MATRIX METALLOPROTEINASE INHIBITORS

The present invention relates to β-hydroxy and amino-substituted carboxylic acids, which act as matrix metalloproteinase inhibitors, particularly diastereomerically pure β-hydroxy carboxylic acids, corresponding processes for their synthesis, and pharmaceutical compositions containing the compounds of the present invention. Compounds of the present invention are useful in the treatment of various inflammatory, autoimmune, and allergic diseases, such as methods of treating asthma, rheumatoid arthritis, COPD, rhinitis, osteoarthritis, psoriatic arthritis, psoriasis, pulmonary fibrosis, wound healing disorders, pulmonary inflammation, acute respiratory distress syndrome, perodontitis, multiple sclerosis, gingivitis, atherosclerosis, neointimal proliferation, which leads to restenosis and ischemic heart failure, stroke, renal diseases, tumor metastasis, and other inflammatory disorders characterized by the over-expression and over-activation of a matrix metalloproteinase. 2. A compound which is selected from:(2S,3R)-2-[2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)ethyl]-5-[6-(3-fluoro-4-methoxyphenyl)pyridin-3-yl]-3-hydroxypentanoic acid (Compound No. 55);(2S,3R)-2-[2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)ethyl]-3-hydroxy-5-[6-(4-methoxyphenyl)pyridin-3-yl]pentanoic acid (Compound No. 57);(2S,3R)-5-[6-(4-chlorophenyl)pyridin-3-yl]-2-[2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)ethyl]-3-hydroxypentanoic acid (Compound No. 59);(2S,3R)-2-[2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)ethyl]-3-hydroxy-5-(6′-methoxy-2,3′-bipyridin-5-yl)pentanoic acid (Compound No. 60);(2S,3R)-5-[4-(4-chlorophenyl)-2-thienyl]-2-[2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)ethyl]-3-hydroxypentanoic acid (Compound No. 61);(2S,3R)-2-[2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)ethyl]-3-hydroxy-5-[4-(6-methoxypyridin-3-yl)-2-thienyl]pentanoic acid (Compound No. 62);(2S,3R)-2-[2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)ethyl]-3-hydroxy-5-{4-[4-(trifluoromethyl)phenyl]-2-thienyl}pentanoic acid (Compound No. 63 ...

MATRIX METALLOPROTEINASE INHIBITORS

The present invention relates to β-hydroxy and amino-substituted carboxylic acids, which act as matrix metalloproteinase inhibitors, particularly diastereomerically pure β-hydroxy carboxylic acids, corresponding processes for their synthesis, and pharmaceutical compositions containing the compounds of the present invention. Compounds of the present invention are useful in the treatment of various inflammatory, autoimmune, and allergic diseases, such as methods of treating asthma, rheumatoid arthritis, COPD, rhinitis, osteoarthritis, psoriatic arthritis, psoriasis, pulmonary fibrosis, wound healing disorders, pulmonary inflammation, acute respiratory distress syndrome, perodontitis, multiple sclerosis, gingivitis, atherosclerosis, neointimal proliferation, which leads to restenosis and ischemic heart failure, stroke, renal diseases, tumor metastasis, and other inflammatory disorders characterized by the over-expression and over-activation of a matrix metalloproteinase. 2. A compound which is selected from:(2S,3R)-5-(3,3′-difluoro-4′-methoxybiphenyl-4-yl)-2-[2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)ethyl]-3-hydroxypentanoic acid (Compound No. 47);(2S,3R)-2-[2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)ethyl]-5-[2-fluoro-4-(6-methoxypyridin-3-yl)phenyl]-3-hydroxypentanoic acid (Compound No. 50);(2S,3R)-5-(4′-chloro-3-fluorobiphenyl-4-yl)-2-[2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)ethyl]-3-hydroxypentanoic acid (Compound No. 56);(2S,3R)-2-[2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)ethyl]-5-β-fluoro-4′-methoxybiphenyl-4-yl)-3-hydroxypentanoic acid (Compound No. 58);(2S,3R)-5-[2-fluoro-4-(6-methoxypyridin-3-yl)phenyl]-3-hydroxy-2-[2-(4-oxo-1,2,3-benzotriazin-3(4H)-yl)ethyl]pentanoic acid (Compound No. 153);(2S,3R)-5-[2-fluoro-4-(6-methoxypyridin-3-yl)phenyl]-3-hydroxy-2-[2-(7-methoxy-4-oxo-1,2,3-benzotriazin-3(4H)-yl)ethyl]pentanoic acid (Compound No. 154);(2S,3R)-5-[2-fluoro-4-(6-methoxypyridin-3-yl)phenyl]-2-[2-(5-fluoro-4-oxo-1,2,3-benzotriazin-3(4H)-yl)ethyl]-3- ...

