Provided herein are compositions and related methods useful for free radical scavenging, with particular selectivity for mitochondria. The compounds comprise a nitroxide-containing group attached to a mitochondria-targeting group. The compounds can be cross-linked into dimers without loss of activity. Also provided herein are methods, for preventing, mitigating and treating damage caused by radiation. The method comprises delivering a compound, as described herein, to a patient in an amount and dosage regimen effective to prevent, mitigate or treat damage caused by radiation.

A compound containing a benzene ring as shown in formula I, a pharmaceutically acceptable salt thereof, a stereoisomer thereof, a tautomer thereof, an isotopic compound thereof, a crystal form thereof, a nitrogen oxide thereof, and a solvate thereof or a solvate of the pharmaceutically acceptable salt thereof are provided. The compound has high P2X4 antagonistic activity, good selectivity, low toxicity and good metabolic stability.

##STR00001##

There are provided substituted 4-carboxamido-isoindolinone derivatives which selectively inhibit the activity of poly (ADP-ribose) polymerase PARP-1 with respect to poly (ADP-ribose) polymerase P ARP-2. The compounds of this invention are therefore useful in treating diseases such as cancer, cardiovascular diseases, central nervous system injury and different forms of inflammation. The present invention also provides methods for preparing these compounds, pharmaceutical compositions comprising these compounds, and methods of treating diseases utilizing pharmaceutical compositions comprising these compounds.

There are provided substituted 4-carboxamido-isoindolinone derivatives which selectively inhibit the activity of poly (ADP-ribose) polymerase PARP-1 with respect to poly (ADP-ribose) polymerase P ARP-2. The compounds of this invention are therefore useful in treating diseases such as cancer, cardiovascular diseases, central nervous system injury and different forms of inflammation. The present invention also provides methods for preparing these compounds, pharmaceutical compositions comprising these compounds, and methods of treating diseases utilizing pharmaceutical compositions comprising these compounds.

A method for the manufacture of a 2-hydrocarbyl-3,3-bis(hydroxyaryl)phthalimidine composition comprises: reacting a phthalimide with a phenol in the presence of a catalyst and optionally a solvent at an elevated temperature to form the 2-hydrocarbyl-3,3-bis(hydroxyaryl)phthalimidine composition.

A method for the manufacture of a 2-hydrocarbyl-3,3-bis(hydroxyaryl)phthalimidine composition comprises: reacting a phthalimide with a phenol in the presence of a catalyst and optionally a solvent at an elevated temperature to form the 2-hydrocarbyl-3,3-bis(hydroxyaryl)phthalimidine composition.

The present invention discloses the preparation and application of heterocyclic compound having immunoregulatory function. Specifically, the present invention discloses a compound having a structure according to Formula I, wherein the definition of each group is as described in the specification. The invention also provides the use of the compounds in regulating immunity and inhibiting PD-1/PD-L1.

##STR00001##

An object of this disclosure provides a novel method for producing a fluorovinyl amide compound and the like. The object is achieved by a method for producing a compound represented by formula (1):

##STR00001##

wherein
Rf is —F or fluoroalkyl,
R.sup.a1 is —H or an organic group, and
R.sup.a2 is —H or an organic group, or
(i) R.sup.a1 and R.sup.a2, (ii) R.sup.a1 and Rf, or (iii) Rf and R.sup.a2, may be linked to each other,
R.sup.b1 is —H or an organic group, and
R.sup.b2 is —H or an organic group, or
R.sup.b1 and R.sup.b2 may be linked together with their adjacent atoms to form a nitrogen-containing ring optionally having one or more substituents,
the method comprising
step A of reacting a compound represented by formula (2):

##STR00002##

wherein
R.sup.x is a leaving group,
with a compound represented by formula (3) or a salt thereof:

##STR00003##

in the presence of a transition metal catalyst.

A stable Crystalline Form II of non-solvate of Apremilast (Formula I), methods of making Form II, pharmaceutical compositions comprising Form II, and their uses are disclosed. Also discloses are mixed crystals comprising Form Hand Form B and methods of making the same. The crystalline forms are characterized using X-ray powder diffractometry (XRPD), infrared spectroscopy (IR), differential scanning calorimetry (DSC), and thermal gravimetric analysis (TG). As compared with Forms A, B, C, D, E, F, and G reported in prior art references, Apremilast Form II of the present invention is more stable to temperature, light, and humidity, and is more suitable for long term storage; the crystallization solvents are safe and can be easily removed; the Form II has a white or off white appearance, and can be directly used in preparation processing; the preparation methods are simple and easy to reproduce, and are suitable for industrialized production.

##STR00001##

A stable Crystalline Form II of non-solvate of Apremilast (Formula I), methods of making Form II, pharmaceutical compositions comprising Form II, and their uses are disclosed. Also discloses are mixed crystals comprising Form Hand Form B and methods of making the same. The crystalline forms are characterized using X-ray powder diffractometry (XRPD), infrared spectroscopy (IR), differential scanning calorimetry (DSC), and thermal gravimetric analysis (TG). As compared with Forms A, B, C, D, E, F, and G reported in prior art references, Apremilast Form II of the present invention is more stable to temperature, light, and humidity, and is more suitable for long term storage; the crystallization solvents are safe and can be easily removed; the Form II has a white or off white appearance, and can be directly used in preparation processing; the preparation methods are simple and easy to reproduce, and are suitable for industrialized production.

##STR00001##