11-Aza prostaglandins for the treatment of glaucoma and ocular hypertension

A compound of formula I:

• wherein:
• R1=CO2R, CONR4R5, CH2OR6, or CH2NR7R8;
• where:
• R=H or cationic salt moiety, or CO2R forms a 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;
• G=CH2 or O;
• R2=H, OH, acyloxy, or alkoxy;
• {overscore (- - -)}=single or non-cumulated double bond, with the provisos that when G=O, a single bond exists between carbons 4 and 5, and that if a double bond is present between carbons 13 and 14 that it be of the trans configuration;
• R3=H, R11, COR11, or CO2R11, where R11=alkyl;
• one of A, B=H, the other=F, OH, acyloxy, or alkoxy;
• or A-B=O(CH2)2O or O as a carbonyl;
• X=(CH2)q or (CH2)qO;
• where q=1-6;
• and
• Y=a phenyl ring 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)m, NR9, CH2CH2, CH═CH, CH2O, CH2S(O)m, CH═N, or CH2NR9;
• where m=0-2, and R9=H, alkyl, or acyl;
• Z=H, alkyl, alkoxy, acyl, acyloxy, halo, trihalomethyl, amino, alkylamino, acylamino, or hydroxy;
• and
• {overscore (- - -)}=single or double bond.

An ophthalmic composition for the treatment of glaucoma and ocular hypertension, comprising a compound of formula I:

• wherein:
• R1=CO2R, CONR4R5, CH2OR6, or CH2NR7R8;
• where:
• R=H or cationic salt moiety, or CO2R forms a 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;
• G=CH2 or O;
• R2=H, OH, acyloxy, alkoxy;
• {overscore (- - -)}=single or non-cumulated double bond, with the provisos that when G=O, a single bond exists between carbons 4 and 5, and that if a double bond is present between carbons 13 and 14 that it be of the trans configuration;
• R3=H, R11, COR11, or CO2R11, where R11=alkyl;
• one of A, B=H, the other=F, OH, acyloxy, or alkoxy;
• or A-B=O(CH2)2O or O as a carbonyl;
• X=(CH2)q or (CH2)qO;
• where q=1-6;
• and
• Y=a phenyl ring 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)m, NR9, CH2CH2, CH═CH, CH2O, CH2S(O)m, CH═N, or
• CH2NR9;
• where m=0-2, and R9=H, alkyl, or acyl;
• Z=H, alkyl, alkoxy, acyl, acyloxy, halo, trihalomethyl, amino, alkylamino, acylamino, or hydroxy;
• and
• {overscore (- - -)}=single or double bond;
• and
• an ophthalmically acceptable vehicle therefor.