1-[2-(aminomethyl)benzyl]-2-thioxo-1,2,3,5-tetrahydro-4H-pyrrolo[3,2-d]pyrimidin-4-ones as inhibitors of myeloperoxidase

There are disclosed certain 1-[2-(aminomethyl)benzyl]-2-thioxo-1,2,3,5-tetrahydro-4H-pyrrolo[3,2-d]pyrimidin-4-one compounds of formula (I), and pharmaceutically acceptable salts thereof, together with compositions containing them and their use in therapy. The compounds are inhibitors of the enzyme MPO and are thereby particularly useful in the treatment or prophylaxis of cardiovascular disorders such as heart failure and coronary artery disease related conditions.

Carbamoyl compounds as DGAT1 inhibitors 190

DGAT-1 inhibitor compounds of formula (I), pharmaceutically-acceptable salts and pro-drugs thereof are described, together with pharmaceutical compositions, processes for making them and their use in treating, for example, obesity wherein, for example, Ring A is optionally substituted 2,6-pyrazindiyl; X is O; Ring B is optionally substituted 1,4-phenylene; Y1 is a direct bond or O; Y2 is (CH2)r wherein r is 2 or 3; n is 0 or n is 1 when Y1 is a direct bond between Ring B and Ring C and when Ring B is 1,4-phenylene and Ring C is (4-6C)cycloalkane; Ring C is optionally substituted (4-6C)cycloalkane, (7-10C)bicycloalkane, (8-12C)tricycloalkane, phenylene or pryidindiyl; L is a direct bond or O; p is 0, 1 or 2 and when p is 1 or 2 RA1 and RA2 are each independently hydrogen or (1-4C)alkyl; Z is carboxy or a mimic or bioisostere thereof.

New Acetyl Coenzyme A Carboxylase (ACC) Inhibitors And Uses In Treatments Of Obesity And Diabetes Mellitus - 087

The present invention relates to Acetyl Coenzyme A Carboxylase (ACC) inhibitors according to formula (I), or an enantiomer thereof, or a pharmaceutically acceptable salt thereof, where R1, R2, R3, R4, R5, E, L, Z and n are as defined herein, to processes for preparing such compounds, to pharmaceutical compositions containing them, to the use of such inhibitors and to methods for their therapeutic use, particularly in the treatments of obesity and diabetes mellitus.

COMPOUNDS AND USES

There is provided compounds of formula I, wherein E 1 , E 2 , E 3 , E 4 , L 1 , Y 1 , Y 2 , Y 3 , R a and z have meanings provided in the description, and pharmaceutically-acceptable salts thereof, which compounds are useful in the treatment of diseases in which inhibition of leukotriene C 4 synthase is desired and/or required, and particularly in the treatment of respiratory diseases and inflammation.

Therapeutic Agents - 550

A compound of formula I or a pharmaceutically acceptable salt thereof, processes for preparing such compounds, their use as Fatty Acid Synthase inhibitors, methods for their therapeutic use, particularly in the treatment of obesity and diabetes mellitus, cancer and infection and pharmaceutical compositions containing them.

1-[2-(aminomethyl)benzyl]-2-thioxo-1,2,3,5-tetrahydro-4H-pyrrolo[3,2-d]pyrimidin-4-ones as inhibitors of myeloperoxidase

There are disclosed certain 1-[2-(aminomethyl)benzyl]-2-thioxo-1,2,3,5-tetrahydro-4H-pyrrolo[3,2-d]pyrimidin-4-one compounds of formula (I),and pharmaceutically acceptable salts thereof, together with compositions containing them and their use in therapy. The compounds are inhibitors of the enzyme MPO and are thereby particularly useful in the treatment or prophylaxis of cardiovascular disorders such as heart failure and coronary artery disease related conditions.

1-[2-(aminomethyl)benzyl]-2-thioxo-1,2,3,5-tetrahydro-4H-pyrrolo[3,2-d]pyrimidin-4-ones as inhibitors of myeloperoxidase

There are disclosed certain 1-[2-(aminomethyl)benzyl]-2-thioxo-1,2,3,5-tetrahydro-4H-pyrrolo[3,2-d]pyrimidin-4-one compounds of formula (I), and pharmaceutically acceptable salts thereof, together with compositions containing them and their use in therapy. The compounds are inhibitors of the enzyme MPO and are thereby particularly useful in the treatment or prophylaxis of cardiovascular disorders such as heart failure and coronary artery disease related conditions.

