Abstract: The application is directed to compounds of formula (I): and their salts and solvates, wherein R1, R2, R3, A1, A2, A3, and n are as set forth in the specification, as well as to a method for their preparation, pharmaceutical compositions comprising the same, and use thereof for the treatment and/or prevention of a lysosomal storage disease, such as Gaucher's, and other diseases or disorders that are synucleinopathies.

Abstract: The application is directed to compounds of formula (I) and their salts and solvates, wherein B, R1, R2, R3, R3’, R4, R4’ and R5 are as set forth in the specification, as well as to methods for their preparation, pharmaceutical compositions comprising the same, and use thereof for the treatment and/or prevention of, e.g., MPS1, optionally in combination with ?-L-iduronidase or an analog or variant thereof, e.g., laronidase.

Abstract: The application is directed to compounds of formulae (IA) and (IB): (IA) and (IB), and their salts and solvates, wherein R1a, R2a, A1, A2, A3, A4, R1b, R2b, B1, B2, B3, and G are as set forth in the specification, as well as to methods for their preparation, N pharmaceutical compositions comprising the same, and use thereof for the treatment and/or prevention of, e.g., lysosomal storage diseases, such as Krabbe's disease, and ?-synucleinopathies, such as Parkinson's disease.

Abstract: The application is directed to compounds of formula (I):(I), and formula (IA):(IA) and their salts and solvates, wherein R1, R2, R3, R4, R5, n, A1, A2, A3, and Y are as set forth in the specification, as well as to a method for their preparation, pharmaceutical compositions comprising the same, and use thereof for the treatment and/or prevention of conditions associated with the alteration of the activity of ?-galactosidase, specially galactosidase beta-1 or GLB 1, including GM 1 gangliosidoses and Morquio syndrome, type B.

Abstract: The application is directed to compounds of formula (I): and their salts and solvates, wherein R1, R2, R3, A1, A2, A3, and n are as set forth in the specification, as well as to a method for their preparation, pharmaceutical compositions comprising the same, and use thereof for the treatment and/or prevention of a lysosomal storage disease, such as Gaucher's, and other diseases or disorders that are synucleinopathies.

Abstract: The application is directed to compounds of formula (I): and their salts and solvates, wherein R1, R2, R3, A1, A2, A3, and n are as set forth in the specification, as well as to a method for their preparation, pharmaceutical compositions comprising the same, and use thereof for the treatment and/or prevention of a lysosomal storage disease, such as Gaucher's, and other diseases or disorders that are synucleinopathies.

Abstract: Described herein are compounds having Formula I or Formula II: wherein each dashed line independently represents a saturated or unsaturated bond; R1 and R?1 are aryl or heteroaryl as defined herein; and R2 and R?2 are as defined herein. Further described is a method of inhibiting nuclear translocation of ERK1/2 in a cell, by contacting the cell with a compound having Formula I or Formula II. The compounds may also be for use in treating a disease or disorder associated with nuclear translocation of ERK1/2.

Abstract: The application is directed to compounds of formula (I):(I), and formula (IA):(IA) and their salts and solvates, wherein R1, R2, R3, R4, R5, n, A1, A2, A3, and Y are as set forth in the specification, as well as to a method for their preparation, pharmaceutical compositions comprising the same, and use thereof for the treatment and/or prevention of conditions associated with the alteration of the activity of ?-galactosidase, specially galactosidase beta-1 or GLB 1, including GM 1 gangliosidoses and Morquio syndrome, type B.

Abstract: The application is directed to compounds of formula (I): and their salts and solvates, wherein R1, R2, R3, A1, A2, A3, and n are as set forth in the specification, as well as to a method for their preparation, pharmaceutical compositions comprising the same, and use thereof for the treatment and/or prevention of a lysosomal storage disease, such as Gaucher's, and other diseases or disorders that are synucleinopathies.

Abstract: The present invention refers to compounds of formula (I): as well as to a method for their preparation, pharmaceutical compositions comprising the same, and use thereof for the treatment and/or prevention of conditions associated with the alteration of the activity of ?-galactosidase, specially galactosidase beta-1 or GLB1, including GM1 gangliosidoses and Morquio syndrome, type B.

Abstract: It is described a method of binding site and binding energy determination by mixed explicit solvent all-atoms molecular dynamics simulations. The macromolecular target for which high affinity binders are sought is simulated in several mixed solvent environments comprising water and at least one amphiphilic organic co-solvent. The simulations are run so that the mixture of solvents are free to react to the presence of the target without the addition of any forces other than those found in the original potential. A correction is applied that helps dissociating the distribution of the different chemical groups found in the amphiphilic organic solvents when calculating their free energies of binding. Additionally, a second correction can be applied accounting for the aggregation of said solvents. The correction helps determining more meaningful absolute, and more accurate relative free energies of binding that can be applied in the rational design of new binders to macromolecular targets.

