Traceless linkers and protein-conjugates thereof

Abstract

To provide compounds, compounds including traceless linkers, and protein conjugates thereof for the treatment of various diseases, disorders, and conditions.SOLUTION: There is provided a compound having the following structure, or a pharmaceutically acceptable salt thereof (wherein R1a and R1b are hydrogen, alkyl, alkoxy, alkenyl, alkynyl, aryl, or the like; R2 is hydrogen, alkylene, heteroalkylene, or an amino acid side chain; R3 is hydrogen, alkyl, alkylene, or heteroalkylene; R4 is hydrogen or alkyl; R5 is oxygen, NR6 or sulfur; R6 is hydrogen or alkyl; D* is an acyl group, or a residue of a biologically active compound comprising hydroxyl, amino, or thiol; and n is 0,1, 2, 3, 4, 5 or 6).SELECTED DRAWING: None

Description

[Technical field]

[0001] (CROSS-REFERENCE TO RELATED APPLICATIONS) This application is a joint venture of U.S. Provisional Application No. 62 / 872,229, filed July 9, 2019; No. 62 / 937,721, filed on January 8, 2019; PCT Patent Application No. P entitled "Steroids and Antibody Conjugates Thereof" CT / US2019 / 012786; and Steroids and Antibody Conjugates Thereof, also filed on January 8, 2019 U.S. Patent Application Serial No. 16 / 2 entitled "Steroids and Antibody Conjugates Thereof" The benefit of each priority patent application is claimed in its entirety for all purposes. is incorporated herein by reference.

[0002] (Field) Provided herein are novel traceless linkers and their protein conjugates. and compounds or payloads via traceless linker-payloads, and their tandems. For treating various diseases, disorders, and conditions, including administering protein conjugates This is the method. [Background technology]

[0003] (background) Antibody-drug conjugates (ADCs) are often delivered with a bioactive small molecule drug, called a payload. The antibody is covalently linked to the target molecule, thus controlling the target specificity of the antibody and the mode of action of the small molecule drug. The therapeutic utility of ADCs has been confirmed in cancer treatment. This is a major ongoing focus of research. bentruximab vedotin) and KADCYLA® (ado-trastuzumab Mutansine is an ADC approved for the treatment of certain types of cancer, and several other ADCs have It is currently under clinical development.

[0004] Glucocorticoids (GCs) are small molecule steroids that bind to the glucocorticoid receptor (GR). It is a glycoside and is used in anti-inflammatory and immunosuppressive therapy. The widespread expression of glucocorticoid receptors in many cell types makes treatment with glucocorticoids possible. Treatment is compromised by toxicity to most organ systems. Side effects arising from administration of glucocorticoids, particularly those resulting from activation of glucocorticoid receptors in non-target cells, Both new glucocorticoids and new therapies that minimize the risk of side effects are needed. This disclosure addresses the above-mentioned needs and other unaddressed needs in the art to which this disclosure pertains. The present disclosure provides a solution to the need. It is an antibody-drug conjugate containing a

[0005] Liver X receptors (LXRs) are involved in cholesterol, lipid, and glucose homeostasis, inflammation, and LXRα and LXR are ligand-dependent transcription factors that regulate the expression of genes involved in innate immunity. LXRα is highly expressed in the liver, intestine, adipose tissue, and differentiated macrophages. LXRs are expressed widely; LXRβ is widely expressed. LXRs act as (i) cholesterol transporters, e.g. For example, the expression of ABCA1 and ABCG1, both of which mediate cellular cholesterol efflux, and (ii) suppressing macrophage inflammatory gene expression through the inhibition of NF-kB activation. LXRs have various biological functions, including negatively regulating atherosclerosis. LXR modules have also been implicated in metabolic disorders, proliferative disorders, neurodegenerative disorders, and inflammation. If ADCs containing LXRs could be developed, it would be possible to regulate LXRs in a targeted manner, thereby Side effects due to off-target regulation of R would be avoided. Furthermore, such ADCs If so, improved modulation of biological targets, improved bioavailability, and improved therapeutic window Therefore, the use of small molecule ADCs of LXR modulators, e.g. There is a continuing need for effective treatments for neurological disorders.

[0006] The linker covalently attaches the payload portion of the ADC, e.g., a small molecule therapeutic drug, to its antibody. The key challenges in linker design are storage, formulation, administration, and patient The payload remains stably linked to the antibody during plasma circulation in the blood, and the antibody is Allows efficient release upon target binding and facile conjugation to payloads under synthesis conditions jugation and release of the intended payload without structural changes The goal of the study was to find a site that allows for the synthesis of a linker having these and other properties. It continues to be needed. Summary of the Invention

[0007] (overview) Provided herein are novel traceless linkers and their protein conjugates. and compounds or payloads via traceless linker-payloads, and The present invention relates to methods for treating a variety of diseases, disorders, and conditions, including administering a protein conjugate to a subject. Included herein are methods for binding to hydroxyl groups of a payload and then and allows release of the payload under appropriate conditions without damaging its hydroxyl groups. It is a linker.

[0008] Provided herein are methods for treating, e.g., inflammatory diseases and autoimmune disorders in a subject. or to treat a disease associated with glucocorticoid receptors, glucocorticoid binding, and / or or any disease, disorder, or condition associated with glucocorticoid receptor signaling; and / or to manage symptoms of dyslipidemia, metabolic disease, inflammation, or neurodegenerative diseases. The present invention relates to compounds, compositions, and methods useful for

[0009] In one embodiment, provided is a compound having the structure of Formula I, or a pharmaceutical thereof. Acceptable salts are: [ka] (In the formula, R 1a and R 1b are independently hydrogen, alkyl, alkoxy, alkenyl, alkynyl, Aryl, arylalkyl, heteroaryl, alkylene, or heteroalkylene. where R 1a When is alkylene or heteroalkylene, the alkylene or heteroalkylene The tert-alkylene further includes R 3 to form a 3-, 4-, 5-, 6-, 7-, or 8-membered heterocyclyl S;R 2 is hydrogen, alkylene, heteroalkylene, or an amino acid side chain, where R 2 When is alkylene or heteroalkylene, the alkylene or heteroalkylene is In addition, R 3 to form a 4-, 5-, or 6-membered heterocyclyl; R 3 is hydrogen, alkyl, alkylene, or heteroalkylene, where R 3 is alkylene or heteroalkyl When the alkylene or heteroalkylene is R 1a or R 2 Binding to the 3 , 4, 5, 6, 7, or 8-membered heterocyclyl; R 4 is hydrogen or alkyl; R 5 teeth , oxygen, NR 6 or sulfur; R 6 is hydrogen or alkyl; D* is acyl or or a residue of a biologically active compound containing a hydroxyl, amino, or thiol; and is 0, 1, 2, 3, 4, 5, or 6).

[0010] In one embodiment, provided is a compound having the structure of Formula I, or a pharmaceutical thereof. Acceptable salts are: [ka] (In the formula, R 1a and R 1b are independently hydrogen, alkyl, alkoxy, alkenyl, alkynyl, Aryl, arylalkyl, heteroaryl, alkylene, or heteroalkylene. where R 1a When is alkylene or heteroalkylene, the alkylene or heteroalkylene The tert-alkylene further includes R 3 to form a 4-, 5-, or 6-membered heterocyclyl; R 2 teeth, hydrogen, alkylene, heteroalkylene, or an amino acid side chain, where R 2 But, Alki When the alkylene or heteroalkylene is an alkylene or heteroalkylene, the alkylene or heteroalkylene may further be R 3 to form a 4-, 5-, or 6-membered heterocyclyl; R 3 is hydrogen, alkyl, alkylene or heteroalkylene, where R 3 is alkylene or heteroalkylene In the case, the alkylene or heteroalkylene may further include R 1a or R 2 4, 5, or 6 R 4 is hydrogen or alkyl; R 5 is oxygen, NR 6 , or sulfur Yellow;R 6 is hydrogen or alkyl; D* is acyl or hydroxyl, a a residue of a biologically active compound containing an amino or thiol; and n is 0, 1, 2, 3, 4, or 5).

[0011] In another embodiment, provided is a linker-payload complex having the structure of formula II. or a pharma- ceutically acceptable salt thereof: [ka] where L is a linker containing a site reactive with an antibody or antigen-binding fragment thereof; R 1a Reach BiR 1b are independently hydrogen, alkyl, alkoxy, alkenyl, alkynyl, aryl, a arylalkyl, heteroaryl, alkylene, or heteroalkylene, where R 1a When is alkylene or heteroalkylene, the alkylene or heteroalkylene Len further added, 3 to form a 3-, 4-, 5-, 6-, 7-, or 8-membered heterocyclyl; R 2teeth, hydrogen, alkylene, heteroalkylene, or an amino acid side chain, where R 2 But, Alki When the alkylene or heteroalkylene is an alkylene or heteroalkylene, the alkylene or heteroalkylene may further be R 3 to form a 4-, 5-, or 6-membered heterocyclyl; R 3 is hydrogen, alkyl, alkylene or heteroalkylene, where R 3 is alkylene or heteroalkylene In the case, the alkylene or heteroalkylene may further include R 1a or R 2 Binds to 3, 4, 5, and 6 , 7-, or 8-membered heterocyclyl; R 4 is hydrogen or alkyl; R 5 is oxygen, NR 6 or sulfur; R 6 is hydrogen or alkyl; D* is acyl or a residue of a biologically active compound containing an xyl, amino, or thiol; and n is 0, 1, 2, 3, 4, 5, or 6).