COMPOUNDS AND USES

There is provided compounds of formula I, wherein E 1 , E 2 , E 3 , E 4 , L 1 , Y 1 , Y 2 , Y 3 , R a and z have meanings provided in the description, and pharmaceutically-acceptable salts thereof, which compounds are useful in the treatment of diseases in which inhibition of leukotriene C 4 synthase is desired and/or required, and particularly in the treatment of respiratory diseases and inflammation.

1-[2-(aminomethyl)benzyl]-2-thioxo-1,2,3,5-tetrahydro-4H-pyrrolo[3,2-d]pyrimidin-4-ones as inhibitors of myeloperoxidase

There are disclosed certain 1-[2-(aminomethyl)benzyl]-2-thioxo-1,2,3,5-tetrahydro-4H-pyrrolo[3,2-d]pyrimidin-4-one compounds of formula (I), and pharmaceutically acceptable salts thereof, together with compositions containing them and their use in therapy. The compounds are inhibitors of the enzyme MPO and are thereby particularly useful in the treatment or prophylaxis of cardiovascular disorders such as heart failure and coronary artery disease related conditions.

Carbamoyl Compounds as DGAT1 Inhibitors 190

DGAT-1 inhibitor compounds of formula (I), pharmaceutically-acceptable salts and pro-drugs thereof are described, together with pharmaceutical compositions, processes for making them and their use in treating, for example, obesity wherein, for example, Ring A is optionally substituted 2,6-pyrazindiyl; X is ═O; Ring B is optionally substituted 1,4-phenylene; Y1 is a direct bond or —O—; Y2 is —(CH2)r— wherein r is 2 or 3; n is 0 or n is 1 when Y1 is a direct bond between Ring B and Ring C and when Ring B is 1,4-phenylene and Ring C is (4-6C)cycloalkane; Ring C is optionally substituted (4-6C)cycloalkane, (7-10C)bicycloalkane, (8-12C)tricycloalkane, phenylene or pryidindiyl; L is a direct bond or —O—; p is 0, 1 or 2 and when p is 1 or 2 RA1 and RA2 are each independently hydrogen or (1-4C)alkyl; Z is carboxy or a mimic or bioisostere thereof.

Compounds and uses

There is provided compounds of formula I, wherein E 1 , E 2 , E 3 , E 4 , L 1 , Y 1 , Y 2 , Y 3 , R a and z have meanings provided in the description, and pharmaceutically-acceptable salts thereof, which compounds are useful in the treatment of diseases in which inhibition of leukotriene C 4 synthase is desired and/or required, and particularly in the treatment of respiratory diseases and inflammation.

Carbamoyl Compounds as DGAT1 Inhibitors 190

DGAT-1 inhibitor compounds of formula (1), pharmaceutically-acceptable salts and pro-drugs thereof are described, together with pharmaceutical compositions, processes for making them and their use in treating, for example, obesity wherein, for example, Ring A is optionally substituted 2,6-pyrazindiyl; X is ═0; Ring B is optionally substituted 1,4-phenylene; Y 1 is a direct bond or —O—; Y 2 is —(CH 2 ) r — wherein r is 2 or 3; n is 0 or n is 1 when Y 1 is a direct bond between Ring B and Ring C and when Ring B is 1,4-phenylene and Ring C is (4-6C)cycloalkane; Ring C is optionally substituted (4-6C)cycloalkane, (7-10C)bicycloalkane, (8-12C)tricycloalkane, phenylene or pryidindiyl; L is a direct bond or —O—; p is 0, 1 or 2 and when p is 1 or 2 R A1 and R A2 are each independently hydrogen or (1-4C)alkyl; Z is carboxy or a mimic or bioisostere thereof.

