AR045730A1 - Moduladores de lta4h - Google Patents
Moduladores de lta4hInfo
- Publication number
- AR045730A1 AR045730A1 ARP040102683A ARP040102683A AR045730A1 AR 045730 A1 AR045730 A1 AR 045730A1 AR P040102683 A ARP040102683 A AR P040102683A AR P040102683 A ARP040102683 A AR P040102683A AR 045730 A1 AR045730 A1 AR 045730A1
- Authority
- AR
- Argentina
- Prior art keywords
- alkyl
- group
- carbon
- co2ry
- heteroatomic
- Prior art date
Links
- 102100022118 Leukotriene A-4 hydrolase Human genes 0.000 title abstract 5
- 101000619898 Homo sapiens Leukotriene A-4 hydrolase Proteins 0.000 title 1
- -1 1,3-dihydro-indole-2-one-1-yl Chemical group 0.000 abstract 27
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 abstract 21
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 abstract 18
- 229910052799 carbon Inorganic materials 0.000 abstract 18
- 125000001424 substituent group Chemical group 0.000 abstract 13
- 229910052757 nitrogen Inorganic materials 0.000 abstract 12
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 abstract 8
- 125000000217 alkyl group Chemical group 0.000 abstract 7
- 125000000623 heterocyclic group Chemical group 0.000 abstract 6
- 108010072713 leukotriene A4 hydrolase Proteins 0.000 abstract 6
- 229910052760 oxygen Inorganic materials 0.000 abstract 6
- 125000006163 5-membered heteroaryl group Chemical group 0.000 abstract 5
- 229910052739 hydrogen Inorganic materials 0.000 abstract 5
- 229910052717 sulfur Inorganic materials 0.000 abstract 5
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 abstract 3
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 abstract 3
- 125000001072 heteroaryl group Chemical group 0.000 abstract 3
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 abstract 3
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 abstract 3
- 125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 abstract 2
- 206010061218 Inflammation Diseases 0.000 abstract 2
- 125000003342 alkenyl group Chemical group 0.000 abstract 2
- 125000000304 alkynyl group Chemical group 0.000 abstract 2
- 150000001875 compounds Chemical class 0.000 abstract 2
- 230000004054 inflammatory process Effects 0.000 abstract 2
- 230000005764 inhibitory process Effects 0.000 abstract 2
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 abstract 2
- 229920006395 saturated elastomer Polymers 0.000 abstract 2
- 125000004299 tetrazol-5-yl group Chemical group [H]N1N=NC(*)=N1 0.000 abstract 2
- 125000006531 (C2-C5) alkyl group Chemical group 0.000 abstract 1
- IQTADKJWOJRVNV-UHFFFAOYSA-N 2-(4-ethylphenoxy)-1,3-benzothiazole Chemical compound C1=CC(CC)=CC=C1OC1=NC2=CC=CC=C2S1 IQTADKJWOJRVNV-UHFFFAOYSA-N 0.000 abstract 1
- GCSDZVIXDKZKFO-UHFFFAOYSA-N 2-(4-ethylphenoxy)-1,3-benzoxazole Chemical compound C1=CC(CC)=CC=C1OC1=NC2=CC=CC=C2O1 GCSDZVIXDKZKFO-UHFFFAOYSA-N 0.000 abstract 1
- HGLXZYVILQDPRO-UHFFFAOYSA-N 2-(4-ethylphenoxy)-1h-benzimidazole Chemical compound C1=CC(CC)=CC=C1OC1=NC2=CC=CC=C2N1 HGLXZYVILQDPRO-UHFFFAOYSA-N 0.000 abstract 1
- PBYPGZHIAKLYFN-UHFFFAOYSA-N 3,9-diazaspiro[5.5]undecane-3-carboxylic acid Chemical compound C1CN(C(=O)O)CCC11CCNCC1 PBYPGZHIAKLYFN-UHFFFAOYSA-N 0.000 abstract 1
- 125000005037 alkyl phenyl group Chemical group 0.000 abstract 1
- 150000001408 amides Chemical class 0.000 abstract 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 abstract 1
- 125000004093 cyano group Chemical group *C#N 0.000 abstract 1
- 125000000392 cycloalkenyl group Chemical group 0.000 abstract 1
- 125000000753 cycloalkyl group Chemical group 0.000 abstract 1
- 230000000694 effects Effects 0.000 abstract 1
- 150000002148 esters Chemical class 0.000 abstract 1
- 125000001153 fluoro group Chemical group F* 0.000 abstract 1
- 125000005843 halogen group Chemical group 0.000 abstract 1
- 125000005842 heteroatom Chemical group 0.000 abstract 1
- 125000002962 imidazol-1-yl group Chemical group [*]N1C([H])=NC([H])=C1[H] 0.000 abstract 1
- 239000003112 inhibitor Substances 0.000 abstract 1