Abstract: Compounds of formula (1) are inhibitors of HSP90 activity in vitro or in vivo, and of use in the treatment of inter alia, cancer: wherein R2 is a group of formula —(Ar1)m-(Alk1)P-(Z)r-(Alk2)S-Q wherein Ar1 is an optionally substituted aryl or heteroaryl radical, Alk? and Alk 2 are optionally substituted divalent C1-C3 alkylene or C2-C3 alkenylene radicals, m, p, r and s are independently 0 or 1, Z is —O—, —S—, —(C?O)—, —(C?S)—, —SO2—, —C(?O)O—, —C(?O)NRA—, —C(?S)NRA—, —SO2NRA—, —NRAC(?O)—, —NRASO2— or —NRA— wherein RA is hydrogen or C1-C6 alkyl, and Q is hydrogen or an optionally substituted carbocyclic or heterocyclic radical; R3 is hydrogen, an optional substituent, or an optionally substituted (C1-C6)alkyl, aryl or heteroaryl radical; and R4 is a carboxylic ester, carboxamide or sulfonamide group.

Abstract: The use of compounds of formula (I) in therapy, particularly for the treatment of a disorder mediated by excessive or inappropriate HSP90 activity formula (I), wherein R2 is a group of formula (IA): —(Ar1)m-(Alk1)p-(Z)r-(Alk2)S-Q??(IA) Ar1, Alk1, Z, Alk2 and Q being as defined in the specification; m, p, r and s are independently 0 or 1; R3 is hydrogen, an optional substituent, or an optionally substituted (C1-C6)alkyl, aryl or heteroaryl radical; and R4 is a carboxylic ester, carboxamide or sulfonamide group; or a salt, N-oxide, hydrate, or solvate thereof.

Abstract: Compounds of formula (1) are inhibitors of HSP90 activity in vitro or in vivo, and of use in the treatment of inter alia, Cancer: wherein R2 is a group of formula —(Ar1)m-(Alk1)P-(Z)r-(Alk 2)S-Q wherein Ar1 is an optionally substituted aryl or heteroaryl radical, Alk? and Alk 2 are optionally substituted divalent C1-C3 alkylene or C2-C3 alkenylene radicals, m, p, r and s are independently 0 or 1, Z is —O—, —S—, —(C?O)—, —(C?S)—, —SO2—, —C(?O)O—, —C(?O)NRA—, —C(?S)NRA—, —SO2NRA—, —NRAC(?O)_, —NRASO2- or —NRA—wherein RA is hydrogen or C1-C6 alkyl, and Q is hydrogen or an optionally substituted carbocyclic or heterocyclic radical; R3 is hydrogen, an optional substituent, or an optionally substituted (C1-C6)alkyl, aryl or heteroaryl radical; and R4 is a carboxylic ester, carboxamide or sulfonamide group.

Abstract: Compounds of formula (1) are inhibitors of HSP90 activity in vitro or in vivo, and of use in the treatment of inter alia, cancer: wherein R2 is a group of formula —(Ar1)m-(Alk1)P-(Z)r-(Alk2)S-Q wherein Ar1 is an optionally substituted aryl or heteroaryl radical, Alk? and Alk 2 are optionally substituted divalent C1-C3 alkylene or C2-C3 alkenylene radicals, m, p, r and s are independently 0 or 1, Z is -0-, —S—, —(C?O)—, —(C?S)—, -S02-, —C(?O)O—, —C(?O)NRA—, —C(?S)NRA—, -S02NRA—, —NRAC(?O)—, —NRAS02- or —NRA— wherein RA is hydrogen or C1-C6 alkyl, and Q is hydrogen or an optionally substituted carbocyclic or heterocyclic radical; R3 is hydrogen, an optional substituent, or an optionally substituted (C1-C6)alkyl, aryl or heteroaryl radical; and R4 is a carboxylic ester, carboxamide or sulfonamide group.

Abstract: Compounds of formula (I) are inhibitors of HSP90, and of utility in the treatment of, for example, cancers: wherein ring A is an aryl or heteroaryl ring or ring system; R1 is hydrogen, fluoro, chloro, bromo, or a radical of formula (IA): —X-Alk1-(Z)m-(Alk2)n-Q (IA) wherein X is a bond, —O—, —S— —S(O)—, —SO2—, or —NH—, Z is —O—, —S—, —(C?O)—, —(C?S)—, —S(O)—, —SO2—, —NRA, or, in either orientation —C(?O)O—, —C(?O)NRA, —C(?S)NRA—, —SO2NRA—, —NRAC(?O)—, or —NRASO2— wherein RA is hydrogen or C1-C6 alkyl in which one or more hydrogens is optionally substituted by fluorine; Alk1 and Alk2 are optionally substituted divalent C1-C3 alkylene or C2-C3 alkenylene radicals, m and n are independently 0 or 1, and Q is hydrogen or an optionally substituted carbocyclic or heterocyclic radical; R2 is cyano (—CN), fluoro, chloro, bromo, methyl, ethyl, —OH, —CH2OH, —C(?O)NH2, —C(?O)H, —C(?O)CH3, or —NH2; R3 and R4 are independently selected from hydrogen, fluoro, chloro, bromo, cyano (—CN), C1-C3alkyl optionally substituted