[0012] In another embodiment, provided is a linker-payload or is a pharma- ceutically acceptable salt thereof: [ka] where L is a linker containing a site reactive with an antibody or antigen-binding fragment thereof; R 1a Reach BiR 1b are independently hydrogen, alkyl, alkoxy, alkenyl, alkynyl, aryl, a arylalkyl, heteroaryl, alkylene, or heteroalkylene, where R 1aWhen is alkylene or heteroalkylene, the alkylene or heteroalkylene Len further added, 3 to form a 4-, 5-, or 6-membered heterocyclyl; R 2 is hydrogen, arsenic alkylene, heteroalkylene, or an amino acid side chain, where R 2 is alkylene or When the alkylene or heteroalkylene is a tert-butyl alkylene, the alkylene or heteroalkylene may further be R 3 Binding to forming a 4-, 5-, or 6-membered heterocyclyl; R 3 is hydrogen, alkyl, alkylene, or heptane. where R is 3 When is alkylene or heteroalkylene, The alkylene or heteroalkylene may further include R 1a or R 2 and the 4-, 5-, or 6-membered heterocyclic Form a cyclyl; R 4 is hydrogen or alkyl; R 5 is oxygen, NR 6 or sulfur; R 6 is hydrogen or alkyl; D* is acyl or is hydroxyl, amino, if or a residue of a biologically active compound that contains a thiol; and n is 0, 1, 2, 3, 4, 5, or 6. be).

[0013] In another embodiment, provided is a compound having the structure of formula III: [ka] where L is a linker; BA is a binding agent; R 1a and R 1b are independently hydrogen, alkyl , alkoxy, alkenyl, alkynyl, aryl, arylalkyl, heteroaryl , alkylene, or heteroalkylene, where R 1a is alkylene or heteroa When the alkylene is alkylene, the alkylene or heteroalkylene may further include R 3 3, 4, R forms a 5-, 6-, 7-, or 8-membered heterocyclyl; 2 is hydrogen, alkylene, heteroalkylene or an amino acid side chain, where R 2 When is alkylene or heteroalkylene, In this case, the alkylene or heteroalkylene may further include R 3 4, 5, or 6 membered heterocyclic Form a cyclyl; R 3 is hydrogen, alkyl, alkylene, or heteroalkylene; Here, R 3 When is alkylene or heteroalkylene, the alkylene or heteroa Lukiren further added, 1a or R 2 is bonded to said 3-, 4-, 5-, 6-, 7-, or 8-membered heterocyclyl Formation; R 4 is hydrogen or alkyl; R 5 is oxygen, NR 6 or sulfur; R 6 is hydrogen or is alkyl; D* is a hydroxyl, amino, or thiol-containing bioactive compound; residue; n is 0, 1, 2, 3, 4, 5, or 6; and k is an integer from 1 to 30.

[0014] In another embodiment, provided is a compound having the structure of formula III: [ka] where L is a linker; BA is a binding agent; R 1a and R 1b are independently hydrogen, alkyl , alkoxy, alkenyl, alkynyl, aryl, arylalkyl, heteroaryl , alkylene, or heteroalkylene, where R 1a is alkylene or heteroa When the alkylene is alkylene, the alkylene or heteroalkylene may further include R 3 3, 4, R forms a 5-, 6-, 7-, or 8-membered heterocyclyl; 2 is hydrogen, alkylene, heteroalkylene or an amino acid side chain, where R 2 When is alkylene or heteroalkylene, In this case, the alkylene or heteroalkylene may further include R 3 4, 5, or 6 membered heterocyclic Form a cyclyl; R 3 is hydrogen, alkyl, alkylene, or heteroalkylene; Here, R 3 When is alkylene or heteroalkylene, the alkylene or heteroa Rukyren further added, 1a or R 2 is bonded to said 3-, 4-, 5-, 6-, 7-, or 8-membered heterocyclyl Formation; R 4 is hydrogen or alkyl; R 5 is oxygen, NR 6 or sulfur; R 6 is hydrogen or is an alkyl; D* is an anti-inflammatory bioactive group containing hydroxyl, amino, or thiol. is a residue of a compound; n is 0, 1, 2, 3, 4, 5, or 6; and k is an integer from 1 to 30. ).

[0015] In another embodiment, provided is a compound having the structure of formula III: [ka] where L is a linker comprising PAB or PABC; BA is a binding agent; R 1a and R 1b is independent to hydrogen, alkyl, alkoxy, alkenyl, alkynyl, aryl, arylalkoxy aryl, heteroaryl, alkylene, or heteroalkylene, where R 1a But, When the alkylene or heteroalkylene is an alkylene or heteroalkylene, the alkylene or heteroalkylene may further be R 3 to form a 3-, 4-, 5-, 6-, 7-, or 8-membered heterocyclyl; R 2 Hydrogen, alkylene alkylene, heteroalkylene, or an amino acid side chain, where R 2 is alkylene or hetero When it is alkylene, the alkylene or heteroalkylene may further comprise R 3 4, 5 or a 6-membered heterocyclyl; R 3 is hydrogen, alkyl, alkylene, or heteroaromatic. where R is 3 When is alkylene or heteroalkylene, the alkyl The olefin or heteroalkylene may further include R 1a or R 2 is bonded to said 3, 4, 5, 6, 7, or 8 membered Forming a heterocyclyl; R 4 is hydrogen or alkyl; R 5 is oxygen, NR 6 , or sulfur Yes;R 6 is hydrogen or alkyl; D* includes hydroxyl, amino, or thiol. a residue of a biologically active compound; n is 0, 1, 2, 3, 4, 5, or 6; and k is an integer from 1 to 30. (It is a number.)

[0016] In another embodiment, provided is a compound having the structure of formula III: [ka] where L is a linker; BA is a binding agent; R 1a and R 1b are independently hydrogen, alkyl , alkoxy, alkenyl, alkynyl, aryl, arylalkyl, heteroaryl , alkylene, or heteroalkylene, where R 1a is alkylene or heteroa When the alkylene is alkylene, the alkylene or heteroalkylene may further include R 3 3, 4, R forms a 5-, 6-, 7-, or 8-membered heterocyclyl; 2 is hydrogen, alkylene, heteroalkylene or an amino acid side chain, where R 2 When is alkylene or heteroalkylene, In this case, the alkylene or heteroalkylene may further include R 3 4, 5, or 6 membered heterocyclic Form a cyclyl; R 3 is hydrogen, alkyl, alkylene, or heteroalkylene; Here, R 3 When is alkylene or heteroalkylene, the alkylene or heteroa Lukiren further added, 1a or R 2 is bonded to said 3-, 4-, 5-, 6-, 7-, or 8-membered heterocyclyl Formation; R 4 is hydrogen or alkyl; R 5 is oxygen, NR 6 or sulfur; R 6 is hydrogen or is alkyl; D* is a hydroxyl, amino, or thiol-containing bioactive compound; residue; n is 0, 1, 2, 3, 4, 5, or 6; where L is the conjugation site for BA. The compound consists of two components: a click chemistry residue, an amide residue, and a single BA chemically bound to L. and k is an integer from 1 to 30.

[0017] In another embodiment, provided is a compound having the structure of formula III: [ka] where L is a linker; BA is a binding agent; R 1a and R 1b are independently hydrogen, alkyl , alkoxy, alkenyl, alkynyl, aryl, arylalkyl, heteroaryl , alkylene, or heteroalkylene, where R 1a is alkylene or heteroa When the alkylene is alkylene, the alkylene or heteroalkylene may further include R 3 4, 5, or a 6-membered heterocyclyl; R 2 is hydrogen, alkylene, heteroalkylene, or a amino acid side chain, where R 2 When is alkylene or heteroalkylene, the alkyl The alkylene or heteroalkylene may further include R 3 is bonded to a 4-, 5-, or 6-membered heterocyclyl Formation; R 3 is hydrogen, alkyl, alkylene, or heteroalkylene, where R 3 When is alkylene or heteroalkylene, the alkylene or heteroalkylene is In addition, R 1a or R 2 to form said 4-, 5-, or 6-membered heterocyclyl; R 4 is hydrogen or is alkyl; R 5 is oxygen, NR 6 or sulfur; R 6 is hydrogen or alkyl; D* is a residue of a biologically active compound containing a hydroxyl, amino, or thiol; n is 0, 1 , 2, 3, 4, 5, or 6; and k is an integer from 1 to 30.

[0018] In another embodiment, provided is a method for detecting glucocorticoid receptor signaling in a subject. A method for treating a disease, disorder, or condition associated with neural transmission, comprising administering to the subject The potency of the compounds described herein, the linker-payload, the antibody-drug conjugates, The method further comprises administering a pharmaceutical composition, a method comprising administering a pharmaceutical composition comprising administering to a subject a subject, a mammal, a mammalian subject, a mammalian subject, a human, a mammalian subject ...

[0019] In another embodiment, provided is a method for treating dyslipidemia, metabolic disease, inflammation in a subject. or a method for treating a neurodegenerative disease, comprising administering to the subject an effective amount of a compound described herein. Compounds, linker-payloads, antibody-drug conjugates, pharmaceutical compositions, and / or the method comprising administering a combination thereof.

[0020] In another embodiment, provided is a method for treating dyslipidemia in a subject. The method includes administering to the subject an effective amount of a compound described herein, a linker-payload, administering an antibody-drug conjugate, pharmaceutical composition, and / or combination thereof. , the method.

[0021] In another embodiment, provided is a method for treating a metabolic disorder in a subject. The method includes administering to the subject an effective amount of a compound described herein, a linker-payload, administering an antibody-drug conjugate, pharmaceutical composition, and / or combination thereof. , the method.

[0022] In another embodiment, provided is a method for treating inflammation in a subject. and administering to the subject an effective amount of a compound described herein, a linker-payload, an antibody-drug administering the compound conjugate, pharmaceutical composition, and / or combination thereof to the subject This is the method.

