| 主权项 |
1. A method for evaluating the ability of a compound to increase the number of CFTR on a cell, comprising the steps of:
(i) contacting said cell with said compound under a first suitable conditions; (ii) contacting said cell with a compound of formula I under a second suitable conditions; and (iii) comparing the activity of CFTR on said cell in the presence and absence of said compound;wherein said compound of formula I is:wherein:
Ar1 is a 5-6 membered aromatic monocyclic ring having 0-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur, wherein said ring is optionally fused to a 5-12 membered monocyclic or bicyclic, aromatic, partially unsaturated, or saturated ring, wherein each ring contains 0-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur, wherein Ar1 has m substituents, each independently selected from —WRW; W is a bond or is an optionally substituted C1-C6 alkylidene chain wherein up to two methylene units of W are optionally and independently replaced by —CO—, —CS—, —COCO—, —CONR′—, —CONR′NR′—, —CO2—, —OCO—, —NR′CO2—, —O—, —NR′CONR′—, —OCONR′—, —NR′NR′, —NR′NR′CO—, —NR′CO—, —S—, —SO, —SO2—, —NR′—, —SO2NR′—, NR'SO2—, or —NR′SO2NR′—; RW is independently R′, halo, NO2, CN, CF3, or OCF3; m is 0-5; each of R1, R2, R3, R4, and R5 is independently —X—RX; X is a bond or is an optionally substituted C1-C6 alkylidene chain wherein up to two methylene units of X are optionally and independently replaced by —CO—, —CS—, —COCO—, —CONR′—, —CONR′NR′—, —CO2—, —OCO—, —NR′CO2—, —O—, —NR′CONR′—, —OCONR′—, —NR′NR′, —NR′NR′CO—, —NR′CO—, —S—, —SO, —SO2—, —NR′—, —SO2NR′—, NR'SO2—, or —NR′SO2NR′—; RX is independently R′, halo, NO2, CN, CF3, or OCF3; R6 is hydrogen, CF3, —OR′, —SR′, or an optionally substituted C1-6 aliphatic group; R7 is hydrogen or a C1-6 aliphatic group optionally substituted with —X—RX; R′ is independently selected from hydrogen or an optionally substituted group selected from a C1-C8 aliphatic group, a 3-8-membered saturated, partially unsaturated, or fully unsaturated monocyclic ring having 0-3 heteroatoms independently selected from nitrogen, oxygen, or sulfur, or an 8-12 membered saturated, partially unsaturated, or fully unsaturated bicyclic ring system having 0-5 heteroatoms independently selected from nitrogen, oxygen, or sulfur; or two occurrences of R′ are taken together with the atom(s) to which they are bound to form an optionally substituted 3-12 membered saturated, partially unsaturated, or fully unsaturated monocyclic or bicyclic ring having 0-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur. |