1-[2-(AMINOMETHYL)BENZYL]-2-THIOXO-1,2,3,5-TETRAHYDRO-4H-PYRROLO[3,2-d]PYRIMIDIN-4-ONES AS INHIBITORS OF MYELOPEROXIDASE

There are disclosed certain 1-[2-(aminomethyl)benzyl]-2-thioxo-1,2,3,5-tetrahydro-4H-pyrrolo[3,2-d]pyrimidin-4-one compounds of formula (I), 117-. (canceled)18. A method of identifying a patient suitable for MPO inhibitor treatment encompassing the measurement of plasma urate levels. The technical field relates to certain 1-[2-(aminomethyl)benzyl]-2-thioxo-1,2,3,5-tetrahydro-4H-pyrrolo[3,2-d]pyrimidin-4-one compounds of formula (I), to their use in the treatment of a myeloperoxidase related disease or condition, for example heart failure and coronary artery disease related conditions, and to pharmaceutical compositions containing them.Myeloperoxidase (MPO) is a heme-containing enzyme found in neutrophilic granulocytes (neutrophils) and monocytes. MPO is one member of a diverse protein family of mammalian peroxidases that also includes eosinophil peroxidase (EPO), thyroid peroxidase (TPO), salivary peroxidase (SPS), lactoperoxidase (LPO), prostaglandin H synthase (PGHS), and others. The mature enzyme is a dimer of identical halves. Each half molecule contains a covalently bound heme that exhibits unusual spectral properties responsible for the characteristic green color of MPO. Cleavage of the disulphide bridge linking the two halves of MPO yields the hemi-enzyme that exhibits spectral and catalytic properties indistinguishable from those of the intact enzyme. The enzyme is activated by hydrogen peroxide, the source of which can be superoxide dismuatase (SOD)-catalyzed NADPH-derived superoxide anion and xanthine oxidase-derived superoxide anion and hydrogen peroxide formed upon purine oxidation. The main physiological substrates of MPO are halides (e.g. chloride) and pseudohalides (like thiocyanate), forming microbicidal hypohalous acids like hypochlorous acid (bleach) and hypothiocyanous acid (2011, 48, 8-19).Neutrophils play an important microbicidal role by phagocytosing (engulfing) and killing microorganisms. The engulfed load is incorporated into vacuoles, ...

1-[2-(AMINOMETHYL)BENZYL]-2-THIOXO-1,2,3,5-TETRAHYDRO-4H-PYRROLO[3,2-d]PYRIMIDIN-4-ONES AS INHIBITORS OF MYELOPEROXIDASE

There are disclosed certain 1-[2-(aminomethyl)benzyl]-2-thioxo-1,2,3,5-tetrahydro-4H-pyrrolo[3,2-d]pyrimidin-4-one compounds of formula (I), 2. A compound according to wherein Ris Cl.3. A compound according to wherein Ris CH.4. A compound according to wherein Ris H.5. A compound according to wherein Ris H.6. A compound according to wherein the carbon atom to which Ris attached has the R-configuration when Ris CHor CH.7. A compound according to selected from 1-{2-[(1R)-4-aminopropyl]-4-chlorobenzyl}-2-thioxo-1 claim 1 ,2 claim 1 ,3 claim 1 ,5-tetrahydro-4H-pyrrolo[3 claim 1 ,2-d]pyrimidin-4-one;1-[2-(1-aminoethyl)-4-chlorobenzyl]-2-thioxo-1,2,3,5-tetrahydro-4H-pyrrolo[3,2-d]pyrimidin-4-one;1-{2-[(1R)-4-aminoethyl]-4-chlorobenzyl}-2-thioxo-1,2,3,5-tetrahydro-4H-pyrrolo[3,2-d]pyrimidin-4-one;1-{2-[(1S)-1-aminoethyl]-4-chlorobenzyl}-2-thioxo-1,2,3,5-tetrahydro-4H-pyrrolo[3,2-d]pyrimidin-4-one;1-{4-chloro-2-[1-(methylamino)ethyl]benzyl}-2-thioxo-1,2,3,5-tetrahydro-4H-pyrrolo[3,2-d]pyrimidin-4-one;1-{4-chloro-2-[(ethylamino)methyl]benzyl}-2-thioxo-1,2,3,5-tetrahydro-4H-pyrrolo[3,2-d]pyrimidin-4-one;1-[2-(aminomethyl)-4-chlorobenzyl]-2-thioxo-1,2,3,5-tetrahydro-4H-pyrrolo[3,2-d]pyrimidin-4-one;1-{4-chloro-2-[(methylamino)methyl]benzyl}-2-thioxo-1,2,3,5-tetrahydro-4H-pyrrolo[3,2-d]pyrimidin-4-one;1-(2-{[(cyclobutylmethyl)amino]methyl}benzyl)-2-thioxo-1,2,3,5-tetrahydro-4H-pyrrolo[3,2-d]pyrimidin-4-one;1-{2-[(cyclobutylamino)methyl]benzyl}-2-thioxo-1,2,3,5-tetrahydro-4H-pyrrolo[3,2-d]pyrimidin-4-one;1-{2-[(cyclopentylamino)methyl]benzyl}-2-thioxo-1,2,3,5-tetrahydro-4H-pyrrolo[3,2-d]pyrimidin-4-one;1-(2-{[(2-methylpropyl)amino]methyl}benzyl)-2-thioxo-1,2,3,5-tetrahydro-4H-pyrrolo[3,2-d]pyrimidin-4-one;1-{2-[(propan-2-ylamino)methyl]benzyl}-2-thioxo-1,2,3,5-tetrahydro-4H-pyrrolo[3,2-d]pyrimidin-4-one;1-[2-(aminomethyl)-4-(trifluoromethyl)benzyl]-2-thioxo-1,2,3,5-tetrahydro-4H-pyrrolo[3,2-d]pyrimidin-4-one;1-{2-[(methylamino)methyl]-4-(trifluoromethyl)benzyl}-2-thioxo-1,2,3,5- ...

