WO2020138499A1 - Composé substitué par un alkyle - Google Patents

Composé substitué par un alkyle Download PDF

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Publication number
WO2020138499A1
WO2020138499A1 PCT/JP2019/051620 JP2019051620W WO2020138499A1 WO 2020138499 A1 WO2020138499 A1 WO 2020138499A1 JP 2019051620 W JP2019051620 W JP 2019051620W WO 2020138499 A1 WO2020138499 A1 WO 2020138499A1
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WO
WIPO (PCT)
Prior art keywords
oxy
azetidin
carboxylic acid
amino
group
Prior art date
Application number
PCT/JP2019/051620
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English (en)
Japanese (ja)
Inventor
祥子 小池
洋平 井熊
惇一郎 上杉
孝幸 深谷
雄貴 水上
展久 福田
砂塚　敏明
吉彦 野口
花木　秀明
葵 君嶋
Original Assignee
大日本住友製薬株式会社
学校法人北里研究所
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Publication date
Application filed by 大日本住友製薬株式会社, 学校法人北里研究所 filed Critical 大日本住友製薬株式会社
Priority to JP2020562554A priority Critical patent/JPWO2020138499A1/ja
Publication of WO2020138499A1 publication Critical patent/WO2020138499A1/fr

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    • 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
    • A61K31/40—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
    • A61K31/407—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 condensed with other heterocyclic ring systems, e.g. ketorolac, physostigmine
    • 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
    • A61K31/4196—1,2,4-Triazoles
    • 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
    • A61K31/425—Thiazoles
    • A61K31/427—Thiazoles not condensed and containing further heterocyclic rings
    • 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
    • A61K31/54—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one sulfur as the ring hetero atoms, e.g. sulthiame
    • A61K31/542—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one sulfur as the ring hetero atoms, e.g. sulthiame ortho- or peri-condensed with heterocyclic ring systems
    • A61K31/545—Compounds containing 5-thia-1-azabicyclo [4.2.0] octane ring systems, i.e. compounds containing a ring system of the formula:, e.g. cephalosporins, cefaclor, or cephalexine
    • A61K31/546—Compounds containing 5-thia-1-azabicyclo [4.2.0] octane ring systems, i.e. compounds containing a ring system of the formula:, e.g. cephalosporins, cefaclor, or cephalexine containing further heterocyclic rings, e.g. cephalothin
    • 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
    • A61K31/69—Boron compounds
    • 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00—Drugs for disorders of the respiratory system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00—Drugs for disorders of the respiratory system
    • A61P11/02—Nasal agents, e.g. decongestants
    • 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
    • A61P13/02—Drugs for disorders of the urinary system of urine or of the urinary tract, e.g. urine acidifiers
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P15/00—Drugs for genital or sexual disorders; Contraceptives
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A61P17/02—Drugs for dermatological disorders for treating wounds, ulcers, burns, scars, keloids, or the like
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00—Drugs for skeletal disorders
    • A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00—Drugs for skeletal disorders
    • A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P27/00—Drugs for disorders of the senses
    • A61P27/02—Ophthalmic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P27/00—Drugs for disorders of the senses
    • A61P27/16—Otologicals
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/04—Antibacterial agents
    • 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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F5/00—Compounds containing elements of Groups 3 or 13 of the Periodic Table
    • C07F5/02—Boron compounds
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
    • Y02P20/00—Technologies relating to chemical industry
    • Y02P20/50—Improvements relating to the production of bulk chemicals
    • Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups

Definitions

  • Non-patent Document 1 Sulbactam, and tazobactam mainly inhibit class A ⁇ -lactamase except KPC (Klebsiella pneumoniae Carbapenemase), and avibactam partially contains class A including KPC, class C and OXA-48. It is known to inhibit ⁇ -lactamase of Escherichia coli (Non-patent Document 1).
  • Y is an oxygen atom, a sulfur atom, or —NR j —
  • R j is a hydrogen atom, a hydroxyl group, or an optionally substituted hydrocarbyl group
  • Ring A is an optionally substituted non-aryl heterocycle
  • L 3 is an oxygen atom, a sulfur atom, an optionally substituted hydrocarbylene group or an optionally substituted heterohydrocarbylene group
  • L 4 is a single bond or an optionally substituted hydrocarbylene group
  • R 5 is a hydrogen atom, a hydroxyl group, an optionally substituted hydrocarbyl group, or an optionally substituted heterohydrocarbyl group
  • the remaining two (which do not have the structure of the formula (2) among R 1 , R 2 and R 3 ) may each independently be the same or different and be a hydrogen atom, a halogen, a hydroxyl group or a substituent.
  • Item 1 Item 2A, or a compound or a pharmaceutically acceptable salt thereof according to any one of Items 2 to 4.
  • (Item 6) The compound according to any one of item 1, item 2A, item 2 to item 5, wherein -L 3 -L 4 -is an optionally substituted C 1-2 alkylene group, or a pharmaceutical thereof. Acceptable salt.
  • R 5 is 1) C 6-10 aryl, 2) 5- to 10-membered heteroaryl, 3) —C( ⁇ O)NR 50 R 51 , 4) —C( ⁇ O)OR 20 or 5)—NR e1 R f1 (provided that R 5 is 5), L 3 and/or L 4 is at least one other than a hydrogen atom.
  • a C 1-6 alkylene group which is necessarily substituted with a group of, and forms at least one C 3-10 alicyclic group or a 4- to 10-membered non-aryl heterocycle with the substituent)
  • Each of the substituents (provided above 1) and 2) may be substituted, and when any two groups are respectively bonded to adjacent atoms in the ring, they are taken together and further condensed.
  • R e1 and R f1 are each independently the same or different, 1) hydrogen atom, 2) a C 1-4 alkyl group, or 3) a C 3-6 alicyclic group, (However, each substituent of the above 2) to 3) may be substituted.
  • 68. The compound or a pharmaceutically acceptable salt thereof according to any one of items 63 to 67, which is any of (Item 69) 69.
  • the compound according to item 89 or item 90, or a pharmaceutically acceptable salt thereof which is: (Item 92)
  • R G is a hydroxyl group, a thiol group, or —NHR a1
  • R a1 , Z, L 1 , L 2 , X, R 1 , R 2 , R 3 , and R 4 are items.
  • 1 has the same meaning as the definition described in any one of 15 to 15, and formula (1a) has the same meaning as that of item 1]
  • the compound of formula (11) has the following formula (12):

