Abstract: A treatment for ocular rosacea using p38 and Erk kinase pathway inhibitors, which are believed to block the initial reaction to rosacea triggers and thus make it possible to prevent or minimize the skin reaction. The treatment is premised on a careful analysis of the alteration of cell-signaling pathways that facilitate the development of rosacea, which led to the identification of discrete targets for highly specific therapeutic intervention in the management of rosacea.

Abstract: The application is directed to efficient and economical processes as described in more detail below for the preparation of the beta 3 agonists of the formula of I-7 and intermediate compounds that can be used for making these agonists. The present disclosure relates to a process for making beta-3 agonists and intermediates using ketoreductase (KRED) biocatalyst enzymes and methods of using the biocatalysts.

Abstract: The present invention provides a compound which has an effect of inhibiting amyloid ? production, especially an effect of inhibiting BACE1, and which is useful as a therapeutic or prophylactic agent for diseases induced by production, secretion and/or deposition of amyloid ? proteins. A compound of the formula (I): wherein X is —C(R3a)(R3b)—, —C(R3a)(R3b)—C(R3c)(R3d)— or —C(R3a)?C(R3c)—, R1 is substituted or unsubstituted alkyl or the like, R2a, R2b, R3a, R3b, R3c and R3d are each independently hydrogen, halogen or the like, R4 is hydrogen or halogen, Ring B is substituted or unsubstituted carbocycle or a substituted or unsubstituted heterocycle, or a pharmaceutically acceptable salt thereof.

Abstract: The present invention provides a compound which has an effect of inhibiting amyloid ? production, especially an effect of inhibiting BACE1, and which is useful as a therapeutic or prophylactic agent for diseases induced by production, secretion and/or deposition of amyloid ? proteins. A compound of the formula (I): wherein X is —C(R3a)(R3b)—, —C(R3a)(R3b)—C(R3c)(R3d)— or —C(R3a)?C(R3c)—, R1 is substituted or unsubstituted alkyl or the like, R2a, R2b, R3a, R3b, R3c and R3d are each independently hydrogen, halogen or the like, R4 is hydrogen or halogen, Ring B is substituted or unsubstituted carbocycle or a substituted or unsubstituted heterocycle, or a pharmaceutically acceptable salt thereof.

Abstract: The present invention provides, for example, a compound mentioned below as a medicament for treating or preventing the diseases induced by production, secretion or deposition of amyloid-? proteins. A compound of the formula (I): wherein R1, R2a, R2b, R3, R4a, R4b, ring A and the dashed lines are defined in the specification, its pharmaceutically acceptable salt or a solvate thereof.

Abstract: The present invention relates to pyrrolopyridinone derivatives which have blocking activities of voltage gated sodium channels as the TTX-S channels, and which are useful in the treatment or prevention of disorders and diseases in which voltage gated sodium channels are involved. The invention also relates to pharmaceutical compositions comprising these compounds and the use of these compounds and compositions in the prevention or treatment of such diseases in which voltage gated sodium channels are involved.

Abstract: The present invention provides compounds of formula (I) having BACE1 and/or BACE2 inhibitory activity, their manufacture, pharmaceutical compositions containing them and their use as therapeutically active substances. The active compounds of the present invention are useful in the therapeutic and/or prophylactic treatment of e.g. Alzheimer's disease and type 2 diabetes.

Abstract: The present invention relates to compounds defined by formula I: wherein the variables A1, A2, Cy1 Cy2, Cy3, E, R1a, R1b, R2, R3, n, and Q are as defined herein, possessing valuable pharmacological activity. Particularly, the compounds are inhibitors of 11 ?-hydroxysteroid dehydrogenase (HSD) 1 and thus are suitable for treatment and prevention of diseases which can be influenced by inhibition of this enzyme, such as metabolic diseases, in particular diabetes type 2, obesity, and dyslipidemia.

Abstract: The present invention relates to ethynyl derivatives of formula I wherein U, V, Y, R1, R2, R2?, R3, R3? and R8 are described herein. It has been found that the compounds of general formula I are allosteric modulators of the metabotropic glutamate receptor subtype 5 (mGluR5).

