ES2506715A1 - Peptide compounds suitable for use as antibiotic agents - Google Patents

Peptide compounds suitable for use as antibiotic agents Download PDF

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Publication number
ES2506715A1
ES2506715A1 ES201330519A ES201330519A ES2506715A1 ES 2506715 A1 ES2506715 A1 ES 2506715A1 ES 201330519 A ES201330519 A ES 201330519A ES 201330519 A ES201330519 A ES 201330519A ES 2506715 A1 ES2506715 A1 ES 2506715A1
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Spain
Prior art keywords
radical
formula
integer
compounds
group
Prior art date
Legal status (The legal status 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 status listed.)
Granted
Application number
ES201330519A
Other languages
Spanish (es)
Other versions
ES2506715B1 (en
Inventor
Francesc Rabanal Anglada
Yolanda C. CAJAL VISA
Ariadna GRAU CAMPISTANY
Jordi VILA ESTAPÉ
Xavier VILA FARRÉS
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.)
Universitat Autonoma de Barcelona UAB
Universitat de Barcelona UB
Fundacio Clinic per a la Recerca Biomedica FCRB
Hospital Clinic de Barcelona
Original Assignee
Universitat Autonoma de Barcelona UAB
Universitat de Barcelona UB
Fundacio Clinic per a la Recerca Biomedica FCRB
Hospital Clinic de Barcelona
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
Application filed by Universitat Autonoma de Barcelona UAB, Universitat de Barcelona UB, Fundacio Clinic per a la Recerca Biomedica FCRB, Hospital Clinic de Barcelona filed Critical Universitat Autonoma de Barcelona UAB
Priority to ES201330519A priority Critical patent/ES2506715B1/en
Priority to PCT/ES2014/070286 priority patent/WO2014167160A1/en
Publication of ES2506715A1 publication Critical patent/ES2506715A1/en
Application granted granted Critical
Publication of ES2506715B1 publication Critical patent/ES2506715B1/en
Withdrawn - After Issue legal-status Critical Current
Anticipated expiration legal-status Critical

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Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K7/00—Peptides having 5 to 20 amino acids in a fully defined sequence; Derivatives thereof
    • C07K7/50—Cyclic peptides containing at least one abnormal peptide link
    • C07K7/54—Cyclic peptides containing at least one abnormal peptide link with at least one abnormal peptide link in the ring
    • C07K7/60—Cyclic peptides containing at least one abnormal peptide link with at least one abnormal peptide link in the ring the cyclisation occurring through the 4-amino group of 2,4-diamino-butanoic acid
    • C07K7/62—Polymyxins; Related peptides
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K7/00—Peptides having 5 to 20 amino acids in a fully defined sequence; Derivatives thereof
    • C07K7/04—Linear peptides containing only normal peptide links
    • C07K7/06—Linear peptides containing only normal peptide links having 5 to 11 amino acids
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/04—Peptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof
    • A61K38/12—Cyclic peptides, e.g. bacitracins; Polymyxins; Gramicidins S, C; Tyrocidins A, B or C
    • 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
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Veterinary Medicine (AREA)
  • Molecular Biology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Genetics & Genomics (AREA)
  • Animal Behavior & Ethology (AREA)
  • Biophysics (AREA)
  • Public Health (AREA)
  • Biochemistry (AREA)
  • Oncology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Epidemiology (AREA)
  • Immunology (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Communicable Diseases (AREA)
  • Engineering & Computer Science (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Peptides Or Proteins (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

The invention relates to compounds of formula (I), wherein R0 is a CH3-(CH2)m- radical, wherein m is an integer between 4 and 10 R1, R3, R4, R7 and R8 are independently selected radicals which have the following formula: GF-(CH2)n- wherein n is an integer between 1 and 4 and GF is a radical selected among the group that consists of -NH2 and -NH-C(=NH)-NH2 R2 is a -CH(CH3)(OH), the CH of R2 being in either of the two configurations, R or S in the formula (I), giving rise to the corresponding epimers or to a mixture thereof R5 is a -(CH2)-R10 radical R6 is a straight or branched C4-alkyl radical R9 is a radical selected among -CONH2 and -COOH and R10 is a phenyl radical substituted with 1 to 5 identical substituents selected from the group that consists of F and (C1-C2)-alkyl, said compounds having been shown to be useful in the treatment of bacterial infections.