N-phosphonoxymethl prodrugs of hydroxyalkyl thiadiazole derivatives

There is a need for a new antibiotic having a novel mechanism of action, which exhibits strong antibacterial activity not only against sensitive bacteria, but also against resistant bacteria thereof, and at the same time possess excellent solubility and safety profile amenable to human use. As a result of intensive research, the present inventors have found that N-phosphonoxymethyl prodrugs of hydroxyalkyl thiadiazole derivatives represented by general formula (I), a regioisomer, a stereoisomer, or a pharmaceutically acceptable salt thereof possess excellent solubility and safety profile for use in human for the treatment of bacterial infectious diseases.

MATRIX METALLOPROTEINASE INHIBITORS

This invention also relates to pharmacological compositions containing the compounds of the present invention, and methods of treating asthma, rheumatoid arthritis, COPD, rhinitis, osteoarthritis, psoriatic arthritis, psoriasis, pulmonary fibrosis, pulmonary inflammation, acute respiratory distress syndrome, periodontitis, multiple sclerosis, gingivitis, gingivitis, atherosclerosis, dry eye, neointimal proliferation, which leads to restenosis and ischemic heart failure, stroke, renal diseases, tumor metastasis, and pounds. 4. A pharmaceutical composition comprising a therapeutically effective amount of a compound according to any one of to , together with a pharmaceutically acceptable carrier , excipient or diluents.5. A compound according to any one of to , for use in the treatment or prophylaxis of an animal or a human suffering from an inflammatory or allergic disease.6. A compound according to claim 5 , wherein the inflammatory disease or allergic disease is asthma claim 5 , rheumatoid arthritis claim 5 , COPD claim 5 , dry eye claim 5 , rhinitis claim 5 , osteoarthritis claim 5 , psoriatic arthritis claim 5 , psoriasis claim 5 , pulmonary fibrosis claim 5 , pulmonary inflammation claim 5 , acute respiratory distress syndrome claim 5 , periodontitis claim 5 , multiple sclerosis claim 5 , gingivitis claim 5 , atherosclerosis claim 5 , dry eye claim 5 , neointimal proliferation associated with restenosis and ischemic heart failure claim 5 , stroke claim 5 , renal disease or tumor metastasis.7. A pharmaceutical composition according to claim 4 , further comprising one or more additional active ingredients selected from:a) Anti-inflammatory agents selected from (i) nonsteroidal anti-inflammatory agents piroxicam, diclofenac, propionic acids, fenamates, pyrazolones, salicylates, PDE-4/p38 MAP Kinase/Cathepsin inhibitors, CCR-3 antagonists, iNOS inhibitors, tryptase and elastase inhibitors, beta-2 integrin antagonists, cell adhesion inhibitors (especially ICAM), ...

