ES2439397B1 - Polyamine compounds and metal complexes that comprise them for use as antiparasitic agents - Google Patents

Polyamine compounds and metal complexes that comprise them for use as antiparasitic agents Download PDF

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Publication number
ES2439397B1
ES2439397B1 ES201331558A ES201331558A ES2439397B1 ES 2439397 B1 ES2439397 B1 ES 2439397B1 ES 201331558 A ES201331558 A ES 201331558A ES 201331558 A ES201331558 A ES 201331558A ES 2439397 B1 ES2439397 B1 ES 2439397B1
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Prior art keywords
metal complexes
antiparasitic agents
polyamine compounds
preferred
iii
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Application number
ES201331558A
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Spanish (es)
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ES2439397A1 (en
Inventor
Xavi RIBAS SALAMAÑA
Miquel Costas Salgueiro
Olaf CUSSÓ FOREST
Anna Company Casadevall
Julio LLORET FILLOL
Manuel SÁNCHEZ MORENO
Clotilde MARÍN SÁNCHEZ
María José ROSALES LOMBARDO
Francisco OLMO ARÉVALO
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.)
Universidad de Granada
Universitat de Girona
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Universidad de Granada
Universitat de Girona
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Priority to ES201331558A priority Critical patent/ES2439397B1/en
Publication of ES2439397A1 publication Critical patent/ES2439397A1/en
Priority to PCT/ES2014/070800 priority patent/WO2015059337A1/en
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Publication of ES2439397B1 publication Critical patent/ES2439397B1/en
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Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
    • C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
    • 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
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
    • A61K31/4439—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
    • 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
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
    • A61K31/444—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a six-membered ring with nitrogen as a ring heteroatom, e.g. amrinone
    • 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
    • Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
    • Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
    • Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

Compuestos poliamínicos y complejos metálicos que los comprenden para su uso como agentes antiparasitarios.#La presente invención se refiere al uso de compuestos de base poliamínica o de sus complejos metálicos para la prevención y/o el tratamiento de enfermedades de origen parasitario como por ejemplo la Tripanosomiasis americana también conocida como enfermedad de Chagas o la Leishmaniasis.Polyamine compounds and metal complexes comprising them for use as antiparasitic agents. # The present invention relates to the use of polyamine-based compounds or their metal complexes for the prevention and / or treatment of diseases of parasitic origin such as American trypanosomiasis also known as Chagas disease or Leishmaniasis.

Description

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P201331558 P201331558

23-10-2013 10-23-2013

bipirrolidina-1,1'-diilbis(metileno)bis(N,N-dimetilpiridina-4-amina): también denominado (S,S’)-(Me2N-Pyr)2-bpbp ó X15: Bipyrrolidine-1,1'-diylbis (methylene) bis (N, N-dimethylpyridine-4-amine): also called (S, S ’) - (Me2N-Pyr) 2-bpbp or X15:

(X15) En otra realización preferida, el compuesto de fórmula (I) es el compuesto de (III): (X15) In another preferred embodiment, the compound of formula (I) is the compound of (III):

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N N

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(III) (III)

10 En una realización más preferida del compuesto de fórmula (III) R1 representa un grupo seleccionado de la lista que comprende hidrógeno, -N(CH3)2, Cl, -OCH3 y – COOCH2CH3. En una realización más preferida, R2 y R3, son iguales o diferentes y representan un hidrógeno o un grupo metilo, aún más preferiblemente R2 y R3 son iguales. In a more preferred embodiment of the compound of formula (III) R1 represents a group selected from the list comprising hydrogen, -N (CH3) 2, Cl, -OCH3 and -COOCH2CH3. In a more preferred embodiment, R2 and R3, are the same or different and represent a hydrogen or a methyl group, even more preferably R2 and R3 are the same.

15 En una realización más preferida del compuesto es de fórmula (III), R1, R2 y R3 son hidrógeno; o R1 es metoxilo y R2 y R3 metilo. In a more preferred embodiment of the compound is of formula (III), R1, R2 and R3 are hydrogen; or R1 is methoxy and R2 and R3 methyl.