1-[2-(AMINOMETHYL)BENZYL]-2-THIOXO-1,2,3,5-TETRAHYDRO-4H-PYRROLO[3,2-d]PYRIMIDIN-4-ONES AS INHIBITORS OF MYELOPEROXIDASE

There are disclosed certain 1-[2-(aminomethyl)benzyl]-2-thioxo-1,2,3,5-tetrahydro-4H-pyrrolo[3,2-d]pyrimidin-4-one compounds of formula (I), and pharmaceutically acceptable salts thereof, together with compositions containing them and their use in therapy. The compounds are inhibitors of the enzyme MPO and are thereby particularly useful in the treatment or prophylaxis of cardiovascular disorders such as heart failure and coronary artery disease related conditions.

1-[2-(AMINOMETHYL)BENZYL]-2-THIOXO-1,2,3,5-TETRAHYDRO-4H-PYRROLO[3,2-d]PYRIMIDIN-4-ONES AS INHIBITORS OF MYELOPEROXIDASE

There are disclosed certain 1-[2-(aminomethyl)benzyl]-2-thioxo-1,2,3,5-tetrahydro-4H-pyrrolo[3,2-d]pyrimidin-4-one compounds of formula (I), 2. A compound according to wherein Ris Cl.3. A compound according to wherein Ris CH.4. A compound according to wherein Ris H.5. A compound according to wherein Ris H.6. A compound according to wherein the carbon atom to which Ris attached has the R-configuration when Ris CHor CH.7. A compound according to selected from1-{2-[(1R)-1-aminopropyl]-4-chlorobenzyl}-2-thioxo-1,2,3,5-tetrahydro-4H-pyrrolo[3,2-d]pyrimidin-4-one;1-[2-(1-aminoethyl)-4-chlorobenzyl]-2-thioxo-1,2,3,5-tetrahydro-4H-pyrrolo[3,2-d]pyrimidin-4-one;1-{2-[(1R)-1-aminoethyl]-4-chlorobenzyl}-2-thioxo-1,2,3,5-tetrahydro-4H-pyrrolo[3,2-d]pyrimidin-4-one;1-{2-[(1S)-1-aminoethyl]-4-chlorobenzyl}-2-thioxo-1,2,3,5-tetrahydro-4H-pyrrolo[3,2-d]pyrimidin-4-one;1-{4-chloro-2-[1-(methylamino)ethyl]benzyl}-2-thioxo-1,2,3,5-tetrahydro-4H-pyrrolo[3,2-d]pyrimidin-4-one;1-{4-chloro-2-[(ethylamino)methyl]benzyl}-2-thioxo-1,2,3,5-tetrahydro-4H-pyrrolo[3,2-d]pyrimidin-4-one;1-[2-(aminomethyl)-4-chlorobenzyl]-2-thioxo-1,2,3,5-tetrahydro-4H-pyrrolo[3,2-d]pyrimidin-4-one;1-{4-chloro-2-[(methylamino)methyl]benzyl}-2-thioxo-1,2,3,5-tetrahydro-4H-pyrrolo[3,2-d]pyrimidin-4-one;1-(2-{[(cyclobutylmethyl)amino]methyl}benzyl)-2-thioxo-1,2,3,5-tetrahydro-4H-pyrrolo[3,2-d]pyrimidin-4-one;1-{2-[(cyclobutylamino)methyl]benzyl}-2-thioxo-1,2,3,5-tetrahydro-4H-pyrrolo[3,2-d]pyrimidin-4-one;1-{2-[(cyclopentylamino)methyl]benzyl}-2-thioxo-1,2,3,5-tetrahydro-4H-pyrrolo[3,2-d]pyrimidin-4-one;1-(2-{[(2-methylpropyl)amino]methyl}benzyl)-2-thioxo-1,2,3,5-tetrahydro-4H-pyrrolo[3,2-d]pyrimidin-4-one;1-{2-[(propan-2-yl)amino)methyl]benzyl}-2-thioxo-1,2,3,5-tetrahydro-4H-pyrrolo[3,2-d]pyrimidin-4-one;1-[2-(aminomethyl)-4-(trifluoromethyl)benzyl]-2-thioxo-1,2,3,5-tetrahydro-4H-pyrrolo[3,2-d]pyrimidin-4-one;1-{2-[(methylamino)methyl]-4-(trifluoromethyl)benzyl}-2-thioxo-1,2,3,5-tetrahydro-4H-pyrrolo[3,2-d]pyrimidin ...