HYDROXYALKYL THIADIAZOLE DERIVATIVES

Problem to be Solved There is a need for a new antibiotic having a novel mechanism of action which exhibit strong antibacterial activity not only against sensitive bacteria but also against resistant bacteria thereof, and at the same time possesses excellent solubility an a safety profile amenable to human use. 3. The compound claim 1 , a stereoisomer claim 1 , a tautomer claim 1 , or a pharmaceutically acceptable salt thereof according to claim 1 , wherein R represents methyl or ethyl.4. The compound according to claim 1 , wherein the compound is selected from:4-Chloro-N-{(3 S,4R)-3-ethoxy-1-[5-(1-hydroxyethyl)-1,3,4-thiadiazol-2-yl]piperidin-4-yl}-5-ethyl-1H-imidazole-2-carboxamide,4-Chloro-5-ethyl-N-{(3S,4R)-1-[5-(1-hydroxy-1-methylethyl)-1,3,4-thiadiazol-2-yl]-3-methoxypiperidin-4-yl}-1H-imidazole-2-carboxamide,4-Chloro-5-ethyl-N-{(3S,4R)-1-[5-(1-hydroxyethyl)-1,3,4-thiadiazol-2-yl]-3-methoxypiperidin-4-yl]-1H-imidazole-2-carboxamide,4-Chloro-5-ethyl-N-[(3S,4R)-1-{5[(1R)-1-hydroxyethyl]-1,3,4-thiadiazol-2-yl}-3-methoxypiperidin-4-yl]-1H-imidazole-2-carboxamide,4-Chloro-5-ethyl-N-[(3S,4R)-1-5-[(1S)-1-hydroxyethyl]-1,3,4-thiadiazol-2-yl}-3-methoxypiperidin-4-yl]-1H-imidazole-2-carboxamide,4-Chloro-5-ethyl-N-{(3S,4R)-1-[5-(1-hydroxypropan-2-yl)-1,3,4-thiadiazol-2-yl]-3-methoxypiperidin-4-yl}-1H-imidazole-2-carboxamide,4-Chloro-N-{(3S,4R)-3-ethoxy-1-[5-(2-hydroxypropan-2-yl)-1,3,4-thiadiazol-2-yl]piperidin-4-yl}-5-ethyl-1H-imidazole-2-carboxamide,4-Chloro-N-[(3S,4R)-1-{5-[(1S)-1,2-dihydroxyethyl]-1,3,4-thiadiazol-2-yl}-3-methoxypiperidin-4-yl]-5-ethyl-1H-imidazole-2-carboxamide,4-Chloro-N-[(3S,4R)-1-{5-[(1R)-1,2-dihydroxyethyl]-1,3,4-thiadiazol-2-yl}-3-methoxypiperidin-4-yl]-5-ethyl-1H-imidazole-2-carboxamide,4-Chloro-N-[(3S,4R)-1-{5-[(2R)-1,2-dihydroxypropan-2-yl]-1,3,4-thiadiazol-2-yl}-3-methoxypiperidin-4-yl]-5-ethyl-1H-imidazole-2-carboxamide,4-Chloro-N-[(3S,4R)-1-{5-[(2S)-1,2-dihydroxypropan-2-yl]-1,3,4-thiadiazol-2-yl}-3-methoxypiperidin-4-yl]-5-ethyl-1H- ...

Matrix metalloproteinase inhibitors

This invention also relates to pharmacological compositions containing the compounds of the present invention, and methods of treating asthma, rheumatoid arthritis, COPD, rhinitis, osteoarthritis, psoriatic arthritis, psoriasis, pulmonary fibrosis, pulmonary inflammation, acute respiratory distress syndrome, perodontitis, multiple sclerosis, gingivitis, atherosclerosis, dry eye, neointimal proliferation, which leads to restenosis and ischemic heart faliure, stroke, renal diseases, tumor metastasis, and other inflammatory disorders characterized by over-expression and over-activation of matrix metalloproteinase using the compounds.