Abstract: Provided are methods of treating a cancer characterized by the presence of a mutant allele of IDH1/2 comprising administering to a subject in need thereof a compound described here.

Abstract: The present invention provides a compound of formula (I) having BACE1 inhibitory activity, their manufacture, pharmaceutical compositions containing them and their use as therapeutically active substances. The active compounds of the present invention are useful in the therapeutic and/or prophylactic treatment of e.g. Alzheimer's disease.

Abstract: Disclosed are compounds represented by Formula (I): or pharmaceutically acceptable salts, enantiomers or diastereomers thereof. Also disclosed are pharmaceutical compositions comprising the compounds of Formula (I) or pharmaceutically acceptable salts, enantiomers or diastereomers thereof for the therapeutic treatment of diseases associated with the modulation or inhibition of 11?-HSD1 in mammals. Values for the variables of Formula (I) are defined herein.

Abstract: Disclosed are compounds represented by Formula (I): or pharmaceutically acceptable salts, enantiomers or diastereomers thereof. Also disclosed are pharmaceutical compositions comprising the compounds of Formula (I) or pharmaceutically acceptable salts, enantiomers or diastereomers thereof for the therapeutic treatment of diseases associated with the modulation or inhibition of 11?-HSD1 in mammals. Values for the variables of Formula (I) are defined herein.

Abstract: The present invention is related to a compound of formula (I), wherein A is a nonaromatic heterocyclic ring, Ar is either absent or phenylene; ? is a radical of formula (II), R2 is a hydrophobic moiety; and G is a radical containing one or more moieties selected from the group consisting of NH, OH and a basic moiety. The compounds are inhibitors of integrins, especially antagonists of the fibronectin receptor alpha5beta1, useful as anti-angiogenic agents.

Abstract: Disclosed is a process for making diastereomeric compound of the formula (I): wherein m, n and R1 to R4 are as defined herein. The process of the invention provides the compound of formula (I) in high yield and substantially free of the corresponding diastereomers. The compounds of formula (I) prepared by the process of the invention are useful for making pharmaceutically active compounds such as 11-?-hydroxysteroid hydrogenase type 1 (11-?-HSD1) inhibitors.

Abstract: This invention relates to compounds that inhibit protein tyrosine kinase activity. In particular the invention relates to compounds that inhibit the protein tyrosine kinase activity of growth factor receptors, resulting in the inhibition of receptor signaling, for example, the inhibition of VEGF receptor signaling. The invention also provides compounds, compositions and methods for treating cell proliferative diseases and conditions and ophthalmic diseases, disorders and conditions.

Abstract: Disclosed are compounds represented by Formula (I): or pharmaceutically acceptable salts, enantiomers or diastereomers thereof. Also disclosed are pharmaceutical compositions comprising the compounds of Formula (I) or pharmaceutically acceptable salts, enantiomers or diastereomers thereof for the therapeutic treatment of diseases associated with the modulation or inhibition of 11?-HSD1 in mammals. Values for the variables of Formula (I) are defined herein.

Abstract: The present invention provides a compound of formula (I): wherein —X? is —CR7? or —N?, ring B is a substituted or unsubstituted carbocycle or a substituted or unsubstituted heterocycle, R1 is substituted or unsubstituted alkyl or the like, R2 a and R2 b are each independently hydrogen, substituted or unsubstituted alkyl or the like, R3 and R4 are each independently hydrogen, halogen, substituted or unsubstituted alkyl or the like, R5 is hydrogen, substituted or unsubstituted alkyl or the like, each R6 is independently halogen, hydroxy, substituted or unsubstituted alkyl or the like, R7 is hydrogen, halogen, hydroxy, substituted or unsubstituted alkyl or the like, p is an integer of 0 to 3, or a pharmaceutically acceptable salt thereof which has an effect of inhibiting amyloid ? production, especially an effect of inhibiting BACE1, and which is useful as a therapeutic or prophylactic agent for diseases induced by production, secretion and/or deposition of amyloid ? proteins.

