Conjugated complement cascade inhibitors
The present invention is directed to conjugated complement cascade inhibitors, and a method of treating a patient using a conjugated complement cascade inhibitor.
1. The compound of having the following formula;
wherein X is C or N; R 1 is —NH(C═O)NH-PEG-OCH 3 or —NH(C═O)NH(CH 2 ) n (C═O)NH-PEG-OCH 3 ;R 2 is ureido or guanidino; R 3 is C 1-4 alkyl; and PEG is a polyethylene glycol having a molecular weight of 20-40 K; and the pharmaceutically acceptable salts thereof.
2. The compound of claim 1 which is
wherein n is from about 17 to about 1400,
and pharmaceutically acceptable salts and esters thereof.
3. The compound of claim 2 which is mPEG 20K 2′-urea of 4-(2′-amino-4′-guanidino-6′-methyl-biphenyl-3-sulfonyl)-5-methylsulfanyl-thiophene-2-carboxamidine.
4. The compound of claim 2 which is the bis-trifluoroacetate salt.
5. The compound of claim 2 which is the bis-hydrochloride salt
6. The compound of claim 2 which is PEG 40K Amide of 6-[3′-(5-Carbamimidoyl-2-methylsulfanyl-thiophene-3-sulfonyl)-4-guanidino-6-methyl-biphenyl-2ylcarbamoyl]-hexanoic acid bis-trifluoroacetate, or bis hydrochloride salt, or pharmaceutically acceptable salts and esters thereof, having the following formula:
7. The compound of claim 1 which is
wherein n is is from about 17 to about 1400.
8. The compound of claim 1 which is mPEG 20-30K amide of 6-[3′-(5-carbamimidoyl-2-methylsulfanyl-thiophene-3-sulfonyl)-4-guanidino-6-methyl-biphenyl-2-ylcarbamoyl]-hexanoic acid, having the following formula:
and pharmaceutically acceptable salts and esters thereof.
9. The compound of claim 8 in which the PEG is 20K.
10. The compound of claim 8 which is the bis-trifluoroacetate salt.
11. The compound of claim 8 which is the bis-hydrochloride salt.