The present invention relates to novel Collagen I translation inhibitors, composition and methods of preparation thereof, and uses thereof for treating Fibrosis including lung, liver, kidney, cardiac and dermal fibrosis, IPF, wound healing, scarring and Gingival fibromatosis, Systemic Sclerosis, and alcoholic and non-alcoholic steatohepatitis (NASH).

The present invention relates to a method for preparing a biomaterial having selectively functionalized tyrosine, a biomaterial having selectively functionalized tyrosine, and a pharmaceutical composition containing the same as an active ingredient. The method for preparing a biomaterial to which a compound represented by formula 2 is coupled, of the present invention, allows the compound represented by formula 2 to be selectively coupled, in a high yield in a biomaterial, to tyrosine, which is present on the surface of an aqueous solution such that the coupling thereof to amino acids other than tyrosine does not occur and, when only one tyrosine is present, heterogeneous mixtures are not present and the inherent activity of the biomaterial is maintained, and thus the compound can be effectively used as a pharmaceutical composition containing a biomaterial drug as an active ingredient. In addition, the method can selectively functionalize tyrosine, and thus can be effectively used for tyrosine functionalization in a biomaterial.

The present invention relates to a method for preparing a biomaterial having selectively functionalized tyrosine, a biomaterial having selectively functionalized tyrosine, and a pharmaceutical composition containing the same as an active ingredient. The method for preparing a biomaterial to which a compound represented by formula 2 is coupled, of the present invention, allows the compound represented by formula 2 to be selectively coupled, in a high yield in a biomaterial, to tyrosine, which is present on the surface of an aqueous solution such that the coupling thereof to amino acids other than tyrosine does not occur and, when only one tyrosine is present, heterogeneous mixtures are not present and the inherent activity of the biomaterial is maintained, and thus the compound can be effectively used as a pharmaceutical composition containing a biomaterial drug as an active ingredient. In addition, the method can selectively functionalize tyrosine, and thus can be effectively used for tyrosine functionalization in a biomaterial.

This invention is directed to selective androgen receptor degrader (SARD) compounds including heterocyclic rings 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.

There is disclosed a compound of Formula (I):

##STR00001##

and any pharmaceutically acceptable salt or zwitterion thereof; wherein: R is hydrogen, methyl or ethyl; R.sup.1 is hydrogen or C.sub.1-C.sub.2 alkoxy; R.sup.2 is methyl or a C.sub.2-C.sub.4 group which may be saturated or unsaturated, branched or linear; and R.sup.3, R.sup.4, R.sup.5 and R.sup.6 each are independently selected from hydrogen, hydroxyl, halogen, methyl optionally substituted with hydroxy, methoxy, ethoxy, and a saturated or unsaturated C.sub.2-C.sub.3 that may be optionally substituted with hydroxyl, with the provisos that: (i) at least two of R.sup.4, R.sup.5, R.sup.6 and R.sup.7 must be hydrogen, and (ii) R.sup.3, R.sup.4, R.sup.5 and R.sup.6 may be selected such that an adjacent pair thereof join to form a ring having at least 5 members. The compound of Formula (I) is believed useful in treating a disease or disorder in a subject which may be alleviated by a 5HT2A agonist (e.g., CNS disorders and one or more symptoms of any one of depression, alcoholism, tobacco addiction, cocaine addiction, inflammation, cluster headache and PTSD in a subject).

There is disclosed a compound of Formula (I):

##STR00001##

and any pharmaceutically acceptable salt or zwitterion thereof; wherein: R is hydrogen, methyl or ethyl; R.sup.1 is hydrogen or C.sub.1-C.sub.2 alkoxy; R.sup.2 is methyl or a C.sub.2-C.sub.4 group which may be saturated or unsaturated, branched or linear; and R.sup.3, R.sup.4, R.sup.5 and R.sup.6 each are independently selected from hydrogen, hydroxyl, halogen, methyl optionally substituted with hydroxy, methoxy, ethoxy, and a saturated or unsaturated C.sub.2-C.sub.3 that may be optionally substituted with hydroxyl, with the provisos that: (i) at least two of R.sup.4, R.sup.5, R.sup.6 and R.sup.7 must be hydrogen, and (ii) R.sup.3, R.sup.4, R.sup.5 and R.sup.6 may be selected such that an adjacent pair thereof join to form a ring having at least 5 members. The compound of Formula (I) is believed useful in treating a disease or disorder in a subject which may be alleviated by a 5HT2A agonist (e.g., CNS disorders and one or more symptoms of any one of depression, alcoholism, tobacco addiction, cocaine addiction, inflammation, cluster headache and PTSD in a subject).

Provided herein are compounds of Formula (I), or pharmaceutically acceptable salt thereof, wherein R.sub.1, R.sub.2, R.sub.3, R.sub.4, R.sub.5, R.sub.8, R.sub.9, X, Y, Z, W, and m are defined herein. Also provided herein are pharmaceutical compositions comprising a compound of Formula (I) or pharmaceutically acceptable salt thereof and a pharmaceutically acceptable excipient. ##STR00001##

Provided herein are compounds of Formula (I), or pharmaceutically acceptable salt thereof, wherein R.sub.1, R.sub.2, R.sub.3, R.sub.4, R.sub.5, R.sub.8, R.sub.9, X, Y, Z, W, and m are defined herein. Also provided herein are pharmaceutical compositions comprising a compound of Formula (I) or pharmaceutically acceptable salt thereof and a pharmaceutically acceptable excipient. ##STR00001##

The present invention is directed to compounds having the Formula (I), (II), (III), (IV), and (V), compositions thereof, and methods for the treatment of a condition associated with a dysfunction in proteostasis.

The present invention is directed to compounds having the Formula (I), (II), (III), (IV), and (V), compositions thereof, and methods for the treatment of a condition associated with a dysfunction in proteostasis.