Abstract: Terminally-branched polymeric prodrug platforms capable of high degrees of loading are disclosed. In preferred aspects of the invention, the prodrug platform releases multiple parent compounds after each branch holding the active agent undergoes a benzyl elimination reaction. Methods of preparing the prodrugs and using the same in the treatment of mammals are also disclosed.

Abstract: The present invention is directed to polymeric-prodrug transport forms of the formula: 1 2

Abstract: The present invention is directed to polymeric-prodrug transport forms of the formula: wherein: E1-4 are independently selected from the group consisting of hydrogen, C1-6 alkyls, C3-12 branched alkyls, C3-8 cycloalkyls, C1-6 substituted alkyls, C3-8 substituted cycloalkyls, aryls, substituted aryls, aralkyls, C1-6 heteroalkyls, substituted C1-6 heteroalkyls, C1-6 alkoxy, phenoxy, C1-6 heteroalkoxy, and at least one of E1-4 includes a B moiety, wherein B is a leaving group, OH, a residue of a hydroxyl-or amino-containing moiety or wherein J1 is the same as J, or another member of the group defining J and E5 is the same as E1-4, or another member of the group defining E1-4; Y1-2 are independently O, S or NR9; M is a heteroatom selected from either X or Q; wherein X is an electron withdrawing group and Q is a moiety containing a free electron pair positioned three to six atoms from C(=Y2); R2-5 and R7-9 are independently selected

Abstract: Branched, substantially non-antigenic polymers are disclosed. Conjugates prepared with the polymers and biologically active molecules such as proteins and peptides demonstrate extended circulating life in vivo. Substantially fewer sites on the biologically active material are used as attachment sites. Methods of forming the polymer, conjugating the polymers with biologically active moieties and methods of using the conjugates are also disclosed.

Abstract: The present invention is directed to polymeric-prodrug transport forms of the formula: wherein: G is a linear or branched, terminally functionalized polymer residue; Y1 is O, S, or NR1; M is X or Q; wherein X is an electron withdrawing group and Q is a moiety containing a free electron pair positioned three to six atoms from C(═Y1); R1-5 are independently selected from the group consisting of hydrogen, C1-6 alkyls, C3-12 branched alkyls, C3-8 cycloalkyls, C1-6 substituted alkyls, C3-8 substituted cycloalkyls, aryls, substituted aryls, aralkyls, C1-6 heteroalkyls, substituted C1-6 heteroalkyls; R6 is OR7 or N3, NH2, NO2 or CN, where R7 is selected from the same group which defines R1-5; R8-9 are independently selected from the group consisting of hydrogen, fluoro, chloro, bromo, iodo, or R6; and a and n are each independently zero or a positive integer.

Abstract: E1a-3a are independently selected from the group consisting of hydrogen, C1-6 alkyls, C3-12 branched alkyls, C3-8 cycloalkyls, C1-6 substituted alkyls, C3-8 substituted cycloalkyls, aryls, substituted aryls, aralkyls, C1-6 heteroalkyls, substituted C1-6 heteroalkyls, C1-6 alkoxy, phenoxy, C1-6heteroalkoxy, 1

Abstract: The present invention includes polymeric transport systems corresponding to the formula: 1

Abstract: The invention is directed primarily to compounds of Formula I: 1

Abstract: The present invention is directed to methods of preparing polymeric conjugates of biologically active agents of the formula: 1

Abstract: A compound of Formula I, providing tetrapartate prodrugs is provided 1

Abstract: The present invention is directed to double prodrugs containing polymeric-based transport forms.

Abstract: Polymeric compounds of the formula: (D)n—M—(R1)m  (I) wherein (m) and (n) independently selected positive integers, preferably from about 1 to about 6 each; D is a residue of a biologically active moiety; M is a multifunctional linker/spacer moiety; and R1 is a polymer residue are disclosed. Methods of preparing the same and methods of treatment using the same are also included as part of the present invention.

Abstract: The present invention is directed to double prodrugs containing polymeric-based transport forms.

Abstract: The present invention is directed to methods of forming esters of tertiary alcohols. The methods include reacting a compound containing a tertiary alcohol with an acyl heteroaromatic ion-based compound of the formula: wherein R1 is an aromatic or aliphatic acid residue; Y is O or S; Z is CR2 or N; X is selected from the group consisting of wherein R2 and R3 are independently selected from the group consisting of H, C1-6 alkyls, C1-6 substituted alkyls, C1-6 heteroalkyls, C3-8 branched alkyls, C3-8 cycloalkyls, C1-6 substituted heteroalkyls, aryls, substituted aryls, C1-6 alkyl aralkyls, C1-6 heteroalkyl aralkyls, C3-8 branched alkyl aralkyls and C3-8 cycloalkyl aralkyls; and R2′ is the same as R2 except that R2′ is not H; in the presence of a lanthanideIII metal-based catalyst and a base.

