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US 6,649,655 B2Granted
11β-fluoro 15β-hydroxy PGF2α analogs as FP receptor antagonists
AssigneeAlcon Manufacturing, Ltd.
InventorsNajam A. Sharif, Brenda W. Griffin
Life of this patent
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Abstract
Methods and compositions for the antagonism of FP receptor-mediated biological responses are disclosed.
Claims16
A method of antagonizing FP receptors, comprising exposing such receptors to a compound of formula I:
- wherein:
- R1=CO2R, CONR4R5, CH2OR6, or CH2NR7R8;
- where:
- R=H or cationic salt moiety, or CO2R=pharmaceutically acceptable ester moiety;
- R4, R5=same or different=H or alkyl;
- R6=H, acyl or alkyl;
- R7, R8=same or different=H, acyl, or alkyl;
- with the proviso that if one of R7, R8=acyl, then the other=H or alkyl;
- n=0 or 2;
- R2, R3=same or different=H, alkyl, or acyl;
- ----=single or non-cumulated double bond, with the provisos that if a double bond is present between carbons 4 and 5, it is of the cis configuration;
- and that if a double bond is present between carbons 13 and 14, it is of the trans configuration;
- X=(CH2)m or (CH2)mO, where m=1-6;
- and
- Y=phenyl, optionally substituted with alkyl, halo, trihalomethyl, alkoxy, acyl, acyloxy, amino, alkylamino, acylamino, or hydroxy;
- or
- X-Y=(CH2)pY1;
- where p=0-6;
- and
- wherein:
- W=CH2, O, S(O)q, NR10, CH2CH2, CH═CH, CH2O, CH2S(O)q, CH═N, or CH2NR9;
- where q=0-2, and R10 H, alkyl, or acyl;
- Z=H, alkyl, alkoxy, acyl, acyloxy, halo, trihalomethyl, amino, alkylamino, acylamino, or hydroxy;
- and
- ----=single or double bond.
22 more elements
A method of determining whether a test compound is an FP agonist, comprising:
- (i) providing a culture of FP receptor containing cells that produce FP receptor product when activated;
- and (ii) comparing the amount of FP receptor product produced when the culture of cells is exposed to the test compound in the absence of an FP antagonist with the amount of FP receptor product produced when the culture of cells is exposed to the test compound in the presence of an FP receptor antagonizing effective amount of a compound of formula I:
- wherein:
- R1=CO2R, CONR4R5, CH2OR6, or CH2NR7R8;
- where:
- R=H or cationic salt moiety, or CO2R=pharmaceutically acceptable ester moiety;
- R4, R5=same or different=H or alkyl;
- R6=H, acyl, or alkyl;
- R7, R8=same or different=H, acyl, or alkyl;
- with the proviso that if one of R7, R8=acyl, then the other=H or alkyl;
- n=0 or 2;
- R2, R3=same or different=H, alkyl, or acyl;
- ----=single or non-cumulated double bond, with the provisos that if a double bond is present between carbons 4 and 5, it is of the cis configuration;
- and that if a double bond is present between carbons 13 and 14, it is of the trans configuration;
- X=(CH2)m or (CH2)mO, where m=1-6;
- and
- Y=phenyl, optionally substituted with alkyl, halo, trihalomethyl, alkoxy, acyl, acyloxy, amino, alkylamino, acylamino, or hydroxy;
- or
- X-Y=(CH2)pY1;
- where p=0-6;
- and
- wherein:
- W=CH2, O, S(O)q, NR10, CH2CH2, CH═CH, CH2O, CH2S(O)q, CH═N, or CH2NR9;
- where q=0-2, and R10=H, alkyl, or acyl;
- Z=H, alkyl, alkoxy, acyl, acyloxy, halo, trihalomethyl, amino, alkylamino, acylamino, or hydroxy;
- and
- ----=single or double bond.
24 more elements
Dependencies are inferred from the claim text.