AR066273A1 - Agentes anti- hipertensivos de accion dual - Google Patents

Agentes anti- hipertensivos de accion dual

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Publication number
AR066273A1
AR066273A1 ARP080101718A AR066273A1 AR 066273 A1 AR066273 A1 AR 066273A1 AR P080101718 A ARP080101718 A AR P080101718A AR 066273 A1 AR066273 A1 AR 066273A1
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AR
Argentina
Prior art keywords
alkylene
alkyl
aryl
cycloalkyl
4alkyl
Prior art date
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English (en)
Inventor
Paul Allegretti
Seok-Ki Choi
Paul R Fatheree
Roland Gendron
Robert Murray Mckinnell
Keith Jendza
Darren Mcmurtrie
Brooke Olson
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Theravance Inc
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Application filed by Theravance Inc filed Critical Theravance Inc
Publication of AR066273A1 publication Critical patent/AR066273A1/es

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    • C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
    • C07D233/56—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, attached to ring carbon atoms
    • C07D233/61—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, attached to ring carbon atoms with hydrocarbon radicals, substituted by nitrogen atoms not forming part of a nitro radical, attached to ring nitrogen atoms
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    • C07D233/66—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two 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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    • 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
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    • A61K31/4164—1,3-Diazoles
    • A61K31/417—Imidazole-alkylamines, e.g. histamine, phentolamine
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    • 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
    • A61K31/4188—1,3-Diazoles condensed with other heterocyclic ring systems, e.g. biotin, sorbinil
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    • 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
    • A61K31/4196—1,2,4-Triazoles
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    • 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
    • A61K31/4412—Non condensed pyridines; Hydrogenated derivatives thereof having oxo groups directly attached to the heterocyclic ring
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    • A61P9/04—Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
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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
    • C07D207/30—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 two double bonds between ring members or between ring members and non-ring members
    • C07D207/34—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 two 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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    • C07D213/02—Heterocyclic 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
    • C07D213/04—Heterocyclic 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
    • C07D213/60—Heterocyclic 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
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    • C07D213/63—One oxygen atom
    • C07D213/64—One oxygen atom attached in position 2 or 6
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    • C07D213/89—Heterocyclic 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 with hetero atoms directly attached to the ring nitrogen atom
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    • C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
    • C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
    • C07D231/14—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three 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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    • C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
