Ester prodrugs of steroids

Details Ester prodrugs of steroids Ester prodrugs of steroids

C - Chemistry, Metallurgy

07

J

260/70

C07J 5/00 (2006.01) C07J 17/00 (2006.01) C07J 21/00 (2006.01) C07J 41/00 (2006.01) C07J 51/00 (2006.01)

Patent

CA 1310009

ABSTRACT ESTER PRODRUGS OF STEROIDS A compound of the formula Image wherein the dotted line between positions C-1 and C-2 means the presence or absence of a double bond; wherein R1 is CH3 or -C2H5; wherein R2 is H, and R3 is in the .alpha.-position and is -OH, -O-alkyl(C1-C12), -O?alkyl(C1-C12), =O?aryl, -C?N(R)2, or -O?OR7 wherein aryl is furyl, thienyl, pyrrolyl, or pyridyl wherein each of said hetero moiety is optionally substituted with one or two (C1-C4)- alkyl groups or aryl is -(CH2)f-phenyl wherein f is 0 to 2 and wherein the phenyl ring is optionally substituted with 1 to 3 groups selected from chlorine, fluorine, bromine, alkyl(C1-C3), alkoxy(C1-C3), thio- alkoxy(C1-C3), Cl3C-, F3C-, -NH2 and -NHCOCH3 and wherein R is hydro- gen, alkyl(C1-C4), or phenyl and each R can be the same or different; and wherein R7 is aryl as herein defined or alkyl(C1-Cl2); or wherein R2 is .alpha.-Cl and R3 is .beta.-Cl; or wherein R2 and R3 taken together are oxygen (-O-) bridging positions C-9 and C-11; or wherein R2 and R3 taken together form a double bond between positions C-9 and C-11. wherein R4 is H, CH3, Cl or F; wherein R5 is H, OH, F, Cl, Br, CH3, phenyl, vinyl or allyl; wherein R6 is H or CH3; wherein R9 is H, OH, CH3, F or =CH2; wherein R10 is H, OH, CH3 or R10 forms a second bond between positions C-16 and C-17; wherein R11 is -CH2CH2COOH, -Y-(CH2)n-X-(CH2)m-SO3H, -Y'-(CH2)p-X'- (CH2)q-NR12R13 or -Z(CH2)rQ, wherein Y is a bond or -O-; Y' is a bond, -O-, or -S-; each of X and X' is a bond, -CON(R14)-, -N(R14)CO-, -O-, -S-, -S(O)-, or -S(O2)-; R14 is hydrogen or alkyl(C1-C4); each of R12 and R13 is a lower alkyl group of from 1 to 4 carbon atoms optionally substituted with one hydroxyl or R12 and R13 taken together with the nitrogen atom to which each is attached forms a monocyclic hetero- cyclic selected from pyrrolidino, piperidino, morpholino, thiomorpho- lino, piperazino or N(lower)alkylpiperazino wherein alkyl has from 1 to 4 carbon atoms; n is an integer of from 4 to 9; m is an integer of from 1 to 5; p is an integer of from 2 to 9; q is an integer of from 1 to 5; Z is a bond or -O-; r is an integer of from 2 to 9; and Q is (1) -R15-CH2COOH wherein R15 is -S-, -S(O)-, -S(O)2-, -SO2N- (R16)-, or -N(R16)SO2-; and R16 is hydrogen or lower alkyl(C1-C4); with the proviso that the total number of carbon atoms in R16 and (CH2)r is not greater than 10; (2) -CO-COOH; or (3) -CON(R17)CH(R18)COOH wherein R17 is H and R18 is H, CH3, CH2COOH, -CH2CH2COOH, -CH2OH, -CH2SH, -CH2CH2SCH3, or -N(R17)- wherein Ph is phenyl and Ph-OH is p-hydroxyphenyl; or R17 is CH3 and R18 is H; or R17 and R18 taken together are -CH2CH2CH2-; or -N(R17)- CH(R18)COOH taken together is -NHCH2CONHCH2COOH; and pharmaceutically acceptable salts thereof; with the further provisos that: (a) when n is 2, R14 is other than hydrogen; (b) the sum of m and n is not greater than 10; (c) the sum of p and q is not greater than 10; (d) when X is a bond the sum of m and n is from 5 to 10; (e) when X' is a bond the sum of p and q is from 4 to 9; (f) when R4 is Cl or F, the C-1 position is saturated; and (g) when R9 is =CH2, R10 is other than a second bond between positions C-16 and C-17; excepting the following compounds: 21-(3-Carboxy-1-oxopropoxy)-6.alpha.-fluoro-17.alpha.-hydroxy-16.alpha.-methyl- pregna-1,3,9(11)triene-3,20-dione, sodium salt; 21-(3-carboxy-1-oxopropoxy)-17.alpha.-hydroxy-16.beta.-methylpregna-1,4,9- (11)triene-3,20-dione; 21-(3-carboxy-1-oxopropoxy)-17.alpha.-hydroxy-l6.alpha.-methylpregna-1,4,9 (11)triene-3,20-dione, sodium salt; 21-(3-carboxy-1-oxopropoxy)-17.alpha.-hydroxy-16.alpha.-methylpregna-4,9(11)- diene-3,20-dione, sodium salt; N-methyltaurine amide of 17.alpha.-hydroxypregna-4,9(11)diene-3,20- dione-21-hemisuberate, sodium salt; N-methyltaurine amide of 17.alpha.-hydroxypregna-1,4,9(11)triene-6.alpha.- 3,20-dione-21-hemisuberate, sodium salt.

476438

Affiliated with

Also associated with

Rating

Ester prodrugs of steroids does not yet have a rating. At this time, there are no reviews or comments for this patent.

If you have personal experience with Ester prodrugs of steroids, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Ester prodrugs of steroids will most certainly appreciate the feedback.

Rate now

Comments { 0 }

Profile ID: LFCA-PAI-O-1275589