Abstract: The present invention discloses a method to discover selective inhibitors of phosphatases.

Abstract: The present invention discloses a method to discover selective inhibitors of phosphatases.

Abstract: The present invention relates to inhibitors of PPP1 R15A and PPP1 R15B and their use in therapy, particularly in the treatment of a disease state alleviated by the inhibition of PPP1 R15A and PPP1 R15B, for example a disorder associated with accumulation of misfolded proteins or proteostatsis disorder. Compounds of the invention include compounds having the formula IA or a pharmaceutically acceptable salt thereof, wherein R1a, R3a, R5a, Xa and Ya are as defined herein.

Abstract: The present invention relates to inhibitors of PPP1 R15A and PPP1 R15B and their use in therapy, particularly in the treatment of a disease state alleviated by the inhibition of PPP1 R15A and PPP1 R15B, for example a disorder associated with accumulation of misfolded proteins or proteostatsis disorder. Compounds of the invention include compounds having the formula IA or a pharmaceutically acceptable salt thereof, wherein R1a, R3a, R5a, Xa and Ya are as defined herein.

Abstract: The present invention relates to inhibitors of PPP1 R15A and PPP1 R15B and their use in therapy, particularly in the treatment of a disease state alleviated by the inhibition of PPP1 R15A and PPP1 R15B, for example a disorder associated with accumulation of misfolded proteins or proteostatsis disorder. Compounds of the invention include compounds having the formula IA or a pharmaceutically acceptable salt thereof, wherein R1a, R3a, R5a, Xa and Ya are as defined herein.

Abstract: The present invention relates to a compound of formula (I), or a tautomer and/or a pharmaceutically acceptable salt thereof, wherein: R1 is alkyl, Cl, F or Br; R2 is H or F; R3 is selected from H and alkyl; R4 is selected from H and C(O)R6; R5 is H; or R4 and R5 are linked to form a heterocyclic group which is optionally substituted with one or more R10 groups; R6 is selected from R7, OR7 and NR8R9; R7, R8 and R9 are each independently selected from alkyl, cycloalkyl, aralkyl, cycloalkenyl, heterocyclyl and aryl, each of which is optionally substituted with one or more R10 groups; each R10 is independently selected from halogen, OH, CN, NO2, COO-alkyl, aralkyl, SO2-alkyl, SO2-aryl, COOH, CO-alkyl, CO-aryl, NH2, NH-alkyl, N(alkyl)2, CF3, alkyl and alkoxy; X and Z are each independently CR11, and Y is selected from CR11 and N; and R11 is H or F; for use in treating a disorder associated with protein misfolding stress and in particular associated with accumulation of misfolded proteins.

Abstract: The present invention relates to inhibitors of PPP1 R15A and PPP1 R15B and their use in therapy, particularly in the treatment of a disease state alleviated by the inhibition of PPP1 R15A and PPP1 R15B, for example a disorder associated with accumulation of misfolded proteins or proteostatsis disorder. Compounds of the invention include compounds having the formula IA or a pharmaceutically acceptable salt thereof, wherein R1a, R3a, R5a, Xa and Ya are as defined herein.

Abstract: The present invention relates to inhibitors of PPP1 R15A and PPP1 R15B and their use in therapy, particularly in the treatment of a disease state alleviated by the inhibition of PPP1 R15A and PPP1 R15B, for example a disorder associated with accumulation of misfolded proteins or proteostatsis disorder. Compounds of the invention include compounds having the formula IA or a pharmaceutically acceptable salt thereof, wherein R1a, R3a, R5a, Xa and Ya are as defined herein.

Abstract: This invention relates to assays for screening test compounds for their ability to modulate holophosphatase activity.

Abstract: The present invention relates to a compound of formula (I), or a tautomer and/or a pharmaceutically acceptable salt thereof, wherein: R1 is alkyl, Cl, F or Br; R2 is H or F; R3 is selected from H and alkyl; R4 is selected from H and C(O)R6; R5 is H; or R4 and R5 are linked to form a heterocyclic group which is optionally substituted with one or more R10 groups; R6 is selected from R7, OR7 and NR8R9; R7, R8 and R9 are each independently selected from alkyl, cycloalkyl, aralkyl, cycloalkenyl, heterocyclyl and aryl, each of which is optionally substituted with one or more R10 groups; each R10 is independently selected from halogen, OH, CN, NO2, COO-alkyl, aralkyl, SO2-alkyl, SO2-aryl, COOH, CO-alkyl, CO-aryl, NH2, NH-alkyl, N(alkyl)2, CF3, alkyl and alkoxy; X and Z are each independently CR11, and Y is selected from CR11 and N; and R11 is H or F; for use in treating a disorder associated with protein misfolding stress and in particular associated with accumulation of misfolded proteins.

