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US 2010/0144675 A1Published application
Regulation of sGC Function by Corrin Derivatives
OwnerEmil Martin, Ferid Muradinventors
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Abstract
We disclose a method of activating soluble guanylyl cyclase (sGC) in a patient, comprising administering to the patient a composition comprising a corrin and a pharmaceutically-acceptable carrier. We also disclose a composition, comprising a corrin, an NO-independent sGC activator selected from the group consisting of BAY 41-2272, BAY 58-2667, HMR1766, YC-I, and S3448, and a pharmaceutically-acceptable carrier.
Claims7
A method of activating soluble guanylyl cyclase (sGC) in a patient, comprising:
- administering to the patient a composition comprising a corrin having the general formula (I)
- wherein R is selected from the group consisting of —CN, —N3-, —OH, —CxH2x+1 wherein x is an integer from 1 to about 10, inclusive, and -deoxyadenosyl;
- R1 is selected from the group consisting of —CN, —N3-, —OH, —CxH2x+1 wherein x is an integer from 1 to about 10, inclusive, -deoxyadenosyl, and dimethylbenzimidazolyl;
- R2 is selected from the group consisting of —H and —CxH2x+1 wherein x is an integer from 1 to about 10, inclusive;
- R3 is selected from the group consisting of —H, —CxH2x+1 wherein x is an integer from 1 to about 10, inclusive, —CyH2yCOOH and salts or esters thereof wherein y is an integer from 1 to about 9, inclusive, and —CyH2yCONH2 wherein y is an integer from 1 to about 9, inclusive;
- R4 is selected from the group consisting of —H and —CxH2x+1 wherein x is an integer from 1 to about 10, inclusive;
- R5 is selected from the group consisting of —H, —CxH2x+1 wherein x is an integer from 1 to about 10, inclusive, —CyH2yCOOH and salts or esters thereof wherein y is an integer from 1 to about 9, inclusive, and —CyH2yCONH2 wherein y is an integer from 1 to about 9, inclusive;
- R6 is selected from the group consisting of —H and —CxH2x+1 wherein x is an integer from 1 to about 10, inclusive;
- R7 is selected from the group consisting of —H and —CxH2x+1 wherein x is an integer from 1 to about 10, inclusive;
- R8 is selected from the group consisting of —H, —CxH2x+1 wherein x is an integer from 1 to about 10, inclusive, —CyH2yCOOH and salts or esters thereof wherein y is an integer from 1 to about 9, inclusive, and —CyH2yCONH2 wherein y is an integer from 1 to about 9, inclusive;
- R9 is selected from the group consisting of —H and —CxH2x+1 wherein x is an integer from 1 to about 10, inclusive;
- R10 is selected from the group consisting of —H and —CxH2x+1 wherein x is an integer from 1 to about 10, inclusive;
- R11 is selected from the group consisting of —H, —CxH2x+1 wherein x is an integer from 1 to about 10, inclusive, —CyH2yCOOH and salts or esters thereof wherein y is an integer from 1 to about 9, inclusive, —CyH2yCONH2 wherein y is an integer from 1 to about 9, inclusive, —CH2CH2CONHCH2CH(OH)CH3, and —CyH2yCONHCH2CHOP(OC5O3H8)O2 wherein y is an integer from 1 to about 9, inclusive, and (C5O3H8) forms a ribose group;
- R12 is selected from the group consisting of —H, —CxH2x+1 wherein x is an integer from 1 to about 10, inclusive, —CyH2yCOOH and salts or esters thereof wherein y is an integer from 1 to about 9, inclusive, and —CyH2yCONH2 wherein y is an integer from 1 to about 9, inclusive;
- R13 is selected from the group consisting of —H and —CxH2x+1 wherein x is an integer from 1 to about 10, inclusive;
- R14 is selected from the group consisting of —H and —CxH2x+1 wherein x is an integer from 1 to about 10, inclusive;
- R15 is selected from the group consisting of —H, —CxH2x+1 wherein x is an integer from 1 to about 10, inclusive, —CyH2yCOOH and salts or esters thereof wherein y is an integer from 1 to about 9, inclusive, and —CyH2yCONH2 wherein y is an integer from 1 to about 9, inclusive;
- R16 is selected from the group consisting of —H and —CxH2x+1 wherein x is an integer from 1 to about 10, inclusive;
- and
- R17 is selected from the group consisting of —H, —CxH2x+1 wherein x is an integer from 1 to about 10, inclusive, —CyH2yCOOH and salts or esters thereof wherein y is an integer from 1 to about 9, inclusive, and —CyH2yCONH2 wherein y is an integer from 1 to about 9, inclusive;
- and a pharmaceutically-acceptable carrier.
