AR085249A1 - DERIVATIVES OF OXIMA AS GPR119 AGONISTS - Google Patents

DERIVATIVES OF OXIMA AS GPR119 AGONISTS

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Publication number
AR085249A1
AR085249A1 ARP120100513A AR085249A1 AR 085249 A1 AR085249 A1 AR 085249A1 AR P120100513 A ARP120100513 A AR P120100513A AR 085249 A1 AR085249 A1 AR 085249A1
Authority
AR
Argentina
Prior art keywords
aryl
optionally substituted
alkyl
cycloalkyl
sulfur
Prior art date
Application number
Other languages
Spanish (es)
Inventor
Hyun Woo Joo
Young Kwan Kim
Eun Sil Choi
Myoung Yeol Kim
Heui Sul Park
Tae Hee Lee
Hyo Shin Kwak
Dong Sup Shim
Original Assignee
Lg Life Sciences Ltd
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 Lg Life Sciences Ltd filed Critical Lg Life Sciences Ltd
Publication of AR085249A1 publication Critical patent/AR085249A1/en

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    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D451/00Heterocyclic 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
    • C07D451/02Heterocyclic 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
    • C07D451/04Heterocyclic 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
    • C07D451/06Oxygen atoms
    • 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
    • A61K31/495Heterocyclic 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
    • A61K31/496Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00Drugs for skeletal disorders
    • A61P19/08Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
    • A61P19/10Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease for osteoporosis
    • 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
    • A61P3/06Antihyperlipidemics
    • 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
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D211/00Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
    • C07D211/04Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D211/06Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
    • C07D211/36Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members 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
    • C07D211/40Oxygen atoms
    • C07D211/44Oxygen atoms attached in position 4
    • C07D211/46Oxygen atoms attached in position 4 having a hydrogen atom as the second substituent in position 4
    • 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
    • C07D401/04Heterocyclic 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 directly linked by a ring-member-to-ring-member bond
    • 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
    • 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
    • C07D401/14Heterocyclic 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 three or more hetero rings
    • 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
    • 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
    • C07D413/04Heterocyclic 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 directly linked by a ring-member-to-ring-member bond
    • 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
    • C07D413/14Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
    • 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
    • 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
    • C07D417/14Heterocyclic 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 three or more hetero rings

