Modulators of ATP-Binding Cassette transporters

The present invention relates to modulators of ATP-Binding Cassette (“ABC”) transporters or fragments thereof, including CF Transmembrane Regulator (“CFTR”), compositions thereof, and methods therewith. The present invention also relates to methods of treating ABC transporter mediated diseases using such modulators.

MODULATORS OF ATP-BINDING CASSETTE TRANSPORTERS

The present invention relates to modulators of ATP-Binding Cassette (“ABC”) transporters or fragments thereof, including CF Transmembrane Regulator (“CFTR”), compositions thereof, and methods therewith. The present invention also relates to methods of treating ABC transporter mediated diseases using such modulators. 1218-. (canceled)220230-. (canceled)231. The method according to claim 219 , wherein Xis CH claim 219 , CF claim 219 , or O.232. The method according to claim 219 , wherein Xis CH.233. The method according to claim 219 , wherein Ais selected from phenyl claim 219 , triazinyl claim 219 , pyrazinyl claim 219 , pyrimidinyl claim 219 , pyridazinyl claim 219 , pyridyl claim 219 , thiadiazolyl claim 219 , triazolyl claim 219 , oxadiazolyl claim 219 , isothiazolyl claim 219 , pyrazolyl claim 219 , imidazolyl claim 219 , thiazolyl claim 219 , oxazolyl claim 219 , pyrrolyl claim 219 , thienyl claim 219 , furanyl claim 219 , indolizinyl claim 219 , indolyl claim 219 , isoindolyl claim 219 , benzofuranyl claim 219 , benzo[b]thienyl claim 219 , 1H-indazolyl claim 219 , benzimidazolyl claim 219 , benzthiazolyl claim 219 , purinyl claim 219 , quinolinyl claim 219 , isoquinolinyl claim 219 , cinnolinyl claim 219 , phthazinyl claim 219 , quinazolinyl claim 219 , quinoxalinyl claim 219 , 1 claim 219 ,8-naphthyridinyl claim 219 , pteridinyl claim 219 , carbazolyl claim 219 , acridinyl claim 219 , phenazinyl claim 219 , phenothiazinyl claim 219 , phenoxazinyl claim 219 , indenyl claim 219 , naphthyl claim 219 , azulinyl claim 219 , or anthracenyl.234. The method according to claim 219 , wherein each Bis independently selected from optionally substituted C6-C10 aryl.235. The method according to claim 219 , wherein each Bis independently an optionally substituted phenyl or naphthyl.236. The method according to claim 219 , wherein each Bis an unsubstituted phenyl.237. The method according to claim 219 , wherein each Bis independently selected from optionally substituted C5- ...

Multiwell plate assembly for use in high throughput assays

A device for characterizing the biological properties of cells can include a plurality of dual-compartment assay chambers wherein the compartments of each chamber are separated by a cell layer across which ions can flow. The biological properties of the cell layer in the presence or absence of experimental compounds can be determined by measuring an electrical gradient across the layer. A individual dual-compartment chamber of this type may be referred to as an “Ussing chamber.”