- 230000002401 inhibitory effect Effects 0.000 abstract 1
- 238000000034 method Methods 0.000 abstract 1
- 239000008194 pharmaceutical composition Substances 0.000 abstract 1
- 230000002265 prevention Effects 0.000 abstract 1
- 125000003373 pyrazinyl group Chemical group 0.000 abstract 1
- 125000004353 pyrazol-1-yl group Chemical group [H]C1=NN(*)C([H])=C1[H] 0.000 abstract 1
- 125000004076 pyridyl group Chemical group 0.000 abstract 1
- 125000000714 pyrimidinyl group Chemical group 0.000 abstract 1
- 150000003839 salts Chemical class 0.000 abstract 1
- 239000012453 solvate Substances 0.000 abstract 1
- 238000006467 substitution reaction Methods 0.000 abstract 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 abstract 1
- 125000003866 trichloromethyl group Chemical group ClC(Cl)(Cl)* 0.000 abstract 1
Classifications
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- C—CHEMISTRY; METALLURGY
- C04—CEMENTS; CONCRETE; ARTIFICIAL STONE; CERAMICS; REFRACTORIES
- C04B—LIME, MAGNESIA; SLAG; CEMENTS; COMPOSITIONS THEREOF, e.g. MORTARS, CONCRETE OR LIKE BUILDING MATERIALS; ARTIFICIAL STONE; CERAMICS; REFRACTORIES; TREATMENT OF NATURAL STONE
- C04B35/00—Shaped ceramic products characterised by their composition; Ceramics compositions; Processing powders of inorganic compounds preparatory to the manufacturing of ceramic products
- C04B35/622—Forming processes; Processing powders of inorganic compounds preparatory to the manufacturing of ceramic products
- C04B35/626—Preparing or treating the powders individually or as batches ; preparing or treating macroscopic reinforcing agents for ceramic products, e.g. fibres; mechanical aspects section B
- C04B35/63—Preparing or treating the powders individually or as batches ; preparing or treating macroscopic reinforcing agents for ceramic products, e.g. fibres; mechanical aspects section B using additives specially adapted for forming the products, e.g.. binder binders
- C04B35/632—Organic additives
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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
- A61K31/41—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
- A61K31/428—Thiazoles condensed with carbocyclic rings
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- 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
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- 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
- A61P11/06—Antiasthmatics
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- 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
- A61P11/08—Bronchodilators
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- 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
- A61P17/06—Antipsoriatics
-
- 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
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
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- 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
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- 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
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- 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
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D235/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings
- C07D235/02—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings condensed with carbocyclic rings or ring systems
- C07D235/04—Benzimidazoles; Hydrogenated benzimidazoles
- C07D235/24—Benzimidazoles; Hydrogenated benzimidazoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached in position 2
- C07D235/26—Oxygen atoms
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D263/00—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings
- C07D263/52—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings condensed with carbocyclic rings or ring systems
- C07D263/54—Benzoxazoles; Hydrogenated benzoxazoles
- C07D263/58—Benzoxazoles; Hydrogenated benzoxazoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached in position 2
