- Stilbene Boronic Acids Form a Covalent Bond with Human Transthyretin and Inhibit Its Aggregation
-
Transthyretin (TTR) is a homotetrameric protein. Its dissociation into monomers leads to the formation of fibrils that underlie human amyloidogenic diseases. The binding of small molecules to the thyroxin-binding sites in TTR stabilizes the homotetramer and attenuates TTR amyloidosis. Herein, we report on boronic acid-substituted stilbenes that limit TTR amyloidosis in vitro. Assays of affinity for TTR and inhibition of its tendency to form fibrils were coupled with X-ray crystallographic analysis of nine TTR·ligand complexes. The ensuing structure-function data led to a symmetrical diboronic acid that forms a boronic ester reversibly with serine 117. This diboronic acid inhibits fibril formation by both wild-type TTR and a common disease-related variant, V30M TTR, as effectively as does tafamidis, a small-molecule drug used to treat TTR-related amyloidosis in the clinic. These findings establish a new modality for covalent inhibition of fibril formation and illuminate a path for future optimization.
- Smith, Thomas P.,Windsor, Ian W.,Forest, Katrina T.,Raines, Ronald T.
-
p. 7820 - 7834
(2017/10/06)
-
- Flow carbonylation of sterically hindered ortho-substituted iodoarenes
-
The flow synthesis of ortho-substituted carboxylic acids, using carbon monoxide gas, has been studied for a number of substrates. The optimised conditions make use of a simple catalyst system compromising of triphenylphosphine as the ligand and palladium acetate as the pre-catalyst. Carbon monoxide was introduced via a reverse "tube-in-tube" flow reactor at elevated pressures to give yields of carboxylated products that are much higher than those obtained under normal batch conditions.
- Mallia, Carl J.,Walter, Gary C.,Baxendale, Ian R.
-
supporting information
p. 1503 - 1511
(2016/08/02)
-
- A simple, safe and efficient synthesis of Tyrian purple (6,6'-Dibromoindigo)
-
6,6'-Dibromoindigo is a major component of the historic pigment Tyrian purple, arguably the most famous dye of antiquity. Over the last century, chemists have been interested in developing practical syntheses of the compound We describe herein a new, reasonably simple and efficient synthesis of Tyrian purple which opens the way to the production of large quantities of the dye with minimal hazards and at low cost.
- Wolk, Joel L.,Frimer, Aryeh A.
-
scheme or table
p. 5561 - 5580
(2010/12/20)
-
- DEPROTECTION OF BOC-PROTECTED COMPOUNDS
-
Organic compounds having t-butyl ester or BOC carbonate protecting groups are effectively deprotected by heating in a fluorinated alcohol solution.
- -
-
Page/Page column 2
(2010/12/29)
-
- Tricyclic fused heterocycle compounds, process for preparing the same and use thereof
-
Compounds represented by formula (1), wherein X is, for example, CH, CH2, CHR (wherein R is a lower alkyl group or a substituted lower alkyl group) or CRR′ (wherein R and R′ are the same as the above defined R); Y is, for example, CH, CH2or C═O; Z is, for example, O, S, S=O or SO2; U is C or N; R1to R4are each independently, for example, a hydrogen atom, OR, SR (wherein R is the same as defined above), or an aromatic ring, a substituted aromatic ring or a heterocycle; at least one of R5and R8is, for example, OH and the remaining of R5and R8are each independently, for example, a hydrogen atom or OH, optical isomers thereof, conjugates thereof or pharmaceutically acceptable salts thereof are provided. These compounds are characterized in having a wide range of pharmacological actions such as an excellent relaxing action of tracheal smooth muscles, an inhibition of airway hypersensitivity and an inhibition of infiltration of inflammatory cells into the airway and, in addition, high safety.
- -
-
-
- TRICYCLIC FUSED HETEROCYCLE COMPOUNDS, PROCESS FOR PREPARING THE SAME AND USE THEREOF
-
Compounds represented by formula (1),???whereinX is, for example, CH, CH2, CHR (wherein R is a lower alkyl group or a substituted lower alkyl group) or CRR' (wherein R and R' are the same as the above defined R);Y is, for example, CH, CH2or C=O;Z is, for exampe, O, S, S=O or SO2;U is C or N;R1to R4are each independently, for example, a hydrogen atom, OR, SR (wherein R is the same as defined above), or an aromatic ring, a substituted aromatic ring or a heterocycle;???at least one of R5and R8is, for example, OH and the remaining of R5and R8are each independently, for example, a hydrogen atom or OH, optical isomers thereof, conjugates thereof or pharmaceutically acceptable salts thereof are provided. These compounds are characterized in having a wide range of pharmacological actions such as an excellentrelaxing action of tracheal smooth muscles, an inhibition of airway hypersensitivity and an inhibition of infiltration of inflammatory cells into the airway and, in addition, high safety.
- -
-
Referential example 1
(2010/01/31)
-