CU20160120A7 - Benzimidazol-2-aminas como inhibidores de midh1 - Google Patents

Benzimidazol-2-aminas como inhibidores de midh1

Info

Publication number
CU20160120A7
CU20160120A7 CUP2016000120A CU20160120A CU20160120A7 CU 20160120 A7 CU20160120 A7 CU 20160120A7 CU P2016000120 A CUP2016000120 A CU P2016000120A CU 20160120 A CU20160120 A CU 20160120A CU 20160120 A7 CU20160120 A7 CU 20160120A7
Authority
CU
Cuba
Prior art keywords
benzimidazol
aminas
midh1
formula
inhibitors
Prior art date
Application number
CUP2016000120A
Other languages
English (en)
Other versions
CU24410B1 (es
Inventor
Hartmut Rehwinkel
Olaf Panknin
Sven Ring
Sonja Anlauf
Holger Siebeneicher
Duy Nguyen
Wolfgang Schwede
Marcus Bauser
Katja Zimmermann
Stefan Kaulfuss
Roland Neuhaus
Paul Matthew Blaney
Original Assignee
Bayer Pharma AG
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
Family has litigation
First worldwide family litigation filed litigation Critical https://patents.darts-ip.com/?family=52462928&utm_source=google_patent&utm_medium=platform_link&utm_campaign=public_patent_search&patent=CU20160120(A7) "Global patent litigation dataset” by Darts-ip is licensed under a Creative Commons Attribution 4.0 International License.
Application filed by Bayer Pharma AG filed Critical Bayer Pharma AG
Publication of CU20160120A7 publication Critical patent/CU20160120A7/es
Publication of CU24410B1 publication Critical patent/CU24410B1/es

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D235/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings
    • C07D235/02—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings condensed with carbocyclic rings or ring systems
    • C07D235/04—Benzimidazoles; Hydrogenated benzimidazoles
    • C07D235/24—Benzimidazoles; Hydrogenated benzimidazoles 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 in position 2
    • C07D235/30—Nitrogen atoms not forming part of a nitro radical
    • 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
    • A61K31/41—Heterocyclic 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
    • A61K31/4164—1,3-Diazoles
    • A61K31/4184—1,3-Diazoles condensed with carbocyclic rings, e.g. benzimidazoles
    • 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
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
    • A61K31/4439—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A61P35/02—Antineoplastic agents specific for leukemia
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A61P35/04—Antineoplastic agents specific for metastasis
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic 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
    • C07D401/02—Heterocyclic 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
    • C07D401/12—Heterocyclic 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2300/00—Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Medicinal Chemistry (AREA)
  • Animal Behavior & Ethology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Oncology (AREA)
  • Hematology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)

Abstract

La presente invención se refiere a benzimidazol-2-aminas con la fórmula general (I): ESPACIO PARA FÓRMULA que inhiben a la isocitrato deshidrogenasa 1 mutada (mIDH1 R123H), donde R1, R2, R3, R4, R5 , R6, R7, R8, R9, R10, R11 y R12 son según se los define aquí, métodos para elaborarlos y compuestos intermediarios útiles su elaboración. Los compuestos de fórmula I son útiles en la profilaxis o el tratamiento de diversas enfermedades, particularmente en los neoplasmas.
CU2016000120A 2014-02-11 2015-02-10 Benzimidazol-2-aminas como inhibidores de midh1 CU24410B1 (es)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
EP14154680 2014-02-11
EP14182002 2014-08-22
PCT/EP2015/052676 WO2015121210A1 (en) 2014-02-11 2015-02-10 Benzimidazol-2-amines as midh1 inhibitors

Publications (2)

Publication Number Publication Date
CU20160120A7 true CU20160120A7 (es) 2016-12-23
CU24410B1 CU24410B1 (es) 2019-05-03

Family

ID=52462928

Family Applications (1)

Application Number Title Priority Date Filing Date
CU2016000120A CU24410B1 (es) 2014-02-11 2015-02-10 Benzimidazol-2-aminas como inhibidores de midh1

