ES2606197T3 - Moduladores pirrolidina de GPR40 - Google Patents

Moduladores pirrolidina de GPR40 Download PDF

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ES2606197T3
ES2606197T3 ES13795972.2T ES13795972T ES2606197T3 ES 2606197 T3 ES2606197 T3 ES 2606197T3 ES 13795972 T ES13795972 T ES 13795972T ES 2606197 T3 ES2606197 T3 ES 2606197T3
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Bruce A. Ellsworth
Elizabeth A. Jurica
Jun Shi
William R. Ewing
Xiang-Yang Ye
Ximao Wu
Yeheng Zhu
Chongqing Sun
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Bristol Myers Squibb Co
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    • 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
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    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
    • A61K31/4025—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil not condensed and containing further heterocyclic rings, e.g. cromakalim
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    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/445—Non condensed piperidines, e.g. piperocaine
    • A61K31/4523—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems
    • A61K31/454—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. pimozide, domperidone
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    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/445—Non condensed piperidines, e.g. piperocaine
    • A61K31/4523—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems
    • A61K31/4545—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a six-membered ring with nitrogen as a ring hetero atom, e.g. pipamperone, anabasine
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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
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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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    • C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D207/04—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom 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
    • C07D207/08—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom 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 hydrocarbon radicals, substituted by hetero atoms, attached to ring carbon atoms
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    • C07D207/04—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom 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
    • C07D207/10—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom 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
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  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Plural Heterocyclic Compounds (AREA)
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Abstract