Condensed isoxaline derivatives as inhibitors of phosphodiesterase type - iv

The present invention relates to isoxazoline derivatives, which can be used as selective inhibitors of phosphodiesterase (PDE) type IV. In particular, compounds disclosed herein can be useful in the treatment of AIDS, asthma, arthritis, bronchitis, chronic obstructive pulmonary disease (COPD), psoriasis, allergic rhinitis, shock, atopic dermatitis, Crohn's disease, adult respiratory distress syndrome (ARDS), eosinophilic granuloma, allergic conjunctivitis, osteoarthritis, ulcerative colitis and other inflammatory diseases in a patient, particularly in humans. The present invention also relates to processes for the preparation of disclosed compounds, as well as pharmaceutical compositions thereof, and their use as phosphodiesterase (PDE) type IV inhibitors.

Hydroxyalkyl thiadiazole derivatives

Problema a ser resuelto. Hay una necesidad por un nuevo antibiótico que tenga un nuevo mecanismo de acción que muestre fuerte actividad antibacteriana no solamente contra bacterias sensibles, sino también contra bacterias resistentes al mismo, y al mismo tiempo posea excelente solubilidad y perfil de solubilidad susceptible para uso humano. Solución al problema. Como un resultado de investigación intensiva, los inventores han encontrado que un compuesto representado por la formula general (I), un estereoisomero, o una sal farmacéuticamente aceptable de mismo inhibe la subunidad GyrB de la DNA girasa y/o la subunidad ParE de la topoisomerasa IV posee excelente solubilidad y perfil de seguridad para uso en humanos en el tratamiento de enfermedades infecciosas bacterianas. Problem to be solved. There is a need for a new antibiotic that has a new mechanism of action that shows strong antibacterial activity not only against sensitive bacteria, but also against bacteria resistant to it, and at the same time possesses excellent solubility and solubility profile susceptible for human use. Solution to the problem. As an intensive research result, the inventors have found that a compound represented by the general formula (I), a stereoisomer, or a pharmaceutically acceptable salt thereof inhibits the GyrB subunit of DNA gyrase and / or the ParE subunit of topoisomerase IV has excellent solubility and safety profile for use in humans in the treatment of bacterial infectious diseases.

Matrix metalloproteinase inhibitors

The present invention relates to β-hydroxy and amino substituted carboxylic acids, which act as matrix metalloprotease inhibitors, particularly diastereomerically pure β-hydroxy carboxylic acids, corresponding processes for the synthesis of and pharmaceutical compositions containing the compounds of the present invention. Compounds of the present invention are useful in the treatment of various inflammatory, autoimmune and allergic diseases, such as methods of treating asthma, rheumatoid arthritis, COPD, rhinitis, osteoarthritis, psoriatic arthritis, psoriasis, pulmonary fibrosis, wound healing disorders, pulmonary inflammation, acute respiratory distress syndrome, perodontitis, multiple sclerosis, gingivitis, atherosclerosis, neointimal proliferation, which leads to restenosis and ischemic heart failure, stroke, renal diseases, tumor metastasis, and other inflammatory disorders characterized by the over-expression and over-activation of a matrix metalloproteinase using the compounds.

CARBOXILIC ACIDS INHIBITORS OF METALPROTEINASA MATRIZ.