MODULATORS OF ATP-BINDING CASSETTE TRANSPORTERS

The present invention relates to modulator of ATP-Binding Cassette (“ABC”) transporters or fragments thereof, including CF Transmembrane Regulator (“CFTR”), compositions thereof, and methods therewith. The present invention also relates to methods of treating ABC transporter mediated diseases using such modulators. 1226-. (canceled)228230-. (canceled)231. The pharmaceutical composition according to claim 227 , wherein Xis CH claim 227 , CF claim 227 , or O.232. The pharmaceutical composition according to claim 227 , wherein Xis CH.233. The pharmaceutical composition according to claim 227 , wherein Ais selected from phenyl claim 227 , triazinyl claim 227 , pyrazinyl claim 227 , pyrimidinyl claim 227 , pyridazinyl claim 227 , pyridyl claim 227 , thiadiazolyl claim 227 , triazolyl claim 227 , oxadiazolyl claim 227 , isothiazolyl claim 227 , pyrazolyl claim 227 , imidazolyl claim 227 , thiazolyl claim 227 , oxazolyl claim 227 , pyrrolyl claim 227 , thienyl claim 227 , furanyl claim 227 , indolizinyl claim 227 , indolyl claim 227 , isoindolyl claim 227 , benzofuranyl claim 227 , benzo[b]thienyl claim 227 , 1H-indazolyl claim 227 , benzimidazolyl claim 227 , benzthiazolyl claim 227 , purinyl claim 227 , quinolinyl claim 227 , isoquinolinyl claim 227 , cinnolinyl claim 227 , phthazinyl claim 227 , quinazolinyl claim 227 , quinoxalinyl claim 227 , 1 claim 227 ,8-naphthyridinyl claim 227 , pteridinyl claim 227 , carbazolyl claim 227 , acridinyl claim 227 , phenazinyl claim 227 , phenothiazinyl claim 227 , phenoxazinyl claim 227 , indenyl claim 227 , naphthyl claim 227 , azulinyl claim 227 , or anthracenyl.234. The pharmaceutical composition according to claim 227 , wherein each Bis independently selected from optionally substituted C6-C10 aryl.235. The pharmaceutical composition according to claim 227 , wherein each Bis independently an optionally substituted phenyl or naphthyl.236. The pharmaceutical composition according to claim 227 , wherein each Bis an unsubstituted ...

Modulators of ATP-binding cassette transporters

The present invention relates to modulators of ATP-Binding Cassette (“ABC”) transporters or fragments thereof, including CF Transmembrane Regulator (“CFTR”), compositions thereof, and methods therewith. The present invention also relates to methods of treating ABC transporter mediated diseases using such modulators.

MODULATORS OF ATP-BINDING CASSETTE TRANSPORTERS

The present invention relates to modulators of ATP-Binding Cassette (“ABC”) transporters or fragments thereof, including CF Transmembrane Regulator (“CFTR”), compositions thereof, and methods therewith. The present invention also relates to methods of treating ABC transporter mediated diseases using such modulators.

Modulators of ATP-Binding Cassette Transporters

The present invention relates to modulators of ATP-Binding Cassette (“ABC”) transporters or fragments thereof, including CF Transmembrane Regulator (“CFTR”), compositions thereof, and methods therewith. The present invention also relates to methods of treating ABC transporter mediated diseases using such modulators. 1228-. (canceled)230. (canceled)231. The method according to claim 229 , wherein Xis CH claim 229 , CF claim 229 , or O.232. The method according to claim 229 , wherein Xis CH.233. The method according to claim 229 , wherein Ais selected from phenyl claim 229 , triazinyl claim 229 , pyrazinyl claim 229 , pyrimidinyl claim 229 , pyridazinyl claim 229 , pyridyl claim 229 , thiadiazolyl claim 229 , triazolyl claim 229 , oxadiazolyl claim 229 , isothiazolyl claim 229 , pyrazolyl claim 229 , imidazolyl claim 229 , thiazolyl claim 229 , oxazolyl claim 229 , pyrrolyl claim 229 , thienyl claim 229 , furanyl claim 229 , indolizinyl claim 229 , indolyl claim 229 , isoindolyl claim 229 , benzofuranyl claim 229 , benzo[b]thienyl claim 229 , 1H-indazolyl claim 229 , benzimidazolyl claim 229 , benzthiazolyl claim 229 , purinyl claim 229 , quinolinyl claim 229 , isoquinolinyl claim 229 , cinnolinyl claim 229 , phthazinyl claim 229 , quinazolinyl claim 229 , quinoxalinyl claim 229 , 1 claim 229 ,8-naphthyridinyl claim 229 , pteridinyl claim 229 , carbazolyl claim 229 , acridinyl claim 229 , phenazinyl claim 229 , phenothiazinyl claim 229 , phenoxazinyl claim 229 , indenyl claim 229 , naphthyl claim 229 , azulinyl claim 229 , or anthracenyl.234. The method according to claim 229 , wherein each Bis independently selected from optionally substituted C6-C10 aryl.235. The method according to claim 229 , wherein each Bis independently an optionally substituted phenyl or naphthyl.236. The method according to claim 229 , wherein each Bis an unsubstituted phenyl.237. The method according to claim 229 , wherein each Bis independently selected from optionally substituted C5-C12 ...