Un compuesto de Formula (I):**Fórmula** o un estereoisomero, un tautomero, una sal farmaceuticamente aceptable o un solvato del mismo, en la que: X se selecciona independientemente entre: un enlace, O, S, NH, N(alquilo C1-4), CH2, CH2CH2, CH(alquilo C1-4), OCH2, CH2O, OCH2CH2 y CH2CH2O; el anillo A es independientemente el anillo B es independientemente un heterociclo saturado de 4 a 7 miembros que contiene atomos de carbono, el atomo de nitrogeno mostrado en el anillo B y 0-1 heteroatomo adicional seleccionado entre N, O y S; y el anillo B esta sustituido con 0-4 R2; R1 es independientemente CO2R9, SO2R9, fenilo, bencilo, naftilo o un heteroarilo de 5 a 10 miembros que contiene atomos de carbono y 1-4 heteroatomos seleccionados entre N, NR11, O y S; en donde cada uno de dichos fenilo, bencilo, naftilo y heteroarilo esta sustituido con 0-3 R6; R2, en cada caso, se selecciona independientemente entre: >=O, OH, halogeno, alquilo C1-6 sustituido con 0-1 R12, alcoxi C1-6 sustituido con 0-1 R12, haloalquilo C1-4 sustituido con 0-1 R12, haloalcoxi C1-4 sustituido con 0-1 R12, -(CH2)m-carbociclo C3-6 sustituido con 0-1 R12 y -(CH2)m-(heteroarilo de 5 a 10 miembros que contiene atomos de carbono y 1-4 heteroatomos seleccionados entre N, NR11, O y S); en donde dicho heteroarilo esta sustituido con 0-1 R12; cuando dos grupos R2 estan unidos a dos atomos de carbono diferentes, pueden combinarse para formar un puente de atomo de carbono de 1 a 3 miembros sobre el anillo B; cuando dos grupos R2 estan unidos al mismo carbono, pueden combinarse, junto con el atomo de carbono al que estan unidos, para formar un anillo espiro de 3 a 6 miembros que contiene atomos de carbono; R3 se selecciona independientemente entre: H, halogeno, CN, OH, CO2H, alquilo, alquenilo C2-6, alquinilo C2-6, haloalquilo C1-6, -N(alquilo C1-4)SO2Ph, OR9, SR9, C(O)OR9, CO2R9, S(O)R9, SO2R9, CONHR9, CON(alquilo C1-4)2, -(O)n-(CH2)m-(fenilo sustituido con 0-2 R10), -(O)n-(CH2)m-(heteroarilo de 5 a 10 miembros que contiene atomos de carbono y 1-4 heteroatomos seleccionados entre N, NR11, O y S; en donde dicho heteroarilo esta sustituido con 0-2 R10); R4 y R4a se seleccionan independientemente entre: H, halogeno, alquilo C1-6, alcoxi C1-6 y -(CH2)mcarbociclo C3-6; R5, en cada caso, se selecciona independientemente entre: halogeno, alquilo C1-6 y alcoxi C1-6; R6, en cada caso, se selecciona independientemente entre: halogeno, OH, alquiltio C1-4, CN, SO2(alquilo C1-2), N(alquilo C1-4)2, haloalquilo C1-4, haloalcoxi C1-4, alquilo C1-8 sustituido con 0-1 R7, alcoxi C1-6 sustituido con 0-1 R7, -(O)n-(CH2)m-(carbociclo C3-10 sustituido con 0-2 R7) y -(CH2)m-(heteroarilo de 5 a 10 miembros que contiene atomos de carbono y 1-4 heteroatomos seleccionados entre N, NR11, O y S); en donde dicho heteroarilo esta sustituido con 0-2 R7; R7, en cada caso, se selecciona independientemente entre: halogeno, OH, alquilo C1-4, alquenilo C2-4, alcoxi C1-4, alquiltio C1-4, haloalquilo C1-4, haloalcoxi C1-4, SCF3, CN, NO2, NH2, NH(alquilo C1-4), N(alquilo C1-4)2, SO2(alquilo C1-2) y fenilo; R8 se selecciona independientemente entre: H y alquilo C1-4; R9, en cada caso, se selecciona independientemente entre: alquilo C1-6, haloalquilo C1-4, -(CH2)m-(cicloalquilo C3-6 sustituido con 0-2 R10) y -(CH2)m-(fenilo sustituido con 0-2 R10); R10 y R12, en cada caso, se seleccionan independientemente entre: OH, halogeno, CN, alquilo C1-4, alcoxi C1-4, haloalquilo C1-4, haloalcoxi C1-4, SCF3, NO2, CO2(alquilo C1-4), SO2(alquilo C1-4) y tetrazolilo; R11, en cada caso, se selecciona independientemente entre: H, alquilo C1-4 y bencilo; m, en cada caso, es independientemente 0, 1 o 2; y n, en cada caso, es independientemente 0 o 1.
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US201261727253P 2012-11-16 2012-11-16
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PCT/US2013/070213 WO2014078609A1 (en) 2012-11-16 2013-11-15 Pyrrolidine gpr40 modulators

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EP (1) EP2925741B1 (es)
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KR (1) KR20150082615A (es)
CN (1) CN105121426B (es)
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BR (1) BR112015010649A2 (es)
CA (1) CA2891569A1 (es)
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Families Citing this family (20)