Abstract: Compounds of formula (I) are inhibitors of HSP90, and useful in the treatment of, for example, cancers: wherein R2 is a group of formula (IA): -(Ar1)m-(Alk1)p-(Z)r-(Alk2)s-Q??(IA) wherein in any compatible combination Ar1 is an optionally substituted aryl or heteroaryl radical, Alk1 and Alk2 are optionally substituted divalent C1-C3 alkylene or C2-C3 alkenylene radicals, m, p, r and s are independently 0 or 1, Z is —O—, —S—, —(C?O)—, —(C?S)—, —SO2—, —C(?O)O—, —C(?O)NRA—, —C(?S)NRA—, —SO2NRA—, —NRAC(?O)—, —NRASO2— or —NRA— wherein RA is hydrogen or C1-C6 alkyl, and Q is hydrogen or an optionally substituted carbocyclic or heterocyclic radical; R3 is hydrogen, an optional substituent, or an optionally substituted (C1-C6)alkyl, aryl or heteroaryl radical; and R4 is (i) hydrogen, a —CN group, a nitro group —NO2, or a —C(?NOH)(NH2) group, or (ii) an optionally substituted C1-C6alkyl, aryl, heterocyclic, aryl(C1-C6alkyl)-, or heterocyclic(C1-C6alkyl)- group, or (iii) a group of formula —C(?O)R5 wherein R5 is

Abstract: The use of compounds of formula (I) in therapy, particularly for the treatment of a disorder mediated by excessive or inappropriate HSP90 activity formula (I), wherein R2 is a group of formula (IA): -(Ar1)m-(Alk1)p-(Z)r-(Alk2)s-Q (IA) Ar1, Alk1, Z, Alk2 and Q being as defined in the specification; m, p, r and s are independently 0 or 1; R3 is hydrogen, an optional substituent, or an optionally substituted (C1-C6)alkyl, aryl or heteroaryl radical; and R4 is a carboxylic ester, carboxamide or sulfonamide group; or a salt, N-oxide, hydrate, or solvate thereof.

Abstract: The present invention pertains to the use of certain 3,4-diarylpyazoles of formula (I), both in vitro and in vivo, to inhibit heat shock protein 90 (HSP90), and in the treatment of conditions mediated by HSP90, including, for example, cancer; wherein: Ar3 is independently: a C5-20aryl group, and is optionally substituted; Ar4 is independently: a C5-20aryl group, and is optionally substituted; R5 is independently: hydrogen; halo; hydroxyl; ether; formyl; acyl; carboxy; ester; acyloxy; oxycarbonyloxy; amido; acylamido; aminocarbonyloxy; tetrazolyl; amino; nitro; cyano; azido; sulfhydryl; thioether; sulfonamide; C1-7alkyl; C3-20heterocycyl; or C5-20aryl; R<SP>N</SP> is independently: —H; C1-7alkyl; C3-20heterocycyl; or, C5-20aryl; and pharmaceutically acceptable salts, solvates, amides, esters, ethers, chemically protected forms, and prodrugs thereof.

Abstract: Compounds of formula (1) are inhibitors of HSP90 activity in vitro or in vivo, and of use in the treatment of inter alia, cancer wherein R2 is a group of formula —(Ar1)m-(Alk1)P-(Z)r-(Alk2)S-Q wherein Ar1 is an optionally substituted aryl or heteroaryl radical, Alk? and Alk 2 are optionally substituted divalent C1-C3 alkylene or C2-C3 alkenylene radicals, m, p, r and s are independently 0 or 1, Z is —0—, —S—, —(C?O)—, —(C?S)—, —S02-, —C(?O)O—, —C(?O)NRA—, —C(?S)NRA—, —S02NRA—, —NRAC(?O)_, —NRAS02- or —NRA—wherein RA is hydrogen or C1-C6 alkyl, and Q is hydrogen or an optionally substituted carbocyclic or heterocyclic radical; R3 is hydrogen, an optional substituent, or an optionally substituted (C1-C6)alkyl, aryl or heteroaryl radical; and R4 is a carboxylic ester, carboxamide or sulfonamide group.