TWI731943B - 結晶型（2s，4r）－5－（5’－氯－2’－氟－［1，1’－聯苯］－4－基）－2－（乙氧基甲基）－4－（3－羥基異㗁唑－5－甲醯胺基）－2－甲基戊酸及其用途 - Google Patents

結晶型（2s，4r）－5－（5’－氯－2’－氟－［1，1’－聯苯］－4－基）－2－（乙氧基甲基）－4－（3－羥基異㗁唑－5－甲醯胺基）－2－甲基戊酸及其用途 Download PDF

Info

Publication number
TWI731943B
TWI731943B TW106107450A TW106107450A TWI731943B TW I731943 B TWI731943 B TW I731943B TW 106107450 A TW106107450 A TW 106107450A TW 106107450 A TW106107450 A TW 106107450A TW I731943 B TWI731943 B TW I731943B
Authority
TW
Taiwan
Prior art keywords
crystalline form
compound
acid
hypertension
administered
Prior art date
Application number
TW106107450A
Other languages
English (en)
Chinese (zh)
Other versions
TW201741290A (zh
Inventor
亞當 Ｄ 休斯
梅莉沙 佛羅瑞
麥洛史夫 瑞帕達
凡凱特 R 泰拉狄
吉尼 提摩西 法斯
麥可 息蒙
Ｒ 麥可 鲍德溫
大衛 L 布德特
Original Assignee
美商施萬生物製藥研發Ｉｐ有限責任公司
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=58387911&utm_source=google_patent&utm_medium=platform_link&utm_campaign=public_patent_search&patent=TWI731943(B) "Global patent litigation dataset” by Darts-ip is licensed under a Creative Commons Attribution 4.0 International License.
Application filed by 美商施萬生物製藥研發Ｉｐ有限責任公司 filed Critical 美商施萬生物製藥研發Ｉｐ有限責任公司
Publication of TW201741290A publication Critical patent/TW201741290A/zh
Application granted granted Critical
Publication of TWI731943B publication Critical patent/TWI731943B/zh

Links

Images

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D261/00—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings
    • C07D261/02—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings not condensed with other rings
    • C07D261/06—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings not condensed with other rings having two or more double bonds between ring members or between ring members and non-ring members
    • C07D261/10—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings not condensed with other rings having two or more 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
    • C07D261/18—Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen
    • 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
    • A61K31/415—1,2-Diazoles
    • 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
    • A61K31/42—Oxazoles
    • 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
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
    • A61K9/4816—Wall or shell material
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P13/00—Drugs for disorders of the urinary system
    • A61P13/12—Drugs for disorders of the urinary system of the kidneys
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/04—Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/12—Antihypertensives
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
    • C07B2200/00—Indexing scheme relating to specific properties of organic compounds
    • C07B2200/13—Crystalline forms, e.g. polymorphs

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Animal Behavior & Ethology (AREA)
  • Medicinal Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Epidemiology (AREA)
  • Cardiology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Urology & Nephrology (AREA)
  • Hospice & Palliative Care (AREA)
  • Physiology (AREA)
  • Nutrition Science (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
  • Medicinal Preparation (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
TW106107450A 2016-03-08 2017-03-07 結晶型（2s，4r）－5－（5’－氯－2’－氟－［1，1’－聯苯］－4－基）－2－（乙氧基甲基）－4－（3－羥基異㗁唑－5－甲醯胺基）－2－甲基戊酸及其用途 TWI731943B (zh)

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
US201662305393P 2016-03-08 2016-03-08
US62/305,393 2016-03-08
US201662346336P 2016-06-06 2016-06-06
US62/346,336 2016-06-06

Publications (2)

Publication Number Publication Date
TW201741290A TW201741290A (zh) 2017-12-01
TWI731943B true TWI731943B (zh) 2021-07-01

Family

ID=58387911

Family Applications (1)

Application Number Title Priority Date Filing Date
TW106107450A TWI731943B (zh) 2016-03-08 2017-03-07 結晶型（2s，4r）－5－（5’－氯－2’－氟－［1，1’－聯苯］－4－基）－2－（乙氧基甲基）－4－（3－羥基異㗁唑－5－甲醯胺基）－2－甲基戊酸及其用途

Country Status (30)