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Publication number Priority date Publication date Assignee Title
US8962660B2 (en) 2013-03-14 2015-02-24 Bristol-Myers Squibb Company Oxabicyclo [2.2.2] acid GPR120 modulators
AU2014372114A1 (en) 2013-11-14 2016-06-09 Cadila Healthcare Limited Novel heterocyclic compounds
BR112016025188A2 (pt) * 2014-05-07 2017-08-15 Bristol Myers Squibb Co moduladores de pirrolidina gpr40 para o tratamento de doenças tal como diabetes
EA033250B1 (ru) * 2014-05-07 2019-09-30 Бристол-Майерс Сквибб Компани Пирролидиновые модуляторы gpr40 для лечения расстройств, таких как диабет
US10301260B2 (en) 2014-05-07 2019-05-28 Bristol-Myers Squibb Company Pyrrolidine GPR40 modulators
EP3177282B1 (en) 2014-08-08 2021-10-06 Merck Sharp & Dohme Corp. Antidiabetic bicyclic compounds
US10968193B2 (en) 2014-08-08 2021-04-06 Merck Sharp & Dohme Corp. Antidiabetic bicyclic compounds
WO2016019587A1 (en) 2014-08-08 2016-02-11 Merck Sharp & Dohme Corp. [7, 6]-fused bicyclic antidiabetic compounds
US10100042B2 (en) 2014-08-08 2018-10-16 Merck Sharp & Dohme Corp. [5,6]—fused bicyclic antidiabetic compounds
AR105889A1 (es) 2015-09-03 2017-11-22 Actelion Pharmaceuticals Ltd Compuestos antibacterianos 1,2-dihidro-3h-pirrolo[1,2-c]imidazol-3-ona sustituidos
WO2018027892A1 (en) 2016-08-12 2018-02-15 Eli Lilly And Company Amino pyrimidine ssao inhibitors
WO2018148856A1 (en) 2017-02-14 2018-08-23 Eli Lilly And Company Diazaspirodecanyl-pyrimidine compounds useful as ssao inhibitors
US10336737B2 (en) 2017-06-20 2019-07-02 The Board Of Trustees Of The University Of Illinois Metal catalyzed dearomative 1,2-carboamination
AU2019222644B2 (en) 2018-02-13 2021-04-01 Gilead Sciences, Inc. PD-1/PD-L1 inhibitors
CN112041311B (zh) 2018-04-19 2023-10-03 吉利德科学公司 Pd-1/pd-l1抑制剂
EP4234030A3 (en) 2018-07-13 2023-10-18 Gilead Sciences, Inc. Pd-1/pd-l1 inhibitors
WO2020086556A1 (en) 2018-10-24 2020-04-30 Gilead Sciences, Inc. Pd-1/pd-l1 inhibitors
WO2020113094A1 (en) 2018-11-30 2020-06-04 Nuvation Bio Inc. Pyrrole and pyrazole compounds and methods of use thereof
MX2023002308A (es) 2020-08-25 2023-07-11 Lilly Co Eli Polimorfos de un inhibidor de ssao.
BR112023023420A2 (pt) 2021-06-16 2024-01-30 Celgene Corp Compostos de azetidinila compreendendo um grupo ácido carboxílico para o tratamento de doenças neurodegenerativas

Family Cites Families (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5614492A (en) 1986-05-05 1997-03-25 The General Hospital Corporation Insulinotropic hormone GLP-1 (7-36) and uses thereof
JP2006525366A (ja) 2003-04-30 2006-11-09 ジ インスチチュート フォー ファーマシューティカル ディスカバリー、エルエルシー 複素環式カルボン酸置換基
US6995183B2 (en) 2003-08-01 2006-02-07 Bristol Myers Squibb Company Adamantylglycine-based inhibitors of dipeptidyl peptidase IV and methods
EP2486005B1 (en) * 2009-10-06 2014-06-18 Bristol-Myers Squibb Company Pyrrolidine gpr40 modulators
CN102686579A (zh) * 2009-10-09 2012-09-19 Irm责任有限公司 作为gpr119活性调节剂的化合物和组合物
AR083904A1 (es) 2010-11-18 2013-04-10 Prosidion Ltd Derivados de 1,4-pirrolidinas disustituidos y 3-il-aminas y sus usos en el tratamiento de desordenes metabolicos
EP2643311A1 (en) * 2010-11-26 2013-10-02 Lupin Limited Bicyclic gpr119 modulators
US8791091B2 (en) 2011-12-02 2014-07-29 Bristol-Myers Squibb Company Aryl dihydropyridinone and piperidinone MGAT2 inhibitors
GB2498976A (en) 2012-02-01 2013-08-07 Prosidion Ltd GPR119 agonists useful in the treatment of type II diabetes

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