Mutations in oncogenes and tumor suppressors contribute to the development and progression of cancer. The present disclosure describes compounds and methods that restore DNA binding affinity of p53 mutants. The compounds of the present disclosure can bind to mutant p53 and restore the ability of the p53 mutant to bind DNA and activate downstream effectors involved in tumor suppression. The disclosed compounds can be used to reduce the progression of cancers that contain a p53 mutation.

New aminoindanes amides are described, having general formula (I)

##STR00001##

the relative phytosanitary compositions and their use for the control of phytopathogenic fungi.

New aminoindanes amides are described, having general formula (I)

##STR00001##

the relative phytosanitary compositions and their use for the control of phytopathogenic fungi.

The invention provides compositions or pharmaceutical compositions of novel high penetration compositions (HPC) of a parent compound, which are capable of crossing biological barriers with high penetration efficiency. The HPCs are capable of being converted to parent drugs or parent drug-related compounds such as metabolites after crossing one or more biological barriers and thus can render treatments for the conditions that the parent drugs or parent drug-related compounds can. Additionally, the HPCs are capable of reaching areas that their parent drugs or parent drug-related compounds may not be able to access or to render a sufficient concentration at the target areas and therefore render novel treatments. For example, HPCs of NSAIA have demonstrated indications such as treating hair loss and bold. A HPC can be administered to a subject through various administration routes, e.g., locally delivered to an action site of a condition with a high concentration or systematically administered to a biological subject and enter the general circulation with a faster rate.

The invention provides compositions or pharmaceutical compositions of novel high penetration compositions (HPC) of a parent compound, which are capable of crossing biological barriers with high penetration efficiency. The HPCs are capable of being converted to parent drugs or parent drug-related compounds such as metabolites after crossing one or more biological barriers and thus can render treatments for the conditions that the parent drugs or parent drug-related compounds can. Additionally, the HPCs are capable of reaching areas that their parent drugs or parent drug-related compounds may not be able to access or to render a sufficient concentration at the target areas and therefore render novel treatments. For example, HPCs of NSAIA have demonstrated indications such as treating hair loss and bold. A HPC can be administered to a subject through various administration routes, e.g., locally delivered to an action site of a condition with a high concentration or systematically administered to a biological subject and enter the general circulation with a faster rate.

A process for preparing and purifying a compound of Formula I is provided:

##STR00001##

thereof, wherein the subscript m is an integer of from 0 to 3; each R.sup.a is independently selected from the group consisting of (C.sub.3-C.sub.8)cycloalkyl, (C.sub.1-C.sub.4)haloalkyl, halogen, —OH, —OR.sup.1, —SH, —SR.sup.1, —S(O)R.sup.1, —S(O).sub.2R.sup.1, —SO.sub.2NH.sub.2, —C(O)NH.sub.2, —C(O)NHR.sup.1, —C(O)N(R.sup.1).sub.2, —C(O)R.sup.1, —C(O)H, —CO.sub.2H, —CO.sub.2R.sup.1, —NO.sub.2, —NH.sub.2, —NHR.sup.1, —N(R.sup.1).sub.2, wherein each R.sup.1 is independently (C.sub.1-C.sub.8)alkyl; L is a linking group selected from the group consisting of a bond or CH.sub.2; Q.sup.a, Q.sup.b, and Q.sup.c are each members independently selected from the group consisting of N, S, O and C(R.sup.q) wherein each R.sup.q is independently selected from the group consisting of H, C.sub.1-8 alkyl, halo and phenyl, and the ring having Q.sup.a, Q.sup.b, Q.sup.c and Y as ring vertices is a five-membered ring having two double bonds; and
Y is selected from the group consisting of C and N.

A process for preparing and purifying a compound of Formula I is provided:

##STR00001##

thereof, wherein the subscript m is an integer of from 0 to 3; each R.sup.a is independently selected from the group consisting of (C.sub.3-C.sub.8)cycloalkyl, (C.sub.1-C.sub.4)haloalkyl, halogen, —OH, —OR.sup.1, —SH, —SR.sup.1, —S(O)R.sup.1, —S(O).sub.2R.sup.1, —SO.sub.2NH.sub.2, —C(O)NH.sub.2, —C(O)NHR.sup.1, —C(O)N(R.sup.1).sub.2, —C(O)R.sup.1, —C(O)H, —CO.sub.2H, —CO.sub.2R.sup.1, —NO.sub.2, —NH.sub.2, —NHR.sup.1, —N(R.sup.1).sub.2, wherein each R.sup.1 is independently (C.sub.1-C.sub.8)alkyl; L is a linking group selected from the group consisting of a bond or CH.sub.2; Q.sup.a, Q.sup.b, and Q.sup.c are each members independently selected from the group consisting of N, S, O and C(R.sup.q) wherein each R.sup.q is independently selected from the group consisting of H, C.sub.1-8 alkyl, halo and phenyl, and the ring having Q.sup.a, Q.sup.b, Q.sup.c and Y as ring vertices is a five-membered ring having two double bonds; and
Y is selected from the group consisting of C and N.

Improved processes for the preparation of tubulysin compounds, tubulysin drug linker compounds, and their intermediates are disclosed.

A nitrogen-containing ring derivative regulator, a preparation method therefor and use thereof. In particular, the present invention relates to a compound as represented by general formula (I), a preparation method therefor, a pharmaceutical composition containing the compound, and use thereof as a G protein-coupled receptor regulator in the treatment or prevention of central nervous system diseases and/or mental diseases.

##STR00001##

Provided are a 2-arylthiazole derivative or pharmaceutically acceptable salt thereof having a specific carboxamide moiety, including a substituted aminoalkyl-carboxamide moiety, a N-containing heterocyclic-alkyl-carboxamide moiety, or a N-containing heterocyclic-carboxamide moiety, a process for the preparation thereof, and a pharmaceutical composition comprising the same.