Country Status (23)

Country Link
US (2) US9957235B2 (es)
EP (1) EP3105209B1 (es)
JP (1) JP6534675B2 (es)
KR (1) KR20160115991A (es)
CN (1) CN106573897B (es)
AP (1) AP2016009371A0 (es)
AU (1) AU2015217788B2 (es)
BR (1) BR112016018604A2 (es)
CA (1) CA2939026A1 (es)
CL (1) CL2016002033A1 (es)
CR (1) CR20160361A (es)
CU (1) CU24410B1 (es)
DO (1) DOP2016000208A (es)
EA (1) EA031655B1 (es)
IL (1) IL246785A0 (es)
MX (1) MX2016010474A (es)
PE (1) PE20170143A1 (es)
PH (1) PH12016501581A1 (es)
SG (1) SG11201605810WA (es)
SV (1) SV2016005257A (es)
TW (1) TWI666202B (es)
UY (1) UY35991A (es)
WO (1) WO2015121210A1 (es)

Families Citing this family (25)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
PE20170143A1 (es) 2014-02-11 2017-03-19 Bayer Pharma AG Benzimidazol-2-aminas como inhibidores de midh1
CN105980365B (zh) 2014-02-11 2019-06-21 拜耳医药股份公司 作为mIDH1抑制剂的苯并咪唑-2-胺
HUE062424T2 (hu) 2014-09-19 2023-11-28 Forma Therapeutics Inc Piridin-2(1H)-on kinolinon származékok mint mutáns izocitrát dehidrogenáz inhibitorok
WO2016044781A1 (en) 2014-09-19 2016-03-24 Forma Therapeutics, Inc. Quinolinone pyrimidines compositions as mutant-isocitrate dehydrogenase inhibitors
US10138226B2 (en) * 2014-10-23 2018-11-27 Bayer Pharma Aktiengesellschaft Benzimidazol-2-amines as MIDH1 inhibitors
JP6672288B2 (ja) 2014-10-23 2020-03-25 バイエル・ファルマ・アクティエンゲゼルシャフト 腫瘍の治療のためのmidh1阻害剤としての1−シクロヘキシル−2−フェニルアミノベンゾイミダゾール
EP3303302B1 (en) * 2015-06-08 2019-03-20 Bayer Pharma Aktiengesellschaft N-menthylbenzimidazoles as midh1 inhibitors
WO2017005674A1 (en) * 2015-07-07 2017-01-12 Bayer Pharma Aktiengesellschaft 2-aryl- and 2-arylalkyl-benzimidazoles as midh1 inhibitors
CN108026052B (zh) * 2015-07-16 2021-10-08 德国癌症研究公共权益基金会 作为mIDH1抑制剂的5-羟烷基苯并咪唑类
EP3121166A1 (en) 2015-07-21 2017-01-25 Bayer Pharma Aktiengesellschaft Fused imidazoles as midh1 inhibitors
TW201708193A (zh) * 2015-07-27 2017-03-01 拜耳製藥公司 突變之異檸檬酸脫氫酶idh1 r132h之抑制劑
TW201718513A (zh) * 2015-07-27 2017-06-01 拜耳製藥公司 製備經取代之3-(2-苯胺-1-環己基-1h-苯并咪唑-5-基)丙酸衍生物之方法
MX2018009633A (es) 2016-02-09 2018-12-17 Inventisbio Inc Inhibidor de indoleamina-2,3-dioxigenasa (ido).
WO2019015672A1 (zh) * 2017-07-21 2019-01-24 南京明德新药研发股份有限公司 吡啶并咪唑类化合物及其应用
JP2020535112A (ja) * 2017-08-01 2020-12-03 ドイッチェス・クレープスフォルシュングスツェントルムDeutsches Krebsforschungszentrum Midh1阻害剤とdna低メチル化剤(hma)との組合せ
US11013734B2 (en) 2018-05-16 2021-05-25 Forma Therapeutics, Inc. Treating patients harboring an isocitrate dehydrogenase-1 (IDH-1) mutation
SMT202300073T1 (it) 2018-05-16 2023-05-12 Forma Therapeutics Inc Inibizione di idh-1 mutante
WO2019222551A1 (en) 2018-05-16 2019-11-21 Forma Therapeutics, Inc. Solid forms of ((s)-5-((1-(6-chloro-2-oxo-1,2-dihydroquinolin-3-yl)ethyl)amino)-1-methyl-6-oxo-1,6-dihydropyridine-2-carbonitrile
US11013733B2 (en) 2018-05-16 2021-05-25 Forma Therapeutics, Inc. Inhibiting mutant isocitrate dehydrogenase 1 (mlDH-1)
US11311527B2 (en) 2018-05-16 2022-04-26 Forma Therapeutics, Inc. Inhibiting mutant isocitrate dehydrogenase 1 (mIDH-1)
AU2019296173B2 (en) * 2018-06-26 2022-01-06 Kpc Pharmaceuticals, Inc. Benzimidazole derivatives and use thereof as IDH1 inhibitors
TWI760017B (zh) * 2019-12-23 2022-04-01 大陸商昆藥集團股份有限公司 一種idh1突變體抑制劑的鹽型、晶型及其製備方法
US12014835B2 (en) 2020-02-19 2024-06-18 Vanderbilt University Methods for evaluating therapeutic benefit of combination therapies
US20230270814A1 (en) * 2020-07-21 2023-08-31 Daiichi Sankyo Company, Limited Combination pharmaceutical of temozolomide and mutant idh1 enzyme inhibitor
CN112062687B (zh) * 2020-09-02 2023-11-21 上海信谊万象药业股份有限公司 一种盐酸阿扎司琼中间体3-氨基-5-氯-2-羟基苯甲酸甲酯的合成方法