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P201331558 P201331558

23-10-2013 10-23-2013

más preferiblemente el compuesto de fórmula (III), R1, R2 y R3 son hidrógeno; o R1 es metoxilo y R2 y R3 metilo. En estos compuestos de fórmula (III) se incluyen tanto las conformaciones S,S’ como R,R’. more preferably the compound of formula (III), R1, R2 and R3 are hydrogen; or R1 is methoxy and R2 and R3 methyl. These compounds of formula (III) include both the S, S ’and R, R’ conformations.

5 En una realización preferida más preferida, el complejo comprende como ligando el compuesto (1R,2R)-N1,N2-bis((4-metoxi-3,5-dimetilpiridin-2-il)metil)-N1,N2dimetilciclohexano-1,2-diamina, o también denominado R,R’-(DMM-Py)2(bpmcn). In a more preferred preferred embodiment, the complex comprises as ligand the compound (1R, 2R) -N1, N2-bis ((4-methoxy-3,5-dimethylpyridin-2-yl) methyl) -N1, N2-dimethylcyclohexane-1 , 2-diamine, or also called R, R '- (DMM-Py) 2 (bpmcn).

En una realización más preferida el metal es divalente y el complejo es de fórmula In a more preferred embodiment the metal is divalent and the complex is of formula

10 (VI), más preferiblemente el metal es Mn y aún más preferiblemente el complejo es X13: 10 (VI), more preferably the metal is Mn and even more preferably the complex is X13:

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imagen13dimetilciclohexano-1,2-diamina}MnII](CF3SO3)2 o también llamada [{R,R’-(DMM image13 dimethylcyclohexane-1,2-diamine} MnII] (CF3SO3) 2 or also called [{R, R '- (DMM

15 Py)2(bpmcn)}MnII](CF3SO3)2. 15 Py) 2 (bpmcn)} MnII] (CF3SO3) 2.

Por “enfermedad parasitaria”, se entiende una enfermedad infecciosa causada por protozoos, vermes (cestodos, trematodos, nematodos) o artrópodos. En particular, en la presente invención, los parásitos son protozoos pertenecientes a los géneros 20 Trypanosoma y Leishmania, por tanto, se puede decir que los compuestos son antiprotozoarios. Especies de las mismas, pueden ser, pero sin limitarse, Trypanosoma cruzi, Trypanosoma brucei, Leishmania infantum, Leishmania brazilensis y Leishmania donovani, entre otras conocidas por un experto en la materia. "Parasitic disease" means an infectious disease caused by protozoa, vermes (cestodes, trematodes, nematodes) or arthropods. In particular, in the present invention, the parasites are protozoa belonging to the genera Trypanosoma and Leishmania, therefore, it can be said that the compounds are antiprotozoals. Species thereof, may be, but are not limited to, Trypanosoma cruzi, Trypanosoma brucei, Leishmania infantum, Leishmania brazilensis and Leishmania donovani, among others known to a person skilled in the art.

25 Las enfermedades parasitarias a tratar podrían ser leishmaniasis o tripanosomiasis. La “Leishmaniasis” es una enfermedad causada por un protozoo del género Leishmania y transmitido, principalmente por dípteros conocidos como “sand fly”, 25 Parasitic diseases to be treated could be leishmaniasis or trypanosomiasis. "Leishmaniasis" is a disease caused by a protozoan of the genus Leishmania and transmitted, mainly by diptera known as "sand fly",

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Claims (1)

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ES201331558A 2013-10-23 2013-10-23 Polyamine compounds and metal complexes that comprise them for use as antiparasitic agents Active ES2439397B1 (en)

Priority Applications (2)

Application Number Priority Date Filing Date Title
ES201331558A ES2439397B1 (en) 2013-10-23 2013-10-23 Polyamine compounds and metal complexes that comprise them for use as antiparasitic agents
PCT/ES2014/070800 WO2015059337A1 (en) 2013-10-23 2014-10-23 Polyamine compounds and metal complexes comprising same for the use thereof as antiparasitic agents

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
ES201331558A ES2439397B1 (en) 2013-10-23 2013-10-23 Polyamine compounds and metal complexes that comprise them for use as antiparasitic agents

Publications (2)

Publication Number Publication Date
ES2439397A1 ES2439397A1 (en) 2014-01-22
ES2439397B1 true ES2439397B1 (en) 2014-11-04

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