Inhibitors of TRPC6 for treating respiratory conditions

A method for treating a disorder associated with vascular hyperpermeability and/or conditions arising therefrom by inhibiting the Transient Receptor Potential C6 ion channel (TRPC6), comprising administering to a patient in need thereof a pharmaceutically effective amount of a TRPC6 inhibitor of formula (I),

• wherein
• L is absent or is methylene or ethylene;
• Y is CH or N;
• A is CH or N;
• R1 is selected from the group consisting of:
• C1-6alkyl optionally substituted with 1 to 3 groups independently selected from the group consisting of halo, C3-6cycloalkyl and OC3-6cycloalkyl;
• phenyl optionally substituted with 1 to 3 groups independently selected from the group consisting of CF3, halo, C3-6cycloalkyl, OC3-6cycloalkyl, and OC1-6alkyl optionally substituted with one to three halo;
• and
• C3-6cycloalkyl optionally substituted with 1 to 3 groups independently selected from the group consisting of halo and C1-6alkyl optionally substituted with 1 to 3 halo;
• R2 is selected from the group consisting of H, C1-6alkyl, OCF3, C3-6cycloalkyl, OC1-6alkyl, and OC3-6cycloalkyl;
• R3 is selected from the group consisting of H, C1-6alkyl, C3-6cycloalkyl, and OC3-6cycloalkyl;
• wherein each of the C1-6alkyl, C3-6cycloalkyl, OC3-6cycloalkyl of the R3 group may be optionally substituted with one to three groups each independently selected from the group consisting of halo, OH, OC1-6alkyl, SC1-6alkyl, and N(C1-6alky)2;
• and
• wherein one to three carbon atoms of the C1-6alkyl of the R3 group may optionally be replaced one or two moieties selected from the group consisting of NH, N(C1-6alkyl), O, and S;
• R4 and R5 are each independently selected from the group consisting of H and C1-6alkyl;
• R3 and R4 can together with the atom to which they are attached join to form a 3 to 9-membered carbocyclyl ring which optionally may contain one to three heteroatoms selected from the group consisting of N, O, and S;
• or
• R3 and R5 can together form a 3 to 9-membered bicyclic ring which optionally may contain one to three heteroatoms selected from the group consisting of N, O, and S;
• R6 is selected from the group consisting of H, C1-6alkyl, CN, CF3, OCF3, C3-6cycloalkyl, OC1-6alkyl, and OC3-6cycloalkyl;
• R7 is selected from the group consisting of H and OC1-6alkyl;
• or a pharmaceutically acceptable salt thereof, wherein
• the disorder associated with vascular hyperpermeability and/or conditions arising therefrom is selected from the group consisting of sepsis, severe sepsis, and septic shock.