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US 6,150,539 AGranted
Triptolide prodrugs having high aqueous solubility
AssigneePharmagenesis, Inc.
InventorJohn H. Musser
Life of this patent
Estimating the term…
Abstract
Compounds useful in immunosuppressive and anti-inflammatory treatment are described. The compounds are hydrolyzable triptolide analogs with improved water solubility and generally lower toxicity than the parent compound.
Claims8
A compound having the structure I:
- ##STR5## where OR.sup.1 is selected from (i) a carboxylic ester, carbonate, or inorganic ester, having a central atom selected from carbon, sulfur, phosphorus, nitrogen, and boron, and having linked to said central atom at least one group of the form --Y--Z or --O--Y--Z, where Y is a branched or unbranched C.sub.1 -C.sub.6 alkyl or alkenyl chain, and Z is hydrogen or a polar group selected from keto, aldehyde, carboxylate, carboxylic ester, hydroxy, alkoxy, polyether, thiol, alkylthio, amino, cyano, nitro, sulfate, nitrate, phosphate, or a 5- to 7-membered heterocycle having ring atoms selected from carbon, nitrogen, oxygen, and sulfur, and three to six carbon ring atoms, and
- (ii) a mono-, di- or trisaccharide linked to C14 at an anomeric center;
- and OR.sup.3 is OH or O--(C.dbd.O)R, where R is lower alkyl.
A compound having the structure II:
- ##STR7## where OR.sup.5 is selected from (i) --O--Y--Z or --O--(C.dbd.O)--Y--Z, where Y is a branched or unbranched C.sub.1 -C.sub.6 alkyl or alkenyl chain, and Z is hydrogen or a polar group selected from keto, aldehyde, carboxylate, carboxylic ester, amino, alkylamino, hydroxy, alkoxy, polyether, thiol, alkylthio, cyano, nitro, inorganic ester, or a 5- to 7-member heterocyclic ring whose ring atoms are selected from the group consisting of carbon, nitrogen, oxygen and sulfur, where the ring atoms include 3 to 6 carbon atoms, and
- (ii) a mono-, di- or trisaccharide linked to C14 at an anomeric center;
- and OR.sup.3 is --O--(C.dbd.O)R, where R is lower alkyl.
A compound having the structure III:
- ##STR9## where R.sup.6 is a leaving group selected from the group consisting of alkyl sulfonate, fluoroalkyl sulfonate, aryl sulfonate, fluorosulfonate, nitrate, alkyl phosphate, alkyl borate, trialkylammonium, and dialkylsulfonium.
Dependencies are inferred from the claim text.