CARBAMOIL COMPOUNDS AS DGAT1 190 INHIBITORS

Se describen compuestos inhibidores de DGAT-1 de la fórmula (I), sales aceptables para uso farmacéutico y prodrogas de los mismos, junto con composiciones farmacéuticas, procesos para elaborarlos y su uso en el tratamiento de, por ejemplo, la obesidad en donde, por ejemplo, el Anillo A es 2,6-pirazindiilo opcionalmente sustituido; X es =O; el Anillo B es 1,4-fenileno opcionalmente sustituido; Y1 es un enlace directo o -O-; Y2 es -(CH2)r- en donde r es 2 ó 3; n es 0 o n es 1 cuando Y1 es un enlace directo entre el Anillo B y el Anillo C y cuando el Anillo B es 1,4-fenileno y el Anillo C es (4-6C)cicloalcano; el Anillo C es (4-6C)cicloalcano, (7-10C)bicicloalcano, (8-12C)tricicloalcano, fenileno o piridindiilo opcionalmente sustituido; L es un enlace directo o -O-; p es 0, 1 ó 2 y cuando p es 1 RA1 y RA2 son, cada uno de manera independiente, hidrógeno o (1-4C)alquilo; Z es carboxi o un mimético o un bioisóstero del mismo.

1-[2-(aminomethyl)benzyl]-2-thioxo-1,2,3,5-tetrahydro-4H-pyrrolo[3,2-d]pyrimidin-4-ones as inhibitors of myeloperoxidase

There are disclosed certain 1-[2-(aminomethyl)benzyl]-2-thioxo-1,2,3,5-tetrahydro-4H- pyrrolo[3,2-d]pyrimidin-4-one compounds of formula (I), and pharmaceutically acceptable salts thereof, together with compositions containing them and their use in therapy. The compounds are inhibitors of the enzyme MPO and are thereby particularly useful in the treatment or prophylaxis of cardiovascular disorders such as heart failure and coronary artery disease related conditions.

Carbamoyl compounds as dgat1 inhibitors 190

DGAT-1 inhibitor compounds of formula (I), pharmaceutically-acceptable salts and pro- drugs thereof are described, together with pharmaceutical compositions, processes for making them and their use in treating, for example, obesity wherein, for example, Ring A is optionally substituted 2,6-pyrazindiyl; X is =O; Ring B is optionally substituted 1,4-phenylene; Y1 is a direct bond or -O-; Y2 is -(CH 2) r- wherein r is 2 or 3; n is 0 or n is 1 when Y1 is a direct bond between Ring B and Ring C and when Ring B is 1,4-phenylene and Ring C is (4-6C)cycloalkane; Ring C is optionally substituted (4-6C)cycloalkane, (7-10C)bicycloalkane, (8-12C)tricycloalkane, phenylene or pryidindiyl; L is a direct bond or -O-; p is 0, 1 or 2 and when p is 1 or 2 RA1 and RA2 are each independently hydrogen or (1-4C)alkyl; Z is carboxy or a mimic or bioisostere thereof.