Multiwell assay apparatus and method for determining biological activity of compounds

A device for characterizing the biological properties of cells can include a plurality of dual-compartment assay chambers wherein the compartments of each chamber are separated by a cell layer across which ions can flow. The biological properties of the cell layer in the presence or absence of experimental compounds can be determined by measuring an electrical gradient across the layer. A individual dual-compartment chamber of this type may be referred to as an “Ussing chamber.”

Modulators of ATP-binding cassette transporters

The present invention relates to modulators of ATP-Binding Cassette (ABC) transporters or fragments thereof, including CF Transmembrane Regulator (CFTR), compositions thereof, and methods therewith. The present invention also relates to methods of treating ABC transporter mediated diseases using such modulators.

Modulators of ATP-binding cassette transporters

The present invention relates to modulator of ATP-Binding Cassette (ABC) transporters or fragments thereof, including CF Transmembrane Regulator (CFTR), compositions thereof, and methods therewith. The present invention also relates to methods of treating ABC transporter mediated diseases using such modulators.

COMPOUNDS USEFUL IN CFTR ASSAYS AND METHODS THEREWITH

The present invention relates to compounds useful in CFTR assays. The present invention also relates to compounds useful in monitoring CFTR activity in therapies for CFTR-mediated diseases. The present invention also provides an assay for use in measuring CFTR correction. 2. The method according to claim 1 , wherein said first suitable conditions are suitable for a correction assay.3. The method according to claim 1 , wherein said first suitable conditions are suitable for an assay suitable to detect a modulator of heat shock proteins.4. The method according to claim 1 , wherein said first suitable conditions are suitable for gene therapy.5. The method according to claim 1 , wherein said second suitable conditions are suitable for a potentiator assay.6. A method for screening a plurality of compounds claim 1 , said method comprising the steps of:(i) contacting each of said plurality of compounds with a cell under a first suitable conditions, wherein said cell has a mutant or wild type CFTR;(ii) contacting said cell with a compound of formula I under a second suitable conditions; and(iii) comparing the activity of said mutant or wild type CFTR on said cell in the presence and absence of said compound;{'claim-ref': {'@idref': 'CLM-00001', 'claim 1'}, 'wherein said compound of formula I is according to .'}75. The method according to claim 1 , wherein said first suitable conditions are according to any one of -.8. The method according to claim 7 , wherein said mutant is a Class I mutation claim 7 , Class II mutation claim 7 , Class III mutation claim 7 , Class IV mutation claim 7 , or a Class V mutation.9. The method according to claim 8 , wherein said mutant is ΔF508-CFTR.10. The method according to claim 7 , wherein said mutant CFTR is a mutation other than ΔF508-CFTR.11. A method of measuring the CFTR activity in a cell resulting from contacting said cell with a compound capable of increasing the number of CFTR on the membrane of said cell claim 1 , said method ...

Modulators of ATP-binding cassette transporters

The present invention relates to modulators of ATP-Binding Cassette ("ABC") transporters or fragments thereof, including CF Transmembrane Regulator ("CFTR"), compositions thereof, and methods therewith. The present invention also relates to methods of treating ABC transporter mediated diseases using such modulators.

COMPOUNDS USEFUL IN CFTR ASSAYS AND METHODS THEREWITH

The present invention relates to compounds useful in CFTR assays. The present invention also relates to compounds useful in monitoring CFTR activity in therapies for CFTR-mediated diseases. The present invention also provides an assay for use in measuring CFTR correction.