Country Link
US (6) US10100021B2 (enExample)
EP (1) EP3408260B1 (enExample)
JP (2) JP7306828B2 (enExample)
KR (2) KR20220035991A (enExample)
CN (1) CN108779084A (enExample)
AU (1) AU2017229466C1 (enExample)
CA (1) CA3015505C (enExample)
CL (1) CL2018002539A1 (enExample)
CO (1) CO2018010568A2 (enExample)
CY (1) CY1124397T1 (enExample)
DK (1) DK3408260T3 (enExample)
ES (1) ES2880123T3 (enExample)
HR (1) HRP20211169T1 (enExample)
HU (1) HUE055546T2 (enExample)
IL (1) IL261244B (enExample)
LT (1) LT3408260T (enExample)
MX (1) MX377177B (enExample)
MY (1) MY198185A (enExample)
PH (1) PH12018501876A1 (enExample)
PL (1) PL3408260T3 (enExample)
PT (1) PT3408260T (enExample)
RS (1) RS62172B1 (enExample)
RU (1) RU2756223C2 (enExample)
SA (1) SA518392325B1 (enExample)
SG (1) SG11201807591VA (enExample)
SI (1) SI3408260T1 (enExample)
SM (1) SMT202100434T1 (enExample)
TW (1) TWI731943B (enExample)
WO (1) WO2017156009A1 (enExample)
ZA (1) ZA201805840B (enExample)

Families Citing this family (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
TWI731943B (zh) 2016-03-08 2021-07-01 美商施萬生物製藥研發Ｉｐ有限責任公司 結晶型（2s，4r）－5－（5’－氯－2’－氟－［1，1’－聯苯］－4－基）－2－（乙氧基甲基）－4－（3－羥基異㗁唑－5－甲醯胺基）－2－甲基戊酸及其用途
WO2021052441A1 (zh) 2019-09-20 2021-03-25 深圳信立泰药业股份有限公司 血管紧张素ii受体拮抗剂代谢产物与nep抑制剂的复合物治疗心衰的用途
KR102485499B1 (ko) * 2022-07-15 2023-01-09 오가노이드사이언스 주식회사 신장 질환의 치료 또는 예방용 조성물

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
TW201410653A (zh) * 2012-08-08 2014-03-16 Theravance Inc 腦啡肽酶抑制劑