Abstract: Compounds having the structure of Formula I, including pharmaceutically acceptable salts of the compounds, are CETP inhibitors and are useful for raising HDL-cholesterol, reducing LDL-cholesterol, and for treating or preventing atherosclerosis.

Abstract: Compounds of Formula (I), including pharmaceutically acceptable salts of the compounds, are CETP inhibitors, and are useful for raising HDL-cholesterol, reducing LDL-cholesterol, and for treating or preventing atherosclerosis. In the compounds of Formula (I), A1 is a cyclic group, and B is a cyclic group which is attached to the heterocyclic ring directly or through a methylene group.

Abstract: This invention relates to novel compounds of the Formula (I), (Ia1-10), (Ib1-10), (Ic1-10), (Id1-7), (Ie1-5) pharmaceutically acceptable salts thereof, and pharmaceutical compositions thereof, which are useful for the therapeutic treatment of diseases associated with the modulation or inhibition of 11?-HSD1 in mammals. The invention further relates to pharmaceutical compositions of the novel compounds and methods for their use in the reduction or control of the production of cortisol in a cell or the inhibition of the conversion of cortisone to cortisol in a cell.

Abstract: The present invention is directed to carbazole compounds, pharmaceutically acceptable compositions comprising compounds of the invention and methods of using said compositions in the treatment of various disorders.

Abstract: The present invention provides a new class of compounds useful for the modulation of beta-secretase enzyme (BACE) activity. The compounds have a general Formula I: wherein variables A4, A5, A6, A8, each of R1 and R2, R3 and R7 of Formula I, independently, are defined herein. The invention also provides pharmaceutical compositions comprising the compounds, and corresponding uses of the compounds and compositions for treatment of disorders and/or conditions related to A-beta plaque formation and deposition, resulting from the biological activity of BACE. Such BACE mediated disorders include, for example, Alzheimer's Disease, cognitive deficits, cognitive impairments, schizophrenia and other central nervous system conditions. The invention further provides compounds of Formulas II and III, and sub-formula embodiments thereof, intermediates and processes and methods useful for the preparation of compounds of Formulas I-III.

Abstract: The present invention provides 4-(3-Amino-phenyl)-5,6-dihydro-4H-[1,3]oxazin-2-ylamines of formula I having BACE1 and/or BACE2 inhibitory activity, their manufacture, pharmaceutical compositions containing them and their use as therapeutically active substances. The active compounds of the present invention are useful in the therapeutic and/or prophylactic treatment of e.g. Alzheimer's disease and type 2 diabetes.

Abstract: A composition having BACE 1 inhibitory activity containing a compound represented by the general formula (I): wherein ring A is an optionally substituted carbocyclic group or an optionally substituted heterocyclic group; E is lower alkylene; X is S, O, or NR1; R1 is a hydrogen atom or lower alkyl; R2a, R2b, R3a, R3b, R4a and R4b is each independently a hydrogen atom, halogen, or hydroxy etc.; n and m are each independently an integer of 0 to 3; n+m is an integer of 0 to 3; R5 is a hydrogen atom or substituted lower alkyl; its pharmaceutically acceptable salt, or a solvate thereof.

Abstract: The present invention provides compounds useful as inhibitors of Btk, compositions thereof, and methods of using the same.

Abstract: The present invention provides compounds of formula I having BACE1 and/or BACE2 inhibitory activity, their manufacture, pharmaceutical compositions containing them and their use as therapeutically active substances. The active compounds of the present invention are useful in the therapeutic and/or prophylactic treatment of e.g. Alzheimer's disease and type 2 diabetes.

