AR053330A1 - DERIVATIVES OF NITROXI SARTAN AS BLOCKERS OF THE ANGIOTESINA II RECEPTOR - Google Patents

DERIVATIVES OF NITROXI SARTAN AS BLOCKERS OF THE ANGIOTESINA II RECEPTOR

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Publication number
AR053330A1
AR053330A1 ARP060100340A ARP060100340A AR053330A1 AR 053330 A1 AR053330 A1 AR 053330A1 AR P060100340 A ARP060100340 A AR P060100340A AR P060100340 A ARP060100340 A AR P060100340A AR 053330 A1 AR053330 A1 AR 053330A1
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AR
Argentina
Prior art keywords
group
ono2
integer
linked
alkyl
Prior art date
Application number
ARP060100340A
Other languages
Spanish (es)
Original Assignee
Nicox Sa
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 Nicox Sa filed Critical Nicox Sa
Publication of AR053330A1 publication Critical patent/AR053330A1/en

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Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D257/00—Heterocyclic compounds containing rings having four nitrogen atoms as the only ring hetero atoms
    • C07D257/02—Heterocyclic compounds containing rings having four nitrogen atoms as the only ring hetero atoms not condensed with other rings
    • C07D257/04—Five-membered rings
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P7/00—Drugs for disorders of the blood or the extracellular fluid
    • A61P7/02—Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
    • 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
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
    • C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
    • C07D403/10—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a carbon chain containing aromatic rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
    • C07D405/14—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
    • C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
    • C07D471/04—Ortho-condensed systems

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Veterinary Medicine (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Cardiology (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Public Health (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Hospice & Palliative Care (AREA)
  • Diabetes (AREA)
  • Hematology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

Pueden utilizarse para tratar enfermedades cardiovasculares y renales y procesos inflamatorios. Reivindicacion 1: Compuestos caracterizados porque son de formula (19 y sales o estereoisomeros aceptables para uso farmacéutico de los mismos, donde R1 se selecciona entre el grupo que consiste en las formulas (1S) a (1n) donde R2 es H, o -W1-Y0-ONO2 donde W1 es -C(O)- o -C(O)O-; Y0 es como se informa más adelante; R3 es H, -Y0-ONO2 o -W2-Y0-ONO2, donde W2 es -CH(CH3)-O(=O)-O-, -CH2-O(=O)O- Y0 es como se informa más adelante; W tiene los siguientes significados: -C(O)-, -C(O)O-, -CH(CH3)O(=O)O-, -CH2-O(=O)O-; Y y Y0 son iguales o diferentes y son radicales bivalentes con los siguientes significados: a) alquileno C1-20 lineal o ramificado, preferentemente alquileno C1-10, más preferentemente alquileno 3-6, está opcionalmente sustituido con uno o más de los sustituyentes seleccionados entre e grupo que consiste en: átomos de halogeno, hidroxi, -ONO2 o T0, donde T0 es -OC(O)-(C1- 10)alquil)-ONO2 o -O-(C1-10 alquil)-ONO2; cicloalquileno con entre 5 a 7 átomos de C, donde el anillo está opcionalmente sustituido con cadenas laterales T, donde T es alquilo lineal o ramificado C1-10, preferentemente T es CH3; b) formula (2) donde n es un entero entre 0 y 20, n1 es un entero entre 1 y 20, n es 0 o 1; c) formula (3) donde n1 es un entero entre 1 y 20, n2 es 0 o 1; X1 es -(CH2)3-OC(O)- o -CH=CH-C(O)O-, y R4es H o CH3; d) formula (4) donde n1 es un entero entre 1 y 20; n2 es 0 o 1; Y1 es -CH=CH-, -(CH2)3-, X2 es -OC(O)-, -C(O)O-, y R4 es H o CH3; cuando Y o Y0 se seleccionan entre los radicales bivalentes de los grupos b), c) o d) el grupo -ONO2 está unido a grupo -(CH2)n1-; g) -CH(R6)-(CH2)n3-X2-[CH-(CH2)n4-X2]n5(R6)- CH(R6)-(CH2)n6-; h) -(CH2)n3-CH(R7)X2-[(CH2)n4-CH-X2]n5(R7)-(CH2)n6-CH(R7) donde X2 es O o S; n3, n4 y n6 son enteros seleccionados en forma independiente entre 0 a 20, n5 es un entero entre 0 y 6; R6 es H, CH3 o un grupo nitrooxi; R7 es CH3 o un grupo nitrooxi; cuando Y o Y0 se seleccionan entre los radicales bivalentes del grupo g) el grupo -ONO2 está unido al grupo -(CH2)n6-; cuando Y o Y0 se seleccionan entre los radicales bivalentes del grupo h) el grupo -ONO2 está unidos al grupo - CH(R7)-, i) -[C]n7(R8)(R10)-Y2-[C]n8(R9)(R11)- donde n7 es un entero entre 0 y 10; n8 es un entero entre 1 y 10; R8, R9, R10, R11 son iguales o diferentes, y son H o alquilo C1-4 lineal o ramificado, preferentemente R8, R9, R10, R11 son H; donde el grupo -ONO2 está unido a -[C]n8< donde n8 es como se ha definido; Y2 es un anillo heterocíclico saturado, insaturado o aromático de 5 o 6 miembros, que contiene uno o más heteroátomos seleccionados entre N, O, S y se selecciona entre los anillos (Y1) a (13).They can be used to treat cardiovascular and kidney diseases and inflammatory processes. Claim 1: Compounds characterized in that they are of formula (19 and salts or stereoisomers acceptable for pharmaceutical use thereof, wherein R1 is selected from the group consisting of formulas (1S) to (1n) where R2 is H, or -W1 -Y0-ONO2 where W1 is -C (O) - or -C (O) O-; Y0 is as reported below; R3 is H, -Y0-ONO2 or -W2-Y0-ONO2, where W2 is - CH (CH3) -O (= O) -O-, -CH2-O (= O) O- Y0 is as reported below; W has the following meanings: -C (O) -, -C (O) O-, -CH (CH3) O (= O) O-, -CH2-O (= O) O-; Y and Y0 are the same or different and are bivalent radicals with the following meanings: a) linear C1-20 alkylene or branched, preferably C1-10 alkylene, more preferably 3-6 alkylene, is optionally substituted with one or more of the substituents selected from the group consisting of: halogen, hydroxy, -ONO2 or T0 atoms, where T0 is -OC (O) - (C1-10) alkyl) -ONO2 or -O- (C1-10 alkyl) -ONO2; cycloalkylene with between 5 to 7 C atoms, where the ring is optionally substituted with side chains T, where T is linear or branched C1-10 alkyl, preferably T is CH3; b) formula (2) where n is an integer between 0 and 20, n1 is an integer between 1 and 20, n is 0 or 1; c) formula (3) where n1 is an integer between 1 and 20, n2 is 0 or 1; X1 is - (CH2) 3-OC (O) - or -CH = CH-C (O) O-, and R4 is H or CH3; d) formula (4) where n1 is an integer between 1 and 20; n2 is 0 or 1; Y1 is -CH = CH-, - (CH2) 3-, X2 is -OC (O) -, -C (O) O-, and R4 is H or CH3; when Y or Y0 are selected from the bivalent radicals of groups b), c) or d) the group -ONO2 is linked to group - (CH2) n1-; g) -CH (R6) - (CH2) n3-X2- [CH- (CH2) n4-X2] n5 (R6) - CH (R6) - (CH2) n6-; h) - (CH2) n3-CH (R7) X2 - [(CH2) n4-CH-X2] n5 (R7) - (CH2) n6-CH (R7) where X2 is O or S; n3, n4 and n6 are integers independently selected from 0 to 20, n5 is an integer between 0 and 6; R6 is H, CH3 or a nitrooxy group; R7 is CH3 or a nitrooxy group; when Y or Y0 are selected from the bivalent radicals of group g) the group -ONO2 is linked to the group - (CH2) n6-; when Y or Y0 are selected from the bivalent radicals of group h) the group -ONO2 is linked to the group - CH (R7) -, i) - [C] n7 (R8) (R10) -Y2- [C] n8 ( R9) (R11) - where n7 is an integer between 0 and 10; n8 is an integer between 1 and 10; R8, R9, R10, R11 are the same or different, and are H or linear or branched C1-4 alkyl, preferably R8, R9, R10, R11 are H; where the group -ONO2 is linked to - [C] n8 <where n8 is as defined; Y2 is a saturated, unsaturated or aromatic 5 or 6 membered heterocyclic ring, which contains one or more heteroatoms selected from N, O, S and is selected from rings (Y1) to (13).