Family Cites Families (48)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4189604A (en) 1975-07-22 1980-02-19 Zaidan Hojin Biseibutsu Kagaku Kenkyu Kai Bestatin
US4206232A (en) 1976-05-10 1980-06-03 E. R. Squibb & Sons, Inc. Relieving hypertension with carboxyalkylacylamino acids
IL58849A (en) 1978-12-11 1983-03-31 Merck & Co Inc Carboxyalkyl dipeptides and derivatives thereof,their preparation and pharmaceutical compositions containing them
FR2480747A1 (fr) 1980-04-17 1981-10-23 Roques Bernard Derives d'acides amines et leur application therapeutique
US4906615A (en) 1980-12-18 1990-03-06 Schering Corporation Substituted dipeptides as inhibitors of enkephalinases
US4722810A (en) 1984-08-16 1988-02-02 E. R. Squibb & Sons, Inc. Enkephalinase inhibitors
US4939261A (en) 1984-06-08 1990-07-03 Ciba-Geigy Corporation N-substituted butyramide derivatives useful for treatment of conditions responsive to inhibition of enkephalinase
EP0225292A3 (en) 1985-12-06 1988-11-30 Ciba-Geigy Ag Certain n-substituted butyramide derivatives
US4929641B1 (en) 1988-05-11 1994-08-30 Schering Corp Mercapto-acylamino acid antihypertensives
KR880007441A (ko) 1986-12-11 1988-08-27 알렌 제이.스피겔 스피로-치환된 글루타르아미드 이뇨제
FR2623498B1 (fr) 1987-11-24 1990-04-06 Bioprojet Soc Civ Nouveaux composes enantiomeres derives d'amino-acides, leur procede de preparation et leurs applications therapeutiques
GB8820844D0 (en) 1988-09-05 1988-10-05 Pfizer Ltd Therapeutic agents
US5599951A (en) 1989-09-15 1997-02-04 Societe Civile Bioprojet Amino acid derivatives, the process for their preparation and their applications to therapy
US5294632A (en) 1991-05-01 1994-03-15 Ciba-Geigy Corporation Phosphono/biaryl substituted dipetide derivatives
US5155100A (en) 1991-05-01 1992-10-13 Ciba-Geigy Corporation Phosphono/biaryl substituted dipeptide derivatives
US5217996A (en) 1992-01-22 1993-06-08 Ciba-Geigy Corporation Biaryl substituted 4-amino-butyric acid amides
US5508272A (en) 1993-06-15 1996-04-16 Bristol-Myers Squibb Company Compounds containing a fused bicycle ring and processes therefor
DE19510566A1 (de) 1995-03-23 1996-09-26 Kali Chemie Pharma Gmbh Benzazepin-, Benzoxazepin- und Benzothiazepin-N-essigsäurederivate sowie Verfahren zu ihrer Herstellung und diese Verbindungen enthaltende Arzneimittel
AU5687396A (en) 1995-04-21 1996-11-07 Novarits Ag N-aroylamino acid amides as endothelin inhibitors
US6660756B2 (en) 2001-03-28 2003-12-09 Pfizer Inc. N-phenpropylcyclopentyl-substituted glutaramide derivatives as inhibitors of neutral endopeptidase
GB0119305D0 (en) 2001-04-12 2001-10-03 Aventis Pharma Gmbh Mercaptoacetylamide derivatives,a process for their preparation and their use
WO2006027680A1 (en) 2004-09-10 2006-03-16 Pfizer Limited 3-(1-carbamoylcyclohexyl) propionic acid derivatives as inhibitors of neutral endopeptidase enzyme
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
EP1984510B1 (en) 2006-02-17 2015-04-08 Monsanto Technology LLC Chimeric regulatory sequences comprising introns from dicotyledons for plant gene expression
WO2007106708A2 (en) 2006-03-10 2007-09-20 Novartis Ag Combinations of the angiotensin ii antagonist valsartan and the nep inhibitor daglutril
ES2602566T3 (es) 2007-01-12 2017-02-21 Novartis Ag Proceso para preparar ácido 5-bifenil-4-amino-2-metil pentanoico
TWI448284B (zh) 2007-04-24 2014-08-11 Theravance Inc 雙效抗高血壓劑
AR070176A1 (es) 2008-01-17 2010-03-17 Novartis Ag Procesos de sintesis de inhibidores de nep, compuestos intermediarios y uso de los mismos en la sintesis
CA2763565A1 (en) * 2009-05-28 2010-12-02 Novartis Ag Substituted aminobutyric derivatives as neprilysin inhibitors
PL2435409T3 (pl) * 2009-05-28 2015-01-30 Novartis Ag Podstawione pochodne aminopropionowe jako inhibitory neprylizyny
JO2967B1 (en) 2009-11-20 2016-03-15 نوفارتس ايه جي Acetic acid derivatives of carbamoyl methyl amino are substituted as new NEP inhibitors
ES2550485T3 (es) 2010-01-22 2015-11-10 Novartis Ag Intermedios de inhibidores de la endopeptidasa neutra y método de preparación de los mismos
US8673974B2 (en) 2010-11-16 2014-03-18 Novartis Ag Substituted amino bisphenyl pentanoic acid derivatives as NEP inhibitors
US8993631B2 (en) 2010-11-16 2015-03-31 Novartis Ag Method of treating contrast-induced nephropathy
CN103261168B (zh) 2010-12-15 2015-08-05 施万生物制药研发Ip有限责任公司 脑啡肽酶抑制剂
SI2651896T1 (sl) 2010-12-15 2015-11-30 Theravance Biopharma R&D Ip, Llc Inhibitorji neprilizina
AU2012217615B2 (en) * 2011-02-17 2016-09-29 Theravance Biopharma R&D Ip, Llc Substituted aminobutyric derivatives as neprilysin inhibitors
US8449890B2 (en) 2011-02-17 2013-05-28 Theravance, Inc. Neprilysin inhibitors
CA2835281A1 (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
ES2699773T3 (es) 2011-05-31 2019-02-12 Theravance Biopharma R&D Ip Llc Inhibidores de neprilisina
TWI560172B (en) 2011-11-02 2016-12-01 Theravance Biopharma R&D Ip Llc Neprilysin inhibitors
CA2871292A1 (en) 2012-05-31 2013-12-05 Theravance Biopharma R&D Ip, Llc Nitric oxide donor neprilysin inhibitors
ES2710932T3 (es) 2012-06-08 2019-04-29 Theravance Biopharma R&D Ip Llc Inhibidores de neprilisina
LT2864292T (lt) 2012-06-08 2017-07-10 Theravance Biopharma R&D Ip, Llc Neprilizino inhibitoriai
KR101811549B1 (ko) * 2013-06-19 2017-12-26 에프. 호프만-라 로슈 아게 인돌린-2-온 또는 피롤로-피리딘/피리미딘-2-온 유도체
MX2016009760A (es) * 2014-01-30 2016-11-08 Theravance Biopharma R&D Ip Llc Inhibidores de neprilisina.
TWI731943B (zh) 2016-03-08 2021-07-01 美商施萬生物製藥研發Ｉｐ有限責任公司 結晶型（2s，4r）－5－（5’－氯－2’－氟－［1，1’－聯苯］－4－基）－2－（乙氧基甲基）－4－（3－羥基異㗁唑－5－甲醯胺基）－2－甲基戊酸及其用途