Modulators of ATP-Binding Cassette Transporters

The present invention relates to modulators of ATP-Binding Cassette (“ABC”) transporters or fragments thereof, including CF Transmembrane Regulator (“CFTR”), compositions thereof, and methods therewith. The present invention also relates to methods of treating ABC transporter mediated diseases using such modulators. 1230-. (canceled)232. The method according to claim 231 , wherein Xis CH claim 231 , CF claim 231 , or O.233. The method according to claim 231 , wherein Xis CH.234. The method according to claim 231 , wherein Ais selected from phenyl claim 231 , triazinyl claim 231 , pyrazinyl claim 231 , pyrimidinyl claim 231 , pyridazinyl claim 231 , pyridyl claim 231 , thiadiazolyl claim 231 , triazolyl claim 231 , oxadiazolyl claim 231 , isothiazolyl claim 231 , pyrazolyl claim 231 , imidazolyl claim 231 , thiazolyl claim 231 , oxazolyl claim 231 , pyrrolyl claim 231 , thienyl claim 231 , furanyl claim 231 , indolizinyl claim 231 , indolyl claim 231 , isoindolyl claim 231 , benzofuranyl claim 231 , benzo[b]thienyl claim 231 , 1H-indazolyl claim 231 , benzimidazolyl claim 231 , benzthiazolyl claim 231 , purinyl claim 231 , quinolinyl claim 231 , isoquinolinyl claim 231 , cinnolinyl claim 231 , phthazinyl claim 231 , quinazolinyl claim 231 , quinoxalinyl claim 231 , 1 claim 231 ,8-naphthyridinyl claim 231 , pteridinyl claim 231 , carbazolyl claim 231 , acridinyl claim 231 , phenazinyl claim 231 , phenothiazinyl claim 231 , phenoxazinyl claim 231 , indenyl claim 231 , naphthyl claim 231 , azulinyl claim 231 , or anthracenyl.235. The method according to claim 231 , wherein each Bis independently selected from optionally substituted C6-C10 aryl.236. The method according to claim 231 , wherein each Bis independently an optionally substituted phenyl or naphthyl.237. The method according to claim 231 , wherein each Bis an unsubstituted phenyl.238. The method according to claim 231 , wherein each Bis independently selected from optionally substituted C5-C12 heteroaryl.239. ...

Modulators of ATP-binding cassette transporters

The present invention provides compounds of Formula I useful as modulators of ABC transporter activity, or a pharmaceutically acceptable salt thereof, wherein R B , n, B, R C , R D , R E , A, and Z are described generally and in classes and subclasses below. The present invention also provides pharmaceutical compositions, methods and kits associated with Formula I, useful for as modulators, and for the treatments of disease and disease conditions associated with ABC transporter proteins.

Modulators of atp-binding cassette transporters

The present invention relates to a compound of formula I: (see formula I) wherein R1, R2, R3, R4, R5, R6, R7 and Ar1 are as described herein, and which may be used as modulators of ATP-Binding Cassette ("ABC") transporteres or fragments thereof.

Pyrimidine derivatives as modulators of atp-binding cassette transporters

The present invention relates to compounds of Formula (I) as modulators of ATP-Binding Cassette (“ABC”) transporters or fragments thereof, including Cystic Fibrosis Transmembrane Regulator (“CFTR”), compositions thereof, and methods therewith. The present invention also relates to methods of treating ABC transporter mediated diseases using such modulators.

ATP CONNECTION CARRIAGE TRANSFORMERS

Η παρούσα εφεύρεση αναφέρεται σε διαμορφωτές μεταφορέων κασέτας σύνδεσης με ATP («ABC») ή θραυσμάτων αυτών, συμπεριλαμβανομένου του ρυθμιστή διαμεμβρανικής αγωγιμότητας κυστικής ίνωσης («CFTR»), σε συνθέσεις αυτών και σε μεθόδους δι' αυτών. Η παρούσα εφεύρεση σχετίζεται επίσης με μεθόδους θεραπείας νόσων διαμεσολαβούμενων από μεταφορείς ABC δια της χρήσης τέτοιων διαμορφωτών. The present invention relates to ATP-binding cassette transporter modulators ("ABCs") or fragments thereof, including cystic fibrosis transmembrane regulator ("CFTR"), to compositions thereof and to methods therefor. The present invention also relates to methods of treating diseases mediated by ABC carriers by the use of such modulators.

Modulators of ATP-binding cassette transporters

The present invention relates to modulators of ATP-Binding Cassette ("ABC") transporters or fragments thereof, including Cystic Fibrosis Transmembrane Conductance Regulator, composition thereof, and methods therewith. The present invention also relates to methods of treating ABC transporter mediated diseases using such modulators.

