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AR075367A1 - Inhibidores de glucosilceramida sintasa - Google Patents

Inhibidores de glucosilceramida sintasa

Info

Publication number
AR075367A1
AR075367A1 ARP100100326A ARP100100326A AR075367A1 AR 075367 A1 AR075367 A1 AR 075367A1 AR P100100326 A ARP100100326 A AR P100100326A AR P100100326 A ARP100100326 A AR P100100326A AR 075367 A1 AR075367 A1 AR 075367A1
Authority
AR
Argentina
Prior art keywords
alkyl
ring
independently
ora1
bond
Prior art date
Application number
ARP100100326A
Other languages
English (en)
Original Assignee
Exelixis Inc
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 Exelixis Inc filed Critical Exelixis Inc
Publication of AR075367A1 publication Critical patent/AR075367A1/es

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    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D213/00Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
    • C07D213/02Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/60Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D213/62Oxygen or sulfur atoms
    • C07D213/63One oxygen atom
    • C07D213/64One oxygen atom attached in position 2 or 6
    • C07D213/6432-Phenoxypyridines; Derivatives thereof
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00Drugs for skeletal disorders
    • A61P19/02Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00Drugs for disorders of the metabolism
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00Drugs for disorders of the metabolism
    • A61P3/08Drugs for disorders of the metabolism for glucose homeostasis
    • A61P3/10Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00Antineoplastic agents
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00Drugs for disorders of the cardiovascular system
    • A61P9/10Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
    • 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
    • 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
    • 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
    • C07D405/14Heterocyclic 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 three or more hetero rings
    • 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
    • C07D471/00Heterocyclic 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
    • C07D471/02Heterocyclic 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
    • C07D471/04Ortho-condensed systems
    • 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

Landscapes

  • Organic Chemistry (AREA)
  • Chemical & Material Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Animal Behavior & Ethology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Diabetes (AREA)
  • Obesity (AREA)
  • Hematology (AREA)
  • Endocrinology (AREA)
  • Emergency Medicine (AREA)
  • Urology & Nephrology (AREA)
  • Vascular Medicine (AREA)
  • Cardiology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Immunology (AREA)
  • Orthopedic Medicine & Surgery (AREA)
  • Rheumatology (AREA)
  • Physical Education & Sports Medicine (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Plural Heterocyclic Compounds (AREA)