[0023] In another embodiment, provided is a method for treating a neurodegenerative disease in a subject. The method comprises administering to the subject an effective amount of a compound described herein, a linker-payload , antibody-drug conjugates, pharmaceutical compositions, and / or combinations thereof. Yes, this is the method. [Brief description of the drawings]

[0024] BRIEF DESCRIPTION OF THE DRAWINGS [Figure 1] FIG. 1 shows the synthetic chemistry schemes for the payload, prodrug, traceless linker, traceless linker-payload, and their protein conjugates. [Diagram 2] FIG. 2 shows the synthetic chemistry schemes for the payload, prodrug, traceless linker, traceless linker-payload, and their protein conjugates. [Diagram 3] FIG. 3 shows the synthetic chemistry schemes for the payload, prodrug, traceless linker, traceless linker-payload, and their protein conjugates. [Figure 4] FIG. 4 shows the synthetic chemistry schemes for the payload, prodrug, traceless linker, traceless linker-payload, and their protein conjugates. [Diagram 5] FIG. 5 shows the synthetic chemistry schemes for the payload, prodrug, traceless linker, traceless linker-payload, and their protein conjugates. [Figure 6]FIG. 6 shows the synthetic chemistry schemes for the payload, prodrug, traceless linker, traceless linker-payload, and their protein conjugates. [Figure 7] FIG. 7 shows the synthetic chemistry schemes for the payload, prodrug, traceless linker, traceless linker-payload, and their protein conjugates. [Figure 8] FIG. 8 shows the synthetic chemistry schemes for the payload, prodrug, traceless linker, traceless linker-payload, and their protein conjugates. [Figure 9] FIG. 9 shows synthetic chemistry schemes for the payload, prodrug, traceless linker, traceless linker-payload, and their protein conjugates. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0025] Description of Exemplary Embodiments (definition) When referring to the compounds provided herein, the following terms are used as defined below unless otherwise indicated. Unless otherwise defined, technical and scientific terms used herein have the following meanings: All terms used herein have the same meaning as commonly understood by one of ordinary skill in the art. In the event that there are a plurality of definitions for a term, those definitions prevail unless stated otherwise. will be done.

[0026] As used herein, "alkyl" refers to a monovalent saturated hydrocarbon radical moiety. Alkyl is optionally substituted and may be linear, branched, or cyclic (i.e., cycloalkyl). Alkyl may be a radical having 1 to 20 carbon atoms, i.e., C 1-20 Alkyl; a radical having 1 to 12 carbon atoms, i.e., C 1-12 Alkyl;1~ Radicals with 8 carbon atoms, i.e., C 1-8 Alkyl; alkyl having 1 to 6 carbon atoms Dical, i.e., C 1-6 alkyl; and radicals having 1 to 3 carbon atoms, i.e., C 1-3 Examples of alkyl moieties include, but are not limited to, methyl. ethyl, n-propyl, i-propyl, n-butyl, s-butyl, t-butyl, i-butyl, cyclopropyl, cyclobutyl, cyclopentyl, and cycloalkyl moieties. Pentyl moieties include, but are not limited to, n-pentyl and Hexyl moieties include, but are not limited to, n-hexyl and i-pentyl. Examples of suitable ion exchange membranes include, but are not limited to, ion exchange membranes.

[0027] As used herein, "alkylene" refers to a divalent alkyl group. Unless otherwise specified, alkylene includes, but is not limited to, 1 to 20 carbon atoms. The alkyl group is optionally substituted as described herein for alkyl. In some embodiments, the alkylene is unsubstituted. Examples of alkylene moieties are: Then, -CH 2 -, -CH 2 CH 2 -, -CH 2 CH 2 CH 2 -, -CH 2 CH 2 CH 2 CH 2 - etc.

[0028] As used herein, "heteroalkylene" refers to an alkyl group in which one or more carbon atoms are bonded to a heteroatom. Unless otherwise specified, heteroalkyl refers to a divalent alkyl group replaced with The olefins include, but are not limited to, aryl groups containing 1 to 20 total atoms (i.e., carbon and heteroatoms). Heteroalkylene groups can be any of the groups described herein for alkyl. In some embodiments, the heteroalkylene is unsubstituted. In some embodiments, the heteroatoms contemplated in the heteroalkylene moiety are , oxygen, nitrogen, sulfur (i.e., sulfoxides, sulfites, sulfates, and sulfur) silicon, and phosphorous (i.e., phosphites and phosphae The heteroalkylene moiety may be a substituted or unsubstituted aryl group, and / or a combination thereof. As a non-limiting exemplary embodiment, -CH 2 O-, -CH 2 OCH 2 -, -CH 2 OCH 2 CH 2 -, -CH 2 CH 2 CH 2 OCH 2 - etc;-CH 2 NR-, -CH 2 NRCH 2 -, -CH 2 NRCH 2 CH 2 -, -CH 2 CH 2 CH 2 NRCH 2 -etc; and -CH 2 S-, -CH 2 SCH 2 -, -CH 2 SCH 2 CH 2 -, -CH 2 CH 2 CH 2 SCH 2 - etc.

[0029] The designation of an amino acid or amino acid residue without specifying its stereochemistry refers to the L-form of that amino acid, the D-form or a racemic mixture thereof.

[0030] As used herein, "haloalkyl" refers to an alkyl group as defined above. wherein the alkyl is a halogen, such as fluorine (F), chlorine (Cl), bromine (Br), or iodine. haloalkyl refers to the above alkyl groups containing at least one substituent selected from fluorine (I). An example of a rule is -CF 3 , -CH 2 CF 3 , -CCl 2 F, -CHF 2 , and -CCl 3 These include Not limited.

[0031] As used herein, "alkenyl" refers to an alkyl group having at least two carbon atoms and one or more aryl groups. Alkenyl refers to a monovalent hydrocarbon radical moiety containing a non-aromatic carbon-carbon double bond. is optionally substituted and can be linear, branched, or cyclic. The radicals are those having 2 to 20 carbon atoms, i.e., C 2-20 Alkenyl; 2 to 12 carbons Radicals with elementary atoms, i.e., C 2-12 Alkenyl; Radical having 2 to 8 carbon atoms le, i.e., C 2-8 Alkenyl; a radical having 2 to 6 carbon atoms, i.e., C 2-6 a alkenyl; and radicals having 2 to 4 carbon atoms, i.e., C 2-4 Alkenyl is an example. Examples of alkenyl moieties include, but are not limited to, vinyl, propenyl, Examples include, but are not limited to, thenyl and cyclohexenyl.

[0032] As used herein, "alkynyl" refers to a group having at least two carbon atoms and one or more alkynyl groups. Alkynyl refers to a monovalent hydrocarbon radical moiety containing a carbon-carbon triple bond of any Alkynyl is substituted with, and can be linear, branched or cyclic. Radicals having 2 to 20 carbon atoms, i.e., C 2-20 Alkynyl; 2 to 12 carbon atoms Radicals with C 2-12 Alkynyl; a radical having 2 to 8 carbon atoms, i.e. Wachi, C 2-8 Alkynyl; a radical having 2 to 6 carbon atoms, i.e., C 2-6 Alkynyl; and radicals having 2 to 4 carbon atoms, i.e., C 2-4 Alkynyl is an example of this. Examples of alkynyl moieties include, but are not limited to, ethynyl, propynyl, and butynyl. Examples of such antimicrobial agents include, but are not limited to, fluorouracil.

[0033] As used herein, "alkoxy" refers to a monovalent saturated hydrocarbon radical moiety. wherein the hydrocarbon contains a single bond to an oxygen atom and the radical is positioned on the oxygen atom. For example, in the case of ethoxy, CH 3 CH 2 An alkoxy substituent is an alkoxy group that is The alkoxy is optionally linked to a compound via this oxygen atom of the alkoxy substituent. It can be substituted and linear, branched, or cyclic, i.e., cycloalkoxy. The alkoxy includes those having 1 to 20 carbon atoms, i.e., C 1-20 Alcoki C; those having 1 to 12 carbon atoms, i.e., C 1-12 Alkoxy; 1 to 8 carbon atoms That is, C 1-8 Alkoxy; having 1 to 6 carbon atoms, i.e., C 1-6 Alkoxy; and those having 1 to 3 carbon atoms, i.e., C 1-3 Alkoxy is mentioned. Examples of alkoxy moieties include, but are not limited to, methoxy, ethoxy, n-propoxy, propoxy, i-propoxy, n-butoxy, s-butoxy, t-butoxy, i-butoxy, pentoxy Cyclopropoxy, cyclobutoxy, cyclopentoxy, and Including, but not limited to, cyclohexoxy.

[0034] As used herein, "haloalkoxy" refers to an alkoxy group as defined above. alkoxy, wherein the alkoxy is at least one selected from halogen, e.g., F, Cl, Br, or I. "Alkoxy" refers to any of the above-mentioned alkoxy groups containing at least one substituent.

[0035] As used herein, "aryl" refers to an aromatic compound whose ring atoms are carbon atoms. Aryl refers to a monovalent moiety that is a radical. Aryl is optionally substituted and may be monocyclic or polycyclic. Examples of aryl moieties include 6 having up to 20 ring carbon atoms, i.e., C 6-20 Aryl; having 6 to 15 ring carbon atoms That is, C 6-15 Aryl, and those having 6 to 10 ring carbon atoms, i.e. , C 6-10 Examples of aryl moieties include, but are not limited to, Phenyl, naphthyl, fluorenyl, azulenyl, anthryl, phenanthryl, and pyridine. Examples include, but are not limited to, lenyl.

[0036] As used herein, "arylalkyl" refers to the radical of an alkyl compound. where the alkyl group is substituted with an aromatic substituent, i.e. That is, the aromatic compound contains a single bond to an alkyl group and the radical is The arylalkyl group is attached to the illustrated chemical structure via the alkyl group. Arylalkyl has the structure, for example: [ka] where B is an aromatic moiety, e.g., aryl or phenyl. The arylalkyl may be optionally substituted, i.e., the aryl and / or alkyl groups may be substituted. The alkyl groups may be substituted as disclosed herein. Examples of arylalkyl include Examples of aryl alkoxy groups include, but are not limited to, benzyl.