Abstract: The present invention relates to a compound of formula (I), or a tautomer and/or a pharmaceutically acceptable salt thereof, wherein R1 is alkyl, Cl, F or Br, R2 is H or F; R3 is selected from H and alkyl; R4 is selected from H and C(O)R6; R5 is H or R4 and R5 are linked to form a heterocyclic group which is optionally substituted with one or more R10 groups R6 is selected from R7, OR7 and NR8R6; R7R8 and R9 are each independently selected from alkyl, cycloalkyl, aralkyl, cycloalkenyl, heterocycyl and aryl, each of which is optionally substituted with one or more R10 groups; each R10 is independently selected from halogen, OH, CN NO1, COO-alkyl, aralkyl, SO2-alkyl, SO2-aryl, COOH, CO-alkyl, CO-aryl, NH2, NH-alkyl, N(alkyl)2, CF3, alkyl and alkoxy, X and Z are each independently CR11 and Y is selected from CR11 and N and R11 is H or F; for use in treating a disorder associated with protein misfolding stress and in particular associated with accumulation of misfolded proteins.

Abstract: The present invention relates to a compound of formula (I), or a tautomer and/or a pharmaceutically acceptable salt thereof, wherein R1 is alkyl, Cl, F or Br, R2 is H or F; R3 is selected from H and alkyl; R4 is selected from H and C(O)R6; R5 is H or R4 and R5 are linked to form a heterocyclic group which is optionally substituted with one or more R10 groups R6 is selected from R7, OR7 and NR8R6; R7R8 and R9 are each independently selected from alkyl, cycloalkyl, aralkyl, cycloalkenyl, heterocycyl and aryl, each of which is optionally substituted with one or more R10 groups; each R10 is independently selected from halogen. OH, CN NO2, COO-alkyl, aralkyl, SO2-alkyl, SO2-aryl, COOH, CO-alkyl, CO-aryl, NH2, NH-alkyl, N(alkyl)2, CF3, alkyl and alkoxy, X and Z are each independently CR11 and Y is selected from CR11 and N and R11 is H or F; for use in treating a disorder associated with protein misfolding stress and in particular associated with accumulation of misfolded proteins.

Abstract: The present invention relates to a compound of formula (I), or a tautomer and/or a pharmaceutically acceptable salt thereof, wherein: R1 is alkyl, Cl, F or Br; R2 is H or F; R3 is selected from H and alkyl; R4 is selected from H and C(O)R6; R5 is H; or R4 and R5 are linked to form a heterocyclic group which is optionally substituted with one or more R10 groups; R6 is selected from R7, OR7 and NR8R9; R7, R8 and R9 are each independently selected from alkyl, cycloalkyl, aralkyl, cycloalkenyl, heterocyclyl and aryl, each of which is optionally substituted with one or more R10 groups; each R10 is independently selected from halogen, OH, CN, NO2, COO-alkyl, aralkyl, SO2-alkyl, SO2-aryl, COOH, CO-alkyl, CO-aryl, NH2, NH-alkyl, N(alkyl)2, CF3, alkyl and alkoxy; X and Z are each independently CR11, and Y is selected from CR11 and N; and R11 is H or F; for use in treating a disorder associated with protein misfolding stress and in particular associated with accumulation of misfolded proteins.

Abstract: The present invention discloses a method to discover selective inhibitors of phosphatases.

Abstract: The present invention relates to inhibitors of PPP1 R15A and PPP1 R15B and their use in therapy, particularly in the treatment of a disease state alleviated by the inhibition of PPP1 R15A and PPP1 R15B, for example a disorder associated with accumulation of misfolded proteins or proteostatsis disorder. Compounds of the invention include compounds having the formula IA or a pharmaceutically acceptable salt thereof, wherein R1a, R3a, R5a, Xa and Ya are as defined herein.

