- Modulators of the Cystic Fibrosis Transmembrane Conductance Regulator Protein and Methods of Use
-
The invention discloses compounds of Formula (I), wherein A1, R1, R2, R3, R4, and n are as defined herein. The present invention relates to compounds and their use in the treatment of cystic fibrosis, methods for their production, pharmaceutical compositions comprising the same, and methods of treating cystic fibrosis by administering a compound of the invention.
- -
-
Paragraph 2203
(2019/03/30)
-
- Lithium-Catalyzed Thiol Alkylation with Tertiary and Secondary Alcohols: Synthesis of 3-Sulfanyl-Oxetanes as Bioisosteres
-
3-Sulfanyl-oxetanes are presented as promising novel bioisosteric replacements for thioesters or benzyl sulfides. From oxetan-3-ols, a mild and inexpensive Li catalyst enables chemoselective C?OH activation and thiol alkylation. Oxetane sulfides are formed from various thiols providing novel motifs in new chemical space and specifically as bioisosteres for thioesters due to their similar shape and electronic properties. Under the same conditions, various π-activated secondary and tertiary alcohols are also successful. Derivatization of the oxetane sulfide linker provides further novel oxetane classes and building blocks. Comparisons of key physicochemical properties of the oxetane compounds to selected carbonyl and methylene analogues indicate that these motifs are suitable for incorporation into drug discovery efforts.
- Croft, Rosemary A.,Mousseau, James J.,Choi, Chulho,Bull, James A.
-
supporting information
p. 818 - 821
(2017/12/26)
-
- Structurally Divergent Lithium Catalyzed Friedel–Crafts Reactions on Oxetan-3-ols: Synthesis of 3,3-Diaryloxetanes and 2,3-Dihydrobenzofurans
-
The first examples of 3,3-diaryloxetanes are prepared in a lithium-catalyzed and substrate dependent divergent Friedel–Crafts reaction. para-Selective Friedel–Crafts reactions of phenols using oxetan-3-ols afford 3,3-diaryloxetanes by displacement of the hydroxy group. These constitute new isosteres for benzophenones and diarylmethanes. Conversely, ortho-selective Friedel–Crafts reactions of phenols afford 3-aryl-3-hydroxymethyl-dihydrobenzofurans by tandem alkylation–ring-opening reactions; the outcome of the reaction diverging to structurally distinct products dependent on the substrate regioselectivity. Further reactivity of the oxetane products is demonstrated, suitable for incorporation into drug discovery efforts.
- Croft, Rosemary A.,Mousseau, James J.,Choi, Chulho,Bull, James A.
-
supporting information
p. 16271 - 16276
(2016/10/30)
-