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.

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.

This disclosure relates to new phthalimide and isoindolinone derivatives and other PFKFB3 inhibitors for use in the treatment of diseases. The invention further relates to pharmaceutical compositions containing such PFKFB3 inhibitors, methods of preparation thereof, methods for their use as therapeutic agents, and methods of preparation of a medicament for use in therapy, as well as kits and other inventions comprising such PFKFB3 inhibitors. These PFKFB3 inhibitors are useful for the treatment and prophylaxis of cancer, neurodegenerative diseases, autoimmune diseases, inflammatory disorders, multiple sclerosis, metabolic diseases, inhibition of angiogenesis and other diseases and conditions, where the modulation of PFKFB3 and/or PFKFB4 has beneficial effect as well as neuroprotection.

Disclosed are a 3-N-cyclopropylmethyl-2-fluorobenzamide compound, a preparation method therefor and the use thereof. The compound has a structure as represented by the following formula I. This compound can be used for the preparation of an m-diamide compound substituted with a 3-N-cyclopropylmethyl derivative. The m-diamide compound substituted with the 3-N-cyclopropylmethyl derivative, when serving as an insecticide, has the characteristics of a good fast-acting property, needing to use a low amount thereof, and being more beneficial for environmental protection. The 3-N-cyclopropylmethyl-2-fluorobenzamide compound is easy to synthesize and has mild conditions, and when used for preparing a m-diamide compound insecticide substituted with a 3-N-cyclopropylmethyl derivative, same is easy to synthesize and has a low synthesis cost and a high yield.

Disclosed are a 3-N-cyclopropylmethyl-2-fluorobenzamide compound, a preparation method therefor and the use thereof. The compound has a structure as represented by the following formula I. This compound can be used for the preparation of an m-diamide compound substituted with a 3-N-cyclopropylmethyl derivative. The m-diamide compound substituted with the 3-N-cyclopropylmethyl derivative, when serving as an insecticide, has the characteristics of a good fast-acting property, needing to use a low amount thereof, and being more beneficial for environmental protection. The 3-N-cyclopropylmethyl-2-fluorobenzamide compound is easy to synthesize and has mild conditions, and when used for preparing a m-diamide compound insecticide substituted with a 3-N-cyclopropylmethyl derivative, same is easy to synthesize and has a low synthesis cost and a high yield.

The present invention relates to hyper-branched compounds, a method of synthesizing the hyper-branched compounds and applications of the hyper-branched compounds. The hyper-branched compounds of the present invention include hyper-branched fluorinated compounds, hyper-branched fluorinated graphene and hyper-branched amine functionalized graphene oxide.

The application is directed to compounds of formulae (IA) and (IB): (IA) and (IB), and their salts and solvates, wherein R.sup.1a, R.sup.2a, .sup.A1, A.sup.2, A.sup.3, A.sup.4, R.sup.1b, R.sup.2b, B.sup.1, B.sup.2, B.sup.3, and G are as set forth in the specification, as well as to methods for their preparation, N pharmaceutical compositions comprising the same, and use thereof for the treatment and/or prevention of, e.g., lysosomal storage diseases, such as Krabbe's disease, and α-synucleinopathies, such as Parkinson's disease.

##STR00001##

A compound of formula (Ic)

##STR00001## wherein X.sup.2 represents a —CO—NR.sub.k— group, wherein R.sub.k represents a hydrogen atom or a methyl group, a —NH—CO—NH— group, a —OCH.sub.2— group, a —CH(OH)— group, a —NH—CO— group, a —O— group, a —O—(CH.sub.2).sub.s—O—, a —CO— group, a —SO.sub.2— group, a divalent 5-membered heteroaromatic ring comprising 1, 2, 3 or 4 heteroatoms, —a NH—SO.sub.2— or a —SO.sub.2—NH— group; Y.sup.2 represents a hydrogen atom, a halogen atom, a hydroxyl group, a (C.sub.1-C.sub.4)alkoxy group, a

##STR00002##

a

##STR00003##

group, a

##STR00004##

group, a morpholinyl group, optionally substituted by a (C.sub.1-C.sub.4)alkyl group, a piperazinyl group, a piperidinyl group, or a —CR.sup.1R.sup.2R.sup.3 group, or any of its pharmaceutically acceptable salt.

Some embodiments of the invention include inventive compounds (e.g., compounds of Formula (I) or (Ia)). Other embodiments include compositions (e.g., pharmaceutical compositions) comprising the inventive compound. Still other embodiments of the invention include compositions (e.g., pharmaceutical compositions) for treating, for example, certain diseases or nerve injury using the inventive compounds. Some embodiments include methods of using the inventive compound (e.g., in compositions or in pharmaceutical compositions) for administering and treating (e.g., for treating disease, such as multiple sclerosis (MS), or for treating nerve damage). Further embodiments include methods for making the inventive compounds. Additional embodiments of the invention are also discussed herein.

Some embodiments of the invention include inventive compounds (e.g., compounds of Formula (I) or (Ia)). Other embodiments include compositions (e.g., pharmaceutical compositions) comprising the inventive compound. Still other embodiments of the invention include compositions (e.g., pharmaceutical compositions) for treating, for example, certain diseases or nerve injury using the inventive compounds. Some embodiments include methods of using the inventive compound (e.g., in compositions or in pharmaceutical compositions) for administering and treating (e.g., for treating disease, such as multiple sclerosis (MS), or for treating nerve damage). Further embodiments include methods for making the inventive compounds. Additional embodiments of the invention are also discussed herein.