Family Cites Families (35)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
FR2643903A1 (fr) 1989-03-03 1990-09-07 Union Pharma Scient Appl Nouveaux derives de benzimidazole, leurs procedes de preparation, intermediaires de synthese, compositions pharmaceutiques les contenant, utiles notamment pour le traitement des maladies cardiovasculaires, et des ulceres duodenaux
CN1161340C (zh) 1998-11-30 2004-08-11 先灵公司 为玻连蛋白受体拮抗剂的苯并咪唑化合物
US6340681B1 (en) 1999-07-16 2002-01-22 Pfizer Inc 2-benzimidazolylamine compounds as ORL-1-receptor agonists
US6448281B1 (en) 2000-07-06 2002-09-10 Boehringer Ingelheim (Canada) Ltd. Viral polymerase inhibitors
US7030150B2 (en) 2001-05-11 2006-04-18 Trimeris, Inc. Benzimidazole compounds and antiviral uses thereof
CA2448737C (en) 2001-07-20 2010-06-01 Boehringer Ingelheim (Canada) Ltd. Viral polymerase inhibitors
CA2477505A1 (en) 2002-03-01 2003-09-12 Smithkline Beecham Corporation Diamino-pyrimidines and their use as angiogenesis inhibitors
US7531553B2 (en) 2003-03-21 2009-05-12 Amgen Inc. Heterocyclic compounds and methods of use
US7714009B2 (en) 2003-10-31 2010-05-11 Takeda Pharmaceutical Company Limited Nitrogen-containing fused heterocyclic compounds
WO2005121132A1 (ja) 2004-06-11 2005-12-22 Shionogi & Co., Ltd. 抗hcv作用を有する縮合ヘテロ環化合物
JPWO2006038738A1 (ja) 2004-10-08 2008-05-15 武田薬品工業株式会社 受容体機能調節剤
US20060223849A1 (en) 2005-03-14 2006-10-05 Mjalli Adnan M Benzazole derivatives, compositions, and methods of use as beta-secretase inhibitors
WO2008153701A1 (en) 2007-05-24 2008-12-18 Schering Corporation Compounds for inhibiting ksp kinesin activity
US8168800B2 (en) 2007-11-02 2012-05-01 The Regents Of The University Of California Aβ-binding small molecules
WO2009116074A2 (en) 2008-02-13 2009-09-24 Cadila Healthcare Limited Substituted benzimidazoles as cannabinoid modulator
UY32138A (es) 2008-09-25 2010-04-30 Boehringer Ingelheim Int Amidas sustituidas del ácido 2-(2,6-dicloro-fenilamino)-6-fluoro-1-metil-1h-bencimidazol-5-carboxílico y sus sales farmacéuticamente aceptables