[0037] As used herein, "alkylaryl" is a radical of an aryl compound. where the aryl compound is substituted with alkyl substituents, and That is, the aryl compound contains a single bond to an alkyl group and the radical is The alkylaryl group is linked to the illustrated chemical structure via the aryl group. Alkylaryl has the structure, for example: [ka] where B is an aromatic moiety, e.g., phenyl. The aryl is optionally substituted, i.e., the aryl and / or alkyl groups are Examples of alkylaryl include toluyl, arylalkyl, and arylalkyl. These include, but are not limited to:

[0038] As used herein, "aryloxy" refers to an aryl group in which the ring atoms are carbon atoms and the A monovalent moiety that is a radical of an aromatic compound in which the ring is substituted with an oxygen radical. That is, the aromatic compound contains a single bond to an oxygen atom and the radical is on the oxygen atom. For example, in the case of phenoxy, [ka] The aryloxy substituent is bonded to the compound it replaces through this oxygen atom. The aryloxy is optionally substituted. The aryloxy is preferably a substituted aryloxy having 6 to 20 carbon atoms. Radicals with ring carbon atoms, i.e., C 6-20 Aryloxy; 6 to 15 ring carbon atoms Those that have, i.e., C 6-15 aryloxy and those having 6 to 10 ring carbon atoms; That is, C 6-10 Examples of aryloxy include, but are not limited to, aryloxy. Examples of aryl moieties include phenoxy, naphthoxy, and anthroxy. However, the present invention is not limited to the above.

[0039] As used herein, "arylene" refers to an aromatized ring in which the ring atoms are only carbon atoms. Arylene refers to a divalent portion of the compound. Arylene is optionally substituted and may be monocyclic or polycyclic, e.g. For example, the arylene moiety may be a bicyclic or tricyclic ring. having ring carbon atoms, i.e., C 6-20 Arylene; having 6 to 15 ring carbon atoms That is, C 6-15 Arylene, and those having 6 to 10 ring carbon atoms, i.e. , C 6-10 These include, but are not limited to, arylene.

[0040] As used herein, "heteroalkyl" refers to an alkyl group in which one or more carbon atoms are heteroatoms. As used herein, "heteroalkenyl" refers to an alkyl substituted with "Alkenyl" refers to an alkenyl in which one or more carbon atoms are replaced by a heteroatom. As used herein, "heteroalkynyl" refers to an alkyl group in which one or more carbon atoms are bonded to a heteroatom. Suitable heteroatoms include nitrogen, oxygen, and Heteroalkyl, heteroalkenyl, heteroaryl, heterocyclic ... and heteroalkynyl are optionally substituted. Examples of heteroalkyl moieties include a Aminoalkyl, sulfonylalkyl, and sulfinylalkyl are examples of the alkyl groups. Examples of heteroalkyl moieties include, but are not limited to, methylamino, methylsulfonyl, and methylsulfinyl.

[0041] As used herein, "heteroaryl" refers to a heteroaryl group in which the ring atoms are carbon atoms and at least A monovalent radical of an aromatic compound containing one oxygen, sulfur, nitrogen, or phosphorus atom. Examples of heteroaryl moieties include those having 5 to 20 ring atoms; 5 to 15 ring atoms; and Examples of heteroaryl include, but are not limited to, those having 5 to 10 ring atoms. is optionally substituted.

[0042] As used herein, "heteroarylene" refers to an aromatic ring in which one or more of the ring atoms is an aromatic ring. Heteroaryl refers to a divalent heteroaryl substituted with a hydrogen, sulfur, nitrogen, or phosphorus atom. The aryl group is optionally substituted.

[0043] As used herein, "heterocycloalkyl" or "heterocyclyl" refers to a heterocyclic group consisting of 1 It refers to a cycloalkyl in which one or more carbon atoms are replaced by a heteroatom. The heteroatoms include nitrogen, oxygen, and sulfur atoms (i.e., sulfoxide and sulfone). Heterocycloalkyl or heterocycloalkyl groups include, but are not limited to, Examples of heterocycloalkyl and heterocyclyl moieties include is morpholinyl, piperidinyl, tetrahydropyranyl, pyrrolidinyl, aziridonyl (aziridnyl), imidazolidinyl, oxazolidinyl, thiazolidinyl, dioxolanyl , dithiolanyl, oxanyl, or thianyl.

[0044] As used herein, a "Lewis acid" refers to a molecule or ion that accepts a lone pair of electrons. The Lewis acids used in the methods described herein are other than protons. Lewis acids include non-metallic acids, metallic acids, hard Lewis acids, and soft Lewis acids. Lewis acids include, but are not limited to, aluminum, boron, iron, tin, and titanium. Tungsten, magnesium, copper, antimony, phosphorus, silver, ytterbium, scandium, nickel Exemplary Lewis acids include, but are not limited to, Lewis acids of zinc, zinc ions, and zinc. AlBr 3 , AlCl 3 , BCl 3 , Boron trichloride methyl sulfide, BF 3 Boron trifluoride methyl Boron trifluoride methylsulfide, Boron trifluoride tetrahydrofuran , dicyclohexylboron trifluoromethanesulfonate, iron(III) bromide, iron(III) chloride , Tin(IV) chloride, Titanium(IV) chloride, Titanium(IV) isopropoxide, Cu(OTf) 2 , CuCl 2 , CuB r 2 , zinc chloride, alkylaluminum halide (R n AIX 3-n (Wherein, R is a hydrocarbyl Zn(OTf) 2 , ZnCl 2 , Yb(OTf) 3 , Sc(OTf) 3 , MgBr 2 , NiCl 2 , Sn(OTf) 2 , Ni(OTf) 2 , and Mg(OTf) 2 These include, but are not limited to:

[0045] As used herein, "N-containing heterocycloalkyl" refers to an N-containing heterocycloalkyl group having one or more carbon atoms in a heterocyclic group. At least one of the substituted heteroatoms is a nitrogen atom. In addition to nitrogen, suitable heteroatoms include oxygen and sulfur atoms. Examples of N-containing heterocycloalkyl include, but are not limited to, optionally substituted N-heterocycloalkyl. Examples of N-containing heterocycloalkyl moieties include morpholinyl, piperidinyl, pyrrolidinyl, and pyrrolidinyl. Examples of the aryl group include azolidinyl, imidazolidinyl, oxazolidinyl, and thiazolidinyl. The present invention is not limited to these.

[0046] As used herein, the term "optionally substituted" is used to describe a radical moiety. For example, optionally substituted alkyl means that such moiety is optionally substituted with one or more substituents. Examples of such substituents are halo, cyano, nitro, halo, amino, hydroxyl, optionally substituted haloalkyl, aminoalkyl, hydroxyl alkyl, azide, epoxy, optionally substituted heteroaryl, optionally substituted aryl Tetracycloalkyl, [ka] (In the formula, R A , R B , and R C Each occurrence independently represents a hydrogen atom, an alkyl, an alkenyl, an a Alkynyl, aryl, alkylaryl, arylalkyl, heteroalkyl, heteroa aryl, or heterocycloalkyl, or R A and R B are combined Together with the atoms in the carbon atom form a saturated or unsaturated carbocyclic ring, which ring is optionally substituted. and one or more ring atoms are optionally replaced with a heteroatom. In one embodiment, the radical moiety is an optionally substituted aryl group. Heteroaryl, optionally substituted heterocycloalkyl, or optionally substituted saturated or unsaturated or an optionally substituted unsaturated carbocyclic ring, said optionally substituted heteroaryl, Optionally substituted heterocycloalkyl or optionally substituted saturated or unsaturated carbon The substituents on the ring, when they are substituted, are optionally further substituted with further substituents. In some embodiments, the aryl group is not substituted with any of the substituents described herein. When a described group is optionally substituted, the substituents attached to the group may be any group other than those defined otherwise. Unless otherwise specified, it is unsubstituted.

[0047] As used herein, a "binding agent" refers to a molecule that specifically binds to a given binding partner, e.g., an antigen. Any molecule capable of isomeric binding, such as a protein, antibody, or fragment thereof. Point to one side.

[0048] As used herein, a "linker" refers to a linker that connects a binding agent to one or more of the linkers described herein. The above compounds can be covalently linked to, for example, payload compounds and enhancers; or divalent, trivalent, or aryl groups that can be covalently linked (e.g., via reactive groups). Or it refers to a multivalent moiety.