New acetyl coenzyme a carboxylase (ACC) inhibitors and uses in treatments of obesity and diabetes mellitus

Carbamoyl compounds as 190 DGAT1 inhibitors

Un compuesto de la fórmula (I), o una sal farmacéuticamente aceptable, o un profármaco del mismo,**Fórmula** en donde el Anillo A es 2,6-pirazindiilo sustituido opcionalmente sobre un átomo de carbono disponible por uno o dos sustituyentes seleccionados independientemente de (1-3C)alquilo, (2-3C)alquenilo, (2-3C)alquinilo, (1-2C)alcoxi, metoximetilo, amino y ciano lineales; X es >=O o >=S; el Anillo B es 1,4-fenileno sustituido opcionalmente sobre un átomo de carbono disponible por uno o dos sustituyentes seleccionados independientemente de halo, amino, ciano, (1-4C)alquilo, (2-3C)alquenilo, (2- 3C)alquinilo, (1-4C)alcoxi y (1-4C)alcoxi-(1-4C)alquilo; Y1 es un enlace directo entre el Anillo B y el Anillo C o Y1 es -O-, -S- o -NRa- en donde Ra es hidrógeno o (1- 4C)alquilo; Y2 es -(CH2)r- en donde r es 2 o 3, e Y2 está enlazado al mismo átomo de carbono que Y1 en el Anillo C e Y2 está enlazado a un átomo de carbono adyacente a Y1 en el Anillo B; n es 0 o n es 1 cuando Y1 es un enlace directo entre el Anillo B y el Anillo C y cuando el Anillo B es 1,4-fenileno y el Anillo C es (4-6C)cicloalcano, de manera que se forma un sistema de anillo espiro de 5 o 6 miembros y el Anillo C es trienlazado; El Anillo C es un anillo o sistema de anillo dienlazado (excluyendo enlaces a través de los mismos átomos o adyacentes) escogido de entre (4-6C)cicloalcano, (7-10C)bicicloalcano y (8-12C)tricicloalcano cada uno sustituido opcionalmente sobre un átomo de carbono disponible, incluyendo el átomo de carbono de anillo que porta el grupo que contiene Z, por un sustituyente seleccionado de entre hidroxi, (1-4C)alquilo, (1-4C)alcoxi y (1-4C)alcoxi(1- 4C)alquilo; o el Anillo C es un anillo o sistema de anillo dienlazado (excluyendo enlaces a través de los mismos enlaces o adyacentes) seleccionado de entre fenileno, piridindiilo, piperidinadiilo Enlazado en N a Y1, piperazinediilo, furandiilo, tiofendiilo, pirroldiilo, oxazoldiilo, tiazoldiilo, imidazoldiilo, isoxazoldiilo, ...

1- [2- (AMINOMETHYL) BENZYL] -2-THIOXO-1,2,3,5-TETRAHYDRO-4H-PYRROLO [3,2-D] PYRIMIDIN-4-ONER AS INHIBITORS OF MYELOPEROXIDASE

1-[2-(aminomethyl)benzyl]-2-thioxo-1,2,3,5-tetrahydro-4H-pyrrolo[3,2-d]pyrimidin-4-ones as inhibitors of myeloperoxidase

在此揭露具有式(I)之某些1-[2-(胺基甲基)苄基]-2-硫基-1,2,3,5-四氫-4H-吡咯並[3,2-d]嘧啶-4-酮化合物， □ 及其藥學上可接受之鹽，連同含有該等化合物之組成物以及該等化合物和組成物在治療中之用途。該等化合物係酶MPO的抑制劑並且因此特別適用於治療或預防心血管疾患，如心臟衰竭和冠狀動脈疾病相關病症。

