Methods of treating conditions associated with an Edg-3 receptor
OwnerDavid Solow-Cordero, Geetha Shankar +2inventors
InventorsDavid Solow-Cordero, Geetha Shankar, Juliet V. Spencer, Charles Gluchowski
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Abstract
In one aspect, the present invention provides a method of inhibiting an Edg-3 receptor mediated biological activity in a cell. A cell expressing the Edg-3 receptor is contacted with an amount of an Edg-3 receptor inhibitor sufficient to inhibit the Edg-3 receptor mediated biological activity. Preferably, the inhibitor is not a phospholipid. In a second aspect, the present invention provides a method where an Edg-3 receptor mediated biological activity is inhibited in a subject. A therapeutically effective amount of an inhibitor of the Edg-3 receptor is administered to the subject. Preferably, the inhibitor is not a phospholipid.
Claims32
A method of modulating an Edg-3 receptor mediated biological activity comprising contacting a cell expressing the Edg-3 receptor with an amount of an modulator of the Edg-3 receptor sufficient to modulate the Edg-3 receptor mediated biological activity wherein compound of the structural formula (I):
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- or a pharmaceutically available solvate or hydrate thereof, wherein;
- each of R1, R2 and R3 is independently —H, -halo, —NO2, —CN, —C(R5)3, —(CH2)mOH, —N(R5)(R5), —O(CH2)mR5, —C(O)R5, —C(O)NR5R5, —C(O)NH(CH2)m(R5), —OCF3, -benzyl, —CO2CH(R5)(R5), —(C1-C10)alkyl, —(C2-C10)alkenyl, —(C2-C10)alkynyl, —(C3-C10)cycloalkyl, —(C8-C14)bicycloalkyl, —(C5-C10)cycloalkenyl, —(C5)heteroaryl, —(C6)heteroaryl, —(C5-C10)heteroaryl, -naphthyl, —(C3-C10)heterocycle, —CO2(CH2)mR5, —N(OH)aryl, —NHC(O)R5, —NHC(O)OR5, —NHC(O)NHR5, -heterocylcoalkyl, —(C1-C10)alkylNHC(O)(CH2)mR5, —(C1-C10)alkylNR5R5, —OC(O)(CH2)mCHR5R5, —CO2(CH2)mCHR5R5, —OC(O)OR5, —SR5, —S(O)R5, —S(O)2R5, —S(O)2NHR5, or
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- R3 is —H —C(R5)3, —(CH2)mOH, —C(O)R5, —C(O)NR5R5, —C(O)NH(CH2)m(R5), -benzyl, —CO2CH(R5)(R5), —(C1-C10)alkyl, —(C2-C10)alkenyl, —(C2-C10)alkynyl, —(C3-C10)cycloalkyl, —(C8-C14)bicycloalkyl, —(C5-C10)cycloalkenyl, —(C5)heteroaryl, —(C6)heteroaryl, —(C5-C10)heteroaryl, -naphthyl, —(C3-C10)heterocycle, —CO2(CH2)mR5, —N(OH)aryl, —NHC(O)R5, —NHC(O)OR5, —NHC(O)NHR5, —N═C(aryl), -heterocylcoalkyl, —(C1-C10)alkylNHC(O)(CH2)mR5, —(C1-C10)alkylNR5R5, —OC(O)(CH2)mCHR5R5, —CO2(CH2)mCHR5R5, —OC(O)OR5, —SR5, —S(O)R5, —S(O)2R5, —S(O)2NHR5, or
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- wherein;
- each R5 and R6 is independently -halo, —NO2, —CN, —OH, —CO2H, —N(C1-C10)alkyl(C1-C10)alkyl, —O(C1-C10)alkyl, —C(O)(C1-C10)alkyl, —C(O)NH(CH2)m(C1-C10)alkyl, —OCF3, -benzyl, —CO2(CH2)mCH((C1-C10)alkyl(C1-C10)alkyl), —CO2(C1-C10)alkyl, —(C1-C10)alkyl, —(C2-C10)alkenyl, —(C2-C10)alkynyl, —(C3-C10)cycloalkyl, —(C8-C14)bicycloalkyl, —(C5-C10)cycloalkenyl, —(C5)heteroaryl, —(C6)heteroaryl, -phenyl, naphthyl, —(C3-C10)heterocycle, —CO2(CH2)m(C1-C10)alkyl, —CO2(CH2)mH, —NHC(O)(C1-C10)alkyl, —NHC(O)NH(C1-C10)alkyl, —NH(aryl), —N═C(aryl), —OC(O)O(C1-C10)alkyl, or —SO2NH2;
- X is O, S, C(R5)(R5) or N(R5);
- R1, R2 or R3 taken in combination can form one or more substituted or unsubstituted 5 or 6 membered cyclic or heterocyclic rings or a 6-membered aromatic ring;
- each m is independently an integer ranging from 0 to 8;
- and
- each p is independently an integer ranging from 0 to 5.
A method of modulating an Edg-3 receptor mediated biological activity in a subject comprising administering to the subject a therapeutically effective amount of a modulator of the Edg-3 receptor wherein the modulator a compound of the structural formula ((II):
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- or a pharmaceutically available solvate or hydrate thereof, wherein:
- R1 is hydrogen, alkyl, substituted alkyl, acylamino, substituted acylamino, alkylamino, substituted alkylamino, alkylthio, substituted alkylthio, alkoxy, substituted alkoxy, alkylarylamino, substituted alkylarylamino, amino, arylalkyloxy, substituted arylalkyloxy, aryl, substituted aryl, arylamino, substituted arylamino, arylalkyl, substituted arylalkyl, dialkylamino, substituted alkyl amino, cycloalkyl, substituted cycloalkyl, cycloheteroalkyl, substituted cycloheteroalkyl, heteroaryloxy, substituted heteroaryloxy, heteroaryl, substituted heteroaryl, heteroalkyl, substituted heteroalkyl sulfonylamino or substituted sulfonylamino;
- X=O or S.
A method for treating or preventing cancers, acute lung diseases, acute inflammatory exacerbation of chronic lung diseases, surface epithelial cell injury, or cardiovascular diseases in a patient comprising administering to a patient in need of such treatment or prevention a therapeutically effective amount of a compound of structural formula (I) or (II).
A method for treating or preventing ovarian cancer, peritoneal cancer, endometrial cancer, cervical cancer, breast cancer, colorectal cancer, uterine cancer, stomach cancer, small intestine cancer, thyroid cancer, lung cancer, kidney cancer, pancreas cancer, prostrate cancer, adult respiratory distress syndrome (ARDS), asthma, transcorneal freezing, cutaneous bums, ischemia or arthesclerosis in a patient comprising administering to a patient in need of such treatment or prevention a therapeutically effective amount of a compound of structural formula (I) or (II).
A method for treating or preventing cancers, acute lung diseases, acute inflammatory exacerbation of chronic lung diseases, surface epithelial cell injury, or cardiovascular diseases in a patient comprising administering to a patient in need of such treatment or prevention a therapeutically effective amount of a compound of structural formula (I) or (II) and one or more agonists or antagonists of an Edg-3 receptor.
A method for treating or preventing cancers, acute lung diseases, acute inflammatory exacerbation of chronic lung diseases, surface epithelial cell injury, or cardiovascular diseases in a patient comprising administering to a patient in need of such treatment or prevention a therapeutically effective amount of a compound of structural formula (I) or (II) and one or more drugs useful in treating or preventing cancers, acute lung diseases, acute inflammatory exacerbation of chronic lung diseases, surface epithelial cell injury, or cardiovascular diseases.
Dependencies are inferred from the claim text.