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Organic Chemistry (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Epidemiology (AREA)
  • Physical Education & Sports Medicine (AREA)
  • Rheumatology (AREA)
  • Pulmonology (AREA)
  • Dermatology (AREA)
  • Orthopedic Medicine & Surgery (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Otolaryngology (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Urology & Nephrology (AREA)
  • Cardiology (AREA)
  • Communicable Diseases (AREA)
  • Oncology (AREA)
  • Immunology (AREA)
  • Ophthalmology & Optometry (AREA)
  • Endocrinology (AREA)
  • Reproductive Health (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)

Abstract

L'objectif de la présente invention est de décrire un nouveau composé qui possède une excellente activité inhibitrice de la β-lactamase. La présente invention concerne : un composé qui possède une excellente activité inhibitrice de la β-lactamase et qui est représenté par la formule (1a), (1b) ou (11) ; ou un sel pharmaceutiquement acceptable de celui-ci. Le composé fournit un agent prophylactique ou thérapeutique qui est utile en cas d'infection bactérienne lorsqu'il est utilisé en combinaison avec un médicament β-lactame ou utilisé seul. La présente invention concerne également un agent prophylactique ou thérapeutique qui est utile pour traiter une variété de maladies en combinaison avec un médicament β-lactame.
PCT/JP2019/051620 2018-12-28 2019-12-27 Composé substitué par un alkyle WO2020138499A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
JP2020562554A JPWO2020138499A1 (ja) 2018-12-28 2019-12-27 アルキル置換化合物

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
JP2018-247951 2018-12-28
JP2018247951 2018-12-28
JP2019-158707 2019-08-30
JP2019158707 2019-08-30

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WO2020138499A1 true WO2020138499A1 (fr) 2020-07-02

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TW (1) TW202038941A (fr)
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Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2016149393A1 (fr) * 2015-03-17 2016-09-22 Rempex Pharmaceuticals, Inc. Dérivés d'acide boronique et leurs utilisations thérapeutiques
JP2017517508A (ja) * 2014-05-19 2017-06-29 レンペックス・ファーマシューティカルズ・インコーポレイテッド ボロン酸誘導体およびその治療的使用
WO2018218154A1 (fr) * 2017-05-26 2018-11-29 VenatoRx Pharmaceuticals, Inc. Inhibiteurs protéiques de liaison à la pénicilline
WO2019009369A1 (fr) * 2017-07-06 2019-01-10 大日本住友製薬株式会社 Dérivé d'imine
WO2019208797A1 (fr) * 2018-04-27 2019-10-31 大日本住友製薬株式会社 Composé à substitution oxo

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2017517508A (ja) * 2014-05-19 2017-06-29 レンペックス・ファーマシューティカルズ・インコーポレイテッド ボロン酸誘導体およびその治療的使用
WO2016149393A1 (fr) * 2015-03-17 2016-09-22 Rempex Pharmaceuticals, Inc. Dérivés d'acide boronique et leurs utilisations thérapeutiques
WO2018218154A1 (fr) * 2017-05-26 2018-11-29 VenatoRx Pharmaceuticals, Inc. Inhibiteurs protéiques de liaison à la pénicilline
WO2019009369A1 (fr) * 2017-07-06 2019-01-10 大日本住友製薬株式会社 Dérivé d'imine
WO2019208797A1 (fr) * 2018-04-27 2019-10-31 大日本住友製薬株式会社 Composé à substitution oxo

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JPWO2020138499A1 (ja) 2021-11-04
TW202038941A (zh) 2020-11-01

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