ARP060100340A 2005-01-31 2006-01-30 DERIVATIVES OF NITROXI SARTAN AS BLOCKERS OF THE ANGIOTESINA II RECEPTOR AR053330A1 (en)

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
US64779105P 2005-01-31 2005-01-31

Publications (1)

Publication Number Publication Date
AR053330A1 true AR053330A1 (en) 2007-05-02

Family

ID=36061565

Family Applications (1)

Application Number Title Priority Date Filing Date
ARP060100340A AR053330A1 (en) 2005-01-31 2006-01-30 DERIVATIVES OF NITROXI SARTAN AS BLOCKERS OF THE ANGIOTESINA II RECEPTOR

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AR (1) AR053330A1 (en)
WO (1) WO2006079610A1 (en)

Families Citing this family (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
TW200831079A (en) 2006-12-13 2008-08-01 Merck & Co Inc Angiotensin II receptor antagonists
EP2250158A2 (en) * 2008-02-26 2010-11-17 Nicox S.A. Angiotensin ii receptor antagonists
EP2313417A1 (en) * 2008-06-09 2011-04-27 Nicox S.A. Angiotensin ii receptor antagonists
WO2010015447A1 (en) * 2008-08-08 2010-02-11 Nicox S.A. Angiotensin ii receptor antagonists
EP2194048A1 (en) * 2008-12-02 2010-06-09 Dirk Sartor Nitrate esters for the treatment of vascular and metabolic diseases
AU2010339691B2 (en) 2010-01-07 2015-04-02 Alkermes Pharma Ireland Limited Prodrugs of heteraromatic compounds
EP2377855B1 (en) * 2010-04-19 2012-07-18 Cardiolynx AG A valsartanamide dinitrate derivative for the treatment of vascular and metabolic diseases
JP2013525323A (en) * 2010-04-19 2013-06-20 カーディオリンクス・アーゲー Nitric oxide donor-supported valsartan derivatives for the treatment of vascular and metabolic diseases
JO3350B1 (en) 2011-03-07 2019-03-13 Merck Sharp & Dohme Heterocyclic derivatives containing primary amino groups and diazeniumdiolates

Family Cites Families (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
IT1301759B1 (en) * 1998-06-19 2000-07-07 Nicox Sa NITRATED SALTS OF ANTI-HYPERTENSIVE DRUGS
ES2299861T3 (en) * 2003-07-31 2008-06-01 Nicox S.A. LOSITAN NITROXI DERIVATIVES AND OTHER SIMILAR BLOCKERS OF THE ANGIOTENSIN II RECEPTOR FOR THE TREATMENT OF CARDIOVASCULAR DISEASES.

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