La presente se relaciona con ácidos carboxílicos sustituidos mediante beta-hidroxi y amino, que actuan como inhibidores de la metaloproteasa matriz, ácidos carboxílicos beta-hidroxi diastereoméricamente puros, procesos correspondientes para la síntesis de composiciones farmacéuticas que contienen los compuestos de la presente. Los compuestos de la presente son utiles en el tratamiento de diversas enfermedades inflamatorias, de autoinmunidad y alérgicas, como ser los métodos para tratar el asma, la artritis reumatoidea, COPD, rinitis, osteoartritis, artritis soriásica, psoriasis, fibrosis pulmonar, desordenes en la cura de heridas, inflamacion pulmonar, síndrome de perturbacion respiratoria agudo, periodontitis, esclerosis multiple, gingivitis, ateroesclerosis, proliferacion neoíntima, que lleva a la restenosis y a la insuficiencia cardiaca isquémica, ataque apopléjico, enfermedades renales, metástasis tumoral y otros desordenes inflamatorios caracterizados por la hiper- expresion e hiper-activacion de una rnetaloproteinasa matriz utilizando los compuestos. Reivindicacion 1: Un compuesto de la formula 1, en donde: * representa un centro asimétrico estereogénico de configuracion definida seleccionada de (R, R), (S, S), (R, S) y (S, R); n es un entero de 1 a 5; R1 es hidrogeno, alquilo, alquenilo, alquinilo, cicloalquilo, arilo, heterociclilo, heteroarilo, aralquilo, alcoxi, ariloxi, alqueniloxi o alquiniloxi opcionalmente sustituido; R2 es heterociclilo, heteroarilo, NR4R5, -NHC(=Y)R4, -NHC(=Y)NR5Rx, -NHC(=O)OR4 , -NHSO2R4, C(=Y)NR4R5, C(=O)OR6, en donde; Y es oxígeno o azufre, OR5,-OC(=O)NR4R5, O-acilo, S(O)mR4, -SO2N(R4)2, ciano, amidino o guanidino; Rx es R4 o -SO2N(R4)2; R6 es hidrogeno, alquilo, cicloalquilo, aralquilo, heteroarilalquilo, heterociclilalquilo o cicloalquilalquilo en donde R4 es alquilo, alquenilo, alquinilo, cicloalquilo, arilo, heterociclilo, heteroarilo, aralquilo, heteroarilalquilo, heterociclilalquilo o cicloalquilalquilo; y m es un entero 0-2 ...

5-phenyl-pentanoic acid derivatives as matrix metalloproteinase inhibitors for the treatment of asthma and other diseases 5--

Matrix metalloproteinase inhibitors

The present invention relates to β-hydroxy and amino substituted carboxylic acids, which act as matrix metalloprotease inhibitors, particularly diastereomerically pure β-hydroxy carboxylic acids, corresponding processes for the synthesis of and pharmaceutical compositions containing the compounds of the present invention. Compounds of the present invention are useful in the treatment of various inflammatory, autoimmune and allergic diseases, such as methods of treating asthma, rheumatoid arthritis, COPD, rhinitis, osteoarthritis, psoriatic arthritis, psoriasis, pulmonary fibrosis, wound healing disorders, pulmonary inflammation, acute respiratory distress syndrome, perodontitis, multiple sclerosis, gingivitis, atherosclerosis, neointimal proliferation, which leads to restenosis and ischemic heart failure, stroke, renal diseases, tumor metastasis, and other inflammatory disorders characterized by the over-expression and over- activation of a matrix metalloproteinase using the compounds.

Matrix metalloproteinase inhibitors.

La presente invención se relaciona a ciertos derivados de ácido sulfona acético de la fórmula 1 como inhibidores de MMP y procesos para su síntesis. La invención también se relaciona a composiciones farmacológicas que contienen los compuestos de la presente invención, y métodos para tratar asma, artritis reumatoide, COPD, rinitis, osteoartritis, artritis psoriática, psoriasis, fibrosis pulmonar, inflamación pulmonar, síndrome de angustia respiratoria aguda, perodontitis, esclerosis múltiple, gingivitis, aterosclerosis, ojo seco, proliferación neoíntima, que conduce a restenosis y falla cardíaca isquémica, ataque apoplético, enfermedad renal, metástasis de tumor y otros trastornos inflamatorios caracterizados por sobre-expresión y sobre-activación de una metaloproteinasa de matriz usando los compuestos.