18 more elements
A composition, comprising:
- a corrin having the general formula (I)
- wherein R is selected from the group consisting of —CN, —N3-, —OH, —CxH2x+1 wherein x is an integer from 1 to about 10, inclusive, and -deoxyadenosyl;
- R1 is selected from the group consisting of —CN, —N3-, —OH, —CxH2x+1 wherein x is an integer from 1 to about 10, inclusive, -deoxyadenosyl, and dimethylbenzimidazolyl;
- R2 is selected from the group consisting of —H and —CxH2x+1 wherein x is an integer from 1 to about 10, inclusive;
- R3 is selected from the group consisting of —H, —CxH2x+1 wherein x is an integer from 1 to about 10, inclusive, —CyH2yCOOH and salts or esters thereof wherein y is an integer from 1 to about 9, inclusive, and —CyH2yCONH2 wherein y is an integer from 1 to about 9, inclusive;
- R4 is selected from the group consisting of —H and —CxH2x+1 wherein x is an integer from 1 to about 10, inclusive;
- R5 is selected from the group consisting of —H, —CxH2x+1 wherein x is an integer from 1 to about 10, inclusive, —CyH2yCOOH and salts or esters thereof wherein y is an integer from 1 to about 9, inclusive, and —CyH2yCONH2 wherein y is an integer from 1 to about 9, inclusive;
- R6 is selected from the group consisting of —H and —CxH2x+1 wherein x is an integer from 1 to about 10, inclusive;
- R7 is selected from the group consisting of —H and —CxH2x+1 wherein x is an integer from 1 to about 10, inclusive;
- R8 is selected from the group consisting of —H, —CxH2x+1 wherein x is an integer from 1 to about 10, inclusive, —CyH2yCOOH and salts or esters thereof wherein y is an integer from 1 to about 9, inclusive, and —CyH2yCONH2 wherein y is an integer from 1 to about 9, inclusive;
- R9 is selected from the group consisting of —H and —CxH2x+1 wherein x is an integer from 1 to about 10, inclusive;
- R10 is selected from the group consisting of —H and —CxH2x+1 wherein x is an integer from 1 to about 10, inclusive;
- R11 is selected from the group consisting of —H, —CxH2x+1 wherein x is an integer from 1 to about 10, inclusive, —CyH2yCOOH and salts or esters thereof wherein y is an integer from 1 to about 9, inclusive, —CyH2yCONH2 wherein y is an integer from 1 to about 9, inclusive, —CH2CH2CONHCH2CH(OH)CH3, and —CyH2yCONHCH2CHOP(OC5O3H8)O2 wherein y is an integer from 1 to about 9, inclusive, and (C5O3H8) forms a ribose group;
- R12 is selected from the group consisting of —H, —CxH2x+1 wherein x is an integer from 1 to about 10, inclusive, —CyH2yCOOH and salts or esters thereof wherein y is an integer from 1 to about 9, inclusive, and —CyH2yCONH2 wherein y is an integer from 1 to about 9, inclusive;
- R13 is selected from the group consisting of —H and —CxH2x+1 wherein x is an integer from 1 to about 10, inclusive;
- R14 is selected from the group consisting of —H and —CxH2x+1 wherein x is an integer from 1 to about 10, inclusive;
- R15 is selected from the group consisting of —H, —CxH2x+1 wherein x is an integer from 1 to about 10, inclusive, —CyH2yCOOH and salts or esters thereof wherein y is an integer from 1 to about 9, inclusive, and —CyH2yCONH2 wherein y is an integer from 1 to about 9, inclusive;
- R16 is selected from the group consisting of —H and —CxH2x+1 wherein x is an integer from 1 to about 10, inclusive;
- and
- R17 is selected from the group consisting of —H, —CxH2x+1 wherein x is an integer from 1 to about 10, inclusive, —CyH2yCOOH and salts or esters thereof wherein y is an integer from 1 to about 9, inclusive, and —CyH2yCONH2 wherein y is an integer from 1 to about 9, inclusive;
- an NO-independent sGC activator selected from the group consisting of BAY 41-2272, BAY 58-2667, HMR1766, YC-1, and S3448;
- and
- a pharmaceutically-acceptable carrier.
20 more elements
Dependencies are inferred from the claim text.