    • C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
    • C07D233/64—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with substituted hydrocarbon radicals attached to ring carbon atoms, e.g. histidine
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    • C07D233/66—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two 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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    • C07D233/66—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two 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
    • C07D233/90—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
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    • C07D249/02—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms not condensed with other rings
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Abstract

Estos compuestos tienen actividad antagonista del receptor AT1 y actividad de inhibicion de nepriIisina. También se relaciona con composiciones farmacéuticas que comprenden dichos compuestos, métodos de uso de dichos compuestos, y procesos eintermediarios para preparar dichos compuestos. Reivindicacion 1: Un compuesto de formula 1: caracterizado porque: r es 0. 1 o 2; Ar se selecciona del grupo de formulas 2; R1 se selecciona de -COOR1a, -NHSO2R1b, -SO2NHR1d, -SO2OH, -C(O)NH- SO2R1c, -P(O)(OH)2, -CN, -O-CH(R1e)-COOH, tetrazol-5-ilo. Y los compuestos de la formula 3;R1a es H, alquilo-C1-6, alquileno-C1-3-arilo, alquileno-C1-3-heteroarilo, cicloalquilo-C3-7, -CH(alquilo-C1-4)OC(O)R1aa, alquileno-C0-6-morfolina, y los compuestos dela formula 4; R1aa es -O-alquilo-C1-6, -O-cicloalquilo-C3-7, -NR1abR1ac, o -CH(NH2)CH2COOCH3; R1ab y R1ac son independientemente seleccionados de H, alquilo-C1-6, y bencilo, o son tomados en forma conjunta como -(CH2)3-6-; R1b es R1c o -NHC(O)R1c;R1c es alquilo-C1-6, alquileno-C0-6-O-R1ca, alquileno-C1-5-NR1cbR1cc, o alquileno-C0-4-arilo; R1ca es H, alquilo-C1-6, o alquileno-C1-6-O-alquilo-C1-6; R1cb y R1cc están independientemente seleccionados de H y alquilo-C1-6, o son tomados en formaconjunta como -(CH2)2-O-(CH2)2- o -(CH2)2-N[C(O)CH3]-(CH2)2-; R1d es H, R1c, -C(O)R1c, o -C(O)NHR1c; R1e es alquilo-C1-4 o arilo; Y es -C(R3)-, Z es -N-, Q es -C(R2)- y A es un enlace; Y es -N-, Z es -C(R3)-, Q es -C(R2)- y A es un enlace; Y es -C(R3)-, Z es -N-, Q es -N- y A es un enlace; Y es -C(R3), Z es -CH-, Q es -N- y A es un enlace; o Y es -C(R3)-, Z es -CH-, Q es -C(R2)- y A es -C(O)-; R2 se selecciona de H, halo, -NO2, alquilo-C1-6, alquenilo-C2-6, cicloalquilo-C3-6, -CN, -C(O)R2a,alquileno-C0-5-OR2b, alquileno-C0-5-NR2cR2d, alquileno-C0-3-arilo. y alquileno-C0-3-heteroarilo; donde R2a se selecciona de H, alquilo-C1-6, cicloalquilo-C3-6. OR2b y -NR2cR2d; R2b se selecciona de H, alquilo-C1-6, cicloalquilo-C3-6, y alquileno-C0-1-arilo; y R2c y R2' están independientemente seleccionados de H, alquilo-C1-4, y alquileno-C0-1-arilo; R3 se selecciona de alquilo-C1-10, alquenilo-C2-10, alquinilo-C3-10, alquileno-C0-3-cicloalquilo-C3-7, alquenileno-C2-3-cicloalquiIo-C3-7,alquinileno-C2-3-cicloalquilo-C3-7, alquileno-C0-5-NR3a-alquileno-C0-5-R3b, aIquileno-C0-5-O-alquileno-C0-5-R3b. alquileno-C1-5-S-alquileno-C1-5-R3b, y alquileno-C0-3-arilo; donde R3a se selecciona de H, alquilo-C1-6, cicloalquilo-C3-7, y alquileno-C0-3-arilo; y R3b se selecciona de H, alquilo-C1-6, cicloalquilo-C3-7, alquenilo-C2-4, alquinilo-C2-4, y arilo; X es alquileno-C1-12, donde al menos una fraccion -CH2- en el alquileno se reemplaza con una fraccion -NR4a-C(O)- o -C(O)NR4a, donde R4ase selecciona de H, -OH, y alquilo-C1-4; R5 se selecciona de alquileno-C0-3-SR5a, alquileno-C0-3-C(O)NR5bR5c, alquileno-C0-3-NR5b-C(O)R5d, -NH-alquileno-C0-1-P(O)(OR5e)2, alquileno-C0-3-P(O)OR5eR5f, alquileno-C0-2-CHR5g-COOH y alquileno-C0-3-C(O)NR5h-CHR5i-COOH; R5a es H o -C(O)-R5aa; R5aa es alquilo-C1-6, alquileno-C0-6-cicloalquilo-C3-7. alquileno-C0-6-arilo, alquileno-C0-6-heteroarilo, alquileno-C0-6-morfolina, alquileno-C0-6-piperazina-CH3, -CH(NH2)-aa donde aa es un aminoácido decadena