[0049] As used herein, "amide synthesis conditions" refers to, for example, carboxylic acids, activated carboxylates, etc. To achieve the formation of an amide by reaction of a carboxylic acid or an acyl halide with an amine. In some instances, amide synthesis conditions refer to suitable reaction conditions for the reaction of a carboxylic acid with an amine. Some of these examples refer to reaction conditions suitable for achieving the formation of an amide bond between In this reaction, the carboxylic acid is first converted to an activated carboxylic acid, and then the activated carboxylic acid is reacted with the activated carboxylic acid. The carboxylic acid reacts with the amine to form an amide. Suitable conditions for achieving amide formation are Examples include, but are not limited to, dicyclohexylcarbodiimide (DCC), diisopropyl Carbodiimide (DIC), (benzotriazol-1-yloxy)tris(dimethylamino)phos Benzonium hexafluorophosphate (BOP), (benzotriazol-1-yloxy)triptyline Lolidinophosphonium hexafluorophosphate (PyBOP), (7-azabenzotriazole -1-yloxy)tripyrrolidinophosphonium hexafluorophosphate (PyAOP), Mototripyrrolidinophosphonium hexafluorophosphate (PyBrOP), O-(benzotriazolidinediamine) 1-(1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate (HBTU ), O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoride Roborate (TBTU), 1-[bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-b]pi Lysinium 3-oxide hexafluorophosphate (HATU), N-ethoxycarbonyl-2- Ethoxy-1,2-dihydroquinoline (EEDQ), N-ethyl-N′-(3-dimethylaminopropyl) carbamide 2-Chloro-1,3-dimethylimidazolidinium hexafluorophosphate (EDC) 2-chloro-4,6-dimethoxy-1,3,5-triazine (CDMT), and carbonyldiimide The present invention utilizes reagents to effect the reaction of carboxylic acids with amines, including carboxydiazole (CDI). In some examples, the carboxylic acid is first , which is then reacted with an amine to form an activated carboxylic acid ester. In one embodiment, the carboxylic acid is treated with a reagent to form an amide bond. The reagent deprotonates the carboxylic acid and then the deprotonated carboxylic acid is reacted with As a result of nucleophilic attack on the protonated reagent by The carboxylic acid is activated by forming a product complex with the acid. Activation of Carboxylic Acids The carboxylic acid ester is more easily reacted with amines than before the carboxylic acid was activated. This results in amide bond formation. Thus, the carboxylic acid is said to be activated. Exemplary reagents include DCC and DIC. Examples include:

[0050] As used herein, the term "positional isomer," "positional isomers," or "positional isomers" refers to a compound that is The "mixture of isomers" can be prepared by treating an appropriate azide (e.g., -N 3 , or P.E. GN 3 Derivatized antibodies) derived 1,3-cycloaddition or strain-promoted alkyne-azide cycloaddition (S The term "PAAC" refers to the product of a click reaction, also known as a click reaction. For example, positional isomers and mixtures of positional isomers can be synthesized by the click reaction products shown below. It is characterized by: [ka] In some embodiments, two or more suitable azides and two or more suitable alkynes are combined with the azide Each pair of -alkynes participates in one or more independent click reactions to produce regioisomeric click reactions. Utilize within a synthetic scheme en route to a product that can give rise to a mixture of reaction products For example, one skilled in the art can independently catalyze the first suitable azide on the way to the product. and a second suitable azide can be reacted independently with a second suitable alkyne. can react with four possible click reaction regioisomers, or As will be appreciated, this results in the production of a mixture of substances in the body.

[0051] As used herein, the term "residue" refers to a chemical residue in a compound that remains after a chemical reaction. For example, the term "amino acid residue" or "N-alkyl amino acid residue" The amide coupling reaction of an amino acid or an N-alkyl amino acid to a suitable coupling partner is carried out. N-alkylated or N-amino acids are preferably N-alkylated or N-alkylated. After peptide coupling of the aryl amino acid amide, for example, a water molecule is expelled to form the amide This results in a product having an N-acid residue or an N-alkyl amino acid residue incorporated therein.

[0052] As used herein, a "therapeutically effective amount" refers to an amount that is effective in the treatment or management of a disease or disorder. Sufficient to provide a therapeutic benefit to a patient or to suppress one or more symptoms associated with the disease or disorder. "Adverse reactions" refers to an amount (e.g., of a compound) that is sufficient to retard or minimize the effects of adverse reactions.

[0053] As used herein, "structural isomers" refers to isomers that have the same molecular formula but differ in the arrangement of atoms. Structural isomers refer to compounds that have different chemical structures due to the way they are synthesized. Exemplary structural isomers include: n-Propyl and isopropyl; n-butyl, sec-butyl, and tert-butyl; and n-butyl Examples of aryl include pentyl, isopentyl, and neopentyl.

[0054] Certain groups, sites, substituents, and atoms are depicted with wavy lines intersecting the bond(s). and indicates the atom through which the group, moiety, substituent or atom is bonded. For example: [ka] A propyl substituted phenyl group, depicted as having the following structure: [ka] As used herein, a cyclic group (e.g., aromatic, heterocyclic, etc.) is defined as a ring structure formed through a bond between the ring atoms. (aromatic, fused ring, and saturated or unsaturated cycloalkyl or heterocycloalkyl) Diagrams showing linked substituents are not intended to be limiting unless otherwise indicated, and are not intended to be limiting unless otherwise indicated. According to techniques known in the art to which the disclosure pertains, the cyclic group may be selected from any of the cyclic or fused ring groups. is meant to indicate that the substituent may be substituted at any ring position on any ring. For example, the following group [ka] (wherein the subscript q is an integer from 0 to 4; and the substituent R 1 The location of is generally described , i.e., directly bonded to any vertex of the bond line structure, i.e., to a specific ring carbon atom. (not shown) is the substituent R 1 The following non-limiting examples of groups are attached to specific ring carbon atoms: include: [ka] .

[0055] As used herein, the phrase "reactive linker" or the abbreviation "RL" refers to, e.g., For example, [ka] where RG is a reactive group and SP is a spacer group. This refers to a monovalent group comprising a reactive group ("RG") and a spacer group ("SP"), as depicted in the figure. The reactive linkers described herein contain two or more reactive groups and two or more spacer groups. The spacer group may be used to link the reactive group to a payload (e.g., a biologically active compound), etc. A reactive linker (RL) is any divalent moiety that bridges to another group. Synthetic precursors for the preparation of the antibody conjugates described herein, together with the payloads The reactive linker provides an intermediate ("linker-payload" or LP) useful as a carboxylate. , a reactive portion of another group, e.g., an antibody, a modified antibody, or an antigen-binding fragment thereof, or an enhancing group. The antibody, modified antibody, or an antigen-binding fragment thereof and the resulting site, together with the linking group, are referred to herein as The "binder linker" ("BL") portion of the conjugates described herein may be used in certain embodiments. In this context, a "reactive group" is a group that reacts with a cysteine ​​or lysine residue on an antibody or antigen-binding fragment thereof. Functional groups or moieties (e.g., maleimide or N-hydroxysuccinimide (NHS) esters) that In one embodiment, the "reactive group" is a group that undergoes a click chemistry reaction. It is a functional group or functional moiety that can be used to synthesize a compound (e.g., click chemistry). try), Huisgen, Proc. Chem. Soc. 1961, Wang et al., J. Am. Chem. Soc. 2003, and (See Agard et al., J. Am. Chem. Soc. 2004). In some embodiments, the reactive group is capable of undergoing a 1,3-cycloaddition reaction with an azide. Suitable reactive groups include strained alkynes, e.g. Suitable for SPAAC (Stimulated Alkyne-Azide Cycloaddition) Octyne, benzannulated alkyne, and alkyne in the absence of copper catalyst Examples of suitable alkynes include, but are not limited to, alkynes capable of 1,3-cycloaddition with The appropriate alkyne is: [ka] Cyclooctyne [ka] Azacyclooctyne [ka] Dibenzoazacyclooctyne or [ka] Dibenzocyclooctyne or [ka] Biarylazacyclooctynone or [ka] Monofluorinated cyclooctynes [ka] Difluorinated cyclooctyne or [ka] Substitution, e.g., fluorinated alkynes, aza-cycloalkynes, bicycle[6.1.0]nonynes (bic ycle[6.1.0]nonyne) or [ka] (BCN, where R is alkyl, alkoxy, or acyl), and derivatives thereof. Particularly useful alkynes include, but are not limited to, [ka] Such a reactive group-containing linker-payload can be functionalized with an azide group. Such functionalized antibodies are useful for conjugating azido-poly(Azide)-coated antibodies. In one embodiment, such antibodies are functionalized with ethylene glycol groups. Such functionalized antibodies are capable of converting at least one glutamine to a carboxyl group in the presence of the enzyme transglutaminase. An antibody having a residue, for example, heavy chain Gln295, is treated with a compound having an amino group and an azide group. This is induced by:

[0056] In some instances, the reactive group is an alkyne, e.g., [ka] which can be converted by click chemistry to azides, e.g. [ka] to produce a click chemistry product, e.g., [ka] In some instances, the group can form a modified antibody or antigen-binding fragment thereof. In some instances, the reactive group is an alkyne, e.g., [ka] which can be converted by click chemistry to azides, e.g. [ka] to produce a click chemistry product, e.g., [ka] In some instances, the reactive group can be an alkyne, e.g., [ka] which can be converted by click chemistry to azides, e.g. [ka] to produce a click chemistry product, e.g., [ka] In some instances, the reactive group can be a functional group, such as [ka] which reacts with cysteine ​​residues on an antibody or antigen-binding fragment thereof to attach carbon atoms thereto. Carbon-sulfur bonds, e.g. [ka] (wherein Ab represents an antibody or an antigen-binding fragment thereof, and S represents the linker through which the functional group binds to Ab. (Indicates the S atom on the corresponding cysteine ​​residue) In some instances, the reactive group is a functional group, e.g., [ka] which reacts with lysine residues on an antibody or antigen-binding fragment thereof to form amides thereto. Bonds, e.g. [ka] (In the formula, Ab represents an antibody or an antigen-binding fragment thereof, and NH represents a functional group bonded to Ab. (The NH atom on the lysine side chain residue is shown.) Form.

[0057] As used herein, the phrase "biodegradable moiety" refers to a moiety that degrades in vivo, typically Non-toxic, biocompatible components that can be removed from the body by biological processes In some embodiments, the biodegradable portion is a portion that is biodegradable in about 90 days or less, about 60 days or less, or completely or substantially degrades in vivo in less than about 30 days, wherein the extent of degradation is , based on the percent mass loss of the biodegradable portion, and complete degradation is 100% Exemplary biodegradable moieties include, but are not limited to, poly( ε-caprolactone) (PCL), poly(3-hydroxybutyrate) (PHB), poly(glycolic acid) (PGA) , poly(lactic acid) (PLA) and its copolymer with glycolic acid (i.e., poly(D,L-lactide- Examples of such aliphatic polyesters include poly(propylene glycolide) (PLGA) (Vert M, Schwach G, Engel R and Coudane J (1998) J Control Release 53(1-3):85-92; Jain RA, ( 2000) Biomaterials 21(23):2475-2490; Uhrich KE, Cannizzaro SM, Langer RS ​​and S Hakesheff KM, (1999) Chemical Reviews 99(11):3181-3198; and Park TG (1995) Biomaterials 16(15):1123-1130 (each of which is incorporated herein by reference in its entirety). (incorporated herein).

