The invention provides a method of sustained delivery of a lactam, imide, amide, sulfonamide, carbamate or urea containing parent drug by administering to a patient an effective amount of a prodrug compound of the invention wherein upon administration to the patient, release of the parent drug from the prodrug is sustained release. Prodrug compounds suitable for use in the methods of the invention are labile conjugates of parent drugs that are derivatized through carbonyl linked prodrug moieties. The prodrug compounds of the invention can be used to treat any condition for which the lactam, imide, amide, sulfonamide, carbamate or urea containing parent drug is useful as a treatment.

The invention provides a method of sustained delivery of a lactam, imide, amide, sulfonamide, carbamate or urea containing parent drug by administering to a patient an effective amount of a prodrug compound of the invention wherein upon administration to the patient, release of the parent drug from the prodrug is sustained release. Prodrug compounds suitable for use in the methods of the invention are labile conjugates of parent drugs that are derivatized through carbonyl linked prodrug moieties. The prodrug compounds of the invention can be used to treat any condition for which the lactam, imide, amide, sulfonamide, carbamate or urea containing parent drug is useful as a treatment.

A process for preparing a compound of Formula I is disclosed, comprising the steps:

##STR00001##

wherein: R.sup.1 is halo; R.sup.2 is halo; R.sup.3 is (C.sub.1-C.sub.6)alkyl or (C.sub.1-C.sub.6)alkyl optionally substituted with heterocycloalkyl; R.sup.4 is (C.sub.1-C.sub.6)alkyl; and Q is CH or N;
comprising: (a) contacting 1,1-cyclopropane dicarboxylic acid with thionyl chloride in a polar aprotic solvent;

##STR00002## (b) adding and a tertiary amine base to the mixture of step (a) to form a compound of Formula A; and

##STR00003## (c) coupling a compound of Formula A with an amine of Formula B to form a compound of Formula I.

##STR00004##

A process for preparing a compound of Formula I is disclosed, comprising the steps:

##STR00001##

wherein: R.sup.1 is halo; R.sup.2 is halo; R.sup.3 is (C.sub.1-C.sub.6)alkyl or (C.sub.1-C.sub.6)alkyl optionally substituted with heterocycloalkyl; R.sup.4 is (C.sub.1-C.sub.6)alkyl; and Q is CH or N;
comprising: (a) contacting 1,1-cyclopropane dicarboxylic acid with thionyl chloride in a polar aprotic solvent;

##STR00002## (b) adding and a tertiary amine base to the mixture of step (a) to form a compound of Formula A; and

##STR00003## (c) coupling a compound of Formula A with an amine of Formula B to form a compound of Formula I.

##STR00004##

This invention provides novel indole, indazole, benzimidazole, indoline, quinolone, isoquinoline, and carbazole selective androgen receptor degrader (SARD) compounds, pharmaceutical compositions and uses thereof in treating prostate cancer, advanced prostate cancer, castration resistant prostate cancer, other AR-expressing cancers, androgenic alopecia or other hyper androgenic dermal diseases, Kennedy's disease, amyotrophic lateral sclerosis (ALS), abdominal aortic aneurysm (AAA), and uterine fibroids, and to methods for reducing the levels (through degradation) and/or activity (through inhibition) of any androgen receptor including androgen receptor-full length (AR-FL) including pathogenic and/or resistance mutations, AR-splice variants (AR-SV), and pathogenic polyglutamine (polyQ) polymorphisms of AR in a subject.

This invention provides novel indole, indazole, benzimidazole, indoline, quinolone, isoquinoline, and carbazole selective androgen receptor degrader (SARD) compounds, pharmaceutical compositions and uses thereof in treating prostate cancer, advanced prostate cancer, castration resistant prostate cancer, other AR-expressing cancers, androgenic alopecia or other hyper androgenic dermal diseases, Kennedy's disease, amyotrophic lateral sclerosis (ALS), abdominal aortic aneurysm (AAA), and uterine fibroids, and to methods for reducing the levels (through degradation) and/or activity (through inhibition) of any androgen receptor including androgen receptor-full length (AR-FL) including pathogenic and/or resistance mutations, AR-splice variants (AR-SV), and pathogenic polyglutamine (polyQ) polymorphisms of AR in a subject.

A process for preparing a compound of Formula I is disclosed, comprising the steps: ##STR00001##
wherein: R.sup.1 is halo; R.sup.2 is halo; R.sup.3 is (C.sub.1-C.sub.6)alkyl or (C.sub.1-C.sub.6)alkyl optionally substituted with heterocycloalkyl; R.sup.4 is (C.sub.1-C.sub.6)alkyl; and Q is CH or N;
comprising: (a) contacting 1,1-cyclopropane dicarboxylic acid with thionyl chloride in a polar aprotic solvent; (b) adding ##STR00002##
and a tertiary amine base to the mixture of step (a) to form a compound of Formula A; and ##STR00003## (c) coupling a compound of Formula A with an amine of Formula B to form a compound of Formula I. ##STR00004##

A process for preparing a compound of Formula I is disclosed, comprising the steps: ##STR00001##
wherein: R.sup.1 is halo; R.sup.2 is halo; R.sup.3 is (C.sub.1-C.sub.6)alkyl or (C.sub.1-C.sub.6)alkyl optionally substituted with heterocycloalkyl; R.sup.4 is (C.sub.1-C.sub.6)alkyl; and Q is CH or N;
comprising: (a) contacting 1,1-cyclopropane dicarboxylic acid with thionyl chloride in a polar aprotic solvent; (b) adding ##STR00002##
and a tertiary amine base to the mixture of step (a) to form a compound of Formula A; and ##STR00003## (c) coupling a compound of Formula A with an amine of Formula B to form a compound of Formula I. ##STR00004##

The invention provides a chemical entity of Formula (I) ##STR00001##
wherein R.sup.1, R.sup.2, R.sup.3, Y, and n have any of the values described herein and compositions comprising such chemical entities; methods of making them; and their use in a wide range of methods, including metabolic and reaction kinetic studies, detection and imaging techniques, and radioactive treatments; and therapies, including inhibiting MAO, and MAO-B selectively, enhancing neuronal plasticity, treating neurological disorders, providing neuroprotection, treating a cognitive impairment associated with a CNS disorder, enhancing the efficiency of cognitive and motor training, providing neurorecovery and neurorehabilitation, enhancing the efficiency of non-human animal training protocols, and treating peripheral disorders (including obesity, diabetes, and cardiometabolic disorders) and their associated co-morbidities.

Disclosed herein, inter alia, are compositions and methods for inhibiting DNA2.