5-phenyl-pentanoic acid derivatives as matrix metalloproteinase inhibitors for the treatment of asthma and other diseases

The present invention relates to C ompounds having the structure of Formula I: wherein n is an integer from 1 to 5; R1 is optionally substituted alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heterocyclyl, heteroaryl, aralkyl, alkoxy, aryloxy, alkenyloxy or alkynyloxy; R2 is alkenyl, allcynyl, aryl, heterocyclyl, heteroaryl, cycloalkyl, NR4R5, -NHC(=Y)R4, - NHC(=Y)NR5Rχ, -NHC(=O)OR4, -NHSO2R4, C(=Y)NR4R5, C(=O)OR6 [wherein Y is oxygen or sulphur], OR5, -O(C=O)NR4R5, O-acyl, S(O)mR4, -SO2N(R4)2, cyano, amidino or guanidino [wherein R4 is alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heterocyclyl, heteroaryl, aralkyl, heteroarylalkyl, heterocyclylalkyl or cycloalkylalkyl and m is an integer 0-2; R5 is hydrogen or R4; Rx is R4 or -SO2N(R4)2 and R6 is hydrogen, alkyl, cycloalkyl, aralkyl, heteroarylalkyl, heterocyclylalkyl or cycloalkylalkyl]; R3 is hydrogen, fluorine, alkyl, cycloalkylalkyl or aralkyl; A is OH, OR4, -OC(=O)NR4R5, O-acyl, NH2, NR4R5, -NHC(=Y)R4, -NHC(=Y)NR5Rx, - NHC(=O)OR4, -NHSO2R4, and to processes for the synthesis of the same. This invention also relates to pharmacological compositions containing the compounds of the present invention, and methods of treating asthma, rheumatoid arthritis, COPD, rhinitis, osteoarthritis, psoriatic arthritis, psoriasis, pulmonary fibrosis pulmonary inflammation, acute respiratory distress syndrome, perodontitis, multiple sclerosis, gingivitis, atherosclerosis, neointimal proliferation, which leads to restenosis and ischemic heart failure, stroke, renal diseases, tumor metastasis, and other inflammatory disorders characterized by over-expression and over-activation of an matrix metalloproteinase, using the compounds.

N-phosphonoxymethyl prodrugs of hydroxyalkyl thiadiazole derivatives

There is a need for a new antibiotic having a novel mechanism of action, which exhibits strong antibacterial activity not only against sensitive bacteria, but also against resistant bacteria thereof, and at the same time possess excellent solubility and safety profile amenable to human use. As a result of intensive research, the present inventors have found that N-phosphonoxymethyl prodrugs of hydroxyalkyl thiadiazole derivatives represented by general formula (I), a regioisomer, a stereoisomer, or a pharmaceutically acceptable salt thereof possess excellent solubility and safety profile for use in human for the treatment of bacterial infectious diseases.

Matrix metalloproteinase inhibitors

The present invention relates to methyl sulfonamides and N-formamides derivatives of formula (I) and to processes for their syntheses. The invention also relates to pharmacological compositions containing these derivatives and methods of treating asthma, rheumatoid arthritis, COPD, rhinitis, osteoarthritis, psoriatie arthritis, psoriasis, pulmonary fibrosis, pulmonary inflammation, acute respiratory distress syndrome, perodontitis, multiple sclerosis, gingivitis, atherosclerosis, dry eye, neointimal proliferation which leads to restenosis and ischemic heart failure, stroke, renal disease, tumor metastasis, and other inflammatory disorders characterized by over expression and over activation of an matrix metalloproteinase using the compounds.