Abstract

Además comprende una composicion que contiene los compuestos, N-oxidos, y/o sus sales aceptables para uso farmacéutico, y el uso de los compuestos y las composiciones para tratar enfermedades en las cuales la GCS es un mediador o está implicada. Además comprende el uso de los compuestos en y para la preparacion de medicamentos, en particular para tratar enfermedades en las cuales la GCS es un mediador o está implicada. Reivindicacion 1: Un compuesto de la formula (1), o un estereoisomero simple o mezcla de estereoisomeros de los mismos sus N-oxidos, y además opcionalmente como su sal aceptable para uso farmacéutico, donde A es isopropilo, t-butilo, cicloalquilo C3-8, heterociclilo, arilo, o heteroarilo, donde el cicloalquilo, heterociclilo, arilo, y heteroarilo están opcionalmente sustituidos con uno, dos o tres grupos RA, donde cada RA es independientemente RA2, alquilo C1-6, haloalquilo C1-4, arilo, arilalquilo C1-4 o alquilo -C1-4-RA2, donde el arilo del grupo arilalquilo C1-4 está opcionalmente sustituido con uno, dos o tres grupos RA2 donde, cada RA2 es independientemente halogeno, ciano, nitro, -ORA1, -SRA1, -N(RA1)2, -C(O)RA1, -S(O)RA1, -S(O)2RA1, -S(O)N(RA1)2, -S(O)2N(RA1)2, -C(O)ORA1, -C(O)N(RA1)2, -N(RA1)C(O)RA1, -N(RA1)C(O)ORA1, -N(RA1)C(O)N(RA1)2, -N(RA1)S(O)2RA1, -N(RA1)C(=NRA1)N(RA1)2, -P(O)(ORA1)2, o -OP(O)(ORA1)2, donde cada RA1 es independientemente hidrogeno, alquilo C1-4, o haloalquilo C1-4, o dos RA unidos a los átomos de carbono adyacentes, tomados juntos, forman -O-(G)y-O-, donde cada G es independientemente -CH2-, -C(H)(F)-, o -CF2-, y y es 1, 2, o 3; E es -(CH2)-, -C(H)(CH3)-, o -C(O)-; L es -[C(RL)2]p-L1-[C(RL)2]g-, donde p es 1, 2, o 3; q es un entero seleccionado de 0 a (3-p); L1 es un enlace, -O- o -NH- y cada RL es independientemente hidrogeno, metilo, o halometilo; R1 es -N(R10)(R11) o un resto de formula (2), donde R10 es hidrogeno o alquilo C1-4; R11 es -R13,-cicloalquilo C3-6-N(R12)2, -cicloalquilo C3-6-R13, alquilo C1-6-N(R12)2, o alquilo C1-6-R13, donde cada R12 es independientemente hidrogeno o alquilo C1-4; y R13 es (a) un anillo heterociclilo monocíclico de 4 a 10 miembros, bicíclico fusionado de 4 a 10 miembros, bicíclico puenteado de 5 a 10 miembros, o espirobicíclico de 5 a 10 miembros, donde el anillo heterociclilo comprende uno, dos o tres átomos de nitrogeno anular, y opcionalmente comprende un oxígeno anular o átomo de azufre, o (b) un heteroarilo monocíclico de 5 o 6 miembros o un heteroarilo bicíclico fusionado de 8 a 10 miembros, donde el carbono a los cuales éstos están unidos, forman un anillo fenilo; m es 0, 1, 2 o 3; n es 1, 2, o 3; y R5 es independientemente halogeno o alquilo C1-4, donde el grupo alquilo está opcionalmente sustituido con uno, dos, o tres grupos R51 donde cada R51 es independientemente hidroxi o halogeno; siempre que cuando X1 sea -N=, E es -C(O)-, L1 es un enlace o -NH-, A es isopropilo o t-butilo, R1 es un resto de formula (2), y el anillo B es pirrolidinilo, entonces R20 no es -C(O)ORB3 o -C(O)N(RB3)2; y R21, cuando está presente, es -C(O)ORB3 o -C(O)N(RB3)2; siempre que cuando L1 es un enlace, E es -CH2- o -CH(CH3)-, y Q es -NH-, entonces A no es isopropilo o ter-butilo; siempre que cuando L1 es un enlace, A es isopropilo o t-butil. E es -CH2- o -CH(CH3)-, y R1 es un resto de formula (2), entonces el anillo B no es pirazolilo, indazolilo, indolilo, o bencimidazolilo; siempre que cuando E es -CH2- o -CH(CH3)-, R1 es un resto de formula (2), entonces el anillo B es un anillo heterociclilo monocíclico de 4 a 10 miembros, entonces R20 y R21, cuando están presentes, no son arilalquilo C1-4; y siempre que cuando L1 es un enlace, E es -C(O)-, R1 es -N(R10)(R11), R11 es R13, y R13 es 8-azabiciclo[3,2,1]octanillo, entonces R13A, cuando está presente, no es arilalquilo C1-4.
ARP100100326A 2009-02-06 2010-02-05 Inhibidores de glucosilceramida sintasa AR075367A1 (es)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US15043409P 2009-02-06 2009-02-06
PCT/US2010/023080 WO2010091104A1 (en) 2009-02-06 2010-02-03 Glucosylceramide synthase inhibitors

Publications (1)

Publication Number Publication Date
AR075367A1 true AR075367A1 (es) 2011-03-30

Family

ID=42148396

Family Applications (1)

Application Number Title Priority Date Filing Date
ARP100100326A AR075367A1 (es) 2009-02-06 2010-02-05 Inhibidores de glucosilceramida sintasa

Country Status (3)

Country Link
AR (1) AR075367A1 (es)
TW (1) TW201040156A (es)
WO (1) WO2010091104A1 (es)

