Multicomponent reactions (MCRs) are one-pot reactions employing more than two starting materials, e.g. 3, 4, … 7, where most of the atoms of the starting materials are incorporated in the final product.1 Several descriptive tags are regularly attached to MCRs (Fig. 1): they are atom economic, e.g. the majority if not all of the atoms of the starting materials are incorporated in the product; they are efficient, e.g. they efficiently yield the product since the product is formed in one-step instead of multiple sequential steps; they are convergent, e.g. several starting materials combine in one reaction to form the product; they exhibit a very high bond-forming-index (BFI), e.g. several non-hydrogen atom bonds are formed in one synthetic transformation.2 Therefore MCRs are often a useful alternative to sequential multistep synthesis.






Open in a separate window


Figure 1


Above: multistep syntheses can be divergent (sequential) or convergent; below: in analogy MCR reactions are convergent and one or two component reactions are divergent or less convergent.

Chemistry and Biology Of Multicomponent Reactions

Palladium-catalyzed amination reactions of aryl halides have undergone rapid development in the last 12 years, largely driven by the implementation of new classes of ligands. Biaryl phosphanes have proven to provide especially active catalysts in this context. This Review discusses the application of these catalysts in C-N cross-coupling reactions in the synthesis of heterocycles and pharmaceuticals, in materials science, and in natural product synthesis.

/pdf/biaryl-phosphane-ligands-in-palladium-catalyzed-amination-5180ia9hmu.pdf

Biaryl Phosphane Ligands in Palladium‐Catalyzed Amination

Dialkylbiaryl phosphines are a valuable class of ligand for Pd-catalyzed amination reactions and have been applied in a range of contexts. This perspective attempts to aid the reader in the selection of the best choice of reaction conditions and ligand of this class for the most commonly encountered and practically important substrate combinations.

/pdf/dialkylbiaryl-phosphines-in-pd-catalyzed-amination-a-user-s-54l9jb3w9l.pdf

Dialkylbiaryl Phosphines in Pd-Catalyzed Amination: A User's Guide.

Dialkylbiaryl phosphines in Pd-catalyzed amination: a user's guide

The human genome contains 40 voltage-gated potassium channels (KV) which are involved in diverse physiological processes ranging from repolarization of neuronal or cardiac action potentials, over regulating calcium signaling and cell volume, to driving cellular proliferation and migration. KV channels offer tremendous opportunities for the development of new drugs for cancer, autoimmune diseases and metabolic, neurological and cardiovascular disorders. This review first discusses pharmacological strategies for targeting KV channels with venom peptides, antibodies and small molecules and then highlights recent progress in the preclinical and clinical development of drugs targeting KV1.x, KV7.x (KCNQ), KV10.1 (EAG1) and KV11.1 (hERG) channels.

/pdf/voltage-gated-potassium-channels-as-therapeutic-targets-1cnxfwemx2.pdf

Voltage-gated potassium channels as therapeutic targets

Compounds having the formula (I), and enantiomers, and diastereomers, pharmaceutically-acceptable salts, and hydrates, thereof, (I) are useful as kinase modulators, including MK2 modulation, wherein one of E and F is a nitrogen atom and the other of E and F is a carbon atom, and Z is N or CR3, and R1, R2, R3, X and Y are as defined herein.

Fused heterocyclic compounds useful as kinase modulators

Pyrazole inhibitors of coactivator associated arginine methyltransferase 1 (CARM1).

In general, the instant invention comprises compounds of Formulas (I) and (II) including pharmaceutically acceptable salts thereof. The compounds of the invention are useful as protein kinase inhibitors and therefore are useful for treating cancer and other protein kinase mediated diseases.

Fused heterocyclic kinase inhibitors

Novel non-steroidal compounds are provided which are glucocorticoid receptor modulators which are useful in treating diseases requiring glucocorticoid receptor agonist or antagonist therapy such as obesity, diabetes, inflammatory and immune disorders, and have the structure formula (I), where Z is CONR1R2 or CH2NR1R2 and where R, Ra, Rb, Rc, Rd, Z, A and B are defined herein.

Tram N. Huynh

Papers

Fused heterocyclic compounds useful as kinase modulators

Pyrazole inhibitors of coactivator associated arginine methyltransferase 1 (CARM1).

Fused heterocyclic kinase inhibitors

Modulators of the glucocorticoid receptor and method

Optimization of pyrazole inhibitors of Coactivator Associated Arginine Methyltransferase 1 (CARM1).