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
- C07D277/60—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings condensed with carbocyclic rings or ring systems
- C07D277/62—Benzothiazoles
- C07D277/68—Benzothiazoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached in position 2
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- 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
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing three or more hetero rings
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D495/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms
- C07D495/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
- C07D495/10—Spiro-condensed systems
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Ceramic Engineering (AREA)
- Pulmonology (AREA)
- Manufacturing & Machinery (AREA)
- Inorganic Chemistry (AREA)
- Biomedical Technology (AREA)
- Heart & Thoracic Surgery (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Structural Engineering (AREA)
- Materials Engineering (AREA)
- Rheumatology (AREA)
- Cardiology (AREA)
- Hospice & Palliative Care (AREA)
- Vascular Medicine (AREA)
- Physical Education & Sports Medicine (AREA)
- Dermatology (AREA)
- Immunology (AREA)
- Pain & Pain Management (AREA)
- Psychiatry (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Urology & Nephrology (AREA)
- Epidemiology (AREA)
- Plural Heterocyclic Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Abstract
Inhibidores de la leucotrieno A4 hidrolasa (LTA4H), composiciones farmacéuticas que los contienen, y métodos para la inhibición de la actividad de la enzima LTA4H, que comprende exponer a la enzima LTA4H a una cantidad inhibidora de por lo menos un modulador de LTA4H seleccionado de dichos compuestos, para la prevención o inhibición de la inflamación y/o afecciones asociadas con la inflamación. Reivindicación 1: Uso de por lo menos un modulador de LTA4H seleccionado de compuestos de fórmula (1), o un enantiómero, diastereómero, racemato, tautómero, hidrato, solvato, o una sal, éster o amidas de los mismos aceptables desde el punto de vista farmacéutico, donde: X se selecciona del grupo formado por NR5, O y S, donde R5 es uno de H y CH3; Y se selecciona del grupo formado por CH2 y O; R4 se selecciona del grupo formado por H, OCH3, Cl, F, Br, I, OH, NH2, CN, CF3 y CH3; R6 es H o F; y R2 y R3 se seleccionan, cada uno en forma independiente, del grupo formado por: A) es H, alquilo, C1-7, alquenilo C3-7, donde el carbono en dicho alquenilo que está unido al elemento nitrógeno sólo tiene enlaces simples, alquinilo C3-7, donde el carbono en dicho alquinilo que está unido al elemento nitrógeno sólo tiene enlaces simples, cicloalquilo C3-7 benzofusionado en forma opcional, cicloalquenilo C5-7, -cicloalquil-(C3-7)-alquilo(C1-7), -alquil-(C1-7)cicloalquilo(C3-7) y fenilo, donde cada uno de los sustituyentes A) está sustituido en forma independiente con 0, 1 ó 2 RQ, y cada uno de dichos RQ es un sustituyente en un elemento carbono que es, por lo menos, un elemento carbono eliminado del elemento nitrógeno; B) un sustituyente HetRa; C) -alquil-(C1-7)C(O)RX, sustituido en forma opcional con CH2RAr o CH2RAr'; D) - alquil-(C2-5)C(O)RX, donde dos elementos carbono con valencia permitida en el alquilo C2-5 de dicho -alquil-(C2-5)C(O)RX son parte de un carbociclo C3-6 saturado; E) -alquil-(C2-5)OH donde dos elementos carbono con valencia permitida en el alquilo C2-5 de dicho -alquil(C2-5)OH son parte de un carbociclo C3-6 saturado; F) -alquil-(C0-4)fenilo, donde el fenilo de dicho -alquil-(C0-4)fenilo está fusionado en dos elementos carbono adyacentes en dicho fenilo a Rf, o es benzofusionado; G) -alquil- (C0-4)AR6, donde AR6 es un heteroarilo de 6 miembros que tiene un punto de unión en el elemento carbono y que tiene uno o dos heteroátomos -N=, y está benzofusionado; H) -alquil-(C0-4)Ar5, donde Ar5 es un heteroarilo de 5 miembros, que tiene un elemento heteroatómico seleccionado del grupo formado por O, S, y >NRY, y que tiene 