5-phenyl-pentanoic acid derivatives as matrix metalloproteinase inhibitors for the treatment of asthma and other diseases

The present invention relates to C ompounds having the structure of Formula I: wherein n is an integer from 1 to 5; R1 is optionally substituted alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heterocyclyl, heteroaryl, aralkyl, alkoxy, aryloxy, alkenyloxy or alkynyloxy; R2 is alkenyl, allcynyl, aryl, heterocyclyl, heteroaryl, cycloalkyl, NR4R5, -NHC(=Y)R4, - NHC(=Y)NR5R.chi., -NHC(=O)OR4, -NHSO2R4, C(=Y)NR4R5, C(=O)OR6 [wherein Y is oxygen or sulphur], OR5, -O(C=O)NR4R5, O-acyl, S(O)mR4, -SO2N(R4)2, cyano, amidino or guanidino [wherein R4 is alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heterocyclyl, heteroaryl, aralkyl, heteroarylalkyl, heterocyclylalkyl or cycloalkylalkyl and m is an integer 0-2; R5 is hydrogen or R4; Rx is R4 or -SO2N(R4)2 and R6 is hydrogen, alkyl, cycloalkyl, aralkyl, heteroarylalkyl, heterocyclylalkyl or cycloalkylalkyl]; R3 is hydrogen, fluorine, alkyl, cycloalkylalkyl or aralkyl; A is OH, OR4, -OC(=O)NR4R5, O-acyl, NH2, NR4R5, -NHC(=Y)R4, -NHC(=Y)NR5Rx, -NHC(=O)OR4, -NHSO2R4, and to processes for the synthesis of the same. This invention also relates to pharmacological compositions containing the compounds of the present invention, and methods of treating asthma, rheumatoid arthritis, COPD, rhinitis, osteoarthritis, psoriatic arthritis, psoriasis, pulmonary fibrosis pulmonary inflammation, acute respiratory distress syndrome, perodontitis, multiple sclerosis, gingivitis, atherosclerosis, neointimal proliferation, which leads to restenosis and ischemic heart failure, stroke, renal diseases, tumor metastasis, and other inflammatory disorders characterized by over-expression and over-activation of an matrix metalloproteinase, using the compounds.

5-FENYL-PENTANOIC ACID DERIVATIVE AS FUNDAMENTAL METAL PROTEIN Suspensions for the Treatment of Asthma and Other Diseases

Η παρούσα εφεύρεση αναφέρεται σε Ενώσεις που έχουν την δομή του Τύπου Ι: όπου το n είναι ένας ακέραιος από 1 έως 5· το R1 είναι προαιρετικά υποκατεστημένο αλκύλιο, αλκενύλιο, αλκινύλιο, κυκλοαλκύλιο, αρύλιο, ετεροκυκλύλιο, ετεροαρύλιο, αραλκύλιο, αλκοξυ, αρυλοξυ, αλκενυλοξυ ή αλκινυλοξυ· το R2 είναι προαιρετικά υποκατεστημένο αλκενύλιο, αλκινύλιο, αρύλιο, ετεροκυκλύλιο, ετεροαρύλιο, κυκλοαλκύλιο, ΝR4R5, -ΝΗC(=Υ)R4, -ΝΗC(=Υ)ΝR5RΧ, -ΝΗC(=Ο)ΟR4, -ΝΗSΟ2R4, C(=Υ)ΝR4R5, C(=Ο)ΟR6 [όπου το Υ είναι οξυγόνο ή θείο], ΟR5, -ΟC(=Ο)ΝR4R5, Ο-ακύλιο, S(O)mR4, -SΟ2Ν(R4)2, κυανό, αμιδινο ή γουανιδινο [όπου το R4 είναι αλκύλιο, αλκενύλιο, αλκινύλιο, κυκλοαλκύλιο, αρύλιο, ετεροκυκλύλιο, ετεροαρύλιο, αραλκύλιο, ετεροαρυλαλκύλιο, ετεροκυκλυλαλκύλιο ή κυκλοαλκυλαλκύλιο και το m είναι ένας ακέραιος 0-2· το R5 είναι υδρογόνο ή R4· το RX είναι R4 ή -SΟ2Ν(R4)2 και το R6 είναι υδρογόνο, αλκύλιο, κυκλοαλκύλιο, αραλκύλιο, ετεροαρυλαλκύλιο, ετεροκυκλυλαλκύλιο ή κυκλοαλκυλαλκύλιο]· το R3 είναι υδρογόνο, φθόριο, αλκύλιο, κυκλοαλκυλαλκύλιο ή αραλκύλιο· το Α είναι ΟΗ, ΟR4, -ΟC(=Ο)ΝR4R5, Ο-ακύλιο, ΝΗ2, ΝR4R5, -ΝΗC(=Υ)R4, -ΝΗC(=Υ)ΝR5RX, -ΝΗC(=Ο)ΟR4, -ΝΗSΟ2R4, και σε μεθόδους σύνθεσης των ιδίων. Η εφεύρεση αυτή σχετίζεται επίσης με φαρμακολογικές συνθέσεις που περιέχουν τις ενώσεις της παρούσας εφεύρεσης, και μεθόδους αγωγής άσθματος, ρευματοειδούς αρθρίτιδας, χρόνιας αποφρακτικής πνευμονοπάθειας (CΟΡD), ρινίτιδας, οστεοαρθρίτιδας, ψωριασικής αρθρίτιδας, ψωρίασης, πνευμονικής ίνωσης, πνευμονικής φλεγμονής, συνδρόμου οξείας αναπνευστικής δυσχέρειας, περιοδοντίτιδας, σκλήρυνσης κατά πλάκας, ουλίτιδας, αρτηριοσκλήρυνσης, ενδοθηλιακής υπερπλασίας, που οδηγεί σε επαναστένωση και ισχαιμική καρδιακή ανεπάρκεια, αποπληξίας, νεφρικών νόσων, νεοπλασματικής μετάστασης, και άλλων φλεγμονωδών διαταραχών χαρακτηριζομένων από

