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 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.

There are two classes of glucose transporters involved in glucose homeostasis in the body, the facilitated transporters or uniporters (GLUTs) and the active transporters or symporters (SGLTs). The ...

Biology of Human Sodium Glucose Transporters

Recent developments in the synthesis and utilization of chiral sulfoxides.

The present invention encompasses albumin fusion proteins. Nucleic acid molecules encoding the albumin fusion proteins of the invention are also encompassed by the invention, as are vectors containing these nucleic acids, host cells transformed with these nucleic acids vectors, and methods of making the albumin fusion proteins of the invention and using these nucleic acids, vectors, and/or host cells. Additionally the present invention encompasses pharmaceutical compositions comprising albumin fusion proteins and methods of treating, preventing, or ameliorating diseases, disorders or conditions using albumin fusion proteins of the invention.

Albumin Fusion Proteins

L'invention concerne des composes inhibiteurs de SGLT2, correspondant a la formule (I), dans laquelle R?1, R2, et R2a? representent, de maniere independante, un groupe hydrogene, OH, OR5, alkyle inferieur, CF?3?, OCHF2 OCF3, SR?5i? ou halogene, ou deux groupes parmi R?1, R2 et R2a? avec les atomes de carbone auxquels ils sont lies peuvent former un carbocycle ou un heterocycle anneles a cinq, six ou sept chainons ; R3 et R4 representent, de maniere independante, un groupe hydrogene, OH, OR5a, Oaryle, OCH?2?aryle, alkyle inferieur, cycloalkyle, CF3, -OCHF2, -OCF3, halogene, -CN, -CO2R?5b, -CO?2H, -COR6b, -CH(OH)R6c, -CH(OR?5h)R6d, -CONR6R6a?, -NHCOR5c, -NHSO?2R?5d, -NHSO?2?aryle, aryle, -SR?5e, -SOR5f, -SO?2R5g, -SO2aryle, ou un heterocycle a cinq, six ou sept chainons, ou R3 et R4 avec les atomes de carbone auxquels ils sont lies forment un carbocycle ou un heterocycle anneles a cinq, six ou sept chainons ; R?5, R5a, R5b, R5c, R5d, R5e, R5f, R5g, R5h, et R5i? representent, de maniere independante, un alkyle inferieur ; R?6, R6a, R6b, R6c et R6d? representent, de maniere independante, un groupe hydrogene, alkyle, aryle, alkylaryle ou cycloalkyle, ou R?6 et R6a? avec les atomes de carbone auxquels ils sont lies forment un heterocycle annele a cinq, six ou sept chainons ; A represente O, S, NH, ou (CH?2?)n, n etant compris entre 0 et 3. L'invention concerne egalement un traitement du diabete et des maladies associees utilisant une quantite du compose de l'invention inhibant SGLT2, seul ou en combinaison avec un autre agent antidiabetique ou therapeutique.

Inhibiteurs de sglt2 a base de glucoside c-aryle

BMS‐201620: A Selective Beta 3 Agonist.

The synthesis and diastereoselective oxidation of novel tetrahydromevinic acid lactone sulfides to sulfoxides is described.

Diastereoselective Oxidation of Sulfides to Sulfoxides. Synthesis of Novel C-6 Sulfoxy Tetrahydromevinic Acids.

L'invention concerne des methodes pour le traitement de l'obesite ou pour provoquer une perte de poids chez un sujet mammifere ou un patient, consistant a administrer a ce dernier une dose therapeutique d'un inhibiteur du SGLT2, seul ou eventuellement combine a un autre agent anti-obesite. L'invention concerne en outre une composition pharmaceutique contenant un inhibiteur SGLT2 seul ou combine a un autre agent anti-obesite, et un excipient pharmaceutiquement acceptable.

William N. Washburn

Papers

Inhibiteurs de sglt2 a base de glucoside c-aryle

BMS‐201620: A Selective Beta 3 Agonist.

Diastereoselective Oxidation of Sulfides to Sulfoxides. Synthesis of Novel C-6 Sulfoxy Tetrahydromevinic Acids.

Méthodes de traitement de l'obésité au moyen d'un inhibiteur du sglt2 et des compositions de celui-ci