Families Citing this family (14)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
RU2018104472A (ru) * 2011-03-18 2019-02-22 Джензим Корпорейшн Ингибиторы глюкозилцерамид-синтазы
JOP20130273B1 (ar) * 2012-09-11 2021-08-17 Genzyme Corp مثبطات انزيم (سينثاز) غلوكوسيل سيراميد
JO3713B1 (ar) 2013-03-15 2021-01-31 Genzyme Corp أشكال ملح (s)-كوينوكليدين-3-يل(2-(2-(4-فلوروفينيل)ثيازول-4-يل)بروبان-2-يل)كارباميت
EP3318277A1 (en) 2016-11-04 2018-05-09 Institut du Cerveau et de la Moelle Epiniere-ICM Inhibitors of glucosylceramide synthase for the treatment of motor neuron diseases
AU2020218185B2 (en) 2019-02-04 2025-01-23 Genzyme Corporation Treatment of ciliopathies using inhibitors of glucosylceramide synthase (GCS)
RS65662B1 (sr) 2019-11-15 2024-07-31 Yuhan Corp Derivati koji imaju 2,3-dihidro-1h-inden ili 2,3-dihidrobenzofuranski deo ili njihovu farmaceutski prihvatljivu so i farmaceutske kompozicije koje ih sadrže
KR20210059633A (ko) * 2019-11-15 2021-05-25 주식회사유한양행 신규의 1,2,3,4-테트라하이드로나프탈렌 모이어티를 갖는 유도체 또는 이의 약학적으로 허용가능한 염, 이의 제조방법, 및 이를 포함하는 약학 조성물
AU2021215396A1 (en) 2020-02-03 2022-09-29 Genzyme Corporation Methods for treating neurological symptoms associated with lysosomal storage diseases
WO2021221953A1 (en) 2020-04-28 2021-11-04 The Regents Of The University Of Michigan Pyridine inhibitors of glucosylceramide synthase and therapeutic methods using the same
US11857512B2 (en) 2020-07-24 2024-01-02 Genzyme Corporation Pharmaceutical compositions comprising venglustat
EP4213843A4 (en) * 2020-09-17 2024-09-11 Merck Sharp & Dohme LLC MODIFIED IMIDAZOPYRIDINES AS GLUCOSYLCERAMIDE SYNTHASE INHIBITORS
EP4213832A4 (en) * 2020-09-18 2024-10-16 Merck Sharp & Dohme LLC Modified benzofuran-carboxamides as glucosylceramide synthase inhibitors
WO2023172475A2 (en) * 2022-03-11 2023-09-14 Merck Sharp & Dohme Llc Non-aromatic cyclic-pyrimidine analogs as glucosylceramide synthase inhibitors
US20250171467A1 (en) * 2022-03-14 2025-05-29 Merck Sharp & Dohme Llc Fused pyrazole amide analogs as glucosylceramide synthase inhibitors

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US4107288A (en) 1974-09-18 1978-08-15 Pharmaceutical Society Of Victoria Injectable compositions, nanoparticles useful therein, and process of manufacturing same
US5145684A (en) 1991-01-25 1992-09-08 Sterling Drug Inc. Surface modified drug nanoparticles
GB0400812D0 (en) 2004-01-14 2004-02-18 Celltech R&D Ltd Novel compounds
US8003617B2 (en) 2004-11-10 2011-08-23 Genzyme Corporation Methods of treating diabetes mellitus
ES2277745B1 (es) * 2005-06-14 2008-06-01 Laboratorios Almirall S.A. Derivados n-amida de 8-azabiciclo /3.2.1/oct-3-ilo como antagonistas de ccr1.
EP2594564B1 (en) * 2007-05-31 2016-09-28 Genzyme Corporation 2-acylaminopropanol-type glucosylceramide synthase inhibitors

Also Published As

Publication number Publication date
TW201040156A (en) 2010-11-16
WO2010091104A8 (en) 2011-04-07
WO2010091104A1 (en) 2010-08-12

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