Abstract: Disclosed is a compound represented by Formula (Im1): or a pharmaceutically acceptable salt, monohydrate, enantiomer or diastereomer thereof. Also disclosed are pharmaceutical compositions comprising the compound of Formula (Im1) or a pharmaceutically acceptable salt, monohydrate, enantiomer or diastereomer thereof and methods of inhibiting 11?-HSD1 activity comprising the step of administering to a mammal in need of such treatment an effective amount of a compound of Formula (Im1), or a pharmaceutically acceptable salt, monohydrate, enantiomer or diastereomer thereof. Values for the variables in Formula (Im1) are defined herein.

Abstract: The present invention provides 4-(3-Amino-phenyl)-5,6-dihydro-4H-[1,3]oxazin-2-ylamines of formula I having BACE1 and/or BACE2 inhibitory activity, their manufacture, pharmaceutical compositions containing them and their use as therapeutically active substances. The active compounds of the present invention are useful in the therapeutic and/or prophylactic treatment of e.g. Alzheimer's disease and type 2 diabetes.

Abstract: Disclosed is a process for making diastereomeric compound of the formula (I): wherein m, n and R1 to R4 are as defined herein. The process of the invention provides the compound of formula (I) in high yield and substantially free of the corresponding diastereomers. The compounds of formula (I) prepared by the process of the invention are useful for making pharmaceutically active compounds such as 11-?-hydroxysteroid hydrogenase type 1 (11-?-HSD1) inhibitors.

Abstract: The present invention provides compounds of formula I having BACE1 and/or BACE2 inhibitory activity, their manufacture, pharmaceutical compositions containing them and their use as therapeutically active substances. The active compounds of the present invention are useful in the therapeutic and/or prophylactic treatment of e.g. Alzheimer's disease and type 2 diabetes. The invention further provides a radio-labelled derivative thereof.

Abstract: This invention relates to novel compounds of the Formula (I), dependent compounds of Formula (II), (II-A), (II-B), (II-C), (II-D), (II-E), (II-F), (II-G), (II-H), (III), (III-A), (III-B), (III-C), (IV), (IV-A), (IV-B), pharmaceutically acceptable salts thereof, and pharmaceutical compositions thereof, which are useful for the therapeutic treatment of diseases associated with the modulation or inhibition of 11?-HSD1 in mammals. The invention further relates to pharmaceutical compositions of the novel compounds and methods for their use in the reduction or control of the production of cortisol in a cell or the inhibition of the conversion of cortisone to cortisol in a cell.

Abstract: This invention relates to novel compounds of the Formula Ik, Im1, Im2, Im5, In1, In2, In5, lo1, lo2, lo5, Ip1, Ip3, pharmaceutically acceptable salts thereof, and pharmaceutical compositions thereof, which are useful for the therapeutic treatment of diseases associated with the modulation or inhibition of 11 ?-HSD1 in mammals. The invention further relates to pharmaceutical compositions of the novel compounds and methods for their use in the reduction or control of the production of Cortisol in a cell or the inhibition of the conversion of cortisone to Cortisol in a cell.

Abstract: The present invention provides compounds of formula (I) having BACE1 and/or BACE2 inhibitory activity, their manufacture, pharmaceutical compositions containing them and their use as therapeutically active substances. The active compounds of the present invention are useful in the therapeutic and/or prophylactic treatment of e.g. Alzheimer's disease and type 2 diabetes.

Abstract: This invention relates to novel compounds of the Formula Ik, Im1, Im2, Im5, In1, In2, In5, Io1, Io2, Io5, Ip1, Ip3, pharmaceutically acceptable salts thereof, and pharmaceutical compositions thereof, which are useful for the therapeutic treatment of diseases associated with the modulation or inhibition of 11?-HSD1 in mammals. The invention further relates to pharmaceutical compositions of the novel compounds and methods for their use in the reduction or control of the production of cortisol in a cell or the inhibition of the conversion of cortisone to cortisol in a cell.

Abstract: The invention relates to novel pyrrolidine derivatives of formula (I): wherein R1, R2 and R3 are as defined herein, as inhibitors of glutaminyl cyclase (QC, EC 2.3.2.5). QC catalyzes the intramolecular cyclization of N-terminal glutamine residues into pyroglutamic acid (5-oxo-prolyl, pGlu*) under liberation of ammonia and the intramolecular cyclization of N-terminal glutamate residues into pyroglutamic acid under liberation of water.