Description

imagen1image 1

imagen2image2

P201330519 P201330519

12-04-2013 04-12-2013

EXPLICACIÓN DE LA INVENCIÓN EXPLANATION OF THE INVENTION

Los inventores han encontrado nuevos compuestos peptídicos con actividad antibiótica 5 que actúan sobre el componente lipídico de las membranas bacterianas y que son activos tanto contra bacterias Gram-positivas como contra Gram-negativas. The inventors have found new peptide compounds with antibiotic activity 5 which act on the lipid component of bacterial membranes and which are active against both Gram-positive and Gram-negative bacteria.

Estructuralmente estos compuestos se caracterizan por contener algunos sustituyentes específicos de entre los mencionados en la solicitud WO2011110716 y Structurally these compounds are characterized by containing some specific substituents from among those mentioned in the application WO2011110716 and

10 por la presencia de un fenilo modificado con átomos de flúor o grupos metilo. Inesperadamente, estos compuestos presentan una actividad mayor frente a determinadas bacterias que la que presentan los compuestos más cercanos del estado de la técnica descritos en la WO2011110716 y además son activos frente a bacterias resistentes a algunos antibióticos convencionales. 10 by the presence of a phenyl modified with fluorine atoms or methyl groups. Unexpectedly, these compounds present a higher activity against certain bacteria than that exhibited by the closest compounds of the state of the art described in WO2011110716 and are also active against bacteria resistant to some conventional antibiotics.

15 Así, un aspecto de la presente invención está relacionado con proporcionar compuestos de fórmula (I), Thus, one aspect of the present invention is related to providing compounds of formula (I),

R5O R5O

20 twenty

imagen3 O image3 O

N N

imagen4image4

HR2 HR2

imagen5 imagen6 imagen7R6 image5 image6 image7 R6

imagen8O imagen9NH HNO image8 OR image9 NH HNO

O OR

H HRimagen100 N N H HR image10 0 NN

N N

N N

imagen11O image11 OR

imagen12 imagen13NH H image12 image13 NH H

H H

O OO O

25 R3 S25 R3 S

R1 R1

imagen14 imagen15R7 image14 image15 R7

S S

imagen16ON O image16 OR NOT

N N

H R9 H R9

30 (I) 30 (I)

donde: R0 es un radical CH3-(CH2)m-, donde m es un número entero entre 4 y 10; R1, R3, R4, R7 y R8 son radicales seleccionados independientemente que tienen la fórmula siguiente: GF-(CH2)n-; donde n es un entero entre 1 y 4; y GF es un radical where: R0 is a radical CH3- (CH2) m-, where m is an integer between 4 and 10; R1, R3, R4, R7 and R8 are independently selected radicals having the following formula: GF- (CH2) n-; where n is an integer between 1 and 4; and GF is a radical

35 seleccionado entre el grupo que consiste en -NH2 y -NH-C(=NH)-NH2; R2 es un Selected from the group consisting of -NH2 and -NH-C (= NH) -NH2; R2 is a

4 4

imagen17image17

imagen18image18

imagen19image19

imagen20image20

imagen21image21

imagen22image22

imagen23image23

imagen24image24

imagen25image25

imagen26image26

imagen27image27

imagen28image28

Claims (1)

