The present invention relates to a compound of formula (I), or a tautomer and/or a pharmaceutically acceptable salt thereof, wherein R.sub.1 is alkyl, Cl, F or Br, R.sub.2 is H or F; R.sub.3 is selected from H and alkyl; R.sub.4 is selected from H and C(O)R.sub.6; R.sub.5 is H or R.sub.4 and R.sub.5 are linked to form a heterocyclic group which is optionally substituted with one or more R.sub.10 groups R.sub.6 is selected from R.sub.7, OR.sub.7 and NR.sub.8R.sub.6; R.sub.7R.sub.8 and R.sub.9 are each independently selected from alkyl, cycloalkyl, aralkyl, cycloalkenyl, heterocycyl and aryl, each of which is optionally substituted with one or more R.sub.10 groups; each R.sub.10 is independently selected from halogen, OH, CN NO.sub.1, COO-alkyl, aralkyl, SO.sub.2-alkyl, SO.sub.2-aryl, COOH, CO-alkyl, CO-aryl, NH.sub.2, NH-alkyl, N(alkyl).sub.2, CF.sub.3, alkyl and alkoxy, X and Z are each independently CR.sub.11 and Y is selected from CR.sub.11 and N and R.sub.11 is H or F; for use in treating a disorder associated with protein misfolding stress and in particular associated with accumulation of misfolded proteins. ##STR00001##

The present invention relates to a compound of formula (I), or a tautomer and/or a pharmaceutically acceptable salt thereof, wherein R.sub.1 is alkyl, Cl, F or Br, R.sub.2 is H or F; R.sub.3 is selected from H and alkyl; R.sub.4 is selected from H and C(O)R.sub.6; R.sub.5 is H or R.sub.4 and R.sub.5 are linked to form a heterocyclic group which is optionally substituted with one or more R.sub.10 groups R.sub.6 is selected from R.sub.7, OR.sub.7 and NR.sub.8R.sub.6; R.sub.7R.sub.8 and R.sub.9 are each independently selected from alkyl, cycloalkyl, aralkyl, cycloalkenyl, heterocycyl and aryl, each of which is optionally substituted with one or more R.sub.10 groups; each R.sub.10 is independently selected from halogen, OH, CN NO.sub.1, COO-alkyl, aralkyl, SO.sub.2-alkyl, SO.sub.2-aryl, COOH, CO-alkyl, CO-aryl, NH.sub.2, NH-alkyl, N(alkyl).sub.2, CF.sub.3, alkyl and alkoxy, X and Z are each independently CR.sub.11 and Y is selected from CR.sub.11 and N and R.sub.11 is H or F; for use in treating a disorder associated with protein misfolding stress and in particular associated with accumulation of misfolded proteins. ##STR00001##

Glucosepane is a structurally complex protein post-translational modification (PTM) believed to exist in all living organisms. Glucosepane possesses a unique chemical structure that incorporates a surprising, never-before-prepared non-aromatic tautomer of imidazole, rendering it a challenging target for chemical synthesis. In this application, the inventors report the first total synthesis of glucosepane and related compounds according to the chemical structure: ##STR00001##
Methods of synthesis, compounds obtained therefrom, pharmaceutical compositions and methods of treatment provide embodiments of the present invention.

Glucosepane is a structurally complex protein post-translational modification (PTM) believed to exist in all living organisms. Glucosepane possesses a unique chemical structure that incorporates a surprising, never-before-prepared non-aromatic tautomer of imidazole, rendering it a challenging target for chemical synthesis. In this application, the inventors report the first total synthesis of glucosepane and related compounds according to the chemical structure: ##STR00001##
Methods of synthesis, compounds obtained therefrom, pharmaceutical compositions and methods of treatment provide embodiments of the present invention.

The invention provides methods for producing analgesia in an animal comprising administering to the animal a compound of the formula Ia, Ib, Ic, and Id:

##STR00001##

and pharmaceutically acceptable salts thereof, wherein the variables A, R.sup.6, R.sup.7, R.sup.8, R.sup.9, R.sup.x, L, X, Y, and Z have the meaning as described herein.

The invention provides methods for producing analgesia in an animal comprising administering to the animal a compound of the formula Ia, Ib, Ic, and Id:

##STR00001##

and pharmaceutically acceptable salts thereof, wherein the variables A, R.sup.6, R.sup.7, R.sup.8, R.sup.9, R.sup.x, L, X, Y, and Z have the meaning as described herein.

This invention relates to compounds that inhibit creatine transport and/or creatine kinase, pharmaceutical compositions including such compounds, and methods of utilizing such compounds and compositions for the treatment of cancer.

This invention relates to compounds that inhibit creatine transport and/or creatine kinase, pharmaceutical compositions including such compounds, and methods of utilizing such compounds and compositions for the treatment of cancer.

Methods for removing an oxyanion from an aqueous source containing said oxyanion, comprising contacting said aqueous source with an aqueous-insoluble hydrophobic solution containing an oxyanion extractant compound dissolved in an aqueous-insoluble hydrophobic solvent to result in formation of an oxyanion salt of said extractant compound and extraction of said oxyanion salt into said aqueous-insoluble hydrophobic solution, wherein said extraction results in an extraction affinity (D) of said oxyanion of at least 1, wherein D is the concentration ratio of said oxyanion in the organic phase divided by the concentration of said oxyanion in the aqueous phase; wherein said extractant compound has the following composition:

##STR00001##

wherein at least one of R.sup.1-R.sup.10 is or contains a hydrocarbon (R) group containing at least 4, 5, 6, 7, 8, 9, 10, 11, or 12 carbon atoms.

Methods for removing an oxyanion from an aqueous source containing said oxyanion, comprising contacting said aqueous source with an aqueous-insoluble hydrophobic solution containing an oxyanion extractant compound dissolved in an aqueous-insoluble hydrophobic solvent to result in formation of an oxyanion salt of said extractant compound and extraction of said oxyanion salt into said aqueous-insoluble hydrophobic solution, wherein said extraction results in an extraction affinity (D) of said oxyanion of at least 1, wherein D is the concentration ratio of said oxyanion in the organic phase divided by the concentration of said oxyanion in the aqueous phase; wherein said extractant compound has the following composition:

##STR00001##

wherein at least one of R.sup.1-R.sup.10 is or contains a hydrocarbon (R) group containing at least 4, 5, 6, 7, 8, 9, 10, 11, or 12 carbon atoms.