CYCLOHEXYL DERIVATIVES AS ACETYL COENZYME CARBOXYLASE INHIBITORS

REFERIDA A UN COMPUESTO DERIVADO DE CICLOHEXILO DE FORMULA (I), DONDE R1 ES -OR6 O -NR7aR7b; R6 ES ALQUILO C1-C6, CICLOALQUILO C3-C8, CICLOALQUENILO C3-C8, ENTRE OTROS; R7a Y R7b SON H, HETEROCICLILO O ALQUILO C1-C6 OPCIONALMENTE SUSTITUIDO CON OH, HALO, ALCOXI C1-C4, ENTRE OTROS; R2 Y R3 SON H, ALQUILO C1-C6, ALCOXI C1-C6, ENTRE OTROS; R4 ES H, ALQUILO C1-C6, ENTRE OTROS; R5 ES H O ALQUILO C1-C6 OPCIONALMENTE SUSTITUIDO CON HALO, OH, ALCOXI C1-C6, ENTRE OTROS; E ES ALQUILENO C1; L ES C(O) O SO2; Z ES ARILO, HETEROARILO, HETEROCICLILO, ENTRE OTROS; n ES 0 O 1. SON COMPUESTOS PREFERIDOS: [(TRANS-4-{[({2-[6-(4-METILPIPERAZIN-1-IL)PIRIDIN-3-IL]QUINOLIN-4-IL}CARBONIL)AMINO]METIL}CICLOHEXIL)METIL]CARBAMATO DE TERC-BUTILO, ({TRANS-4-[({[2-(2-METIL-6-OXO-1,6-DIHIDROPIRIDIN-3-IL)QUINOLIN-4-IL]CARBONIL}AMINO)METIL]CICLOHEXIL}METIL)CARBAMATO DE TERC-BUTILO, {[TRANS-4-({[2-PIRAZIN-2-ILQUINOLIN-4-IL)CARBONIL]AMINO}METIL)CICLOHEXIL]METIL}CARBAMATO DE TERC-BUTILO, ENTRE OTROS. TAMBIEN ESTA REFERIDA A UNA COMPOSICION FARMACEUTICA. DICHOS COMPUESTOS SON INHIBIDORES DE LA ACETIL COENZIMA A CARBOXILASA (ACC) Y SON UTILES EN EL TRATAMIENTO DE LA OBESIDAD Y DIABETES MELLITUS

Cyclopropane carboxylic acid derivatives and pharmaceutical uses thereof

There is provided compounds of formula (I), wherein E1, E2, E3, E4, L1, Y1, Y2, Y3, Ra and z have meanings provided in the description, and pharmaceutically-acceptable salts thereof, which compounds are useful in the treatment of diseases in which inhibition of leukotriene C4 synthase is desired and/or required, and particularly in the treatment of respiratory diseases and inflammation.

Cyclopropane carboxylic acid derivatives and pharmaceutical uses thereof.

Se proporcionan compuestos de fórmula I, (ver Fórmula) donde los grupos E1, E2, E3, E4, L1, Y1, Y2, Y3, Ra y z tienen los significados proporcionados en la descripción y sales farmacéuticamente de estos, donde los compuestos son útiles en el tratamiento de enfermedades en las que se desea y/o requiere la inhibición de la leucotrieno C4-sintasa, y particularmente en el tratamiento de enfermedades respiratorias e inflamación.

Derivados de ácido ciclopropano carboxílico y sus usos como inhibidores de leucotrieno c₄ sintasa

Los compuestos son útiles para el tratamiento de enfermedades en las que se desea y/o requiere la inhibición de leucotrieno C₄ sintasa, y particularmente, para el tratamiento de enfermedades respiratorias e inflamación. Reivindicación 1: Un compuesto de la fórmula (1), donde: cada uno de E¹, E², E³ y E⁴ representa individualmente cualquiera de -C(R¹)=, -C(R²)=, -C(R³)= y C(R⁴)=; y/o uno o dos de los E¹, E², E³ y E⁴ pueden representar independientemente -N=; cada uno de R¹ a R⁴ representa independientemente hidrógeno o un sustituyente seleccionado de X¹; y/o cualquiera de R¹ a R⁴ puede representar independientemente -OY⁴; si está presente, cada Rᵃ representa independientemente fluoro o alquilo C₁₋₆ (donde el último grupo se sustituye de forma opcional por uno o más fluoro); z representa 0 a 4; L¹ representa un enlace directo o un grupo enlazador alquilo C₁₋₃, donde el último grupo se sustituye de forma opcional por uno o más sustituyentes seleccionados de Z¹ y G¹; Y¹ representa -C(O)OR¹ᵃ, -C(O)N(H)S(O)₂R¹ᵇ o un grupo tetrazolilo de la fórmula (2); R¹ᵃ representa: (i) hidrógeno o (ii) alquilo C₁₋₃, que se sustituye de forma opcional por uno o más fluoro; R¹ᵇ representa: A) un grupo arilo que se sustituye de forma opcional por uno o más sustituyentes seleccionados de B¹; B) un grupo heteroarilo, que se sustituye de forma opcional por uno o más sustituyentes seleccionados de B²; o C) alquilo C₁₋₈ o un grupo heterocicloalquilo, donde ambos se sustituyen de forma opcional por uno o más sustituyentes seleccionados de G² y/o Z²; R¹ᶜ representa H o alquilo, C₁₋₆, (donde el ultimo grupo se sustituye de forma opcional por uno o más sustituyentes seleccionados de G³ y/o Z³); Y², Y³ e Y⁴ cada uno representa independientemente: a) un grupo arilo, que se sustituye de forma opcional por uno o más sustituyentes seleccionados de A¹; b) un grupo heteroarilo, que se sustituye de forma opcional por uno o más sustituyentes seleccionados de A²; c) un alquilo C₁₋₁₂ (p. ej.: un cicloalquilo ...