lateral, -2-pirrolidina, aIquileno-C0-6-OR5ab, -O-alquileno-C0-6-arilo, alquileno-C1-2-OC(O)-alquilo-C1-6, alquileno-C1-2-OC(O)-alquileno-C0-6-arilo, o -O-alquileno-C1-2-OC(O)O-alquilo-C1-6; R5ab es H o alquilo-C1-6; R5b es H, -OH, -OC(O)R5ba, -CH2COOH, -O-bencilo, -piridilo, o -OC(S)NR5bbR5bc; R5ba es alquilo-C1-6. -OCH2-arilo, -CH2O-arilo, o -NR5bbR5bc; R5bb y R5bc son independientemente seleccionados de H y alquilo-C1-4; R5c es H, alquilo-C1-6, o -C(O)-R5ca; R5ca es alquilo-C1-6, cicloalquilo-C3-7, arilo, o heteroarilo; R5d es H, alquilo-C1-4, alquileno-C0-3-arilo, -NR5daR5db, -CH2SH, o -O-alquilo-C1-6; R5da y R5db son independientemente seleccionados de H y alquilo-C1-4; R5e es H, alquilo-C1-6, alquileno-C1-3-arilo,alquileno-C1-3-heteroarilo, cicloalquilo-C3-7, -CH(CH3)-O-C(O)R5ea; y los compuestos de la formula 4; R5ea es -O-alquilo-C1-6, -O-cicloalquilo-C3-7, -NR5ebR5ec,. o -CH(NH2)CH2COOCH3; R5eb y R5ec son independientemente seleccionados de H, alquilo-C1-4, y alquileno-C1-3-arilo, o son tomados en forma conjunta como -(CH2)3-6-; R5f es H, alquilo-C1-4, alquileno-C0-3-arilo, alquileno-C1-3-NR5faR5fb, o alquileno-C1-3(aril)-alquileno-C0-3-NR5faR5fb; R5fa y R5fb están independientemente seleccionadosde H y alquilo-C1-4; R5g es H, alquilo-C1-6, alquileno-C1-3-arilo, o -CH2-O-(CH2)2-O-CH3; R5h es H o alquilo-C1-4; y R5i es H, alquilo-C1-4, o alquileno-C0-3-arilo; R6 se selecciona de alquilo-C1-6, -CH2O(CH2)2-O-CH3, alquileno-C1-6-O-alquilo-C1-6,alquileno-C0-3-arilo, alquileno-C0-3-heteroarilo. y alquileno-C0-3-cicloalquilo-C3-7; y R7 es H o es tomado en forma conjunta con R6 para formar cicloalquilo-C3-8 en donde: cada grupo -CH2- en -(CH2)r- está opcionalmente sustituido con 1 o 2sustituyentes independientemente seleccionados de alquilo-C1-4 y fluor; cada anillo en Ar y cada arilo en R1-3 y R5-6 está opcionalmente sustituido con 1 a 3 sustituyentes independientemente seleccionados de -OH, alquilo-C1-6, alquenilo-C2-4,alquinilo-C2-4, -CN, halo, -O-alquilo-C1-6, -S-alquilo-C1-6, -S(O)-alquilo-C1-6. -S(O)2- alquilo-C1-4, -fenilo, -NO2, -NH2, -NH-alquilo-C1-6 y -N(alquilo-C1-6)2, en donde cada alquilo, alquenilo y alquinilo está opcionalmente sustituido con 1 a 5átomos de fluor; cada átomo de carbono en X está opcionalmente sustituido con uno o más grupos R4b y una fraccion -CH2- en X puede estar reemplazada con un grupo seleccionado de cicloalquileno-C4-8, -CR4d=CH-, y -CH=CR4d-; en donde R4b se seleccionade alquileno-C0-5-COOR4c, alquilo-C1-6, alquileno-C0-1-CONH2, alquileno-C1-2-OH, alquileno-C0-3-cicloalquilo-C3-7, 1H-indol-3-ilo, bencilo, y hidroxibencilo, donde R4c es H o alquilo-C1-4; y R4d se selecciona de -CH2-tiofeno y fenilo; cada alquilo ycada arilo en R1-3, R4a-4d y R5-6 está opcionalmente sustituido con 1 a 7 átomos de fluor; y sales farmacéuticamente aceptables del mismo.
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Families Citing this family (63)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
TW200838501A (en) 2007-02-02 2008-10-01 Theravance Inc Dual-acting antihypertensive agents
TWI448284B (zh) 2007-04-24 2014-08-11 Theravance Inc 雙效抗高血壓劑
TWI406850B (zh) 2007-06-05 2013-09-01 Theravance Inc 雙效苯并咪唑抗高血壓劑
WO2009035543A1 (en) 2007-09-07 2009-03-19 Theravance, Inc. Dual-acting antihypertensive agents
US8212052B2 (en) 2007-12-11 2012-07-03 Theravance, Inc. Dual-acting benzoimidazole antihypertensive agents
JP2011518884A (ja) * 2008-04-29 2011-06-30 セラヴァンス， インコーポレーテッド 二重活性抗高血圧剤
JP2011529072A (ja) * 2008-07-24 2011-12-01 セラヴァンス， インコーポレーテッド 二重作用血圧降下薬
TW201014830A (en) * 2008-09-30 2010-04-16 Theravance Inc Crystalline form of an alkoxyimidazol-1-ylmethyl biphenyl carboxylic acid
US8232306B2 (en) * 2008-10-16 2012-07-31 Theravance, Inc. Methods for detecting sulfhydryl-containing compounds in a biological test sample
AU2010251967B9 (en) 2009-05-28 2014-04-03 Novartis Ag Substituted aminopropionic derivatives as neprilysin inhibitors
MX2011012627A (es) 2009-05-28 2011-12-14 Novartis Ag Derivados aminobutiricos sustituidos como inhibidores de nepralisina.
