Provided is a method of preparing 3-fluoroalkyl-1-substituted pyrazol-4-carboxylic acid by air oxidation. The methoduses 3-fluoroalkyl-1-substituted pyrazol-4-formaldehyde as raw material for reaction in a neutral or alkaline condition under the action of a catalyst and with air as an oxidizing agent, to obtain 3-fluoroalkyl-1-substituted pyrazol-4-carboxylic acid. The method employs a mild, safe and clean reaction, and is suitable for industrial mass production.

This invention is directed to pyrrole, pyrazole, imidazole, triazole, and morpholine based selective androgen receptor degrader (SARD) compounds including heterocyclic anilide rings and their synthetic precursors, R-isomers, and non-hydroxylated and/or non-chiral propanamides, and pharmaceutical compositions and uses thereof in treating prostate cancer, advanced prostate cancer, castration resistant prostate cancer, triple negative breast cancer, other cancers expressing the androgen receptor, androgenic alopecia or other hyperandrogenic dermal diseases, Kennedy's disease, amyotrophic lateral sclerosis (ALS), abdominal aortic aneurysm (AAA), and uterine fibroids, and to methods for reducing the levels of androgen receptor-full length (AR-FL) including pathogenic or resistance mutations, AR-splice variants (AR-SV), and pathogenic polyglutamine (polyQ) polymorphisms of AR in a subject.

This invention is directed to pyrrole, pyrazole, imidazole, triazole, and morpholine based selective androgen receptor degrader (SARD) compounds including heterocyclic anilide rings and their synthetic precursors, R-isomers, and non-hydroxylated and/or non-chiral propanamides, and pharmaceutical compositions and uses thereof in treating prostate cancer, advanced prostate cancer, castration resistant prostate cancer, triple negative breast cancer, other cancers expressing the androgen receptor, androgenic alopecia or other hyperandrogenic dermal diseases, Kennedy's disease, amyotrophic lateral sclerosis (ALS), abdominal aortic aneurysm (AAA), and uterine fibroids, and to methods for reducing the levels of androgen receptor-full length (AR-FL) including pathogenic or resistance mutations, AR-splice variants (AR-SV), and pathogenic polyglutamine (polyQ) polymorphisms of AR in a subject.

Compounds of the formula (I), wherein the substituents are as defined in claim 1, useful as a pesticides, especially as fungicides.

##STR00001##

Compounds of the formula (I), wherein the substituents are as defined in claim 1, useful as a pesticides, especially as fungicides.

##STR00001##

This invention is directed to pyrrole, pyrazole, imidazole, triazole, and morpholine based selective androgen receptor degrader (SARD) compounds including cyclic and heterocyclic anilide rings and their synthetic precursors, and mono-, di-, or multi-substituted N-heterocyclic rings, R-isomers, non-hydroxylated and/or non-chiral propanamides in treating androgen receptor dependent diseases and conditions such as hyperproliferations of the prostate including pre-malignancies and benign prostatic hyperplasia, prostate cancer, advanced prostate cancer, castration resistant prostate cancer, triple negative breast cancer, other cancers expressing the androgen receptor, androgenic alopecia or other hyperandrogenic dermal diseases, Kennedy's disease, amyotrophic lateral sclerosis (ALS), abdominal aortic aneurysm (AAA), and uterine fibroids, and to methods for reducing the levels of androgen receptor-full length (AR-FL) including pathogenic or resistance mutations, AR-splice variants (AR-SV), and pathogenic polyglutamine (polyQ) polymorphisms of AR in a subject.

A compound represented by Formula (I), or a salt or N-oxide compound thereof is provided.

##STR00001##

In Formula (I), A.sup.1 to A.sup.4 each independently represents a carbon atom or nitrogen atom, X.sup.1 represents a C1-6 alkyl group or the like, n represents the number of X.sup.1 groups, R.sup.1 represents a C1-6 alkylthio group or the like, and D is a group represented by Formula (D-1) or (D-2), and

##STR00002##

in Formula (D-1) and (D-2), * represents a binding position, Q represents a C1-6 alkyl group or the like, B.sup.1 and B.sup.2 each independently represents a nitrogen atom or the like, R.sup.2 represents a C1-6 alkyl group or the like that is bound to one of the nitrogen atoms in Formula (D-1), B.sup.3 and B.sup.4 each independently represents a nitrogen atom or carbon atom, R.sup.4 represents a C1-6 alkyl group or the like, and m represents the number of R.sup.4 groups.

A compound represented by Formula (I), or a salt or N-oxide compound thereof is provided.

##STR00001##

In Formula (I), A.sup.1 to A.sup.4 each independently represents a carbon atom or nitrogen atom, X.sup.1 represents a C1-6 alkyl group or the like, n represents the number of X.sup.1 groups, R.sup.1 represents a C1-6 alkylthio group or the like, and D is a group represented by Formula (D-1) or (D-2), and

##STR00002##

in Formula (D-1) and (D-2), * represents a binding position, Q represents a C1-6 alkyl group or the like, B.sup.1 and B.sup.2 each independently represents a nitrogen atom or the like, R.sup.2 represents a C1-6 alkyl group or the like that is bound to one of the nitrogen atoms in Formula (D-1), B.sup.3 and B.sup.4 each independently represents a nitrogen atom or carbon atom, R.sup.4 represents a C1-6 alkyl group or the like, and m represents the number of R.sup.4 groups.

A compound represented by Formula (I), or a salt or N-oxide compound thereof is provided. ##STR00001## In Formula (I), A.sup.1 to A.sup.4 each independently represents a carbon atom or nitrogen atom, X.sup.1 represents a C1-6 alkyl group or the like, n represents the number of X.sup.1 groups, R.sup.1 represents a C1-6 alkylthio group or the like, and D is a group represented by Formula (D-1) or (D-2), and ##STR00002## in Formula (D-1) and (D-2), * represents a binding position, Q represents a C1-6 alkyl group or the like, B.sup.1 and B.sup.2 each independently represents a nitrogen atom or the like, R.sup.2 represents a C1-6 alkyl group or the like that is bound to one of the nitrogen atoms in Formula (D-1), B.sup.3 and B.sup.4 each independently represents a nitrogen atom or carbon atom, R.sup.4 represents a C1-6 alkyl group or the like, and m represents the number of R.sup.4 groups.

A compound represented by Formula (I), or a salt or N-oxide compound thereof is provided. ##STR00001## In Formula (I), A.sup.1 to A.sup.4 each independently represents a carbon atom or nitrogen atom, X.sup.1 represents a C1-6 alkyl group or the like, n represents the number of X.sup.1 groups, R.sup.1 represents a C1-6 alkylthio group or the like, and D is a group represented by Formula (D-1) or (D-2), and ##STR00002## in Formula (D-1) and (D-2), * represents a binding position, Q represents a C1-6 alkyl group or the like, B.sup.1 and B.sup.2 each independently represents a nitrogen atom or the like, R.sup.2 represents a C1-6 alkyl group or the like that is bound to one of the nitrogen atoms in Formula (D-1), B.sup.3 and B.sup.4 each independently represents a nitrogen atom or carbon atom, R.sup.4 represents a C1-6 alkyl group or the like, and m represents the number of R.sup.4 groups.