Abstract: The present invention provides a compound of formula (I): wherein —X? is —CR7? or —N?, ring B is a substituted or unsubstituted carbocycle or a substituted or unsubstituted heterocycle, R1 is substituted or unsubstituted alkyl or the like, R2 a and R2 b are each independently hydrogen, substituted or unsubstituted alkyl or the like, R3 and R4 are each independently hydrogen, halogen, substituted or unsubstituted alkyl or the like, R5 is hydrogen, substituted or unsubstituted alkyl or the like, each R6 is independently halogen, hydroxy, substituted or unsubstituted alkyl or the like, R7 is hydrogen, halogen, hydroxy, substituted or unsubstituted alkyl or the like, p is an integer of 0 to 3, or a pharmaceutically acceptable salt thereof which has an effect of inhibiting amyloid ? production, especially an effect of inhibiting BACE1, and which is useful as a therapeutic or prophylactic agent for diseases induced by production, secretion and/or deposition of amyloid ? proteins.

Abstract: The present invention provides compounds of Formula (I), pharmaceutical compositions thereof, and method of using the same in the treatment or prevention of diseases mediated by the activation of ?3-adrenoceptor.

Abstract: This invention relates to novel compounds of the Formula Formulas (I), (Ia1-20), (Ib1-20), (Ic1-20), pharmaceutically acceptable salts thereof, and pharmaceutical compositions thereof, which are useful for the therapeutic treatment of diseases associated with the modulation or inhibition of 11?-HSD1 in mammals. The invention further relates to pharmaceutical compositions of the novel compounds and methods for their use in the reduction or control of the production of cortisol in a cell or the inhibition of the conversion of cortisone to cortisol in a cell.

Abstract: Disclosed is a compound represented by Formula (Im1): or a pharmaceutically acceptable salt, monohydrate, enantiomer or diastereomer thereof. Also disclosed are pharmaceutical compositions comprising the compound of Formula (Im1) or a pharmaceutically acceptable salt, monohydrate, enantiomer or diastereomer thereof and methods of inhibiting 11?-HSD1 activity comprising the step of administering to a mammal in need of such treatment an effective amount of a compound of Formula (Im1), or a pharmaceutically acceptable salt, monohydrate, enantiomer or diastereomer thereof. Values for the variables in Formula (Im1) are defined herein.

Abstract: The present invention relates to derivatives of general formula I wherein: —W represents nitrogen, —R1 represents: •a hydrogen or a linear or branched C1-C5 alkyl radical or, •a C1-C3 alkyl radical substituted with groups such as trifluoromethyl, nitrile, hydroxy, C1-C3 alcoxy, C3-C6 alkoxyalkoxy, indolyl, thiophenyl, oxothiophenyl, C1-C3 N-alkylcarbamoyl groups or, •a phenyl or pyridyl or naphthyl, or thiophenyl group optionally substituted with one or more groups such as halogen atoms, nitro, nitrile, trifluoromethyl, vinyl, methylsulfanyl, linear branched C1-C4 alkyl, linear or branched C1-C3 alkoxy groups, •a C6 2-oxocycloalkyl radical—R2 represents a methyl or heptyl, -m, n are equal to 1, —V represents CH2, —X—Y represents —N— (C?O)—, —CH—O—, —Z represents a phenyl group substituted with one or more trifluoromethyl groups, halogen atoms or linear C1-C4 alkyl groups.

Abstract: This invention relates to novel compounds of an 11 ?-HSD1 inhibitor disclosed herein, pharmaceutically acceptable salts thereof, and pharmaceutical compositions thereof, which are useful for the therapeutic treatment of diseases associated with the modulation or inhibition of 11/3-HSD1 in mammals. The invention further relates to pharmaceutical compositions of the novel compounds and methods for their use in the reduction or control of the production of Cortisol in a cell or the inhibition of the conversion of cortisone to Cortisol in a cell.

