C07D487/00

Bone fracture repair by targeting of agents that promote bone healing

Aspects of the present disclosure generally relate to compounds for targeting and healing bone fractures. Some of these compounds include a negatively charged oligopeptide comprising an acidic oligopeptide, a linker, which may be hydrolyzable or may be a substrate for the protease cathepsin K, and at least one molecule that promotes bone healing. In some compounds the molecule that promotes bone healing is an anabolic compound that inhibits GSK3, in some compounds the molecule that promotes the healing of bone fracture is a pro-inflammatory agent such as PGE1. Other embodiments include methods of treating a bone fracture comprising administering a therapeutic amount of any one of the compounds disclosed herein.

Cyclopenta[d]pyrimidines and substituted cyclopenta[d]pyrimidines as antitubulin and microtubule targeting agents, monocyclic pyrimidines as tubulin inhibitors, and pyrrolopyrimidines as targeted antifolates and tubulin and multiple receptor tyrosine kinase inhibition and antitumor agents

The present invention provides a compound of Formula I, and salts thereof, and a pharmaceutical composition comprising a compound of Formula I: ##STR00001##
wherein R.sub.1 is selected from the group consisting of ##STR00002##
and R.sub.2 is an alkyl group having from one to ten carbon atoms, or
wherein R.sub.2 is selected from the group consisting of ##STR00003##
R.sub.1 is an alkyl group having from one to ten carbon atoms; and R is H, or an alkyl group having from one to ten carbon atoms, and R.sub.3 is H, an alkyl group having from one to ten carbon atoms, or a halogen. Preferably the compound of Formula V includes wherein R.sub.3 is a halogen, and most preferably wherein the halogen is chlorine. Methods of treating a patient with cancer with these compounds are also provided.

ANTI-FOLATE RECEPTOR ANTIBODY CONJUGATES, COMPOSITIONS COMPRISING ANTI-FOLATE RECEPTOR ANTIBODY CONJUGATES, AND METHODS OF MAKING AND USING ANTI-FOLATE RECEPTOR ANTIBODY CONJUGATES

The present disclosure relates to antibody conjugates with binding specificity for folate receptor alpha (FOLR1) and its isoforms and homologs, and compositions comprising the antibody conjugates, including pharmaceutical compositions. Also provided are methods of producing the antibody conjugates and compositions as well as methods of using the antibody conjugates and compositions, such as in therapeutic and diagnostic methods.

Methods for predicting anti-cancer response

The present invention is based, in part, on the identification of novel methods for defining predictive biomarkers of response to anti-cancer drugs.

Anti-folate receptor alpha antibody conjugated with hemiasterlins

The present disclosure relates to antibody conjugates with binding specificity for folate receptor alpha (FOLR1) and its isoforms and homologs, and compositions comprising the antibody conjugates, including pharmaceutical compositions. The variable light chains are those of trastuzumab. Also provided are methods of producing the antibody conjugates and compositions as well as methods of using the antibody conjugates and compositions, such as in therapeutic and diagnostic methods. The antibody conjugates comprise a non-natural amino acid at a site selected from the group consisting of HC-F404, HC-K121, HC-Y180, HC-F241, HC-221, LC-T22, LC-S7, LC-N152, LC-K42, LC-E161, LC-D170, HC-S136, HC-S25, HC-A40, HC-S119, HC-S190, HC-K222, HC-R19, HC-Y52, or HC-S70, according to the Kabat, Chothia, or EU numbering scheme.

Substituted pteridines useful for the treatment and prevention of viral infections

The invention provides 4,6-di- and 2,4,6-tri-substituted pteridine derivatives with a specific substitution pattern which exhibit a significant and selective activity against certain types of viral infections, in particular selectively inhibit replication of Flaviridae such as the hepatitis C virus, and are useful for the prevention and treatment of such viral infections.

Chimeric compounds targeting proteins, compositions, methods, and uses thereof

The present invention provides chimeric compounds that modulate protein function, to restore protein homeostasis, including cytokine, aiolos, and/or ikaros activity, TNF-alpha activity, CK1-alpha activity and cell-cell adhesion. The invention provides methods of modulating protein-mediated diseases, such as cytokine-mediated diseases, disorders, conditions, or responses. Compositions, including in combination with other cytokine and inflammatory mediators, are provided. Methods of treatment, amelioration, or prevention of protein-mediated diseases, disorders, and conditions, such as cytokine-mediated diseases, disorders, and conditions, including inflammation, fibromyalgia, rheumatoid arthritis, osteoarthritis, ankylosing spondylitis, psoriasis, psoriatic arthritis, inflammatory bowel diseases, Crohn's disease, ulcerative colitis, uveitis, inflammatory lung diseases, chronic obstructive pulmonary disease, Alzheimer's disease, organ transplant rejection, and cancer, are provided.

Chimeric compounds targeting proteins, compositions, methods, and uses thereof

The present invention provides chimeric compounds that modulate protein function, to restore protein homeostasis, including cytokine, aiolos, and/or ikaros activity, TNF-alpha activity, CK1-alpha activity and cell-cell adhesion. The invention provides methods of modulating protein-mediated diseases, such as cytokine-mediated diseases, disorders, conditions, or responses. Compositions, including in combination with other cytokine and inflammatory mediators, are provided. Methods of treatment, amelioration, or prevention of protein-mediated diseases, disorders, and conditions, such as cytokine-mediated diseases, disorders, and conditions, including inflammation, fibromyalgia, rheumatoid arthritis, osteoarthritis, ankylosing spondylitis, psoriasis, psoriatic arthritis, inflammatory bowel diseases, Crohn's disease, ulcerative colitis, uveitis, inflammatory lung diseases, chronic obstructive pulmonary disease, Alzheimer's disease, organ transplant rejection, and cancer, are provided.

Organic electroluminescent compound and organic electroluminescent device comprising the same

The present disclosure relates to an organic electroluminescent compound, and an organic electroluminescent device comprising the same. It is possible to provide an organic electroluminescent device which can be deposited at a low deposition temperature and/or in which clogging is reduced.

Organic electroluminescent compound and organic electroluminescent device comprising the same

The present disclosure relates to an organic electroluminescent compound, and an organic electroluminescent device comprising the same. It is possible to provide an organic electroluminescent device which can be deposited at a low deposition temperature and/or in which clogging is reduced.