0 o 1 elemento heteroatómico adicional -N=, que contiene en forma opcional dos grupos carbonilo, y está benzofusionado en forma opcional; I) -alquil-(C1-4)Ar5', donde Ar5' es un heteroarilo de 5 miembros que contiene 3 ó 4 elementos nitrógeno, sustituido en forma opcional con RY, y que tiene un sitio de valencia permitida como punto de unión; J) -alquil-(C0-4)Ar6-6, donde Ar6-6 es un fenilo unido a alquilo C0-4 fusionado en sitios de valencia permitida a un heteroarilo de 6 miembros, donde dicho heteroarilo de 6 miembros tiene uno o dos elementos heteroatómicos -N=; K) -alquil-(C0-4)Ar6-5, donde Ar6-5 es un fenilo unido a alquilo C0-4 fusionado en sitios de valencia permitida a un heteroarilo de 5 miembros, teniendo dicho heteroarilo de 5 miembros un elemento heteroatómico seleccionado del grupo formado por O, S, y >NRY, y dicho heteroarilo de 5 miembros tiene 0 ó 1 elemento heteroatómico adicional que es -N=; y L) uno de 2-(4-etil-fenoxi)-benzotiazol, 2-(4-etil-fenoxi)-benzooxazol, y 2-(4-etil-fenoxi)-1H-benzoimidazol; y M) SO2-alquilo (C1-4); en forma alternativa R2 y R3 se toman junto con el nitrógeno al cual están unidos para formar un anillo heterocíclico que contiene por lo menos un elemento heteroatómico que es dicho nitrógeno de unión, seleccionándose dicho anillo heterocíclico del grupo formado por: i) un anillo heterocíclico de 4-7 miembros HetRb, teniendo dicho anillo heterocíclico de 4-7 miembros HetRb un elemento heteroatómico que es dicho nitrógeno de unión, y está sustituido con 0, 1 ó 2 sustituyentes en los mismos elementos de sustitución u otros diferentes, seleccionándose dichos sustituyentes del grupo formado por -RY, -CN, -C(O)RY, -alquil-(C0-4)CO2RY, -alquil-(C0-4)C(O)CO2RY, -alquil-(C0-4)ORY, -alquil-(C0-4)C(O)NRYRZ, -alquil-(C0-4)NRYC(O)RZ, -C(O)NRZORY, -alquil-(C0-4)NRYC(O)CH2ORY, -alquil-(C0-4)NRYC(O)-CH2C(O)RY, -alquil-(C0- 4)NRYCO2RY, -alquil-(C0-4)NRYC(O)NRYRZ, -alquil-(C0-4)NRYC(S)NRYRZ, -NRYC(O)CO2RY, -NRYRZ, -alquil-(C0-4)-NRWSO2RY, 1,3-dihidro-indol-2-ona-1-ilo, 1,3-dihidro-benzoimidazol-2-ona-1-ilo, tetrazol-5-ilo, 1-RY-1H-tetrazol-5-ilo, RY-triazolilo, 2-RY-2H- tetrazol-5-ilo, pirrolidin-2-tion-1-ilo, piperidin-2-tion-1-ilo, -alquil-(C0-4)C(O)N(RY)(SO2RY), -alquil-(C0-4)N(RY)(SO2)NRYRY, -alquil-(C0-4)N(RY)(SO2)NRYCO2RY, halo o un grupo de fórmulas (2); ii) un anillo heterocíclico de 5-7 miembros HetRc, teniendo dicho anillo heterocíclico de 5-7 miembros HetRc un elemento heteroatómico adicional separado de dicho nitrógeno de unión por lo menos por un elemento carbono, seleccionándose dicho elemento heteroatómico adicional del grupo formado por O, S(=O)0-2, y >NRM, teniendo dicho anillo heterocíclico de 5-7 miembros HetRc 0 ó 1 carbonilo, y estando sustituido con 0, 1 ó 2 sustituyentes en los mismos elementos de sustitución de carbono u otros diferentes, seleccionándose dichos sustituyentes del grupo formado por -C(O)RY, -CO2RY, -alquil-(C3-4)CO2RY y RZ; iii) uno de imidazolidin-1-ilo, 2-imidazolin-1-ilo, pirazol-1-ilo, imidazol-1-ilo, 2H-tetrazol-2-ilo, 1H-tetrazol-1-ilo, pirrol-1-ilo, 2-pirrolin-1-ilo, y 3-pirrolin-1-ilo, donde cada uno de dichos 2H-tetrazol-2-ilo y 1H-tetrazol-1-ilo está sustituido en el elemento carbono con 0 ó 1 de -alquil-(C0-4)RZ, -alquil-(C0-4)SRY, -alquil-(C0-4)CO2RY, y el sustituyente HetRa; y iv) uno de 1,2,3,4-tetrahidro-quinolin-1-ilo, 1,2,3,4- tetrahidro-isoquinolin-2-ilo, indol-1-ilo, isoindol-2-ilo, indolin-1-ilo, benzoimidazol-1-ilo, 2,8-diaza-espiro[4.5]decan-1-ona-8-ilo, 4-{[(2-ter-butoxicarbonilamino-ciclobutancarbonil)-amino]-metil}-piperidin-1-ilo, 4-{[(2-amino-ciclobutancarbonil)- amino]-metil}-piperidin-1-ilo, 9-il-ter-butil éster del ácido 3,9-diaza-espiro[5.5]undecan-3-carboxílico, 4-oxo-1-fenil-1,3,8-triaza-espiro[4.5]dec-8-ilo y 4-oxo-1,3,8-triaza-espiro[4.5]dec-8-ilo; donde el sustituyente HetRa es un anillo heterocíclico de 4-7 miembros que tiene un punto de unión en el elemento carbono y que contiene un elemento >NRM como elemento heteroatómico, y dicho