Patent classifications
C07D279/20
10H-phenothiazine ferroptosis inhibitor as well as the preparative method and the use thereof
10H-phenothiazine derivatives capable of inhibiting ferroptosis has structural formula (I). The derivatives, pharmaceutically acceptable salts thereof, crystal forms thereof, or solvates thereof exhibit inhibitory effect on ferroptosis, and therapeutic effect on a rat model of focal cerebral ischemia and thus can be used as a main active ingredient in the preparation of ferroptosis inhibitors. The compounds and the inhibitors prepared by the compounds have good medicinal potential and are expected to be used as drug candidates for the treatment of stroke. ##STR00001##
3, 7-diamino-10H-phenothiazine salts and their use
Described are methods of preparing reduced 3,7-diamino-10H-phenothiazine (DAPTZ) compounds of formula: ##STR00001##
wherein: R.sup.1 and R.sup.9 are independently selected from: —H; C.sub.1-4alkyl; C.sub.2-4alkenyl; and halogenated C.sub.1-4alkyl; each of R.sup.3NA and R.sup.3NB is independently selected from: —H; C.sub.1-4alkyl; C.sub.2-4alkenyl; and halogenated C.sub.1-4alkyl; each of R.sup.7NA and R.sup.7NB is independently selected from: —H; C.sub.1-4alkyl; C.sub.2-4alkenyl; and halogenated C.sub.1-4alkyl; each of HX.sup.1 and HX.sup.2 is independently a protic acid; and pharmaceutically acceptable salts, solvates, and hydrates thereof. These methods are particularly useful for producing stable reduced forms, and with high purity. The stability and purity are especially relevant for pharmaceutical compositions for the treatment of disease. The compounds are useful for treatment of e.g. tauopathies, such as Alzheimer's disease, and also as prodrugs for the corresponding oxidized thioninium drugs.
3, 7-diamino-10H-phenothiazine salts and their use
Described are methods of preparing reduced 3,7-diamino-10H-phenothiazine (DAPTZ) compounds of formula: ##STR00001##
wherein: R.sup.1 and R.sup.9 are independently selected from: —H; C.sub.1-4alkyl; C.sub.2-4alkenyl; and halogenated C.sub.1-4alkyl; each of R.sup.3NA and R.sup.3NB is independently selected from: —H; C.sub.1-4alkyl; C.sub.2-4alkenyl; and halogenated C.sub.1-4alkyl; each of R.sup.7NA and R.sup.7NB is independently selected from: —H; C.sub.1-4alkyl; C.sub.2-4alkenyl; and halogenated C.sub.1-4alkyl; each of HX.sup.1 and HX.sup.2 is independently a protic acid; and pharmaceutically acceptable salts, solvates, and hydrates thereof. These methods are particularly useful for producing stable reduced forms, and with high purity. The stability and purity are especially relevant for pharmaceutical compositions for the treatment of disease. The compounds are useful for treatment of e.g. tauopathies, such as Alzheimer's disease, and also as prodrugs for the corresponding oxidized thioninium drugs.
PHENOTHIAZINE DIAMINIUM SALTS AND THEIR USE
- Colin Marshall ,
- Scott Clunas ,
- John Mervyn David Storey ,
- James Peter Sinclair ,
- Thomas Craven Baddeley ,
- Ahtsham Ishaq ,
- Michael Simpson ,
- Craig Williamson ,
- Barry Alan Wood ,
- Claude Michel Wischik ,
- Charles Robert Harrington ,
- Janet Elizabeth Rickard ,
- David Horsley ,
- Yin Sze Loh ,
- Karrar Ahmad Khan ,
- Christopher Paul Larch
Disclosed are compounds of general formula (I):
##STR00001##
and pharmaceutically acceptable salts thereof, formulations, methods and uses in, for example, the treatment of disease.
PHENOTHIAZINE DIAMINIUM SALTS AND THEIR USE
- Colin Marshall ,
- Scott Clunas ,
- John Mervyn David Storey ,
- James Peter Sinclair ,
- Thomas Craven Baddeley ,
- Ahtsham Ishaq ,
- Michael Simpson ,
- Craig Williamson ,
- Barry Alan Wood ,
- Claude Michel Wischik ,
- Charles Robert Harrington ,
- Janet Elizabeth Rickard ,
- David Horsley ,
- Yin Sze Loh ,
- Karrar Ahmad Khan ,
- Christopher Paul Larch
Disclosed are compounds of general formula (I):
##STR00001##
and pharmaceutically acceptable salts thereof, formulations, methods and uses in, for example, the treatment of disease.
PHENOTHIAZINE ANALOGUES AS MITOCHONDRIAL THERAPEUTIC AGENTS
The present disclosure provides phenothiazine derivative compounds and salts thereof, compositions comprising these compounds, and methods of using these compounds in a variety of applications, such as treatment or suppression of diseases associated with decreased mitochondrial function resulting in diminished ATP production and/or oxidative stress and/or lipid peroxidation.
PHENOTHIAZINE ANALOGUES AS MITOCHONDRIAL THERAPEUTIC AGENTS
The present disclosure provides phenothiazine derivative compounds and salts thereof, compositions comprising these compounds, and methods of using these compounds in a variety of applications, such as treatment or suppression of diseases associated with decreased mitochondrial function resulting in diminished ATP production and/or oxidative stress and/or lipid peroxidation.
Ligand compound, transition metal compound, and catalyst composition including the same
The present invention provides a novel ligand compound, a transition metal compound and a catalyst composition including the same.
METHODS OF SYNTHESIS AND/OR PURIFICATION OF DIAMINOPHENOTHIAZINIUM COMPOUNDS
Disclosed are methods of synthesis and/or purification of certain 3,7-diamino-phenothiazin-5-ium compounds (“diaminophenothiazinium compounds”) including Methylthioninium Chloride (MTC) (Methylene Blue), and the resulting high purity characterized by a purity greater than 98%, and very low levels of heavy metals and organic impurities Azure A, B, C and MVB. Also disclosed are methods of treatment of a tauopathy or methemoglobinemia in a patient in need thereof, comprising administering to the patient a therapeutically effective amount of the high-purity diaminophenothiazinium compound.
METHODS OF SYNTHESIS AND/OR PURIFICATION OF DIAMINOPHENOTHIAZINIUM COMPOUNDS
Disclosed are methods of synthesis and/or purification of certain 3,7-diamino-phenothiazin-5-ium compounds (“diaminophenothiazinium compounds”) including Methylthioninium Chloride (MTC) (Methylene Blue), and the resulting high purity characterized by a purity greater than 98%, and very low levels of heavy metals and organic impurities Azure A, B, C and MVB. Also disclosed are methods of treatment of a tauopathy or methemoglobinemia in a patient in need thereof, comprising administering to the patient a therapeutically effective amount of the high-purity diaminophenothiazinium compound.