EP2436675A1 (en) * 2009-05-29 2012-04-04 Kowa Company, Ltd. Novel -phenoxybenzeneacetic acid derivative and pharmaceutical preparation comprising same
ES2611107T3 (es) 2009-07-07 2017-05-04 Theravance Biopharma R&D Ip, Llc Agentes antihipertensivos de pirazol, de doble acción
JP2012533626A (ja) * 2009-07-22 2012-12-27 セラヴァンス， インコーポレーテッド 二重作用オキサゾール降圧剤
TWI545114B (zh) * 2009-09-29 2016-08-11 施萬生物製藥研發Ｉｐ有限責任公司 製備聯苯基咪唑化合物之方法
JO2967B1 (en) 2009-11-20 2016-03-15 نوفارتس ايه جي Acetic acid derivatives of carbamoyl methyl amino are substituted as new NEP inhibitors
WO2011090929A1 (en) 2010-01-19 2011-07-28 Theravance, Inc. Dual-acting thiophene, pyrrole, thiazole and furan antihypertensive agents
US8399501B2 (en) * 2010-03-04 2013-03-19 Theravance, Inc. Crystalline alkoxyimidazol-1-ylmethyl biphenyl carboxylic acid and methods for preparing thereof
EP2605650A4 (en) 2010-08-18 2014-05-21 Del Mar Pharmaceuticals COMPOSITIONS AND METHODS FOR IMPROVING PROFIT TREATMENT OF CHEMICAL COMPOUNDS IN ADMINISTRATION WAY SUB-OPTIMAL INCLUDING hexitols SUBSTITUTED AS DIANHYDROGALACTITOL COMPOSITIONS AND DIACÉTYLDIANHYDROGALACTITOL AND METHODS TO IMPROVE THE THERAPEUTIC BENEFIT OF CHEMICAL COMPOUNDS IN ADMINISTRATION WAY SUB-OPTIMAL AS DIANHYDROGALACTITOL AND DIACÉTYLDIANHYDROGALACTITOL
RU2013126403A (ru) * 2010-11-10 2014-12-20 ТЕРЕВАНС БАЙОФАРМА Р энд Д ИП,ЛЛС Кристаллические формы алкоксиимидазол-1-илметилбифенилкарбоновых кислот
US8993631B2 (en) 2010-11-16 2015-03-31 Novartis Ag Method of treating contrast-induced nephropathy
MX354476B (es) 2010-12-15 2018-03-07 Theravance Inc Inhibidores de neprilisina.
WO2012082853A1 (en) 2010-12-15 2012-06-21 Theravance, Inc. Neprilysin inhibitors
MX342212B (es) 2011-02-17 2016-09-20 Theravance Inc Inhibidores de neprilisina.
ES2564275T3 (es) 2011-02-17 2016-03-21 Theravance Biopharma R&D Ip, Llc Derivados aminobutíricos sustituidos como inhibidores de neprilisina
CA2835220A1 (en) 2011-05-31 2012-12-06 Theravance, Inc. Neprilysin inhibitors
ES2653215T3 (es) 2011-05-31 2018-02-06 Theravance Biopharma R&D Ip, Llc Inhibidores de neprilisina
JP5885832B2 (ja) * 2011-05-31 2016-03-16 セラヴァンス バイオファーマ アール＆ディー アイピー， エルエルシー ネプリライシン阻害剤
WO2014081405A2 (en) 2011-08-17 2014-05-30 Dennis Brown Compositions and methods to improve the therapeutic benefit of suboptimally administered chemical compounds including substituted hexitols such as dibromodulcitol
US10370409B2 (en) * 2011-10-25 2019-08-06 The Scripps Research Institute Synthesis of libraries of peptide tertiary amides
TWI560172B (en) 2011-11-02 2016-12-01 Theravance Biopharma R&D Ip Llc Neprilysin inhibitors
KR20220137154A (ko) 2012-01-20 2022-10-11 데니스 엠. 브라운 다형교모세포종 및 수모세포종을 비롯한 신생종양 질환 및 암 줄기세포의 치료를 위한 디안히드로갈락티톨 및 유사체를 비롯한 치환된 헥시톨의 용도
TW201336839A (zh) 2012-02-15 2013-09-16 Theravance Inc （２ｓ，４ｒ）－５－聯苯－４－基－２－羥甲基－２－甲基－４－［（１ｈ－［１，２，３］三唑－４－羰基）－胺基］－戊酸５－甲基－２－酮基－［１，３］二氧雜環戊烯－４－基甲酯之結晶型
