The present invention relates to novel compounds for the treatment, alleviation or prevention of a group of diseases, disorders and abnormalities which are responsive to the modulation or inhibition of the activation of a component of the NLRP3 inflammasome pathway. In particular, the component of the inflammasome pathway is a NOD-like receptor (NLR) family, pyrin domain-containing protein 3 (NLRP3) inflammasome. More particularly, the compounds of the present invention have the capability to modulate the NLRP3 inflammasome pathway. Further, the compounds of the present invention are suitable for the treatment, alleviation or prevention of a group of diseases, disorders and abnormalities which are responsive to the modulation, in particular decrease, IL-1 beta and/or IL-18 levels.

The present invention relates to novel compounds for the treatment, alleviation or prevention of a group of diseases, disorders and abnormalities which are responsive to the modulation or inhibition of the activation of a component of the NLRP3 inflammasome pathway. In particular, the component of the inflammasome pathway is a NOD-like receptor (NLR) family, pyrin domain-containing protein 3 (NLRP3) inflammasome. More particularly, the compounds of the present invention have the capability to modulate the NLRP3 inflammasome pathway. Further, the compounds of the present invention are suitable for the treatment, alleviation or prevention of a group of diseases, disorders and abnormalities which are responsive to the modulation, in particular decrease, IL-1 beta and/or IL-18 levels.

Described herein, inter alia, are compounds for treating cancer and methods of use. This disclosure features chemical entities (e.g., small hairpin RNAs (shRNAs), micro RNA (miRNAs), small interfering RNA (siRNAs), small molecule inhibitors, antisense nucleic acids, peptides, viruses, CRISPR-sgRNAs, or combinations thereof) that inhibit one or more of m6A writers (e.g., methyltransferase like 3 (Mettl3 or MT-A70) or methyltransferase like-14 (Mettl14)), m6Am writers (e.g., phosphorylated CTD interacting factor I (PCIF 1), or Mettl3/14), m6A erasers (e.g., fat-mass and obesity-associated protein (FTO) or ALKB homolog 5 (ALKBH5)), m6Am erasers (e.g., FTO), m6A readers (e.g., YTH domain-containing family proteins (YTHs)), YTF domain family member 1 (YTHDF 1), YTF domain family member 2 (YTHDF 2), YTF domain family member 3 (YTHDF 3), or tyrosine-protein phosphatase non-receptor type 2 (PTPN2).

The disclosure provides a naphthylurea compound having a formula I. In the formula, m and n represent a number of CH.sub.2, and are an integer from 1 to 10; k and z represent a number of CH.sub.2, and are an integer from 0 to 6; and p represents a number of CH.sub.2, and is 1, 2 or 3; and X is O or S.

The disclosure provides a naphthylurea compound having a formula I. In the formula, m and n represent a number of CH.sub.2, and are an integer from 1 to 10; k and z represent a number of CH.sub.2, and are an integer from 0 to 6; and p represents a number of CH.sub.2, and is 1, 2 or 3; and X is O or S.

A compound represented by formula (2) or pharmaceutically acceptable salt thereof:

##STR00001##

wherein R.sup.1 represents a hydrogen atom or the like; R.sup.2 represents a methoxy group or the like; R.sup.3 represents a hydrogen atom or the like; R.sup.4 represents an optionally substituted C.sub.1-6 alkyl group or the like; m represents 0, 1, or 2; n represents 0, 1, 2, or 3; L.sup.1 represents —NH—C(═O)—, —C(═O)—NH—, or the like; L.sup.2 represents a single bond or the like; X represents optionally substituted phenyl or the like; Y represents optionally substituted phenyl or the like; and X and Y are bonded at a carbon atom on each ring.

A compound represented by formula (2) or pharmaceutically acceptable salt thereof:

##STR00001##

wherein R.sup.1 represents a hydrogen atom or the like; R.sup.2 represents a methoxy group or the like; R.sup.3 represents a hydrogen atom or the like; R.sup.4 represents an optionally substituted C.sub.1-6 alkyl group or the like; m represents 0, 1, or 2; n represents 0, 1, 2, or 3; L.sup.1 represents —NH—C(═O)—, —C(═O)—NH—, or the like; L.sup.2 represents a single bond or the like; X represents optionally substituted phenyl or the like; Y represents optionally substituted phenyl or the like; and X and Y are bonded at a carbon atom on each ring.

This disclosure provides large-scale processes for preparing a modulator of alpha-1 antitrypsin (AAT) activity that may be useful for treating alpha-1 antitrypsin deficiency (AATD), such as 4-(5-(4-fluorophenyl)-6-(tetrahydro-2H-pyran -4-yl)-1,5-dihydropyrrolo[2,3-f]indazol-7-yl)benzoic acid (Compound 1), 3-[5-(4-fluorophenyl)-6-isopropyl-1H-pyrrolo[2,3-f]inda-zol-7-yl]propanoic acid (Compound 2), or a pharmaceutically acceptable salt of any of the foregoing.

This disclosure provides large-scale processes for preparing a modulator of alpha-1 antitrypsin (AAT) activity that may be useful for treating alpha-1 antitrypsin deficiency (AATD), such as 4-(5-(4-fluorophenyl)-6-(tetrahydro-2H-pyran -4-yl)-1,5-dihydropyrrolo[2,3-f]indazol-7-yl)benzoic acid (Compound 1), 3-[5-(4-fluorophenyl)-6-isopropyl-1H-pyrrolo[2,3-f]inda-zol-7-yl]propanoic acid (Compound 2), or a pharmaceutically acceptable salt of any of the foregoing.

The present invention comprises novel aromatic molecules, which can be used in the treatment of pathological conditions, such as cancer, skin diseases, muscle disorders, and immune system-related disorders such as disorders of the haematopoietic system including the haematologic system in human and veterinary medicine.