rings
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
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    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/50—Pyridazines; Hydrogenated pyridazines
    • A61K31/5025—Pyridazines; Hydrogenated pyridazines ortho- or peri-condensed with heterocyclic ring systems
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/506—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
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    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
    • A61K31/7052—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides
    • A61K31/706—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom
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    • A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
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    • C07D451/02—Heterocyclic compounds containing 8-azabicyclo [3.2.1] octane, 9-azabicyclo [3.3.1] nonane, or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane or granatane alkaloids, scopolamine; Cyclic acetals thereof containing not further condensed 8-azabicyclo [3.2.1] octane or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane; Cyclic acetals thereof
    • C07D451/04—Heterocyclic compounds containing 8-azabicyclo [3.2.1] octane, 9-azabicyclo [3.3.1] nonane, or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane or granatane alkaloids, scopolamine; Cyclic acetals thereof containing not further condensed 8-azabicyclo [3.2.1] octane or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane; Cyclic acetals thereof with hetero atoms directly attached in position 3 of the 8-azabicyclo [3.2.1] octane or in position 7 of the 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring system
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    • C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
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    • C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
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  • Diabetes (AREA)
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  • Obesity (AREA)
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  • Hospice & Palliative Care (AREA)

Abstract

SE REFIERE A COMPUESTOS DERIVADOS DE OXAZOL DE FORMULA (I) DONDE Z ES FENILENO, CICLOALQUILENO(C5-C7) O HETEROARILO MONOCICLICO O BICICLICO DE 5 A 10 MIEMBROS OPCIONALMENTE SUSTITUIDO CON HALOGENO, ALCOXILO(C1-C6), CICLOPROPILO, ENTRE OTROS; R1 ES FENILO, PIRIDILO, BICICLO[3.1.0]HEXANILO, ESPIRO[2,3]HEXANILO, ENTRE OTROS; R2 ES ALQUILO(C1-C3), HALOALQUILO(C1-C3) O CICLOPROPILO; R3 ES HIDROXIALQUILO(C1-C6), CONR4R5, TETRAZOLILO, ENTRE OTROS, EN DONDE R4 Y R5 SON CADA UNO H O ALQUILO(C1-C6). SON COMPUESTOS PREFERIDOS: 2-[3-({5-CICLOPROPIL-3-[2-(TRIFLUOROMETOXI)FENIL]-1,2-OXAZOL-4-IL}METOXI)-8-AZABICICLO[3.2.1]OCTAN-8-IL]-4-FLUORO-1,3-BENZOTIAZOL-6-CARBOXILATO DE METILO; 2-[(1R,5S)-3-({5-CICLOPROPIL-3-[2-(TRIFLUOROMETOXI)FENIL]-1,2-OXAZOL-4-IL}METOXI)-8-AZABICICLO[3.2.1]OCTAN-8-IL]-4-FLUORO-1,3-BENZOTIAZOL-6-CARBOXILATO DE METILO; ENTRE OTROS. TAMBIEN SE REFIERE A UNA COMPOSICION FARMACEUTICA. DICHOS COMPUESTOS SON MODULADORES DE LA ACTIVIDAD DE LOS RECEPTORES X FERNESOIDES (FXR) SIENDO UTILES EN EL TRATAMIENTO DE COLESTASIS, CIRROSIS BILIAR PRIMARIA, CALCULOS BILIARES
PE2013001456A 2010-12-20 2011-11-30 Composiciones y metodos para modular el fxr PE20140207A1 (es)

Applications Claiming Priority (2)

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US201061425189P 2010-12-20 2010-12-20
US201161554297P 2011-11-01 2011-11-01

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PE20140207A1 true PE20140207A1 (es) 2014-02-23

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EP (1) EP2655370B1 (es)
JP (1) JP5740483B2 (es)
KR (1) KR101626046B1 (es)
CN (1) CN103443099B (es)
AP (1) AP3414A (es)
AR (1) AR084425A1 (es)
AU (1) AU2011345233B2 (es)
BR (1) BR112013015452B1 (es)
CA (1) CA2819825C (es)
CL (1) CL2013001677A1 (es)
CO (1) CO6801729A2 (es)
CR (1) CR20130307A (es)
CU (1) CU24152B1 (es)
CY (1) CY1119530T1 (es)
DK (1) DK2655370T3 (es)
EA (1) EA025569B1 (es)
ES (1) ES2645728T3 (es)
GT (1) GT201300159A (es)
HR (1) HRP20171615T1 (es)
HU (1) HUE034150T2 (es)
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LT (1) LT2655370T (es)
MA (1) MA34767B1 (es)
MX (1) MX338845B (es)
MY (1) MY163216A (es)
NZ (1) NZ613234A (es)
PE (1) PE20140207A1 (es)
PH (1) PH12013501256A1 (es)
PL (1) PL2655370T3 (es)
PT (1) PT2655370T (es)
RS (1) RS56335B1 (es)
SG (1) SG191046A1 (es)
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TW (1) TWI427078B (es)
UY (1) UY33815A (es)
WO (1) WO2012087519A1 (es)
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CU24152B1 (es) * 2010-12-20 2016-02-29 Irm Llc 1,2 oxazol-8-azabiciclo[3,2,1]octano 8 il como moduladores de fxr
EP2545964A1 (en) 2011-07-13 2013-01-16 Phenex Pharmaceuticals AG Novel FXR (NR1H4) binding and activity modulating compounds
PE20150400A1 (es) 2012-05-22 2015-03-27 Genentech Inc Benzamidas n-sustituidas y su uso en el tratamiento del dolor
CN103007081B (zh) * 2012-11-27 2013-12-04 鞠法红 一种治疗非酒精性脂肪肝的中药组合物
US9370515B2 (en) 2013-03-07 2016-06-21 Califia Bio, Inc. Mixed lineage kinase inhibitors and method of treatments
KR102350357B1 (ko) * 2013-11-05 2022-01-14 노파르티스 아게 파르네소이드 x 수용체의 조정을 위한 조성물 및 방법
US10208081B2 (en) 2014-11-26 2019-02-19 Enanta Pharmaceuticals, Inc. Bile acid derivatives as FXR/TGR5 agonists and methods of use thereof
EP3034499A1 (en) 2014-12-17 2016-06-22 Gilead Sciences, Inc. Novel FXR (NR1H4) modulating compounds
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