Abstract: The present invention is directed to double prodrugs containing polymeric-based transport forms.

Abstract: Substantially non-antigenic polymers containing pI and/or pH optimum modulating moieties are disclosed. The polymers are useful as intermediates for synthesis of amine-based polymers and in the formation of activated polymers for conjugation with nucleophiles. Conjugates and methods of preparation and treatment with the conjugates are also disclosed.

Abstract: The present invention is directed to polymeric- prodrug transport forms of the formula: ##STR1## wherein: B is a leaving group, OH, a residue of a hydroxyl-containing moiety or ##STR2## wherein B.sub.1 is a leaving group, OH or a residue of a hydroxyl-containing moiety;Y.sub.1-2 are independently O or S;M is selected from either X or Q; wherein X is an electron withdrawing group and Q is a moiety containing a free electron pair positioned three to six atoms from C(.dbd.Y.sub.2); R.sub.2-5 are independently selected from the group consisting of hydrogen, C.sub.1-6 alkyls, C.sub.3-12 branched alkyls, C.sub.3-8 cycloalkyls, C.sub.1-6 substituted alkyls, C.sub.3-8 substituted cycloalkyls, aryls, substituted aryls, aralkyls, C.sub.1-6 heteroalkyls and substituted C.sub.1-6 heteroalkyls;(m) is zero or one;(n) is a positive integer;(p) is zero or a positive integer;Z is an electron withdrawing group; andR.sub.

Abstract: The present invention is directed compositions of the formula: ##STR1## wherein: D is a residue of a biologically active moiety;X is an electron withdrawing group;Y and Y' are independently O or S;(n) is zero (0) or a positive integer, preferably from 1 to about 12;R.sub.1 and R.sub.2 are independently selected from the group consisting of H, C.sub.1-6 alkyls, aryls, substituted aryls, aralkyls, heteroalkyls, substituted heteroalkyls and substituted C.sub.1-6 alkyls;R.sub.3 is a substantially non-antigenic polymer, C.sub.1-12 straight or branched alkyl or substituted alkyl, C.sub.5-8 cycloalkyl or substituted cycloalkyl, carboxyalkyl, carboalkoxy alkyl, dialkylaminoalkyl, phenylalkyl, phenylaryl or ##STR2## R.sub.4 and R.sub.5 are independently selected from the group consisting of H, C.sub.1-6 alkyls, aryls, substituted aryls, aralkyls, heteroalkyls, substituted heteroalkyls, and substituted C.sub.1-6 alkyls or jointly form a cyclic C.sub.5 -C.sub.7 ring.

Abstract: Branched, substantially non-antigenic polymers are disclosed. Conjugates prepared with the polymers and biologically active molecules such as proteins and peptides demonstrate extended circulating life in vivo. Substantially fewer sites on the biologically active material are used as attachment sites. Methods of forming the polymer, conjugating the polymers with biologically active moieties and methods of using the conjugates are also disclosed.

Abstract: The present invention is directed to methods of forming esters of tertiary alcohols. The methods include reacting a compound containing a tertiary alcohol with an acyl heteroaromatic ion-based compound of the formula: ##STR1## wherein R.sub.1 is an aromatic or aliphatic acid residue;Y is O or S;Z is R.sub.2 N;X is selected from the group consisting of ##STR2## wherein R.sub.2 and R.sub.3 are independently selected from the group consisting ofH, C.sub.1-6 alkyls, C.sub.1-6 substituted alkyls, C.sub.1-6 heteroalkyls, C.sub.3-8, branched alkyls, C.sub.3-8 cycloalkyls, C.sub.1-6 substituted heteroalkyls, aryls, substituted aryls, except that R.sub.2 is not H when X is ##STR3## C.sub.1-6 alkyl aralkyls, C.sub.1-6 heteroalkyl aralkyls, C.sub.3-8, branched alkyl aralkyls and C.sub.3-8 cycloalkyl aralkyls; and R.sub.2 ' is the same as R.sub.2 except that R.sub.2 ' is not H;in the presence of a lanthanide.sup.III metal-based catalyst and a base.