Hydroxyalkyl thiadiazole derivatives

Un compuesto representado por la fórmula general (I) o una sal farmacéuticamente aceptable del mismo; **(Ver fórmula)** en la que R representa alquilo (C1-C3), y A representa las siguientes fórmulas: **(Ver fórmula)** o **(Ver fórmula)** con la codición de que, en la fórmula general (I), se incluyan tautómeros con un hidrógeno en diferentes posiciones del anillo imidazol. A compound represented by the general formula (I) or a pharmaceutically acceptable salt thereof; ** (See formula) ** in which R represents (C1-C3) alkyl, and A represents the following formulas: ** (See formula) ** or ** (See formula) ** with the proviso that, in the general formula (I), tautomers with a hydrogen in different positions of the imidazole ring are included.

Hydroxyalkyl thiadiazole derivatives

Problem to be Solved There is a need for a new antibiotic having a novel mechanism of action, which exhibits strong antibacterial activity not only against sensitive bacteria, but also against resistant bacteria thereof, and at the same time possess excellent solubility and safety profile amenable to human use. Solution to the Problem As a result of intensive research, the present inventors have found that a compound represented by general formula (I), a stereoisomer, or a pharmaceutically acceptable salt thereof inhibits DNA gyrase GyrB subunit and/or topoisomerase IV ParE subunit, possess excellent solubility and safety profile for use in human for the treatment of bacterial infectious diseases.

Telomerase inhibitor compounds

Provided are telomerase inhibitor compounds. Some compounds include a lactone or lactam group that is covalently bonded to a phenyl ring, which is itself bonded to a pyrazole group. In other cases, a sulfonamide-containing moiety is covalently bonded to a phenyl ring, which is itself bonded to a pyrazole group. In some embodiments, the telomerase inhibitor compound has a vinyl sulfonamide group bonded to an amide moiety and an aromatic group. In other cases, the inhibitor compound has an isothiazolidine 1,1-dioxide core that is bonded to a phenyl group. Aspects of the invention also include pharmaceutical compositions comprising the subject telomerase inhibitor compounds, as well as methods of treating telomerase-related diseases or conditions.