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
TW201410653A (zh) * 2012-08-08 2014-03-16 Theravance Inc 腦啡肽酶抑制劑

Also Published As

Publication number Publication date
US10100021B2 (en) 2018-10-16
US20240327360A1 (en) 2024-10-03
CL2018002539A1 (es) 2018-10-26
JP7306828B2 (ja) 2023-07-11
HRP20211169T1 (hr) 2021-11-12
US11718591B2 (en) 2023-08-08
US10752599B2 (en) 2020-08-25
IL261244A (en) 2018-10-31
EP3408260A1 (en) 2018-12-05
CN108779084A (zh) 2018-11-09
WO2017156009A1 (en) 2017-09-14
ZA201805840B (en) 2019-07-31
BR112018068170A2 (pt) 2019-01-29
EP3408260B1 (en) 2021-05-05
US11230536B2 (en) 2022-01-25
SA518392325B1 (ar) 2022-08-03
CA3015505C (en) 2024-03-05
RU2018135072A3 (enExample) 2020-10-15
MX377177B (es) 2025-03-07
IL261244B (en) 2022-02-01
PH12018501876A1 (en) 2019-01-28
US20210061776A1 (en) 2021-03-04
ES2880123T3 (es) 2021-11-23
PT3408260T (pt) 2021-07-23
US20200157061A1 (en) 2020-05-21
JP2022017433A (ja) 2022-01-25
US20190002416A1 (en) 2019-01-03
MX2018010727A (es) 2019-01-24
US20220242836A1 (en) 2022-08-04
KR20220035991A (ko) 2022-03-22
RU2756223C2 (ru) 2021-09-28
DK3408260T3 (da) 2021-08-02
AU2017229466A1 (en) 2018-09-13
JP2019509286A (ja) 2019-04-04
CA3015505A1 (en) 2017-09-14
LT3408260T (lt) 2021-07-26
CO2018010568A2 (es) 2018-10-22
MY198185A (en) 2023-08-09
SMT202100434T1 (it) 2021-09-14
US20170275259A1 (en) 2017-09-28
HUE055546T2 (hu) 2021-12-28
KR20180114225A (ko) 2018-10-17
AU2017229466C1 (en) 2021-02-11
US10472335B2 (en) 2019-11-12
AU2017229466B2 (en) 2020-08-13
PL3408260T3 (pl) 2021-11-08
RU2018135072A (ru) 2020-04-08
CY1124397T1 (el) 2022-07-22
SI3408260T1 (sl) 2021-08-31
US12351561B2 (en) 2025-07-08
TW201741290A (zh) 2017-12-01
SG11201807591VA (en) 2018-10-30
RS62172B1 (sr) 2021-08-31

Similar Documents

Publication Publication Date Title
US11642332B2 (en) (2R,4R)-5-(5′-chloro-2′-fluorobiphenyl-4-yl)-2-hydroxy-4-[(5-methyloxazole-2-carbonyl)amino]pentanoic acid
US12351561B2 (en) Crystalline (2S,4R)-5-(5'-chloro-2'-fluoro-[1,1'-biphenyl]-4-yl)-2-(ethoxymethyl)-4-(3-hydroxyisoxazole-5-carboxamido)-2-methylpentanoic acid and uses thereof
TWI702203B (zh) (２s,４r)-５-(５'-氯-２'-氟聯苯-４-基)-４-(乙氧基草醯基胺基)-２-羥甲基-２-甲基戊酸
HK40001155B (en) Crystalline (2s,4r)-5-(5’-chloro-2-fluoro-[1,1’-biphenyl]-4-yl)-2-(ethoxymethyl)-4-(3-hydroxyisoxazole-5-carboxamido)-2-methylpentanoic acid and uses thereof
HK1245772B (en) (2r,4r)-5-(5'-chloro-2'-fluorobiphenyl-4-yl)-2-hydroxy-4-[(5-methyloxazole-2-carbonyl)amino]pentanoic acid