Compounds Currently in Phase II−III Clinical Trials of Major Pharmaceutical Companies: New Structural Trends and Therapeutic Areas Yu Zhou,† Jiang Wang,† Zhanni Gu,† Shuni Wang,† Wei Zhu,† Jose ́ Luis Aceña,*,‡,§ Vadim A. Soloshonok,*,‡,∥ Kunisuke Izawa,* and Hong Liu*,† †Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zu Chong Zhi Road, Shanghai 201203, China ‡Department of Organic Chemistry I, Faculty of Chemistry, University of the Basque Country UPV/EHU, Paseo Manuel Lardizab́al 3, 20018 San Sebastiań, Spain Department of Organic Chemistry, Autońoma University of Madrid, Cantoblanco, 28049 Madrid, Spain IKERBASQUE, Basque Foundation for Science, María Díaz de Haro 3, 48013 Bilbao, Spain Hamari Chemicals Ltd., 1-4-29 Kunijima, Higashi-Yodogawa-ku, Osaka, Japan 533-0024

Next Generation of Fluorine-Containing Pharmaceuticals, Compounds Currently in Phase II–III Clinical Trials of Major Pharmaceutical Companies: New Structural Trends and Therapeutic Areas

The Golden Age of Transfer Hydrogenation

The electronic properties and relatively small size of fluorine endow it with considerable versatility as a bioisostere and it has found application as a substitute for lone pairs of electrons, the hydrogen atom, and the methyl group while also acting as a functional mimetic of the carbonyl, carbinol, and nitrile moieties. In this context, fluorine substitution can influence the potency, conformation, metabolism, membrane permeability, and P-gp recognition of a molecule and temper inhibition of the hERG channel by basic amines. However, as a consequence of the unique properties of fluorine, it features prominently in the design of higher order structural metaphors that are more esoteric in their conception and which reflect a more sophisticated molecular construction that broadens biological mimesis. In this Perspective, applications of fluorine in the construction of bioisosteric elements designed to enhance the in vitro and in vivo properties of a molecule are summarized.

Fluorine and Fluorinated Motifs in the Design and Application of Bioisosteres for Drug Design.

Palladium-catalyzed carbonylation reactions of aromatic halides in the presence of various nucleophiles have undergone rapid development since the pioneering work of Heck and co-workers in 1974, such that nowadays a plethora of palladium catalysts are available for different carbonylative transformations. The carboxylic acid derivatives, aldehydes, and ketones prepared in this way are important intermediates in the manufacture of dyes, pharmaceuticals, agrochemicals, and other industrial products. In this Review, the recent academic developments in this area and the first industrial processes are summarized.

Palladium-catalyzed carbonylation reactions of aryl halides and related compounds.

The last 15 years of hydroformylation and carbonylation chemistry are reviewed, including technical and commercial aspects.

Progress in hydroformylation and carbonylation

A series of novel analogs of acyclovir, substituted with an alkyl (methyl, ethyl, n-butyl) or phenyl group at the positions 1', 4', and/or 5', has been obtained in a direct one-pot coupling reaction of guanosine and the respective 1,3-dioxolanes. The new acyclonucleosides were essentially inactive in antiviral (HSV, VV, VSV, HBV) evaluation in vitro.

New analogs of acyclovir substituted at the side chain.

https://chemistry-europe.onlinelibrary.wiley.com/doi/pdf/10.1002/ejoc.202100485

Asymmetric Synthesis of N-Fmoc-(S)-7-aza-tryptophan via Alkylation of Chiral Nucleophilic Glycine Equivalent

Compounds represented by formula (II): wherein M is a hydrogen atom, sodium, potassium, or lithium; P is a hydrogen atom, an alkyl group, and the like; and the wavy line indicates a cis form, a trans form, or a mixture thereof for the double bond to which it is attached, may be prepared by hydrolyzing a compound represented by formula (I), or a salt thereof: wherein R1 and R2 are the same or different and each is an alkyl group, or R1 and R2 together with the adjacent nitrogen atom may form an aliphatic heterocycle, and P and the wavy line are as defined above, in the presence of alkali metal hydroxide.

Azlactone compound and method for preparation thereof

The present invention relates to a process for the preparation of compound (XV), which includes hydrolysis of compound (I) to give compound (II), then reaction with reagent (III) to give compound (IV), then reaction with compound (V) to give compound (VI), then condensation with compound (XII) to give compound (XI), and preferably deprotection by an enzyme reaction. This method is useful for the preparation of a pyrimidine derivative and a synthetic intermediate, which is useful as an enzyme inhibitor.

Process for the preparation of pyrimidine derivative, intermediate therefor and process for the preparation thereof

The invention provides a process wherein a 3'-deoxy-3'-halopurine
nucleoside compound is treated with perfluoroalkanesulfonyl
fluoride in the presence of a base to give a
2',3'-didehydro-2',3'-dideoxypurine nucleoside compound. The
resulting compound may be subjected to a catalytic hydrogenolysis
to obtain a 2',3'-dideoxypurine nucleoside compound.

Kunisuke Izawa

Papers

New analogs of acyclovir substituted at the side chain.

Asymmetric Synthesis of N-Fmoc-(S)-7-aza-tryptophan via Alkylation of Chiral Nucleophilic Glycine Equivalent

Azlactone compound and method for preparation thereof

Process for the preparation of pyrimidine derivative, intermediate therefor and process for the preparation thereof

A process for the production of purine nucleoside compounds