WO2019149658A1 - Pyrazole- and indazole-substituted oxadiazolopyridine derivatives for use as ghrelin o-acyl transferase (goat) inhibitors - Google Patents

Pyrazole- and indazole-substituted oxadiazolopyridine derivatives for use as ghrelin o-acyl transferase (goat) inhibitors Download PDF

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Publication number
WO2019149658A1
WO2019149658A1 PCT/EP2019/051991 EP2019051991W WO2019149658A1 WO 2019149658 A1 WO2019149658 A1 WO 2019149658A1 EP 2019051991 W EP2019051991 W EP 2019051991W WO 2019149658 A1 WO2019149658 A1 WO 2019149658A1
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WO
WIPO (PCT)
Prior art keywords
group
alkyl
optionally substituted
heterocyclyl
phenyl
Prior art date
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Ceased
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PCT/EP2019/051991
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English (en)
French (fr)
Inventor
Cédrickx GODBOUT
Thomas Trieselmann
Viktor VINTONYAK
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Boehringer Ingelheim International GmbH
Original Assignee
Boehringer Ingelheim International GmbH
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Filing date
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Application filed by Boehringer Ingelheim International GmbH filed Critical Boehringer Ingelheim International GmbH
Priority to US16/966,485 priority Critical patent/US11136337B2/en
Priority to JP2020541971A priority patent/JP7225253B2/ja
Priority to CN201980009508.9A priority patent/CN111630055B/zh
Priority to EP19702084.5A priority patent/EP3746449B1/en
Publication of WO2019149658A1 publication Critical patent/WO2019149658A1/en
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D498/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D498/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
    • C07D498/04—Ortho-condensed systems
    • 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
    • A61K31/4353—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 ortho- or peri-condensed with heterocyclic ring systems
    • A61K31/437—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 ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a five-membered ring having nitrogen as a ring hetero atom, e.g. indolizine, beta-carboline
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/04—Anorexiants; Antiobesity agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
    • A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D519/00—Heterocyclic compounds containing more than one system of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring system not provided for in groups C07D453/00 or C07D455/00

Definitions

  • compound(s) according to this invention denote the compounds of the formula (I) according to the present invention including their tautomers, stereoisomers and mixtures thereof and the salts thereof, in particular the pharmaceutically acceptable salts thereof, and the solvates and hydrates of such compounds, including the solvates and hydrates of such tautomers, stereoisomers and salts thereof.
  • the compounds of general formula I according to the invention are suitable for the treatment of all those diseases or conditions which may be affected or which are mediated by the inhibition of ghrelin O-acyl transferase (GOAT).
  • the compounds of the invention are used for treating obesity, body weight regain, type 2 diabetes and insulin resistance.
  • the present invention relates a method for treating a disease or condition mediated by the inhibition of ghrelin O-acyl transferase (GOAT) in a patient that includes the step of administering to the patient, preferably a human, in need of such treatment a therapeutically effective amount of a compound of the present invention in combination with a therapeutically effective amount of one or more additional therapeutic agents described in hereinbefore and hereinafter,
  • GOAT ghrelin O-acyl transferase
  • the use of the compound according to the invention in combination with the additional therapeutic agent may take place simultaneously or at staggered times.
  • Eluent A Water (0.1 % NFI 4 OFI); Eluent B: Acetonitrile Gradient: Time (min.) % Eluent B Flow [mL/min] Temp [°C]
  • 3,3-Difluoropyrrolidine hydrochloride (49 mg; 0.35 mmol) is dissolved in 3 ml_ tetrahydrofuran and trimethylaluminium (2 M in hexane; 0.173 ml_; 0.35 mmol) is added and the mixture is stirred for 5 minutes.
  • Example 1.6 (Methyl 1 -( ⁇ 7-amino-5- methyl-[1 ,2,5]oxadiazolo[3,4-b]pyridin-6-yl ⁇ methyl)-1 H-pyrazole-3-carboxylate, 50 mg; 0.17 mmol) is added and the mixture is stirred at 70°C for 1 hour. The reaction is quenched with methanol / acidic acid and purified by reverse phase chromatography- HPLC (modifier: trifluoroacetic acid).

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  • Chemical & Material Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Organic Chemistry (AREA)
  • Diabetes (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Hematology (AREA)
  • Obesity (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Child & Adolescent Psychology (AREA)
  • Epidemiology (AREA)
  • Emergency Medicine (AREA)
  • Endocrinology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
PCT/EP2019/051991 2018-02-02 2019-01-28 Pyrazole- and indazole-substituted oxadiazolopyridine derivatives for use as ghrelin o-acyl transferase (goat) inhibitors Ceased WO2019149658A1 (en)

Priority Applications (4)