Cyclopropane carboxylic acid derivatives and pharmaceutical uses thereof

There is provided compounds of formula (I), wherein E 1 , E 2 , E 3 , E 4 , L 1 , Y 1 , Y 2 , Y 3 , R a and z have meanings provided in the description, and pharmaceutically-acceptable salts thereof, which compounds are useful in the treatment of diseases in which inhibition of leukotriene C 4 synthase is desired and/or required, and particularly in the treatment of respiratory diseases and inflammation.

derivados do ácido ciclopropanocarboxílico e seus usos farmacêuticos

são proporcionados compostos da fórmula (i), em que e1, e2, e3, e4, l1, y1, y2, y3, ra e z têm significados proporcionados na descrição e seus sais farmaceuticamente aceitáveis, compostos esses que são úteis no tratamento de doenças nas quais a inibição de leucotrieno c4 sintase é desejada e/ou requerida, e particularmente no tratamento de doenças respiratórias e inflamação.

1-[2-(aminometil)bencil]-2-tioxo-1,2,3,5-tetrahidro-4h-pirrolo[3,2-d]pirimidin-4-onas como inhibidores de la mieloperoxidasa

Reivindicación 1: Un compuesto de fórmula (1) donde R¹ es H, F, Cl o CF₃; R² es H, CH₃ o C₂H₅; y R³ es H, CH₃, C₂H₅, n-propilo, isopropilo, n-butilo, isobutilo, sec-butilo, terc-butilo, ciclopropilo, ciclopropilmetilo, ciclobutilo, ciclobutilmetilo o ciclopentilo; o una sal farmacéuticamente aceptable de este.

1-[2-(aminometil)bencil]-2-tioxo-1,2,3,5-tetrahidro-4h-pirrolo[3,2-d] pirimidin-4-onas como inhibidores de mieloperoxidasa

Se dan a conocer determinados compuestos de 1-[2-(aminometil)bencil]-2-tioxo-1,2,3,5-tetrahidro-4H-pirrolo[3,2-d]pirimidin-4-ona de fórmula (I),y sales farmacéuticamente aceptable de los mismos, junto con composiciones que los contienen y su uso en terapia. Los compuestos son inhibidores de la enzima MPO y de este modo son particularmente útiles en el tratamiento o profilaxis de trastornos cardiovasculares tales como insuficiencia cardíaca y estados relacionados con arteriopatía coronaria. NHNNHOSR2NHR3R1(I)

1-[2-(aminomethyl)benzyl]-2-thioxo-1,2,3,5-tetrahydro-4h-pyrrolo[3,2-d]pyrimidin-4-ones as inhibitors of myeloperoxidase

There are disclosed certain 1-[2-(aminomethyl)benzyl]-2-thioxo-1,2,3,5-tetrahydro-4H- pyrrolo[3,2- d]pyrimidin-4-one compounds of formula (I), and pharmaceutically acceptable salts thereof, together with compositions containing them and their use in therapy. The compounds are inhibitors of the enzyme MPO and are thereby particularly useful in the treatment or prophylaxis of cardiovascular disorders such as heart failure and coronary artery disease related conditions.

Cyclopropane carboxylic acid derivatives and pharmaceutical uses thereof

There is provided compounds of formula (I), wherein E1, E2, E3, E4, L1, Y1, Y2, Y3, Ra and z have meanings provided in the description, and pharmaceutically-acceptable salts thereof, which compounds are useful in the treatment of diseases in which inhibition of leukotriene C4 synthase is desired and/or required, and particularly in the treatment of respiratory diseases and inflammation.