UY32470A (es) 2009-03-05 2010-10-29 Boehringer Ingelheim Int Derivados de 2-{2-cloro-5-[(sustituido) metil]fenilamino} -1-metil]fenilamino}-1-metilbencimidazol-5-carboxamidas-n-(sustituidas) y sus sales fisiológicamente aceptables, composiciones conteniéndolos y aplicaciones
JP5868851B2 (ja) * 2009-06-23 2016-02-24 ザ・トランスレーショナル・ジェノミクス・リサーチ・インスティチュート ベンズアミド誘導体
WO2011072174A1 (en) 2009-12-09 2011-06-16 Agios Pharmaceuticals, Inc. Therapeutically active compounds for use in the treatment of cancer characterized as having an idh mutation
WO2012172043A1 (en) * 2011-06-15 2012-12-20 Laboratoire Biodim Purine derivatives and their use as pharmaceuticals for prevention or treatment of bacterial infections
CN102827170A (zh) 2011-06-17 2012-12-19 安吉奥斯医药品有限公司 治疗活性组合物和它们的使用方法
CN103435554A (zh) 2013-09-06 2013-12-11 中国药科大学 2-苯氨基苯并咪唑类化合物及其用途
CN105980365B (zh) 2014-02-11 2019-06-21 拜耳医药股份公司 作为mIDH1抑制剂的苯并咪唑-2-胺
PE20170143A1 (es) 2014-02-11 2017-03-19 Bayer Pharma AG Benzimidazol-2-aminas como inhibidores de midh1
US10138226B2 (en) 2014-10-23 2018-11-27 Bayer Pharma Aktiengesellschaft Benzimidazol-2-amines as MIDH1 inhibitors
JP6672288B2 (ja) 2014-10-23 2020-03-25 バイエル・ファルマ・アクティエンゲゼルシャフト 腫瘍の治療のためのmidh1阻害剤としての1−シクロヘキシル−2−フェニルアミノベンゾイミダゾール
AU2016264220A1 (en) 2015-05-18 2018-01-04 Translational Drug Development Llc Heterocyclic compounds as kinase inhibitors
CN107921126A (zh) 2015-05-22 2018-04-17 转化药物开发有限责任公司 苯甲酰胺和活性化合物的组合物及其使用方法
EP3303302B1 (en) 2015-06-08 2019-03-20 Bayer Pharma Aktiengesellschaft N-menthylbenzimidazoles as midh1 inhibitors
WO2017005674A1 (en) 2015-07-07 2017-01-12 Bayer Pharma Aktiengesellschaft 2-aryl- and 2-arylalkyl-benzimidazoles as midh1 inhibitors
CN108026052B (zh) 2015-07-16 2021-10-08 德国癌症研究公共权益基金会 作为mIDH1抑制剂的5-羟烷基苯并咪唑类
EP3121166A1 (en) 2015-07-21 2017-01-25 Bayer Pharma Aktiengesellschaft Fused imidazoles as midh1 inhibitors
TW201708193A (zh) 2015-07-27 2017-03-01 拜耳製藥公司 突變之異檸檬酸脫氫酶idh1 r132h之抑制劑
TW201718513A (zh) 2015-07-27 2017-06-01 拜耳製藥公司 製備經取代之3-(2-苯胺-1-環己基-1h-苯并咪唑-5-基)丙酸衍生物之方法
CA3053238A1 (en) 2016-03-02 2017-09-08 Translational Drug Development Llc Aminobenzimidazole derivatives