WO2013148768A1 (en) 2012-03-28 2013-10-03 Theravance, Inc. Crystalline forms of (r)-3-[n-(3'-chlorobiphenyl-4-ylmethyl)-n'-(3-hydroxyisoxazole-5-carbonyl)hydrazino]-2-hydroxypropionic acid isopropyl ester
US9814693B2 (en) 2012-05-09 2017-11-14 Delmar Pharmaceuticals, Inc. Veterinary use of dianhydrogalactitol, diacetyldianhydrogalactitol, and dibromodulcitol to treat malignancies
EP2855464B1 (en) 2012-05-31 2016-10-26 Theravance Biopharma R&D IP, LLC Nitric oxide donor neprilysin inhibitors
EP2858650B1 (en) 2012-06-08 2018-11-14 Theravance Biopharma R&D IP, LLC Neprilysin inhibitors
ES2700152T3 (es) 2012-06-08 2019-02-14 Theravance Biopharma R&D Ip Llc Inhibidores de neprilisina
SG10201805807PA (en) 2012-06-26 2018-08-30 Del Mar Pharmaceuticals Methods for treating tyrosine-kinase-inhibitor-resistant malignancies in patients with genetic polymorphisms or ahi1 dysregulations or mutations employing dianhydrogalactitol, diacetyldianhydrogalactitol, dibromodulcitol, or analogs or derivatives thereof
AU2013299642B2 (en) 2012-08-08 2017-06-08 Theravance Biopharma R&D Ip, Llc Neprilysin inhibitors
UY35144A (es) 2012-11-20 2014-06-30 Novartis Ag Miméticos lineales sintéticos de apelina para el tratamiento de insuficiencia cardiaca
CU24330B1 (es) 2013-02-14 2018-03-13 Novartis Ag Derivados del ácido 4-((1,1) bifenil-4-il)-3-(3-fosfonopropanamido) butanoico, activos como inhibidores de nep (endopeptidasa neutral)
US9102635B2 (en) 2013-02-14 2015-08-11 Novartis Ag Substituted bisphenyl butanoic acid derivatives as NEP inhibitors with improved in vivo efficacy
CA2902456A1 (en) 2013-03-05 2014-09-12 Theravance Biopharma R&D Ip, Llc Neprilysin inhibitors
WO2014145331A1 (en) * 2013-03-15 2014-09-18 University Of Southern California Methods, compounds, and compositions for the treatment of angiotensin-related diseases
KR20160061911A (ko) 2013-04-08 2016-06-01 데니스 엠. 브라운 최적하 투여된 화학 화합물의 치료 효과
JP6501775B2 (ja) 2013-07-25 2019-04-17 ノバルティス アーゲー 心不全治療用の環状ポリペプチド
EA201690282A1 (ru) 2013-07-25 2016-09-30 Новартис Аг Биоконъюгаты синтетических апелиновых полипептидов
SG11201606057PA (en) 2014-01-30 2016-08-30 Theravance Biopharma R&D Ip Llc 5-biphenyl-4-heteroarylcarbonylamino-pentanoic acid derivatives as neprilysin inhibitors
AU2015210983B2 (en) 2014-01-30 2018-10-04 Theravance Biopharma R&D Ip, Llc Neprilysin inhibitors
SG11201608303QA (en) 2014-04-04 2016-11-29 Del Mar Pharmaceuticals Use of dianhydrogalactitol and analogs or derivatives thereof to treat non-small-cell carcinoma of the lung and ovarian cancer
MA41580A (fr) 2015-01-23 2017-11-29 Novartis Ag Conjugués d'acides gras de l'apeline synthétique présentant une demi-vie améliorée
RU2726623C2 (ru) 2015-02-11 2020-07-15 ТЕРЕВАНС БАЙОФАРМА Ар энд Ди АйПи, ЭлЭлСи (2s,4r)-5-(5'-хлор-2'-фторбифенил-4-ил)-4-(этоксиоксалиламино)-2-гидроксиметил-2-метилпентановая кислота