[0058] As used herein, the phrase "binder linker" or "BL" refers to a binder (e.g., For example, an antibody or antigen-binding fragment thereof may be coupled to a payload compound (e.g., a globulin molecule) described herein. lysine) and, optionally, any bivalent linker, linker, or bonder to one or more side chain compounds; Generally, the antibody conjugates described herein are A suitable binder linker for the antibody conjugate should be sufficiently long to take advantage of the circulating half-life of the antibody conjugate. and at the same time, the conjugate is stable to antigen-mediated internalization. A linker is a molecule that can release its payload after the initial internalization of the molecule. The cleavable linker may be cleavable or non-cleavable. After localization, the protein is cleaved by intracellular metabolism, e.g., hydrolysis, reduction, or enzymatic cleavage. A non-cleavable linker is a linker that is cleaved after internalization and prevents the lysosomal partitioning of the antibody. A linker that releases the attached payload upon dissolution. For linkers, acid labile linkers, hydrolytically unstable linkers, enzymatically cleavable linkers, etc. These include linkers that are non-cleavable, reduction-labile, self-immolative, and non-cleavable. Suitable linkers include, but are not limited to, peptides, glucuronides, succinates, and the like. Imido-thioethers, polyethylene glycol (PEG) units, hydrazones, malcaps mal-caproyl unit, dipeptide unit, valine-citrulline unit, and para- para-aminobenzyloxycarbonyl (PABC), para-aminobenzyl (PAB) units or In some embodiments, the binder may include, but is not limited to, The linker (BL) is a linker between the reactive group (RG) of the reactive linker (RL) and a binding agent, e.g., an antibody, a modified antibody, or an antigen-binding fragment thereof.

[0059] In some examples, the BL comprises the following site: [ka] (In the formula, [ka] is a bond to the binding agent). In some examples, the BL comprises the following moiety: [ka] (In the formula, [ka] is a bond to the binding agent). In some examples, the BL comprises the following moiety: [ka] (In the formula, [ka] is a bond to the binding agent). In some examples, the BL comprises the following moiety: [ka] (In the formula, [ka] In some examples, the binding of the cysteine ​​to the antibody or antigen-binding fragment thereof is BL is the following site: [ka] (In the formula, [ka] is the attachment to a lysine of the antibody or antigen-binding fragment thereof).

[0060] As used herein, an "amino acid side chain" refers to a primary or secondary amine and carboxyl group of an amino acid. refers to an additional chemical moiety on the same carbon as the carbon bearing the carboxylic acid. As would be expected, there are 21 "standard" amino acids. Acids include, but are not limited to, alanine, serine, proline, arginine, and Aspartic acid. Other amino acids include cysteine, selenocysteine, and glycine (e.g., where the carbon bearing the primary amine and carboxylic acid of glycine is the same as (The additional chemical moiety on the same carbon is a hydrogen atom.) Exemplary amino acid side chains include: Examples include, but are not limited to, methyl (i.e., alanine), sec-buytl ) (i.e., isoleucine), iso-butyl (i.e., leucine), -CH 2 CH 2 SCH 3 (i.e. , methionine), -CH 2 Ph (i.e., phenylalanine), [ka] (i.e. tryptophan), [ka] (i.e., tyrosine), isopropyl (i.e., valine), hydroxymethyl (i.e. , serine), -CH(OH)CH 3 (i.e., threonine), -CH 2 C(O)NH 2 (i.e., asparagine) , -CH 2 CH 2 C(O)NH 2 (i.e., glutamine), -CH 2 SH (i.e., cysteine), -CH 2 SeH( i.e., selenocysteine), -CH 2 NH 2 (i.e., glycine), propylene or -CH 2 CH 2 CH 2 - (i.e., proline), -CH 2 CH 2 CH 2 NHC(=NH)NH 2 (i.e., arginine), [ka] (i.e., histidine), -CH 2 CH 2 CH 2 CH 2 NH 2 (i.e., lysine), -CH 2 COOH (i.e. Aspartic acid), and -CH 2 CH 2 COOH (i.e., glutamic acid).

[0061] As used herein, a "biologically active compound" refers to a compound that, when administered to a biological entity, Refers to a compound, prodrug, or payload that elicits a biological response. Targeted responses include, but are not limited to, increased or decreased DNA or protein synthesis, These include upregulation or downregulation of signal transduction pathways, and increased or decreased cell proliferation. .

[0062] (Compound, Prodrug, or Payload) Provided herein are compounds or payloads. The compounds include, but are not limited to, anti-inflammatory bioactive compounds, steroids, steroid derivatives, and / or LXR modulators, and derivatives thereof, e.g., prodrugs thereof. The terms "compound," "biologically active compound," "prodrug," and "payload" are used interchangeably. The terms or phrases are used interchangeably throughout this disclosure. In certain embodiments, The biologically active compound (D*) or a residue thereof may have a hydroxyl functionality (e.g., D*-OH or D*-OR). In certain embodiments herein, for example, for convenience, R 5 It is recognized by those skilled in the art As will be appreciated, the hydroxyl, amino, and a thiol functional group or portion thereof, such as -O-, -N(R)-, or -S-; or Those skilled in the art will recognize that R 5 may be part of a bioactive compound (e.g., D*) described herein. It will be appreciated that the present invention may also be used as a functional group for conjugation. In one embodiment, the hydroxyl functionality is a primary hydroxyl moiety (e.g., D*- CH 2 OH or D*-CH 2 OR; ORD*-C(O)CH 2 OH or D*-C(O)CH 2 OR). In such a case, the hydroxyl functionality is a secondary hydroxyl moiety (e.g., D*-CH(OH)R or is D*-CH(OR)R; or D*-C(O)CH(R)(OH) or D*-C(O)CH(R)(OR)). In the formula (I), the hydroxyl functionality is a tertiary hydroxyl moiety (e.g., D*-C(R 1 )(R 2 )(OH) Or D*-C(R 1 )(R 2 )(OR);orD*-C(O)C(R 1 )(R 2 )(OH) or D*-C(O)C(R 1 )(R 2)(OR)) Those skilled in the art will appreciate that each functional group in the previous sentence can be part of a biologically active compound D*, It is recognized that the embodiments may be illustrated simultaneously for clarity, convenience, and / or emphasis. In another embodiment, D* containing a hydroxyl functionality may be an aryl hydride. D*-Ar-OH, D*-Ar-OR. In an embodiment, the bioactive compound (D*) containing a hydroxyl functionality (D*-OH) is dexamethasone. and the residue containing hydroxyl functionality is [ka] is (In the ceremony [ka] is a prodrug moiety (as shown in Formula Ia and / or Formula Ib) as described herein. In one embodiment, the hydroxy group is a linker, a linker, and / or a linker to a binder. The biologically active compound (D*) containing a hydroxyl functionality is dexamethasone, The residues are [ka] is (In the formula, [ka] is a prodrug moiety (as shown in Formula Ia and / or Formula Ib) as described herein. In one embodiment, the hydroxy group is a linker, a linker, and / or a linker to a binder. The biologically active compound (D*) containing a hydroxyl functionality (D*-OH) is budesonide, The residue containing [ka] is (In the formula, [ka] is a prodrug moiety (as shown in Formula Ia and / or Formula Ib) as described herein. In one embodiment, the hydroxy group is a linker, a linker, and / or a linker to a binder. The biologically active compound (D*) containing a hydroxyl functionality is budesonide, The base is [ka] is (In the formula, [ka] is a prodrug moiety (as shown in Formula Ia and / or Formula Ib) as described herein. In one embodiment, the hydroxy group is a linker, a linker, and / or a linker to a binder. The biologically active compound (D*) containing a hydroxyl functionality (D*-OH) is 6,11-2F-budesonide. The residue containing the aryl functionality is [ka] is (In the formula, [ka] is a prodrug moiety (as shown in Formula Ia and / or Formula Ib) as described herein. In one embodiment, the hydroxy group is a linker, a linker, and / or a linker to a binder. The biologically active compound (D*) containing a hydroxyl functionality is 6,11-2F-budesonide, The residue containing [ka] is (In the formula, [ka] is a prodrug moiety (as shown in Formula Ia and / or Formula Ib) as described herein. In one embodiment, the linker and / or binder is a bioactivatable Compound (D*) is an LXR agonist, in which the residue containing the hydroxyl functionality is [ka] is (In the formula, [ka] is a prodrug moiety (as shown in Formula Ia and / or Formula Ib) as described herein. In one embodiment, the hydroxy group is a linker, a linker, and / or a linker to a binder. The biologically active compound (D*) containing a hydroxyl functionality is an LXR agonist and The residues are [ka] is (In the formula, [ka] is a prodrug moiety (as shown in Formula Ia and / or Formula Ib) as described herein. In one embodiment, the linker and / or binder is a linker to a biologically active agent. The compound (D*) or a residue thereof may have an amino functionality (e.g., D*-NR 2 or D*-N(R)-R). In embodiments, the amino functionality is a primary amino moiety (e.g., D*-CH 2NR 2 Or D*-CH 2 N( R)-R; or D*-C(O)CH 2 NR 2 Or D*-C(O)CH 2 In another embodiment, the The amino functionality is a secondary amino moiety (e.g., D*-CH(NR 2 )R or D*-CH(NR-R)R; or D*-C(O) CH(R)(NR 2 ) or D*-C(O)CH(R)(NR-R)). In another embodiment, the amino functionality is a tertiary amino moiety (e.g., D*-C(R 1 )(R 2 )(NR 2 ) or D*-C(R 1 )(R 2 )(N(R)-R); or D*- C(O)C(R 1 )(R 2 )(NR 2 ) or D*-C(O)C(R 1 )(R 2 )(N(R)-R)). In another embodiment D* containing an amino functionality is an arylamine (e.g., D*-Ar-NR 2 , D*-Ar-N(R)-R). In some embodiments, the biologically active compound (D*) or a residue thereof has a thiol functionality (e.g. , D*-SH or D*-SR). In one embodiment, the thiol functionality comprises a primary thiol moiety. (For example, D*-CH 2 SH or D*-CH 2 SR; or D*-C(O)CH 2 SH or D*-C(O)CH 2 SR) In another embodiment, the thiol functionality is a secondary thiol moiety (e.g., D*-CH(SH)R). or D*-CH(SR)R; or D*-C(O)CH(R)(SH) or D*-C(O)CH(R)(SR)). In embodiments, the thiol functionality is a tertiary thiol moiety (e.g., D*-C(R 1 )(R 2 )(SH) or is D*-C(R 1 )(R 2 )(SR); or D*-C(O)C(R 1 )(R 2 )(SH) or D*-C(O)C(R 1 )(R 2 )(SR)) In another embodiment, D* containing a thiol functionality is an arylthiol or thiophene. In certain embodiments, D* is a group that can be easily understood by those of skill in the art (e.g., D*-Ar-SH, D*-Ar-SR). As will be appreciated, tetra- or penta-cyclic steroidal scaffolds In some embodiments, the compound is delivered to a cell as part of a conjugate. In some embodiments, the compound can be administered to a target, e.g., a target cell, or Among them, steroids, steroid derivatives, LXR modulators, or derivatives thereof A compound may have one or more additional activities. This can be done.