Also Published As

Publication number Publication date
CN106573897B (zh) 2019-09-24
AP2016009371A0 (en) 2016-08-31
MX2016010474A (es) 2016-10-31
UY35991A (es) 2015-09-30
SV2016005257A (es) 2018-10-02
PE20170143A1 (es) 2017-03-19
US20170197921A1 (en) 2017-07-13
CL2016002033A1 (es) 2017-03-31
KR20160115991A (ko) 2016-10-06
IL246785A0 (en) 2016-08-31
CN106573897A (zh) 2017-04-19
JP2017505790A (ja) 2017-02-23
PH12016501581A1 (en) 2017-02-06
BR112016018604A2 (pt) 2017-08-08
EA201691590A1 (ru) 2017-02-28
JP6534675B2 (ja) 2019-06-26
AU2015217788A1 (en) 2016-08-04
US10442772B2 (en) 2019-10-15
US9957235B2 (en) 2018-05-01
EP3105209B1 (en) 2019-08-21
US20190062285A1 (en) 2019-02-28
CR20160361A (es) 2016-10-03
CU24410B1 (es) 2019-05-03
TW201613874A (en) 2016-04-16
SG11201605810WA (en) 2016-08-30
EP3105209A1 (en) 2016-12-21
WO2015121210A1 (en) 2015-08-20
CA2939026A1 (en) 2015-08-20
EA031655B1 (ru) 2019-02-28
TWI666202B (zh) 2019-07-21
AU2015217788B2 (en) 2019-06-27
DOP2016000208A (es) 2016-09-15

Similar Documents

Publication Publication Date Title
CU24410B1 (es) Benzimidazol-2-aminas como inhibidores de midh1
JOP20190194A1 (ar) مركبات نيوكليوتيدات ثنائية حلقية لعلاج السرطان
MX2020001757A (es) Compuestos, sales de los mismos y metodos para el tratamiento de enfermedades.
CL2017002483A1 (es) Compuestos heterocíclicos como inhibidores de lsd1
MX375970B (es) Compuestos de triazolopirimidina y usos de los mismos.
PH12018500177A1 (en) Compositions useful for treating disorders related to kit and pdfgr
UY35898A (es) ?compuestos inhibidores de syk y composiciones que los comprenden?.
DOP2017000278A (es) Piridinas sustituidas y método de uso
CU24411B1 (es) Compuesto derivado de benzamida sustituida con 1,3-tiazol-2-ilo útil para el tratamiento de trastornos neurogénicos
CO2017001884A2 (es) Polimorfos de selinexor
MX2017001279A (es) Usos y composiciones de la flagelina.
CR20210079A (es) Sulfamoilarilamidas y su uso como medicamentos para el tratamiento de la hepatitis b
MX2017008444A (es) Picolinamidas como fungicidas.
MA40076A (fr) Inhibiteurs de syk
MX2016001304A (es) Polimorfo de inhibidores de syk.
MX2016006975A (es) Compuestos, composicion farmaceutica y metodos para su uso en el tratamiento de enfermedades inflamatorias.
CU20170007A7 (es) Compuestos de imidazopiridazina
DOP2016000120A (es) Nuevos inhibidores de dgat2
DOP2016000170A (es) Compuestos derivados de hidroxiformamida y usos del mismo
MX2015010728A (es) Metodos y composiciones para el tratamiento de leucemia.
MX2017005044A (es) Activador de canales de kcnq2-5.
CU20160003A7 (es) Pirazololpiridinaminas sustituidas
MX374385B (es) Apilimod para uso en el tratamiento de melanoma.
UY36070A (es) Triterpenoides con actividad inhibidora de la maduración de hiv
MX369857B (es) Pirazinas moduladoras de receptor 6 acoplado a la proteina g (gpr6).