RS61325B1 (sr) 2015-02-19 2021-02-26 Theravance Biopharma R&D Ip Llc (2r,4r)-5-(5'-hloro-2'-fluorobifenil-4-il)-2-hidroksi-4-[(5-metiloksazol-2-karbonil)amino]pentanska kiselina
CN105017226A (zh) * 2015-06-29 2015-11-04 千辉药业（安徽）有限责任公司 一种三苯甲基洛沙坦的合成方法
KR20220035991A (ko) 2016-03-08 2022-03-22 세라밴스 바이오파마 알앤디 아이피, 엘엘씨 (2s,4r)-5--2-메틸펜탄산 결정 및 그 용도
TWI776812B (zh) * 2016-06-02 2022-09-11 荷蘭商菲林公司 血管收縮素-1-受體拮抗劑
UY38072A (es) 2018-02-07 2019-10-01 Novartis Ag Compuestos derivados de éster butanoico sustituido con bisfenilo como inhibidores de nep, composiciones y combinaciones de los mismos
UY38485A (es) 2018-11-27 2020-06-30 Novartis Ag Compuestos tetrámeros cíclicos como inhibidores de proproteína convertasa subtilisina/kexina tipo 9 (pcsk9), método de tratamiento, uso y su preparación
US20230089867A1 (en) 2018-11-27 2023-03-23 Novartis Ag Cyclic pentamer compounds as proprotein convertase subtilisin/kexin type 9 (pcsk9) inhibitors for the treatment of metabolic disorder
JP2022509184A (ja) 2018-11-27 2022-01-20 ノバルティス アーゲー 代謝性障害の処置のためのプロタンパク質コンバターゼスブチリシン／ケキシン９型（ｐｃｓｋ９）阻害剤としての環状ペプチド
US20230321123A1 (en) * 2020-08-25 2023-10-12 Helmholtz-Zentrum für Infektionsforschung GmbH INHIBITORS OF PSEUDOMONAS AERUGINOSA VIRULENCE FACTOR LasB
TW202333563A (zh) 2021-11-12 2023-09-01 瑞士商諾華公司 用於治療疾病或障礙之二胺基環戊基吡啶衍生物

Family Cites Families (76)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US1201216A (en) * 1915-05-05 1916-10-10 H C Dear Collapsible poultry-coop.
GB500297A (en) * 1937-08-07 1939-02-07 Evelyn Wilkins Improvements in or relating to brassieres
FR2480747A1 (fr) 1980-04-17 1981-10-23 Roques Bernard Derives d'acides amines et leur application therapeutique
US4610816A (en) 1980-12-18 1986-09-09 Schering Corporation Substituted dipeptides as inhibitors of enkephalinases
US4722810A (en) 1984-08-16 1988-02-02 E. R. Squibb & Sons, Inc. Enkephalinase inhibitors
US4929641B1 (en) * 1988-05-11 1994-08-30 Schering Corp Mercapto-acylamino acid antihypertensives
ZA875052B (en) * 1986-07-11 1989-03-29 Du Pont Angiotensin ii receptor blocking imidazoles
US5138069A (en) 1986-07-11 1992-08-11 E. I. Du Pont De Nemours And Company Angiotensin II receptor blocking imidazoles
KR880007441A (ko) 1986-12-11 1988-08-27 알렌 제이.스피겔 스피로-치환된 글루타르아미드 이뇨제
US5015651A (en) 1988-01-07 1991-05-14 E. I. Du Pont De Nemours And Company Treatment of hypertension with 1,2,4-angiotensin II antagonists
SU1709907A3 (ru) * 1988-01-07 1992-01-30 Е.И.Дюпон Де Немур Энд Компани (Фирма) Способ получени азолов
EP0361365A1 (en) 1988-09-30 1990-04-04 E.R. SQUIBB & SONS, INC. Aminobenzoic and aminocyclohexane-carboylic acid compounds, compositions, and their method of use
DE3928177A1 (de) * 1989-04-08 1991-02-28 Thomae Gmbh Dr K Benzimidazole, diese verbindungen enthaltende arzneimittel und verfahren zu ihrer herstellung
ATE113281T1 (de) 1989-08-02 1994-11-15 Takeda Chemical Industries Ltd Pyrazol-derivate, verfahren zu deren herstellung und anwendung.