elemento heteroatómico está separado de dicho punto de unión al elemento carbono por lo menos por un elemento carbono adicional; RK se selecciona del grupo formado por H, -alquilo C1-4, -alquil-(C0-4)RAr, cada uno sustituido en forma opcional con 1, 2 ó 3 sustituyentes RN; RL se selecciona del grupo formado por -CO2RS y -C(O)NRSRS'; RM se selecciona del grupo formado por RZ, indol-7-ilo, -SO2RY, -alquil-(C3-4)-CO2RY, -CO2RY, -C(O)NRZORY, -C(O)RY, -C(O)alquil-(C1-4)ORY, -alquil-(C0-4)C(O)NRSRS', alquil-(C1-4)C(O)CO2RY, 1,3-dihidro-indol-2-ona-1-ilo, 1,3-dihidro-benzoimidazol-2-ona-1- ilo, tetrazol-5-ilo, 1-RY-1H-tetrazol-5-ilo, RY-triazolilo, 2-RY-2H-tetrazol-5-ilo y -alquil-(C0-4)C(O)N(RY)(SO2RY), cada uno sustituido en forma opcional con 1, 2 ó 3 sustituyentes RN; RN se selecciona del grupo formado por OCH3, Cl, F, Br, I, OH, NH2, CN, CF3, CH3, OC(O)CH3, y NO2; RP se selecciona del grupo formado por RY, -alquil-(C2-4)ORY, RAr, -alquil-(C1-2)-CO2RY, -alquil-(C1-2)CONRSRS', indol-7-ilo, y -SO2alquilo(C1-4), RQ se selecciona del grupo formado por fluoro, cloro, bromo, yodo, trifluorometilo, triclorometilo, -CN, -alquilo C1-4, -alquil-(C0-4)RAr, -alquil-(C0-4)RAr', -alquil-(C0-4)ORY, -alquil-(C0-4)CO2RY, -alquil-(C0-4)NRYRZ, -alquil-(C0-4)NRYCORY, -alquil-(C0-4)NRYCONRYRZ, -alquil-(C0-4)NRYSO2RY y -alquil-(C0-4)SRY; RS y RS' se seleccionan en forma independiente del grupo formado por H, -alquilo C1-4, y -alquil-(C0-4)fenilo; en forma alternativa, RS y RS' se toman junto con el elemento nitrógeno al cual dichos RS y RS' están unidos para formar un anillo heterocíclico de 4-7 miembros que tiene 0 o 1 elemento heteroatómico adicional seleccionado del grupo formado por O, S y >NRY, siempre que dicho elemento heteroatómico adicional esté separado por lo menos por dos elementos carbono de dicho elemento nitrógeno al cual dichos RS y RS' están unidos, y siempre que cuando RY sea alquil-(C0-4)RAr, entonces RAr no esté sustituido con RL; RW se selecciona del grupo formado por RY y -cicloalquilo C3-7; RX se selecciona del grupo formado por -ORY, - NRYRZ, -alquilo C1-4, y -alquil-(C0-4)RAr; RY se selecciona del grupo formado por H, -alquilo C1-4, -alquil-(C0-4)RAr y -alquil-(C0-4)RAr', cada uno sustituido en forma opcional con 1, 2 ó 3 sustituyentes RN; RZ se selecciona del grupo formado por RY, -alquil-(C2-4)ORY, -alquil-(C1-2)CO2RY, -alquil-(C1-2)C(O)NRSRS' y -alquil-(C2-4)NRSRS'; cuando RY y RZ están unidos a un elemento nitrógeno, RY y RZ se seleccionan como se definió con anterioridad, o RY y RZ se toman junto con el elemento nitrógeno unido a RY y RZ para formar un anillo heterocíclico de 4-7 miembros HetRd que tiene 0 ó 1 elementos heteroatómicos adicionales seleccionados del grupo formado por O, S, y >NRM, teniendo dicho anillo heterocíclico de 4-7 miembros HetRd 0 ó 1 miembro carbonilo, y teniendo dicho anillo heterocíclico de 4-7 miembros HetRd 0 ó 1 elementos carbono de valencia permitida sustituidos por lo menos con uno de RM, -CO2H, y -alquil-(C0-1)ORY; RAr es un resto con un punto de unión en el elemento de carbono y dicho resto se selecciona del grupo formado por fenilo, piridilo, pirimidilo, y pirazinilo, donde cada elemento carbono de valencia permitida en cada uno de dichos restos está sustituido en forma independiente por lo menos con uno de 0, 1, 2 ó 3 RN, y 0 ó 1 RL; RAr' es un anillo de 3-8 miembros, que tiene 0, 1 ó 2 elementos heteroatómicos seleccionados del grupo f
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| US7541466B2 (en) * | 2003-12-23 | 2009-06-02 | Genzyme Corporation | Tetrahydroisoquinoline derivatives for treating protein trafficking diseases |
| AU2006224842B2 (en) * | 2005-03-16 | 2011-09-29 | Meda Pharma Gmbh & Co Kg | The combination of anticholinergics and leukotriene receptor antagonists for the treatment of respiratory diseases |
| TW200906396A (en) * | 2007-02-14 | 2009-02-16 | Janssen Pharmaceutica Nv | LTA4H modulators and uses thereof |
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