The disclosure describes methods of synthesis of pyridazinone compounds as thyroid hormone analogs and their prodrugs. Preferred methods according to the disclosure allow for large-scale preparation of pyridazinone compounds having high purity. In some embodiments, preferred methods according to the disclosure also allow for the preparation of pyridazinone compounds in better yield than previously used methods for preparing such compounds. Also disclosed are morphic forms of a pyridazinone compound. Further disclosed is a method for treating resistance to thyroid hormone in a subject having at least one TRβ mutation.

The subject matter disclosed herein relates generally to cancer therapy and to anticancer compounds and imaging agents. More specifically, the subject matter disclosed herein relates to agents that target MC1R and their use in the treatment of cancer. Methods of screening for MC1R targeted agents are also disclosed.

The invention provides a novel method for producing an oligonucleotide using a nucleoside or oligonucleotide that is easy to isolate and has high storage stability. The oligonucleotide production method includes a step of subjecting a nucleoside or oligonucleotide having a pseudo solid phase-protecting group in at least one location selected from the group consisting of 2′-position, 3′-position, 5′-position and a nucleobase moiety and having a 5′-hydroxyl group or a 3′-hydroxyl group, to H-phosphonation to convert the 5′-hydroxyl group or the 3′-hydroxyl group into an H-phosphonated form.

The present invention relates to a novel compound and a composition for an anti-diabetes and anti-obesity comprising the same as an active ingredient. The compound or pharmaceutically acceptable salt thereof according to the present invention selectively and specifically acts as an agonist of GPR39, activates the mechanism of glucose-dependent insulin secretion in pancreatic beta cells, and significantly increases glucose tolerance and an anti-diabetic effect, and therefore can be utilized as a composition for improving, preventing, or treating diabetes mellitus. In addition, the compound or pharmaceutically acceptable salt thereof according to the present invention acts on GPR39 so as to have lipolytic ability in adipocytes and adipose tissue, and therefore can be utilized as a composition for improving, preventing, or treating obesity.

The present invention relates to a targeted protease degradation (TED) platform, and specifically to a conjugate of target molecule-linker-E3 ligase ligand as shown in formula I, R.sub.T-L1-R.sub.E3 (formula I), wherein R.sub.T is a monovalent group of the target molecule, R.sub.E3 is a monovalent group of the E3 ligase ligand, L1 is the linker linking A and B, and L1 is as shown in formula II below: —W-L2-W.sup.2— (II).

Described herein is a method for obtaining a selective estrogen receptor degrader, and compounds used in preparing the selective estrogen receptor degrader.

The present invention belongs to the technical field of medicines, and particularly relates to a method for synthesizing an anti-tumor compound and intermediates thereof. The synthesis method of the present invention has improved operability and allows for a simplified process, in which higher purity can be achieved without the complicated process of recrystallizing the synthesized target compound, and thus less of the three wastes is produced, making the method more suitable for industrial mass production. Where the intermediates according to the present invention are used for preparing an anti-tumor compound, by-products are effectively reduced during reactions, and thus the overall yield of the reactions are improved, and is at least twice as high as that obtained using the existing synthesis method.

The present invention belongs to the field of pharmaceutical chemistry, and relates to a substituted pyrazine compound, a pharmaceutical composition comprising same, and the use thereof. In particular, the present invention relates to a compound with the structure of formula (I), which exhibits a good SHP2 inhibiting activity, and can act as an efficient SHP2 inhibitor for preventing and/or treating SHP2-related diseases.

##STR00001##

Disclosed are processes for preparing oligonucleotides. The process comprises: (a) converting a compound of Formula X-1 into a compound of Formula X-2: where R.sup.10 is a residue of an oligonucleotide (e.g., a phosphorodiamidate morpholino oligomer); R.sup.11 is an amine protecting group; wherein the compound of Formula X-1 is not bound to a solid support; and; (b) optionally removing protecting groups in the compound of Formula X-2 to obtain the olignucleotide. The synthetic processes described herein are advantageous in many aspects, including but not limited to improved yields and purities of target phosphorodiamidate morpholino oligomers with reduced 4-nitrostyrene adduct impurities. (X-1), (X-2)

##STR00001##

The disclosure provides conjugates of an isolated humanized anti-CD22 antibody and PBD dimers.