CA2032289A1 (en) * 1989-12-29 1991-06-30 Joseph A. Finkelstein Substituted 5-(alkyl) carboxamide imidazoles
ATE134624T1 (de) * 1990-02-19 1996-03-15 Ciba Geigy Ag Acylverbindungen
US5270317A (en) * 1990-03-20 1993-12-14 Elf Sanofi N-substituted heterocyclic derivatives, their preparation and the pharmaceutical compositions in which they are present
US5196444A (en) 1990-04-27 1993-03-23 Takeda Chemical Industries, Ltd. 1-(cyclohexyloxycarbonyloxy)ethyl 2-ethoxy-1-[[2'-(1H-tetrazol-5-yl)biphenyl-4-yl]methyl]benzimidazole-7-carboxylate and compositions and methods of pharmaceutical use thereof
NZ238688A (en) * 1990-06-28 1992-05-26 Smithkline Beecham Corp Substituted histidines: pharmaceutical compositions, preparation and uses thereof
AU8534291A (en) * 1990-08-10 1992-03-02 G.D. Searle & Co. Renal-selective angiotensin ii antagonists for treatment of hypertension
AU1256692A (en) 1991-02-06 1992-09-07 Schering Corporation Combination of an angiotensin II antagonist or renin inhibitor with a neutral endopeptidase inhibitor
US5591762A (en) 1991-02-06 1997-01-07 Dr. Karl Thomae Gmbh Benzimidazoles useful as angiotensin-11 antagonists
US5616599A (en) * 1991-02-21 1997-04-01 Sankyo Company, Limited Angiotensin II antagosist 1-biphenylmethylimidazole compounds and their therapeutic use
IS1756B (is) * 1991-02-21 2000-12-28 Sankyo Company Limited Hliðstæðuaðferð til framleiðslu 1-Biphenylmethylimidazole afleiða
US5196537A (en) * 1991-03-21 1993-03-23 G. D. Searle & Co. 5-apylheteroarylalkyl-1,3,5-trisubstituted-1,2,4-triazole compounds for treatment of circulatory disorders
WO1992016552A1 (en) * 1991-03-25 1992-10-01 Glaxo Group Limited 1-imidazolgemethyl benzofuran derivatives as inhibitors of angiotensin ii activity
US5155100A (en) 1991-05-01 1992-10-13 Ciba-Geigy Corporation Phosphono/biaryl substituted dipeptide derivatives
US5294632A (en) * 1991-05-01 1994-03-15 Ciba-Geigy Corporation Phosphono/biaryl substituted dipetide derivatives
US5332750A (en) * 1991-09-04 1994-07-26 Merck Patent Gesellschaft Mit Beschrankter Haftung 1,2-dihydro-2-oxopyridines
US5217996A (en) 1992-01-22 1993-06-08 Ciba-Geigy Corporation Biaryl substituted 4-amino-butyric acid amides
DE69329982T2 (de) * 1992-06-02 2001-09-27 Sankyo Co 4-Carboxyimidazolderivate als Angiotensin-II-Antagonisten und ihre therapeutische Verwendung
RU2118956C1 (ru) * 1992-10-23 1998-09-20 Байер А.Г. Производные пиридонбифенила и их соли
DE4319041A1 (de) 1992-10-23 1994-04-28 Bayer Ag Trisubstituierte Biphenyle
JP3118738B2 (ja) 1992-12-22 2000-12-18 小野薬品工業株式会社 （チオ）ウレア誘導体
EP0978515A3 (en) * 1993-03-24 2000-05-17 G.D. Searle & Co. 1-(substituted phenyl)-4-biphenylmethyl-imidazol-2-one derivatives, their preparation and their use as angiotensin II antagonists
JPH0748360A (ja) 1993-05-31 1995-02-21 Yoshitomi Pharmaceut Ind Ltd ビフェニルテトラゾール誘導体
US5508272A (en) 1993-06-15 1996-04-16 Bristol-Myers Squibb Company Compounds containing a fused bicycle ring and processes therefor
CA2168066A1 (en) 1995-02-08 1996-08-09 James R. Powell Treatment of hypertension and congestive heart failure
US5587375A (en) * 1995-02-17 1996-12-24 Bristol-Myers Squibb Company Azepinone compounds useful in the inhibition of ACE and NEP
EP1045836B1 (en) * 1997-12-18 2008-03-05 Boehringer Ingelheim Pharmaceuticals Inc. Pyridones as src family sh2 domain inhibitors
US6638937B2 (en) * 1998-07-06 2003-10-28 Bristol-Myers Squibb Co. Biphenyl sulfonamides as dual angiotensin endothelin receptor antagonists
EP2002837A1 (en) 1998-07-06 2008-12-17 Bristol-Myers Squibb Company Biphenyl sulfonamides as dual angiotensin endothelin receptor antagonists
BR9917112A (pt) * 1998-12-24 2002-01-29 Fujisawa Pharmaceutical Co Compostos de imidazol e seu uso medicinal