P201330519 P201330519 12-04-2013 04-12-2013 REIVINDICACIONES 1. Compuesto de fórmula (I), 5 1. Compound of formula (I), 5 R5R5 O O N O O N imagen1HR2 image 1 HR2 imagen2image2 imagen3 imagen4 imagen5R6 image3 image4 image5 R6 imagen6O imagen7NH HNO O image6 OR image7 NH HNO O H HRimagen80 N H HR image8 0 N N 10 No. 10 N N N N imagen9O image9 OR imagen10 imagen11NH H image10 image11 NH H H H O O O O imagen12S image12 S imagen13 imagen14 R7 image13 image14 R7 R1 R3S R1 R3S ON O N ON O N H R9 H R9 15 (I) 15 (I) 20 donde: R0 es un radical CH3-(CH2)m-, donde m es un número entero entre 4 y 10; R1, R3, R4, R7 y R8 son radicales seleccionados independientemente que tienen la Where: R0 is a radical CH3- (CH2) m-, where m is an integer between 4 and 10; R1, R3, R4, R7 and R8 are independently selected radicals having the 25 fórmula siguiente: GF-(CH2)n-; donde n es un entero entre 1 y 4; y GF es un radical seleccionado entre el grupo que 30 consiste en -NH2 y -NH-C(=NH)-NH2; R2 es un -CH(CH3)(OH), estando en la fórmula (I) el CH del R2 en cualquiera de las dos configuraciones, R o S, dando lugar a los correspondientes epímeros a una mezcla de los mismos; Following formula: GF- (CH2) n-; where n is an integer between 1 and 4; and GF is a radical selected from the group consisting of -NH2 and -NH-C (= NH) -NH2; R2 is a -CH (CH3) (OH), the CH of R2 being in formula (I) in either of the two configurations, R or S, giving rise to the corresponding epimers in a mixture thereof; 17 17 imagen15image15 imagen16image16
ES201330519A 2013-04-12 2013-04-12 Peptide compounds useful as antibiotic agents Withdrawn - After Issue ES2506715B1 (en)

Priority Applications (2)

Application Number Priority Date Filing Date Title
ES201330519A ES2506715B1 (en) 2013-04-12 2013-04-12 Peptide compounds useful as antibiotic agents
PCT/ES2014/070286 WO2014167160A1 (en) 2013-04-12 2014-04-10 Peptide compounds suitable for use as antibiotic agents

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
ES201330519A ES2506715B1 (en) 2013-04-12 2013-04-12 Peptide compounds useful as antibiotic agents

Publications (2)

Publication Number Publication Date
ES2506715A1 true ES2506715A1 (en) 2014-10-13
ES2506715B1 ES2506715B1 (en) 2015-07-22

Family

ID=51660740

Family Applications (1)

Application Number Title Priority Date Filing Date
ES201330519A Withdrawn - After Issue ES2506715B1 (en) 2013-04-12 2013-04-12 Peptide compounds useful as antibiotic agents

Country Status (2)

Country Link
ES (1) ES2506715B1 (en)
WO (1) WO2014167160A1 (en)

Families Citing this family (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP3173421A1 (en) 2015-11-30 2017-05-31 Universitat de Barcelona Peptidic compounds useful as antibacterial agents
EP3636659A1 (en) 2018-10-08 2020-04-15 Universitat de Barcelona Polymyxin-based compounds useful as antibacterial agents

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2010029196A1 (en) * 2008-09-10 2010-03-18 Universidad De Barcelona Antibacterial peptide compounds
WO2011104378A1 (en) * 2010-02-26 2011-09-01 Novo Nordisk A/S Peptides for treatment of obesity
WO2011110716A2 (en) * 2010-03-10 2011-09-15 Universidad De Barcelona Peptide compounds that can be used as antibacterial agents

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2010029196A1 (en) * 2008-09-10 2010-03-18 Universidad De Barcelona Antibacterial peptide compounds
WO2011104378A1 (en) * 2010-02-26 2011-09-01 Novo Nordisk A/S Peptides for treatment of obesity
WO2011110716A2 (en) * 2010-03-10 2011-09-15 Universidad De Barcelona Peptide compounds that can be used as antibacterial agents

Also Published As

Publication number Publication date
ES2506715B1 (en) 2015-07-22
WO2014167160A1 (en) 2014-10-16

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