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Substituted tricyclics and method of use
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A substituent, monocyclic technology applied in the field of substituted tricyclics and uses, which can solve problems such as limited treatment options
Pending Publication Date: 2022-01-11
ABBVIE INC +1
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[1432] 1. a compound with formula (I) or a pharmaceutically acceptable salt thereof,
[1439] R 2A , R 2B , R 2C , and R 2D each independently hydrogen or halogen;
[1440] R 3 , R 4 , R 6 , and R 7 independently hydrogen, C 1 -C 3 alkyl, or halogen;
[1441] R 5 independently at each occurrence hydrogen, C 1 -C 3 Alkyl, C 2 -C 4 Alkenyl, or C 1 -C 3 haloalkyl;
[1442] X 1A is O or CH 2 ;
[1443] X 1B is O or CH 2 ;
[1444] Y is -G 1 , or Y is formula (c), (d), (e), (f), or (g);
[1445]
[1446] in
[1447] G 1 is phenyl or monocyclic heteroaryl, each of which is optionally followed by 1, 2 or 3 independently selected R p group substitution; where each R p independently is C 1 -C 6 Alkyl, halogen, C 1 -C 6 haloalkyl, G 2 , C 1 -C 3 Alkoxy, C 1 -C 3 Haloalkoxy, -C(O)-G A , C(O)NR A R B , or -NR A R ...
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[2074]All reagents were commercial grade and used as received without further purification unless otherwise indicated. Commercially available anhydrous solvents were used for the reactions carried out under an inertatmosphere. Reagent grade solvents were used in all other cases unless otherwise specified. 1 The chemical shifts (δ) of the H NMR spectra are expressed relative to tetramethylsilane as an internal standard (δ 0.00) or the appropriate residual solvent peak (i.e. CHCl). 3 (δ7.27)) in parts per million (ppm). Multiplicities are given as singlet (S), doublet (d), triplet (t), quartet (q), quintet (quin), multiplet (m) and broad (br). For microwave heating The initiator is carried out.
[2075] Enantiomeric purity was determined on an Agilent HP1100 system with UV detection. Column used: ChiralpakIA (4.6×250 mm, 5 μm). Solvents used: isopropanol and tert-butyl methyl ether.
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Abstract
The invention relates to substituted tricyclics and a method of use. The invention provides a compound of Formula (I) in which X, Y, and R1 have any of the values defined in the specification, and pharmaceutically acceptable salts thereof, that are useful as agents in the treatment of diseases and conditions mediated and modulated by CFTR, including cystic fibrosis, Sjogren's syndrome, pancreatic insufficiency, chronic obstructive lung disease, and chronic obstructive airwaydisease. Also provided are pharmaceutical compositions comprised of one or more compounds of formula (I).
Description
[0001] This application is a divisional application of Chinese patent application No. 201680053240.5 "Substituted tricyclic rings and methods of use" with an application date of July 14, 2016. [0002] CROSS-REFERENCE TO RELATED APPLICATIONS [0003] This application claims priority to US Provisional Application No. 62 / 193,391, filed July 16, 2015, and US Provisional Application No. 62 / 299,633, filed February 25, 2016, both of which are incorporated by reference for all purposes here. technical field [0004] The present invention is directed to substituted tricyclic compounds that are modulators of cystic fibrosis transmembrane conductance regulator (CFTR) proteins useful in the treatment of diseases and disorders mediated and regulated by CFTR. In addition, the present invention relates to compositions containing the compounds of the present invention and methods for their preparation. Background technique [0005] ABC transporters are a family of homologous membrane tra...
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