US6191147B1 (en) * 1998-12-24 2001-02-20 Ppd Discovery, Inc. Pyrazole compounds and uses thereof
WO2001036395A1 (en) * 1999-11-15 2001-05-25 Janssen Pharmaceutica N.V. Triazoles as farnesyl transferase inhibitors
DE10063008A1 (de) * 2000-12-16 2002-06-20 Merck Patent Gmbh Carbonsäureamidderivate
GB0119305D0 (en) * 2001-04-12 2001-10-03 Aventis Pharma Gmbh Mercaptoacetylamide derivatives,a process for their preparation and their use
US6777443B2 (en) * 2001-05-15 2004-08-17 Novartis Ag Dipeptide derivatives
JP2003045574A (ja) 2001-07-30 2003-02-14 Canon Inc カードアダプタ
JP4842463B2 (ja) 2001-08-03 2011-12-21 株式会社ポーラファルマ 新規ビフェニルウレイド誘導体及びこれを有効成分とする医薬
US7468390B2 (en) * 2002-01-17 2008-12-23 Novartis Ag Methods of treatment and pharmaceutical composition
GB0416062D0 (en) * 2004-07-19 2004-08-18 Amersham Plc Improved N4 chelator conjugates
DE102004001458B4 (de) * 2004-01-08 2012-01-19 Schott Ag Glas mit deutlich verbesserter Stabilität gegen Strahlenbeschädigungen, ein Verfahren zu seiner Herstellung sowie dessen Verwendung
US20060046978A1 (en) * 2004-08-31 2006-03-02 Morphochem Ag Novel compounds that inhibit dipeptidyl peptidase (DPP-IV) and neprilysin (NEP) and/or angiotensin converting enzyme (ACE)
WO2006027680A1 (en) 2004-09-10 2006-03-16 Pfizer Limited 3-(1-carbamoylcyclohexyl) propionic acid derivatives as inhibitors of neutral endopeptidase enzyme
MY146830A (en) 2005-02-11 2012-09-28 Novartis Ag Combination of organic compounds
WO2007045663A2 (en) 2005-10-19 2007-04-26 Novartis Ag Combination of an ati receptor antagonist and a np inhibitor fro treating ia hypertension and heartfailure
AR057882A1 (es) 2005-11-09 2007-12-26 Novartis Ag Compuestos de accion doble de bloqueadores del receptor de angiotensina e inhibidores de endopeptidasa neutra
WO2007106708A2 (en) 2006-03-10 2007-09-20 Novartis Ag Combinations of the angiotensin ii antagonist valsartan and the nep inhibitor daglutril
WO2007109456A2 (en) 2006-03-16 2007-09-27 Pharmacopeia, Inc. Substituted biphenyl isoxazole sulfonamides as dual angiotensin endothelin receptor antagonists
TW200838501A (en) 2007-02-02 2008-10-01 Theravance Inc Dual-acting antihypertensive agents
TWI448284B (zh) * 2007-04-24 2014-08-11 Theravance Inc 雙效抗高血壓劑
CN101765590B (zh) 2007-05-24 2015-11-25 埃尔德鲁格股份有限公司 1，(3)，5-取代的咪唑、它们在治疗高血压中的用途以及它们的制备方法
TWI406850B (zh) 2007-06-05 2013-09-01 Theravance Inc 雙效苯并咪唑抗高血壓劑
WO2009035543A1 (en) 2007-09-07 2009-03-19 Theravance, Inc. Dual-acting antihypertensive agents
US8212052B2 (en) 2007-12-11 2012-07-03 Theravance, Inc. Dual-acting benzoimidazole antihypertensive agents
JP2011518884A (ja) 2008-04-29 2011-06-30 セラヴァンス， インコーポレーテッド 二重活性抗高血圧剤
JP2011529072A (ja) 2008-07-24 2011-12-01 セラヴァンス， インコーポレーテッド 二重作用血圧降下薬
TW201014830A (en) 2008-09-30 2010-04-16 Theravance Inc Crystalline form of an alkoxyimidazol-1-ylmethyl biphenyl carboxylic acid
US8232306B2 (en) 2008-10-16 2012-07-31 Theravance, Inc. Methods for detecting sulfhydryl-containing compounds in a biological test sample
ES2611107T3 (es) * 2009-07-07 2017-05-04 Theravance Biopharma R&D Ip, Llc Agentes antihipertensivos de pirazol, de doble acción
JP2012533626A (ja) 2009-07-22 2012-12-27 セラヴァンス， インコーポレーテッド 二重作用オキサゾール降圧剤
TWI545114B (zh) 2009-09-29 2016-08-11 施萬生物製藥研發Ｉｐ有限責任公司 製備聯苯基咪唑化合物之方法
WO2011090929A1 (en) 2010-01-19 2011-07-28 Theravance, Inc. Dual-acting thiophene, pyrrole, thiazole and furan antihypertensive agents
US8399501B2 (en) 2010-03-04 2013-03-19 Theravance, Inc. Crystalline alkoxyimidazol-1-ylmethyl biphenyl carboxylic acid and methods for preparing thereof
RU2013126403A (ru) 2010-11-10 2014-12-20 ТЕРЕВАНС БАЙОФАРМА Р энд Д ИП,ЛЛС Кристаллические формы алкоксиимидазол-1-илметилбифенилкарбоновых кислот

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