Conjugates of 2,3-dihydroxynaphthalene and its derivatives with enzyme cleavable groups are chromogenic substrates that form colored compounds when complexed with metal ions, e.g. iron ions, on cleavage by enzymes, and are useful in microbial detection and identification. The cleavage products form purple or red-brown colored complexes, that can easily be observed by the naked eye. Microbes can be grown in the presence of the substrates and the metal salts that provide the metal ion for complexing with the 2,3-dihydroxynaphthalene product. Substituents in the naphthalene ring may affect the solubility of the substrates and also the diffusibility and color of the metal complexes. Some of the substrates yield soluble complexes on cleavage and are of particular value in liquid growth media. Other substrates produce less soluble complexes that are more suitable for use in solid agar media. Some substrates are new compounds, such as those having the general formula II ##STR00001## wherein one of the following applies i) m=0, R.sup.4R.sup.5=Z.sup.1H, Y.sup.1 is selected from the group consisting of D-glucuronyl and D-ribofuranosyl; ii) m=2, each R.sup.6 is Br, R.sup.4R.sup.5H or Br, Z.sup.1H, Y.sup.1 is glycosyl or phosphate; iii) m=1, R.sup.6 is SO.sub.3X, X is H or M.sup.+ wherein M.sup.+ is an alkali metal cation or a non-metal cation, Y.sup.1 is glycosyl and R.sup.4R.sup.5=Z.sup.1H; iv) m=0, R.sup.4NO.sub.2, R.sup.5Z.sup.1H, Y.sup.1=glycosyl. Methods of synthesizing the substrates are described.

Conjugates of 2,3-dihydroxynaphthalene and its derivatives with enzyme cleavable groups are chromogenic substrates that form colored compounds when complexed with metal ions, e.g. iron ions, on cleavage by enzymes, and are useful in microbial detection and identification. The cleavage products form purple or red-brown colored complexes, that can easily be observed by the naked eye. Microbes can be grown in the presence of the substrates and the metal salts that provide the metal ion for complexing with the 2,3-dihydroxynaphthalene product. Substituents in the naphthalene ring may affect the solubility of the substrates and also the diffusibility and color of the metal complexes. Some of the substrates yield soluble complexes on cleavage and are of particular value in liquid growth media. Other substrates produce less soluble complexes that are more suitable for use in solid agar media. Some substrates are new compounds, such as those having the general formula II ##STR00001## wherein one of the following applies i) m=0, R.sup.4R.sup.5=Z.sup.1H, Y.sup.1 is selected from the group consisting of D-glucuronyl and D-ribofuranosyl; ii) m=2, each R.sup.6 is Br, R.sup.4R.sup.5H or Br, Z.sup.1H, Y.sup.1 is glycosyl or phosphate; iii) m=1, R.sup.6 is SO.sub.3X, X is H or M.sup.+ wherein M.sup.+ is an alkali metal cation or a non-metal cation, Y.sup.1 is glycosyl and R.sup.4R.sup.5=Z.sup.1H; iv) m=0, R.sup.4NO.sub.2, R.sup.5Z.sup.1H, Y.sup.1=glycosyl. Methods of synthesizing the substrates are described.

The present invention encompasses compounds and methods for treating urinary tract infections.

The present invention encompasses compounds and methods for treating urinary tract infections.

Conjugates of 2,3-dihydroxynaphthalene and its derivatives with enzyme cleavable groups are chromogenic substrates that form coloured compounds when complexed with metal ions, e.g. iron ions, on cleavage by enzymes, and are useful in microbial detection and identification. The cleavage products form purple or red-brown coloured complexes, that can easily be observed by the naked eye. Microbes can be grown in the presence of the substrates and the metal salts that provide the metal ion for complexing with the 2,3-dihydroxynaphthalene product. Substituents in the naphthalene ring may affect the solubility of the substrates and also the diffusibility and colour of the metal complexes. Some of the substrates yield soluble complexes on cleavage and are of particular value in liquid growth media. Other substrates produce less soluble complexes that are more suitable for use in solid agar media.

Some substrates are new compounds, such as those having the general formula II

##STR00001## wherein one of the following applies i) m=0, R.sup.4=R.sup.5=Z.sup.1=H, Y.sup.1 is selected from the group consisting of D-glucuronyl and D-ribofuranosyl; ii) m=2, each R.sup.6 is Br, R.sup.4=R.sup.5=H or Br, Z.sup.1=H, Y.sup.1 is glycosyl or phosphate; iii) m=1, R.sup.6 is SO.sub.3X, X is H or M.sup.+ wherein M.sup.+ is an alkali metal cation or a non-metal cation, Y.sup.1 is glycosyl and R.sup.4=R.sup.5=Z.sup.1=H; iv) m=0, R.sup.4=NO.sub.2, R.sup.5=Z.sup.1=H, Y.sup.1=glycosyl.