[0063] In certain embodiments, described herein are compounds having the structure of formula Ia, or is a pharma- ceutically acceptable salt of: [ka] (In the formula, R 1a and R 1b are independently hydrogen, alkyl, alkoxy, alkenyl, alkynyl, aryl, arylalkyl, heteroaryl, or alkylene, where R1a but , when it is alkylene, the alkylene may further be R 3 4, 5, or 6 membered heterocyclic Form a cyclyl; R 2 is hydrogen or an amino acid side chain; R 3 is hydrogen, alkyl, or alkoxy. Kiren, where R 3 is alkylene, the alkylene may further comprise R 1a In conclusion combine with each other to form said 4-, 5-, or 6-membered heterocyclyl; D* is acyl or hydroxyl. and n is 0, 1, 2, 3, 4, or 5).

[0064] In certain embodiments, described herein are compounds having the structure of formula Iaa: and pharma- ceutically acceptable salts thereof: [ka] (In the formula, R 1a and R 1b are independently hydrogen, alkyl, alkoxy, alkenyl, alkynyl, Aryl, arylalkyl, heteroaryl, alkylene, or heteroalkylene. where R 1a When is alkylene or heteroalkylene, the alkylene or heteroalkylene The tert-alkylene further includes R 3 to form a 4-, 5-, or 6-membered heterocyclyl; R 2 teeth, hydrogen, alkylene, heteroalkylene, or an amino acid side chain, where R 2 But, Alki When the alkylene or heteroalkylene is an alkylene or heteroalkylene, the alkylene or heteroalkylene may further be R 3 to form a 4-, 5-, or 6-membered heterocyclyl; R 3 is hydrogen, alkyl, alkylene or heteroalkylene, where R 3 is alkylene or heteroalkylene In the case, the alkylene or heteroalkylene may further include R 1a or R 2 4, 5, or 6 R 6 is hydrogen or alkyl; D* is acyl or is a residue of an amino-containing biologically active compound; and n is 0, 1, 2, 3, 4, or 5).

[0065] In certain embodiments, described herein are compounds having the structure of formula Iaaa, and pharma- ceutically acceptable salts thereof: [ka] (In the formula, R 1a and R 1b are independently hydrogen, alkyl, alkoxy, alkenyl, alkynyl, Aryl, arylalkyl, heteroaryl, alkylene, or heteroalkylene. where R 1a When is alkylene or heteroalkylene, the alkylene or heteroalkylene The tert-alkylene further includes R 3 to form a 4-, 5-, or 6-membered heterocyclyl; R 2 teeth, hydrogen, alkylene, heteroalkylene, or an amino acid side chain, where R 2 But, Alki When the alkylene or heteroalkylene is an alkylene or heteroalkylene, the alkylene or heteroalkylene may further be R 3 to form a 4-, 5-, or 6-membered heterocyclyl; R 3 is hydrogen, alkyl, alkylene or heteroalkylene, where R 3 is alkylene or heteroalkylene In the case, the alkylene or heteroalkylene may further include R 1a or R 2 4, 5, or 6 D* is an acyl or a bioactive compound containing a thiol. and n is 0, 1, 2, 3, 4, or 5).

[0066] In certain embodiments, described herein are compounds having the structure of formula Ib, or is a pharma- ceutically acceptable salt of: [ka] (In the formula, R 1a and R 1b are independently hydrogen, alkyl, alkoxy, alkenyl, alkynyl, aryl, arylalkyl, heteroaryl, or alkylene, where R 1a but , when it is alkylene, the alkylene may further be R 3 4, 5, or 6 membered heterocyclic Form a cyclyl; R 2 is hydrogen or an amino acid side chain; R 3 is hydrogen, alkyl, or alkoxy. Kiren, where R 3 is alkylene, the alkylene may further comprise R 1a In conclusion combine with each other to form said 4-, 5-, or 6-membered heterocyclyl; D* is acyl or hydroxyl. and n is 0, 1, 2, 3, 4, or 5).

[0067] In certain embodiments, described herein are compounds having the structure of formula Ibb, or and pharma- ceutically acceptable salts thereof: [ka] (In the formula, R 1aand R 1b are independently hydrogen, alkyl, alkoxy, alkenyl, alkynyl, Aryl, arylalkyl, heteroaryl, alkylene, or heteroalkylene. where R 1a When is alkylene or heteroalkylene, the alkylene or heteroalkylene The tert-alkylene further includes R 3 to form a 4-, 5-, or 6-membered heterocyclyl; R 2 teeth, hydrogen, alkylene, heteroalkylene, or an amino acid side chain, where R 2 But, Alki When the alkylene or heteroalkylene is an alkylene or heteroalkylene, the alkylene or heteroalkylene may further be R 3 to form a 4-, 5-, or 6-membered heterocyclyl; R 3 is hydrogen, alkyl, alkylene or heteroalkylene, where R 3 is alkylene or heteroalkylene In the case, the alkylene or heteroalkylene may further include R 1a or R 2 4, 5, or 6 R 6 is hydrogen or alkyl; D* is acyl or is a residue of an amino-containing biologically active compound; and n is 0, 1, 2, 3, 4, or 5).

[0068] In certain embodiments, described herein are compounds having the structure of formula Ibbb, or and pharma- ceutically acceptable salts thereof: [ka] (In the formula, R 1a and R 1b are independently hydrogen, alkyl, alkoxy, alkenyl, alkynyl, Aryl, arylalkyl, heteroaryl, alkylene, or heteroalkylene. where R 1a When is alkylene or heteroalkylene, the alkylene or heteroalkylene The tert-alkylene further includes R 3 to form a 4-, 5-, or 6-membered heterocyclyl; R 2 teeth, hydrogen, alkylene, heteroalkylene, or an amino acid side chain, where R 2 But, Alki When the alkylene or heteroalkylene is an alkylene or heteroalkylene, the alkylene or heteroalkylene may further be R 3 to form a 4-, 5-, or 6-membered heterocyclyl; R 3 is hydrogen, alkyl, alkylene or heteroalkylene, where R 3 is alkylene or heteroalkylene In the case, the alkylene or heteroalkylene may further include R 1a or R 2 4, 5, or 6 D* is an acyl or a bioactive compound containing a thiol. and n is 0, 1, 2, 3, 4, or 5).