Application Number Priority Date Filing Date Title
US16/966,485 US11136337B2 (en) 2018-02-02 2019-01-28 Pyrazole- and indazole-substituted oxadiazolopyridine derivatives for use as ghrelin O-acyl transferase (GOAT) inhibitors
JP2020541971A JP7225253B2 (ja) 2018-02-02 2019-01-28 グレリンｏ－アシルトランスフェラーゼ（ｇｏａｔ）阻害剤として使用するためのピラゾール置換及びインダゾール置換オキサジアゾロピリジン誘導体
CN201980009508.9A CN111630055B (zh) 2018-02-02 2019-01-28 用作饥饿素o-酰基转移酶(goat)抑制剂的吡唑取代的和吲唑取代的噁二唑并吡啶衍生物
EP19702084.5A EP3746449B1 (en) 2018-02-02 2019-01-28 Pyrazole- and indazole-substituted oxadiazolopyridine derivatives for use as ghrelin o-acyl transferase (goat) inhibitors

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
EP18154826.4 2018-02-02
EP18154826 2018-02-02

Publications (1)

Publication Number Publication Date
WO2019149658A1 true WO2019149658A1 (en) 2019-08-08

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PCT/EP2019/051991 Ceased WO2019149658A1 (en) 2018-02-02 2019-01-28 Pyrazole- and indazole-substituted oxadiazolopyridine derivatives for use as ghrelin o-acyl transferase (goat) inhibitors

Country Status (5)

Country Link
US (1) US11136337B2 (https=)
EP (1) EP3746449B1 (https=)
JP (1) JP7225253B2 (https=)
CN (1) CN111630055B (https=)
WO (1) WO2019149658A1 (https=)

Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2021174048A1 (en) 2020-02-28 2021-09-02 Kallyope, Inc. Gpr40 agonists
WO2021233882A1 (en) 2020-05-22 2021-11-25 Boehringer Ingelheim International Gmbh Process for manufacturing alkyl 7-amino-5-methyl-[1,2,5]oxadiazolo[3,4-b]pyridine-carboxylate
WO2021233884A1 (en) 2020-05-22 2021-11-25 Boehringer Ingelheim International Gmbh Continuous process for manufacturing alkyl 7-amino-5-methyl-[1,2,5]oxadiazolo[3,4-b]pyridine-carboxylate
US11254688B2 (en) 2018-02-02 2022-02-22 Boehringer Ingelheim International Gmbh Benzyl-, (pyridin-3-yl)methyl -or (pyridin-4-yl)-methyl-substituted oxadiazolopyridine derivatives as ghrelin O-acyl transferase (GOAT) inhibitors
US11583532B2 (en) 2018-02-02 2023-02-21 Boehringer Ingelheim International Gmbh Triazolopyrimidine derivatives for use as ghrelin o-acyl transferase (GOAT) inhibitors

Families Citing this family (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US9994591B2 (en) * 2016-08-05 2018-06-12 Boehringer Ingelheim International Gmbh Oxadiazolopyridine derivates for use as ghrelin O-acyl transferase (GOAT) inhibitors
CN116082437A (zh) * 2022-01-26 2023-05-09 石家庄迪斯凯威医药科技有限公司 一种多环化合物及其作为胃饥饿素受体激动剂的用途

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Cited By (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US11254688B2 (en) 2018-02-02 2022-02-22 Boehringer Ingelheim International Gmbh Benzyl-, (pyridin-3-yl)methyl -or (pyridin-4-yl)-methyl-substituted oxadiazolopyridine derivatives as ghrelin O-acyl transferase (GOAT) inhibitors
US11583532B2 (en) 2018-02-02 2023-02-21 Boehringer Ingelheim International Gmbh Triazolopyrimidine derivatives for use as ghrelin o-acyl transferase (GOAT) inhibitors
WO2021174048A1 (en) 2020-02-28 2021-09-02 Kallyope, Inc. Gpr40 agonists
US12264171B2 (en) 2020-02-28 2025-04-01 Kallyope, Inc. GPR40 agonists
WO2021233882A1 (en) 2020-05-22 2021-11-25 Boehringer Ingelheim International Gmbh Process for manufacturing alkyl 7-amino-5-methyl-[1,2,5]oxadiazolo[3,4-b]pyridine-carboxylate
WO2021233884A1 (en) 2020-05-22 2021-11-25 Boehringer Ingelheim International Gmbh Continuous process for manufacturing alkyl 7-amino-5-methyl-[1,2,5]oxadiazolo[3,4-b]pyridine-carboxylate
US11518771B2 (en) 2020-05-22 2022-12-06 Boehringer Ingelheim International Gmbh Process for manufacturing alkyl 7-amino-5-methyl-[1,2,5]oxadiazolo[3,4-b]pyridine-carboxylate
CN115884974A (zh) * 2020-05-22 2023-03-31 勃林格殷格翰国际有限公司 制备烷基7-氨基-5-甲基-[1,2,5]噁二唑并[3,4-b]吡啶羧酸酯的方法
US11976082B2 (en) 2020-05-22 2024-05-07 Boehringer Ingelheim International Gmbh Continuous process for manufacturing alkyl 7-amino-5-methyl-[1,2,5]oxadiazolo[3,4-b]pyridine-carboxylate

Also Published As

Publication number Publication date
EP3746449B1 (en) 2022-03-30
CN111630055A (zh) 2020-09-04
JP7225253B2 (ja) 2023-02-20
US20210040113A1 (en) 2021-02-11
CN111630055B (zh) 2023-07-14
US11136337B2 (en) 2021-10-05
EP3746449A1 (en) 2020-12-09
JP2021512125A (ja) 2021-05-13

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