Methods of synthesising the substrates are described.

Conjugates of 2,3-dihydroxynaphthalene and its derivatives with enzyme cleavable groups are chromogenic substrates that form coloured compounds when complexed with metal ions, e.g. iron ions, on cleavage by enzymes, and are useful in microbial detection and identification. The cleavage products form purple or red-brown coloured complexes, that can easily be observed by the naked eye. Microbes can be grown in the presence of the substrates and the metal salts that provide the metal ion for complexing with the 2,3-dihydroxynaphthalene product. Substituents in the naphthalene ring may affect the solubility of the substrates and also the diffusibility and colour of the metal complexes. Some of the substrates yield soluble complexes on cleavage and are of particular value in liquid growth media. Other substrates produce less soluble complexes that are more suitable for use in solid agar media.

Some substrates are new compounds, such as those having the general formula II

##STR00001## wherein one of the following applies i) m=0, R.sup.4=R.sup.5=Z.sup.1=H, Y.sup.1 is selected from the group consisting of D-glucuronyl and D-ribofuranosyl; ii) m=2, each R.sup.6 is Br, R.sup.4=R.sup.5=H or Br, Z.sup.1=H, Y.sup.1 is glycosyl or phosphate; iii) m=1, R.sup.6 is SO.sub.3X, X is H or M.sup.+ wherein M.sup.+ is an alkali metal cation or a non-metal cation, Y.sup.1 is glycosyl and R.sup.4=R.sup.5=Z.sup.1=H; iv) m=0, R.sup.4=NO.sub.2, R.sup.5=Z.sup.1=H, Y.sup.1=glycosyl.

Methods of synthesising the substrates are described.

In one aspect, the present disclosure provides shishijimicin analogs of the formula: wherein the variables are as defined herein. In another aspect, the present disclosure also provides methods of preparing the compounds disclosed herein. In another aspect, the present disclosure also provides pharmaceutical compositions and methods of use of the compounds disclosed herein. Additionally, antibody drug conjugates of the compounds are also provided.

Certain compounds, or pharmaceutically acceptable salts or prodrugs thereof, are provided herein. Also provided are pharmaceutical compositions comprising at least one compound, or pharmaceutically acceptable salt or prodrug thereof, described herein and one or more pharmaceutically acceptable vehicle. Methods of treating patients suffering from certain diseases and disorders responsive to the inhibition of KMO activity are described, which comprise administering to such patients an amount of at least one compound, or pharmaceutically acceptable salt or prodrug thereof, described herein effective to reduce signs or symptoms of the disease or disorder are disclosed. These diseases include neurodegenerative disorders such as Huntington's disease. Also described are methods of treatment include administering at least one compound, or pharmaceutically acceptable salt or prodrug thereof, described herein as a single active agent or administering at least one compound, or pharmaceutically acceptable salt or prodrug thereof, described herein in combination with one or more other therapeutic agents. Also provided are methods for screening compounds capable of inhibiting KMO activity.

Certain compounds, or pharmaceutically acceptable salts or prodrugs thereof, are provided herein. Also provided are pharmaceutical compositions comprising at least one compound, or pharmaceutically acceptable salt or prodrug thereof, described herein and one or more pharmaceutically acceptable vehicle. Methods of treating patients suffering from certain diseases and disorders responsive to the inhibition of KMO activity are described, which comprise administering to such patients an amount of at least one compound, or pharmaceutically acceptable salt or prodrug thereof, described herein effective to reduce signs or symptoms of the disease or disorder are disclosed. These diseases include neurodegenerative disorders such as Huntington's disease. Also described are methods of treatment include administering at least one compound, or pharmaceutically acceptable salt or prodrug thereof, described herein as a single active agent or administering at least one compound, or pharmaceutically acceptable salt or prodrug thereof, described herein in combination with one or more other therapeutic agents. Also provided are methods for screening compounds capable of inhibiting KMO activity.

Disclosed are compounds which can act as a positive allosteric modulator for erythropoietin and erythropoietin receptor and have the activity in promoting erythropoiesis. Also disclosed are pharmaceutical compositions comprising said compounds and treatment methods utilizing said compounds.