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

Abstract

La presente se refiere a derivados de oxima de la fórmula (1), a un método para su preparación, a una composición farmacéutica que los contiene y al uso de los mismos. Los derivados de oxima de acuerdo con la presente actúan como agonistas de GPR119 para estimular la secreción de insulina y promover la formación de GLP-1 para la prevención o el tratamiento de la diabetes tipo 2, las complicaciones de la diabetes, la obesidad, la dislipidemia o la osteoporosis. En donde, RA, RB, n, Ar, A, B, R1 y R2 son como se definen en la presente.Reivindicación 1: Derivados de oxima de la fórmula (1), o sales o isómeros farmacéuticamente aceptables de los mismos, caracterizados porque: RA representa un cicloalquilo de 4 a 7 miembros parcialmente o completamente saturado; RB representa un heterociclo de 4 a 7 miembros parcialmente o completamente saturado, o un sistema de anillo fusionado [5.5], [5.6], [5.7], [6.6] ó [6.7] que consiste en dos anillos; R1 y R2 representan independientemente hidrógeno, halógeno o alquilo; n representa un entero de 0 a 10 en cada anillo; A representa nitrógeno o carbono; B es seleccionado entre el grupo de fórmulas (2), en donde: D representa carbono, nitrógeno, oxígeno o azufre; R3, R4 y R5 son independientemente hidrógeno o halógeno, o representan en cada caso arilo, arilalquilo, alquilo, cicloalquilo, cicloalquilalquilo, heterociclilo, heterociclilalquilo o amina, opcionalmente sustituidos; con la condición de que, cuando D es oxígeno o azufre, ambos, R3 y R4, no existen; cuando D es azufre, R5 no es amina; cuando D es nitrógeno, R3 no existe; cuando D es carbono, dos grupos seleccionados entre R3, R4 y R5 están unidos entre si para formar un heterociclo o cicloalquilo de 3 a 7 miembros opcionalmente sustituido, o para formar un heteroarilo o arilo de 5 ó 6 miembros, opcionalmente sustituido; E, F, G, H e I representan independientemente carbono, nitrógeno, oxígeno o azufre para formar un heteroarilo o arilo de 6 miembros, o formar un heteroarilo o arilo de 5 miembros, opcionalmente benzo-fusionado, excluyendo uno de E, F, G, H e I; n representa un entero de 0 a 5; R6 es hidrógeno o halógeno; o representa alquilo, cicloalquilo, arilo, arilalquilo, heterocicloalquilo o heteroarilalquilo, opcionalmente sustituidos; o representa hidroxi o amina opcionalmente sustituidos con 1 ó 2 alquilo o arilo, en donde dos sustituyentes de amina están unidos entre sí para formar un heterociclilo de 3 a 7 miembros; J representa sulfonilo o alquileno C1-4, opcionalmente sustituido; R7 es hidrógeno o halógeno, o representa alquilo, cicloalquilo, arilo, heteroarilo o heterociclilo, opcionalmente sustituidos; y Ar representa heteroarilo o arilo, opcionalmente sustituido.This refers to oxime derivatives of the formula (1), a method for their preparation, a pharmaceutical composition containing them and the use thereof. Oxime derivatives according to the present act as agonists of GPR119 to stimulate insulin secretion and promote the formation of GLP-1 for the prevention or treatment of type 2 diabetes, complications of diabetes, obesity, dyslipidemia or osteoporosis. Wherein, RA, RB, n, Ar, A, B, R1 and R2 are as defined herein. Claim 1: Oxime derivatives of the formula (1), or pharmaceutically acceptable salts or isomers thereof, characterized because: RA represents a partially or fully saturated cycloalkyl of 4 to 7 members; RB represents a partially or fully saturated 4- to 7-membered heterocycle, or a fused ring system [5.5], [5.6], [5.7], [6.6] or [6.7] consisting of two rings; R1 and R2 independently represent hydrogen, halogen or alkyl; n represents an integer from 0 to 10 in each ring; A represents nitrogen or carbon; B is selected from the group of formulas (2), where: D represents carbon, nitrogen, oxygen or sulfur; R3, R4 and R5 are independently hydrogen or halogen, or in each case represent aryl, arylalkyl, alkyl, cycloalkyl, cycloalkylalkyl, heterocyclyl, heterocyclyl alkyl or amine, optionally substituted; with the proviso that, when D is oxygen or sulfur, both R3 and R4 do not exist; when D is sulfur, R5 is not amine; when D is nitrogen, R3 does not exist; when D is carbon, two groups selected from R3, R4 and R5 are linked together to form an optionally substituted 3- or 7-membered heterocycle or cycloalkyl, or to form an optionally substituted 5- or 6-membered heteroaryl or aryl; E, F, G, H and I independently represent carbon, nitrogen, oxygen or sulfur to form a 6-membered heteroaryl or aryl, or form a 5-membered heteroaryl or aryl, optionally benzo-fused, excluding one of E, F, G, H and I; n represents an integer from 0 to 5; R6 is hydrogen or halogen; or represents optionally substituted alkyl, cycloalkyl, aryl, arylalkyl, heterocycloalkyl or heteroarylalkyl; or represents hydroxy or amine optionally substituted with 1 or 2 alkyl or aryl, wherein two amine substituents are linked together to form a 3- to 7-membered heterocyclyl; J represents sulfonyl or C1-4 alkylene, optionally substituted; R7 is hydrogen or halogen, or represents optionally substituted alkyl, cycloalkyl, aryl, heteroaryl or heterocyclyl; and Ar represents heteroaryl or aryl, optionally substituted.

ARP120100513 2011-02-17 2012-02-16 DERIVATIVES OF OXIMA AS GPR119 AGONISTS AR085249A1 (en)

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
KR20110014298 2011-02-17

Publications (1)

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AR085249A1 true AR085249A1 (en) 2013-09-18

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KR (1) KR101456286B1 (en)
AR (1) AR085249A1 (en)
TW (1) TW201309639A (en)
UY (1) UY33912A (en)
WO (1) WO2012111995A1 (en)

Families Citing this family (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
AR091739A1 (en) 2012-07-11 2015-02-25 Elcelyx Therapeutics Inc COMPOSITIONS AND METHODS TO REDUCE CARDIOMETABOLIC RISK
SG10201900631TA (en) 2014-08-01 2019-02-27 Nuevolution As Compounds active towards bromodomains
CN106632302A (en) * 2016-12-15 2017-05-10 苏州汉德创宏生化科技有限公司 Synthesis method of 1-(thiazole-2-yl)piperidine-4-ol

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* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB0302548D0 (en) * 2003-02-04 2003-03-12 Syngenta Participations Ag Avermectins substituted in the 4"- and 4' -positions having pesticidal properties
JP2009525961A (en) * 2006-01-20 2009-07-16 シェーリング コーポレイション Heterocycles as nicotinic acid receptor agonists for the treatment of dyslipidemia
KR20110017431A (en) * 2008-06-10 2011-02-21 아보트 러보러터리즈 Novel tricyclic compounds

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WO2012111995A1 (en) 2012-08-23
TW201309639A (en) 2013-03-01
KR101456286B1 (en) 2014-11-03
UY33912A (en) 2012-09-28
KR20120094859A (en) 2012-08-27

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