Abstract: The invention relates to the field of blood coagulation. Novel oxazolidinone derivatives of the general formula (I) processes for their preparation and their use as medicinally active compounds for the prophylaxis and/or treatment of disorders are described.

Abstract: This invention relates to novel compounds of the Formula Il Ik, Im3, Im4, Im6-12, In3, In4, In6-12, lo3, lo4, lo6-12, Ip2, Ip4-7, pharmaceutically acceptable salts thereof, and pharmaceutical compositions thereof, which are useful for the therapeutic treatment of diseases associated with the modulation or inhibition of 11?-HSD1 in mammals. The invention further relates to pharmaceutical compositions of the novel compounds and methods for their use in the reduction or control of the production of Cortisol in a cell or the inhibition of the conversion of cortisone to Cortisol in a cell.

Abstract: This invention relates to novel compounds of the Formula (I), (Ia), (Ic), (Ie), (If), (Ig), (Ih), (Ii), pharmaceutically acceptable salts thereof, and pharmaceutical compositions thereof, which are useful for the therapeutic treatment of diseases associated with the modulation or inhibition of 11?-HSD1 in mammals. The invention further relates to pharmaceutical compositions of the novel compounds and methods for their use in the reduction or control of the production of cortisol in a cell or the inhibition of the conversion of cortisone to cortisol in a cell.

Abstract: This invention relates to novel compounds of the Formula Ik, Im1, Im2, Im5, In1, In2, In5, lo1, lo2, lo5, Ip1, Ip3, pharmaceutically acceptable salts thereof, and pharmaceutical compositions thereof, which are useful for the therapeutic treatment of diseases associated with the modulation or inhibition of 11 ?-HSD1 in mammals. The invention further relates to pharmaceutical compositions of the novel compounds and methods for their use in the reduction or control of the production of Cortisol in a cell or the inhibition of the conversion of cortisone to Cortisol in a cell.

Abstract: Disclosed are compounds represented by Formula (I): or pharmaceutically acceptable salts, enantiomers or diastereomers thereof. Also disclosed are pharmaceutical compositions comprising the compounds of Formula (I) or pharmaceutically acceptable salts, enantiomers or diastereomers thereof and methods of inhibiting 11?-HSD1 activity comprising the step of administering to a mammal in need of such treatment an effective amount of a compound of Formula (I), or a pharmaceutically acceptable salt, enantiomer or diastereomer thereof. Values for the variables in Formula (I) are defined herein.

Abstract: This invention relates to novel compounds of the Formula I, Ik, Iq1-21, Ir1-21, Is1-21, It1-7, pharmaceutically acceptable salts thereof, and pharmaceutical compositions thereof, which are useful for the therapeutic treatment of diseases associated with the modulation or inhibition of 11 ?-HSD1 in mammals. The invention further relates to pharmaceutical compositions of the novel compounds and methods for their use in the reduction or control of the production of cortisol in a cell or the inhibition of the conversion of cortisone to cortisol in a cell.

Abstract: The present invention relates to ethynyl compounds of formula I wherein R1, R2, R2?, R3, R3?, R4, R4?, U, V, W, Y, m, and n are as defined herein and to a pharmaceutically acceptable acid addition salts, to a racemic mixtures, or to its corresponding enantiomers and/or optical isomers and/or stereoisomers thereof. Compounds of formula I are allosteric modulators of the metabotropic glutamate receptor subtype 5 (mGluR5).

Abstract: The present invention relates to compounds defined by formula I: wherein the variables A1, A2, Cy1 Cy2, Cy3, E, R1a, R1b, R2, R3, n, and Q are as defined herein, possessing valuable pharmacological activity. Particularly, the compounds are inhibitors of 11?-hydroxysteroid dehydrogenase (HSD) 1 and thus are suitable for treatment and prevention of diseases which can be influenced by inhibition of this enzyme, such as metabolic diseases, in particular diabetes type 2, obesity, and dyslipidemia.