Modulators of atp-binding cassette transporters containing cycloalkyl or pyranyl groups

The present invention provides compounds of Formula (I) useful as modulators of ABC transporter activity, or a pharmaceutically acceptable salt thereof, wherein RB, n, B, RC, RD, RE, A, and Z are described generally and in classes and subclasses below. The present invention also provides pharmaceutical compositions, methods and kits associated with Formula (I), useful for as modulators, and for the treatments of disease and disease conditions associated with ABC transporter proteins.

Modulators of atp-binding cassette transporters

The present invention relates to a compound having formula A-I: (see formula A-I); wherein G1, G2 and G3 are as described herein, and processes for making such compounds.

Pyrimidine derivatives as modulators of atp-binding cassette transporters

The present invention relates to compounds of Formula (I) as modulators of ATP-Binding Cassette (“ABC”) transporters or fragments thereof, including Cystic Fibrosis Transmembrane Regulator (“CFTR”), compositions thereof, and methods therewith. The present invention also relates to methods of treating ABC transporter mediated diseases using such modulators.

Modulators of atp-binding cassette transporters

The present invention relates to processes for making (see formula I and II), which are intermediates that may be used in the preparation of modulators of ATP-Binding Cassette ("ABC") transporters or fragments thereof, including Cystic Fibrosis Transmembrane Conductance Regulator. G4 and G5 are as defined in the specification. The invention also relates to (see formula III).

Modulators of ATP-binding cassette transporters

Modulators of ATP-binding cassette transporters containing cycloalkyl or pyranyl groups

Disclosed is a compound of formula II wherein A is C(O) or SO2, RC and RD taken together form a 3-6 membered cycloalkyl ring; RB is (C1-C4)alkoxy, Z is a substituent of formula I and wherein the rest of the substituents are disclosed within the specification. Also disclosed is the modulating ARP- Binding Cassette (ABC) transporter activity of the compound of formula II.

Modulators of ATP-binding cassette transporters

The present invention relates to modulators of ATP-Binding Cassette ("ABC") transporters or fragments thereof, including Cystic Fibrosis Transmembrane Conductance Regulator, composition thereof, and methods therewith. The present invention also relates to methods of treating ABC transporter mediated diseases using such modulators.

Modulators of ATP-binding cassette transporters

Modulators of atp-binding cassette transporters

Modulators of atp-binding cassette transporters

The present invention relates to modulators of ATP-Binding Cassette ("ABC") transporters or fragments thereof, including CF Transmembrane Regulator ("CFTR"), compositions thereof, and methods therewith. The present invention also relates to methods of treating ABC transporter mediated diseases using such modulators.

Modulators of ATP-binding cassette transporters

Pyrazole modulators of atp-binding cassette transporters

The present invention relates to pyrazoles of formula (I) which are modulators of ATP­Binding Cassette ('ABC') transporters or fragments thereof, including Cystic Fibrosis Transmembrane Regulator ('CFTR'), compositions thereof, and methods therewith. The present invention also relates to methods of treating ABC transporter mediated diseases using such modulators.

Modulators of ATP-binding cassette transporters

The present invention relates to modulators of ATP-Binding Cassette ("ABC") transporters or fragments thereof, including Cystic Fibrosis Transmembrane Conductance Regulator, composition thereof, and methods therewith. The present invention also relates to methods of treating ABC transporter mediated diseases using such modulators.

Modulators of ATP-Binding Cassette Transporters

The present invention relates to modulators of ATP-Binding Cassette ("ABC") transporters or fragments thereof, including Cystic Fibrosis Transmembrane Conductance Regulator, compositions thereof, and methods therewith. The present invention also relates to methods of treating ABC transporter mediated diseases using such modulators.

Modulators of ATP-binding cassette transporters

The present invention relates to modulators of ATP-Binding Cassette ("ABC") transporters or fragments thereof, including Cystic Fibrosis Transmembrane Conductance Regulator, composition thereof, and methods therewith. The present invention also relates to methods of treating ABC transporter mediated diseases using such modulators.

Modulators of atp-binding cassette transporters

4-amido-pyrimidine compounds, derivatives and compositions thereof, and synthetic methods described herein are useful for modulating ATP-Binding Cassette (“ABC”) transporters or fragments thereof, including Cystic Fibrosis Transmembrane Conductance Regulator (“CFTR”). The present invention also relates to methods of treating ABC transporter mediated diseases using such modulators.