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US 2007/0167644 A1Published application
Bifunctional energy-reversible acyl-compositions
AssigneeCryolife, Inc.
InventorsCarl Gilbert, Eleanor McGowan, Kirby Black, T. Gregory Harper
Life of this patent
Estimating the term…
Abstract
Energy-reversible acyl conjugates, intermediates, and related compositions are disclosed. In preferred aspects, examples of such compositions include:
Claims32
A compound comprising the formula:
- wherein:
- R1 and R2 are individually selected from the group consisting of H, CH3, C2-C10 alkyls, C2-C10 alkenyls or C2-C10 alkynyls, straight or branched;
- C2-C10 heteroalkyls, C2-C10 heteroalkenyls or C2-C10 heteroalkynyls and —(CR15R16)p-D;
- wherein:
- R15 and R16 are individually selected from the group consisting of H, CH3, C2-C10 alkyls, C2-C10 alkenyls or C2-C10 alkynyls, straight or branched;
- and C2-C10 heteroalkyls, C2-C10 heteroalkenyls or C2-C10 heteroalkynyls;
- p is a positive integer from 1 to about 12;
- D is selected from among —SH, —OH, X2, —CN, —OR19, NHR20,
- wherein:
- R17 is H, CH3 or X3;
- R18 is H, a C1-4 alkyl or benzyl;
- R19 is H, a C1-4 alkyl, X2 or benzyl;
- R20 is H, a C1-10 alkyl or —C(O)R21,
- wherein
- R21 is H, a C1-4 alkyl or alkoxy, t-butoxy or benzyloxy;
- X2 and X3 are independently selected halogens;
- R3 is H, CH3, or —C(═O)(CR15R16)w-D,
- where w is 0 or an integer from 1 to about 12, and D is H or as described for R1 and R2;
- J is O, NH or S;
- R4, R5, and R6 are independently selected from the group consisting of H, CH3, C2-C10 alkyls, C2-C10 alkenyls or C2-C10 alkynyls, straight or branched;
- C2-C10 heteroalkyls, heteroalkenyls or heteroalkynyls and halogens;
- Z is NR7R8 or
- wherein
- R7 is selected from among H, CH3, C2-C10 alkyls, alkenyls or alkynyls straight or branched;
- C2-C10 heteroalkyls, heteroalkenyls or heteroallynyls, or —(CR23R24)q-aryl, or R8,
- wherein
- R23 and R24 are independently selected from the group consisting of H and C1-C10 alkyls;
- q is an integer from 1 to about 6;
- R8 is selected from the group consisting of (CR9R10)n—NR22—R 11, (CR9R10)n—CH2—NHC(O)R26 and (CR9R10)n—CH2-E;
- wherein
- R9 and R10 are independently selected from the group consisting of H, CH3, C2-C10 alkyls, C2-C10 alkenyls or C2-C10 alkynyls, straight or branched;
- C2-C10 heteroaakyls, C2-C10 heteroalkenyls or
- C2-C10 heteroalkynyls and halogens;
- R26 is H, CH3, O-t-butyl, O-benzyl;
- E is OH, SH or O—C(O)R27,
- wherein R27 is a C1-C6 alkyl, benzyl or phenyl;
- R22 is H or CH3;
- n is a positive integer from 1 to about 10;
- R11 is H or-L-B,
- wherein
- L is a positive linker covalently linking NR22 to B;
- and
- B is selected from the group consisting of polymers, biologically active materials and polymeric supports;
- R25 is H, —C(O)—R28 or —C(O)—O—R29,
- wherein R28 is a C1-C6 alkyl or benzyl;
- and R29 is CH3, t-butyl or benzyl;
- X1 is O, NH, or S;
- and
- A is A2
- wherein X1A2 is an enzyme.
47 more elements
A method of preparing a conjugate, comprising:
- reacting a compound of Formula (IV)
- wherein:
- R1 and R2 are individually selected from the group consisting of H, CH3, C2-C10 alkyls, C2-C10 alkenyls or C2-C10 alkynyls, straight or branched;
- C2-C10 heteroalkyls, C2-C10 heteroalkenyls or C2-C10 heteroalkynyls and —(CR15R16)p-D
- wherein:
- R15 and R16 are individually selected from the group consisting of H, CH3, C2-C10 alkyls, C2-C10 alkenyls and C2-C10 alkynyls, straight or branched;
- and C2-C10 heteroalkyls, C2-C10 heteroalkenyls or C2-C10 heteroalkynyls;
- p is a positive integer from 1 to about 12;
- D is selected from among —SH, —OH, X2, —CN, —OR19, NHR20,
- wherein:
- R17 is H, a CH3 or X3;
- R18 is H, a C1-4 alkyl or benzyl;
- R19 is H, a C1-4 alkyl, X2 or benzyl;
- R20 is H, a C1-10 alkyl or —C(O)R21
- wherein
- R21 is H, a C1-4 alkyl or alkoxy, t-butoxy or benzyloxy;
- X2 and X3 are independently selected halogens;
- R3 is H, CH3, or —C(═O)(CR15R16)w-D,
- where w is 0 or an integer from 1 to about 12, and D is H or as described for R1 and R2,
- J is O, NH or S;
- R4, R5 and R6 independently selected from the group consisting of H, CH3, C2-C10 alkyls, C2-C10 alkenyls or C2-C10 aLkynyls, straight or branched;
- C2-C10 heteroalkyls, heteroalkenyls or heteroalkynyls and halogens;
- R7 is selected from among H, CH3 and C2-C10 alkyls;
- X1 is O, NH, or S;
- R22 is H or CH3;
- and
- A is A2
- wherein X1A2 is an enzyme
- with a compound of the Formula (V):
- L1−B1 (V)
- wherein
- L1 is a moiety containing a functional group capable of reacting with the NHR22 of Formula (IV);
- and
- B1 is selected from the group consisting of polymers, biologically active materials and polymeric supports.
31 more elements
Dependencies are inferred from the claim text.