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.9; R.sub.7, R.sub.8 and R.sub.9 are each independently selected from alkyl, cycloalkyl, aralkyl, cycloalkenyl, heterocyclyl 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.2, 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.

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.

Glucosepane is a structurally complex protein post-translational modification (PTM) believed to exist in all living organisms. Research in humans suggests that glucosepane plays a critical role in the pathophysiology of both diabetes and human aging; yet comprehensive biological investigations of this metabolite have been greatly hindered by a scarcity of chemically homogeneous material available for study. Glucosepane possesses a unique chemical structure that incorporates a surprising, never-before-prepared non-aromatic tautomer of imidazole (hereafter termed an iso-imidazole), rendering it a challenging target for chemical synthesis. In this application, the inventors report the first total synthesis of glucosepane, enabled by the development of a novel one-pot method for preparation of the iso-imidazole core. The synthesis of the present invention is concise (8-steps starting from commercial materials), convergent, high-yielding (12% overall), and enantioselective. These results should prove useful to the art and practice of heterocyclic chemistry, and critical for the study of glucosepane and its role in human health and disease, especially the treatment of diabetic disorders or its impact on aging processes. 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. Research in humans suggests that glucosepane plays a critical role in the pathophysiology of both diabetes and human aging; yet comprehensive biological investigations of this metabolite have been greatly hindered by a scarcity of chemically homogeneous material available for study. Glucosepane possesses a unique chemical structure that incorporates a surprising, never-before-prepared non-aromatic tautomer of imidazole (hereafter termed an iso-imidazole), rendering it a challenging target for chemical synthesis. In this application, the inventors report the first total synthesis of glucosepane, enabled by the development of a novel one-pot method for preparation of the iso-imidazole core. The synthesis of the present invention is concise (8-steps starting from commercial materials), convergent, high-yielding (12% overall), and enantioselective. These results should prove useful to the art and practice of heterocyclic chemistry, and critical for the study of glucosepane and its role in human health and disease, especially the treatment of diabetic disorders or its impact on aging processes. Methods of synthesis, compounds obtained therefrom, pharmaceutical compositions and methods of treatment provide embodiments of the present invention.

A hydrogen sulfide donor in an organic salt form and a preparation method thereof. The hydrogen sulfide donor exists as a salt formed by organic compounds with an alkaline motif and hydrogen sulfide with weak acidity. The hydrogen sulfide donor features with a simple structure, and an easy preparation method. Moreover, hydrogen sulfide donors in different forms can be prepared according to research and development needs. After the hydrogen sulfide donor enters an organism, the process of in vivo dissociation and hydrogen sulfide supply is simple, rapid, and effective, and there is no requirement for enzyme or any other complicated condition, and thus, the hydrogen sulfide donor has a great application prospect and value.

The gas generating agent of the present invention comprises an oxalic acid salt of an aminoguanidine compound represented by general formula (1) below.

##STR00001##

The gas generating agent of the present invention comprises an oxalic acid salt of an aminoguanidine compound represented by general formula (1) below.

##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.9; R.sub.7, R.sub.8 and R.sub.9 are each independently selected from alkyl, cycloalkyl, aralkyl, cycloalkenyl, heterocyclyl 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.2, 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.

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.9; R.sub.7, R.sub.8 and R.sub.9 are each independently selected from alkyl, cycloalkyl, aralkyl, cycloalkenyl, heterocyclyl 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.2, 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.