Abstract: The present invention relates to a compound of formula (I), or a tautomer and/or a pharmaceutically acceptable salt thereof, wherein: R1 is alkyl, Cl, F or Br; R2 is H or F; R3 is selected from H and alkyl; R4 is selected from H and C(O)R6; R5 is H; or R4 and R5 are linked to form a heterocyclic group which is optionally substituted with one or more R10 groups; R6 is selected from R7, OR7 and NR8R9; R7, R8 and R9 are each independently selected from alkyl, cycloalkyl, aralkyl, cycloalkenyl, heterocyclyl and aryl, each of which is optionally substituted with one or more R10 groups; each R10 is independently selected from halogen, OH, CN, NO2, COO-alkyl, aralkyl, SO2-alkyl, SO2-aryl, COOH, CO-alkyl, CO-aryl, NH2, NH-alkyl, N(alkyl)2, CF3, alkyl and alkoxy; X and Z are each independently CR11, and Y is selected from CR11 and N; and R11 is H or F; for use in treating a disorder associated with protein misfolding stress and in particular associated with accumulation of misfolded proteins.

Abstract: The present invention relates to a compound of formula (I), or a tautomer and/or a pharmaceutically acceptable salt thereof, wherein: R1 is alkyl, Cl, F or Br; R2 is H or F; R3 is selected from H and alkyl; R4 is selected from H and C(O)R6; R5 is H; or R4 and R5 are linked to form a heterocyclic group which is optionally substituted with one or more R10 groups; R6 is selected from R7, OR7 and NR8R9; R7, R8 and R9 are each independently selected from alkyl, cycloalkyl, aralkyl, cycloalkenyl, heterocyclyl and aryl, each of which is optionally substituted with one or more R10 groups; each R10 is independently selected from halogen, OH, CN, NO2, COO-alkyl, aralkyl, SO2-alkyl, SO2-aryl, COOH, CO-alkyl, CO-aryl, NH2, NH-alkyl, N(alkyl)2, CF3, alkyl and alkoxy; X and Z are each independently CR11, and Y is selected from CR11 and N; and R11 is H or F; for use in treating a disorder associated with protein misfolding stress and in particular associated with accumulation of misfolded proteins.

Abstract: The present invention relates to a compound of formula (I), or a tautomer and/or a pharmaceutically acceptable salt thereof, wherein: R1 is alkyl, Cl, F or Br; R2 is H or F; R3 is selected from H and alkyl; R4 is selected from H and C(O)R6; R5 is H; or R4 and R5 are linked to form a heterocyclic group which is optionally substituted with one or more R10 groups; R6 is selected from R7, OR7 and NR8R9; R7, R8 and R9 are each independently selected from alkyl, cycloalkyl, aralkyl, cycloalkenyl, heterocyclyl and aryl, each of which is optionally substituted with one or more R10 groups; each R10 is independently selected from halogen, OH, CN, NO2, COO-alkyl, aralkyl, SO2-alkyl, SO2-aryl, COOH, CO-alkyl, CO-aryl, NH2, NH-alkyl, N(alkyl)2, CF3, alkyl and alkoxy; X and Z are each independently CR11, and Y is selected from CR11 and N; and R11 is H or F; for use in treating a disorder associated with protein misfolding stress and in particular associated with accumulation of misfolded proteins.

Abstract: The invention relates to chlorine Guanabenz derivatives for treating Huntington's disease and other polyglutamine expansion associated diseases. More specifically, it relates to the use of the molecule of formula (I) wherein R?H or Cl and the phenyl group is at least substituted twice, or a pharmaceutically acceptable salt thereof, for the manufacture of a medicament for treating polyglutamine expansion associated diseases.

Abstract: A kit and a method for identifying compounds having anti-prion activity are provided. The kit comprises a yeast of phenotype [PSI+]; an antibiogram; and a prion curing agent in a sub-effective dose, wherein the yeast has the adel-14 allele of the ADE1 gene and an inactivated ERG6 gene. Compounds and pharmaceutical compositions having anti-prion activity are also provided, which are useful for treating various neurodegenerative diseases, including polyglutamines expansion associated diseases; Huntington's disease; Kennedy disease; amyotrophic lateral sclerosis; cerebellous autosomic ataxies; dentalorubral-pallidoluysian atrophy; and spino-bulbar amyotrophy.