Synthesis and application of microbubble-forming compounds
AssigneeCalifornia Institute of Technology
InventorsVanessa M. Marx, Robert H. Grubbs
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Abstract
The present disclosure is directed to fatty-acid glycerol ester derivative compounds containing a targeting bisphosphonate group. The disclosure further includes pharmaceutical or biomedical compositions comprising these compounds, and methods of using these compounds and compositions forming microbubbles. The microbubbles have affinity for metal-containing, especially calcium-containing, bodies and/or biological targets. In certain embodiments, these compositions are useful for providing targeted placement of microbubbles capable of cavitation on application of high frequency energy.
Claims13
A method for binding a physiological plaque, the method comprising the step of delivering an effective amount of a compound to a subject in need thereof, wherein the compound has the formula selected from the group consisting of formula (I), formula (Ia), formula (II), formula (III), formula (IV) and formula (V):
- wherein:
- each n is independently selected from 0-7;
- each m is independently selected from 0-26;
- each p is independently selected from 7-26;
- each q is independently selected from 1-90;
- each R1 is independently selected from the group consisting of:
- hydrogen, C1-C26 alkyl, C1-C26 substituted alkyl, C1-C26 alkenyl, C1-C26 substituted alkenyl, C1-C26 alkynyl, C1-C26 substituted alkynyl, C1-C26 alkyl aryl, C1-C26 substituted alkyl aryl, C1-C26 alkenyl aryl, C1-C26 substituted alkenyl aryl, C1-C26 alkynyl aryl, C1-C26 substituted alkynyl aryl;
- each R2 is independently selected from the group consisting of:
- hydrogen, C1-C26 alkyl, C1-C26 substituted alkyl, C1-C26 alkenyl, C1-C26 substituted alkenyl, C1-C26 alkynyl, C1-C26 substituted alkynyl, C1-C26 alkyl aryl, C1-C26 substituted alkyl aryl, C1-C26 alkenyl aryl, C1-C26 substituted alkenyl aryl, C1-C26 alkynyl aryl, C1-C26 substituted alkynyl aryl, C3-C8 cycloalkyl, C3-C8 substituted cycloalkyl, C3-C8 aryl, C3-C8 substituted aryl, C3-C8 heterocycloalkyl, C3-C8 substituted heterocycloalkyl, C3-C8 heteroaryl, C3-C8 substituted heteroaryl, acyl, aminoacyl, thioacyl, aminocarbonyl, aminoacyl carbonyloxy, aminothiocarbonyl, aminosulfonyl, amidino, substituted sulfonyl, substituted sulfinyl, carboxy ester, phthalimido, SO3H and PO3H;
- C is selected from the group consisting of:
- B is selected from the group consisting of:
- a covalent bond, ethylene glycol, and polyethylene glycol;
- A is selected from the group consisting of:
- a covalent bond, acyl, acylamino, aminoacyl, acyloxy, thioacyl, aminocarbonyl, aminoacyl carbonyloxy, aminothiocarbonyl, aminocarbonylamino, aminothiocarbonylamino, aminocarbonyloxy, aminosulfonyloxy, aminosulfonylamino, aminosulfonyl, amidino, and carboxy ester, wherein any of these functional groups listed for A may be covalently bonded on either side to the
- moiety;
- Y is selected from the group consisting of:
- a covalent bond, acyl, acylamino, aminoacyl, acyloxy, thioacyl, aminocarbonyl, aminoacyl carbonyloxy, aminothiocarbonyl, aminocarbonylamino, aminothiocarbonylamino, aminocarbonyloxy, aminosulfonyloxy, aminosulfonylamino, aminosulfonyl, amidino, and carboxy ester, wherein any of these functional groups listed for A may be covalently bonded on either side to either one of the
- moieties;
- X is selected from the group consisting of:
- hydrogen, silyl, acyl, aminoacyl, thioacyl, aminocarbonyl, aminoacyl carbonyloxy, aminothiocarbonyl, aminosulfonyl, amidino, substituted sulfonyl, substituted sulfinyl, carboxy ester, phthalimido, SO3H and POSH;
- W is selected from the group consisting of:
- O, NR2, and S;
- Z is selected from the group consisting of:
- a covalent bond, CH2, O, NR2, and S;
- M is selected from the group consisting of:
- a covalent bond, CH2—CH2, CH2—CH2—Z, CH2—Z and CH2;
- or a tautomer and/or a pharmaceutically acceptable salt thereof.
Dependencies are inferred from the claim text.