Modulators of cystic fibrosis transmembrane conductance regulator
This invention relates to a compound of Formula I: or a pharmaceutically acceptable salt thereof, wherein R is COOH or CH 2 OH.
1. A compound of Formula I:
or a pharmaceutically acceptable salt thereof, wherein R is COOH or CH 2 OH.
2. A compound according to claim 1 , wherein R is CH 2 OH.
3. A compound according to claim 1 , wherein R is COOH.
4. A pharmaceutical composition comprising:
a compound of Formula I, according to claim 1 ; and
a pharmaceutically acceptable carrier or adjuvant.
5. The pharmaceutical composition according to claim 4 , wherein the compound of Formula I is a compound of the structure:
6. The pharmaceutical composition according to claim 4 , wherein the compound of Formula I is a compound of the structure:
7. The pharmaceutical composition of claim 4 , further comprising an additional agent selected from a mucolytic agent, a bronchodilator, an antibiotic, an anti-invective agent, an anti-inflammatory agent, a CFTR modulator, or a nutritional agent.
8. A kit for use in measuring the activity of CFTR or a fragment thereof in a biological sample in vitro or in vivo, comprising:
i. a composition comprising a compound of Formula I, according to claim 1 ; and
ii. instructions for:
a. contacting the composition with the biological sample; and
b. measuring the activity of said CFTR or a fragment thereof.
9. The kit of claim 8 , further comprising instructions for:
i. contacting an additional compound with the biological sample;
ii. measuring the activity of said CFTR or a fragment thereof in the presence of said additional compound; and
iii. comparing the activity of the CFTR or a fragment thereof in the presence of the additional compound with the activity of the CFTR or a fragment thereof in the presence of a composition of Formula I.
10. The kit according to claim 9 , wherein the step of comparing the activity of said CFTR or a fragment thereof provides a measure of the density of said CFTR or a fragment thereof.
11. The kit according to claim 8 , wherein the compound of Formula I has the structure:
12. The kit according to claim 8 , wherein the compound of Formula I has the structure: