Molecular containers and methods of making and using same
Acyclic CB[n]-type compounds, methods of making such compounds, and uses of the compounds. For example, these compounds can be used as nanocontainers to solubilize pharmaceutical agents. Also provided are compositions and methods of using them for therapy or prophylaxis of a wide variety of conditions for which therapy or prophylaxis is desirable.
1. A method for enhancing the therapeutic effect of a poorly water soluble drug in an individual in need of the therapeutic effect, wherein the poorly soluble drug has a solubility of less than 1.0 mM in water or an aqueous buffer, the method comprising administering to the individual a composition comprising the poorly water soluble drug and a compound having the following structure:
or a salt, a partial salt, a hydrate, or a stereoisomer thereof,
wherein each R is independently hydrogen, C 1 to C 20 alkyl group, C 3 to C 20 carbocyclic group, C 1 to C 20 heterocyclic group, carboxylic acid group, ester group, amide group, hydroxy, or ether group;
wherein, optionally, adjacent R groups form a C 3 to C 20 carbocyclic ring or heterocyclic ring;
wherein each
is independently a C 5 to C 20 carbocyclic ring system or C 2 to C 20 heterocyclic ring system, wherein the ring system comprises one or more rings;
wherein at least one ring system has at least one solubilizing group selected from sulfonic acid group, sulfonate salt group, phosphonic acid group, phosphonate salt group, and polyethylene glycol group;
wherein, optionally, the ring system has a targeting group; and
wherein n is 1 to 5.
2. The method of claim 1 , wherein each
is independently a C 5 to C 20 carbocyclic ring system having one of the following structures:
wherein at each occurrence of
R 1 to R 16 is independently hydrogen, C 1 to C 20 alkyl group, halo group, hydroxyl group, nitro group, carboxylic acid group, ester group, amide group, ether group, C 3 to C 20 carbocyclic group, or C 1 to C 20 heterocyclic group,
provided that at least one of R 1 to R 16 in the compound has the following structure:
wherein LG is a linking group and X is the solubilizing group; and
wherein optionally one or more adjacent R 1 to R 16 groups are connected forming a carbocyclic ring or heterocyclic ring.
3. The method of claim 2 , wherein
has the following structure:
wherein each i is 1 to 20.
4. The method of claim 2 , wherein at least one of the R 1 to R 16 groups in the structure has the following structure:
and wherein LG is a linking group and wherein TG is the targeting group.
5. The method of claim 2 , wherein the
groups are the same.
6. The method of claim 3 , wherein the compound has one of the following structures:
wherein Z is PEG group having a molecular weight of 200 to 10,000.
7. The method of claim 1 , wherein the compound has one of the following structures:
wherein A + is H + , Na + , K + , Ca 2+ , Mg 2+ , Zn 2+ , H 4 N + , Et 3 NH + , Me 4 N + , (HOCH 2 CH 2 ) 3 NH + , or a cationic form of ethylenediamine, piperazine, and trishydroxymethyl aminomethane (TRIS).