[0069] In any one or more of the preceding embodiments, the bioactive compound is a hydroxyl group. or in the residue of the biologically active compound, D*, in certain embodiments, linked to the remainder of the molecule via a hydroxyl residue (i.e., bond to oxygen); The following embodiments of Formula I and / or Formula Ib are contemplated. In one embodiment, R 1a is hydrogen Yes and R 1b is hydrogen; R 2 is hydrogen; R 3 is hydrogen; D* is hydrogen; and n is 0. In another embodiment, R 1a is hydrogen and R 1b is an alkyl Yes;R 2 is hydrogen; R 3 is hydrogen; D* is hydrogen; and n is 0. In the embodiment, R 1a is hydrogen and R 1b is alkoxy; R 2 is hydrogen; R 3 is hydrogen; D* is hydrogen; and n is 0. In another embodiment, R 1a teeth , hydrogen, and R 1b is alkenyl; R 2 is hydrogen; R 3 is hydrogen; D* is , hydrogen; and n is 0. In another embodiment, R 1a is hydrogen and R 1b is alkynyl; R 2 is hydrogen; R 3 is hydrogen; D* is hydrogen; and n is , 0. In another embodiment, R 1a is hydrogen and R 1b is aryl; R 2 is hydrogen; R 3 is hydrogen; D* is hydrogen; and n is 0. In R 1a is hydrogen and R 1b is arylalkyl; R 2 is hydrogen; R 3 is hydrogen; D* is hydrogen; and n is 0. In another embodiment, R 1a teeth , hydrogen, and R 1b is heteroaryl; R 2 is hydrogen; R 3is hydrogen; D* is hydrogen; and n is 0. In another embodiment, R 1a is an alkylene wherein the alkylene further comprises R 3 to form a 4-, 5-, or 6-membered heterocyclyl And R 1b is hydrogen; R 2 is hydrogen; R 3 is hydrogen; D* is hydrogen; or In another embodiment, R 1a is alkylene, Killen further added that 3 to form a 4-, 5-, or 6-membered heterocyclyl; and R 1b A RuKil is;R 2 is hydrogen; R 3 is hydrogen; D* is hydrogen; and n is 0. In another embodiment, R 1a is alkylene, wherein the alkylene is further , R 3 to form a 4-, 5-, or 6-membered heterocyclyl; and R 1b is an alkoxyl R 2 is hydrogen; R 3 is hydrogen; D* is hydrogen; and n is 0. In an embodiment, R 1a is alkylene, wherein the alkylene further comprises R 3 Combined to to form a 4-, 5-, or 6-membered heterocyclyl; and R 1b is alkenyl; R 2 is hydrogen ;R 3 is hydrogen; D* is hydrogen; and n is 0. , R 1a is alkylene, wherein the alkylene further comprises R 34, 5, or forms a six-membered heterocyclyl; and R 1b is alkynyl; R 2 is hydrogen; R 3 teeth D* is hydrogen; and n is 0. In another embodiment, R 1a A alkylene, wherein the alkylene is further selected from the group consisting of R 3 4, 5, or 6-membered heterocyclic and R 1b is aryl; R 2 is hydrogen; R 3 is hydrogen; D * is hydrogen; and n is 0. In another embodiment, R 1a is an alkylene wherein the alkylene further comprises R 3 to form a 4-, 5-, or 6-membered heterocyclyl And R 1b is arylalkyl; R 2 is hydrogen; R 3 is hydrogen; D* is hydrogen; and n is 0. In any of the embodiments of this paragraph, R 4 Water In any of the embodiments of this paragraph, R 4 is alkyl.

[0070] In another embodiment, R 1a is alkylene, wherein the alkylene is further , R 3 to form a 4-, 5-, or 6-membered heterocyclyl; and R 1b is a heteroaryl Yes;R 2 is hydrogen; R 3 is hydrogen; D* is hydrogen; and n is 0. In the embodiment, R 1a is hydrogen and R 1bis hydrogen; R 2 is an amino acid side chain R 3 is hydrogen; D* is hydrogen; and n is 0. In another embodiment, R 1a is hydrogen and R 1b is alkyl; R 2 is an amino acid side chain; R 3 is hydrogen D* is hydrogen; and n is 0. In another embodiment, R 1a is hydrogen , and R 1b is alkoxy; R 2 is an amino acid side chain; R 3 is hydrogen; D* is water and n is 0. In another embodiment, R 1a is hydrogen and R 1b teeth, alkenyl; R 2 is an amino acid side chain; R 3 is hydrogen; D* is hydrogen; and n is 0. In another embodiment, R 1a is hydrogen and R 1b is alkynyl R 2 is an amino acid side chain; R 3 is hydrogen; D* is hydrogen; and n is 0. In another embodiment, R 1a is hydrogen and R 1b is aryl; R 2 Amino R is an acid side chain; 3 is hydrogen; D* is hydrogen; and n is 0. Hey, R 1a is hydrogen and R 1b is arylalkyl; R 2 is the amino acid side chain ;R 3is hydrogen; D* is hydrogen; and n is 0. , R 1a is hydrogen and R 1b is heteroaryl; R 2 is an amino acid side chain; R 3 is hydrogen; D* is hydrogen; and n is 0. In another embodiment, R 1a teeth, alkylene, wherein the alkylene is further selected from the group consisting of R 3 4, 5, or 6-membered hexafluorophosphate Forming a tetracyclyl; and R 1b is hydrogen; R 2 is an amino acid side chain; R 3 is hydrogen D* is hydrogen; and n is 0. In another embodiment, R 1a is an alkylene wherein the alkylene further comprises R 3 4, 5, or 6-membered heterocyclyl and R 1b is alkyl; R 2 is an amino acid side chain; R 3 is hydrogen; D * is hydrogen; and n is 0. In another embodiment, R 1a is an alkylene wherein the alkylene further comprises R 3 to form a 4-, 5-, or 6-membered heterocyclyl And R 1b is alkoxyl; R 2 is an amino acid side chain; R 3 is hydrogen; D* is hydrogen; and n is 0. In another embodiment, R 1a is alkylene; wherein the alkylene further comprises R 3 to form a 4-, 5-, or 6-membered heterocyclyl S; and R 1bis alkenyl; R 2 is an amino acid side chain; R 3 is hydrogen; D* is and n is 0. In another embodiment, R 1a is alkylene, wherein the alkylene further comprises R 3 to form a 4-, 5-, or 6-membered heterocyclyl; R 1b is alkynyl; R 2 is an amino acid side chain; R 3 is hydrogen; D* is hydrogen and n is 0. In another embodiment, R 1a is alkylene, where The alkylene may further include R 3 to form a 4-, 5-, or 6-membered heterocyclyl; and R 1b is aryl; R 2 is an amino acid side chain; R 3 is hydrogen; D* is hydrogen; or In another embodiment, R 1a is alkylene, Killen further added that 3 to form a 4-, 5-, or 6-membered heterocyclyl; and R 1b A R is aryl alkyl; 2 is an amino acid side chain; R 3 is hydrogen; D* is hydrogen; and n is 0. In any of the embodiments of this paragraph, R 4 is hydrogen. In any of the embodiments of paragraph R 4 is alkyl.

[0071] In another embodiment, R 1a is alkylene, wherein the alkylene is further , R 3to form a 4-, 5-, or 6-membered heterocyclyl; and R 1b is a heteroaryl Yes;R 2 is an amino acid side chain; R 3 is hydrogen; D* is hydrogen; and n is 0. In another embodiment, R 1a is hydrogen and R 1b is hydrogen; R 2 is hydrogen R 3 is alkyl; D* is hydrogen; and n is 0. , R 1a is hydrogen and R 1b is alkyl; R 2 is hydrogen; R 3 is an alkyl D* is hydrogen; and n is 0. In another embodiment, R 1a is hydrogen , and R 1b is alkoxy; R 2 is hydrogen; R 3 is alkyl; D* is hydrogen and n is 0. In another embodiment, R 1a is hydrogen and R 1b Is, Al Kenyl;R 2 is hydrogen; R 3 is alkyl; D* is hydrogen; and n is 0. In another embodiment, R 1a is hydrogen and R 1b is alkynyl; R 2 teeth , hydrogen; R 3 is alkyl; D* is hydrogen; and n is 0. In this regard, R 1a is hydrogen and R 1b is aryl; R 2 is hydrogen; R 3 teeth, D* is hydrogen; and n is 0. In another embodiment, R 1a teeth, Hydrogen and R 1b is arylalkyl; R 2 is hydrogen; R 3 is an alkyl D* is hydrogen; and n is 0. In another embodiment, R 1a is hydrogen , and R 1b is heteroaryl; R 2 is hydrogen; R 3 is alkyl; D* is water and n is 0. In another embodiment, R 1a is alkylene, The alkylene further comprises R 3 to form a 4-, 5-, or 6-membered heterocyclyl; and R 1b is hydrogen; R 2 is hydrogen; R 3 is alkyl; D* is hydrogen; and n is , 0. In another embodiment, R 1a is alkylene, where Furthermore, R 3 to form a 4-, 5-, or 6-membered heterocyclyl; and R 1b is an alkyl ;R 2 is hydrogen; R 3 is alkyl; D* is hydrogen; and n is 0. In another embodiment, R 1a is alkylene, wherein the alkylene further comprises R 3 to form a 4-, 5-, or 6-membered heterocyclyl; and R 1b is alkoxyl; R 2 is hydrogen; R 3 is alkyl; D* is hydrogen; and n is 0. In an embodiment, R 1a is alkylene, wherein the alkylene further comprises R 3 Combined to to form a 4-, 5-, or 6-membered heterocyclyl; and R 1b is alkenyl; R 2 is hydrogen ;R 3 is alkyl; D* is hydrogen; and n is 0. And R 1a is alkylene, wherein the alkylene further comprises R 3 4, 5 or a 6-membered heterocyclyl; and R 1b is alkynyl; R 2 is hydrogen; R 3 is alkyl; D* is hydrogen; and n is 0. In another embodiment, R 1a is alkylene, wherein the alkylene further comprises R 3 4, 5, or 6-membered bond and R 1b is aryl; R 2 is hydrogen; R 3 Is, Alki D* is hydrogen; and n is 0. In another embodiment, R 1a Is, Alki wherein the alkylene further comprises R 3 4, 5, or 6-membered heterocyclic Forms krill; and R 1b is arylalkyl; R 2 is hydrogen; R 3 is an alkyl D* is hydrogen; and n is 0. In another embodiment, R 1a Alkire wherein the alkylene further comprises R 3 4-, 5-, or 6-membered heterocyclic R 1b is heteroaryl; R 2 is hydrogen; R 3 is an alkyl D* is hydrogen; and n is 0. In another embodiment, R 1a is hydrogen, And R 1b is hydrogen; R 2 is an amino acid side chain; R 3 is alkyl; D* is hydrogen and n is 0. In another embodiment, R 1a is hydrogen and R 1b Is, Al Kill;R 2 is an amino acid side chain; R 3 is alkyl; D* is hydrogen; and n is 0. In any of the embodiments of this paragraph, R 4 is hydrogen. In any of the embodiments of the graph, R 4 is alkyl.

[0072] In another embodiment, R 1a is hydrogen and R 1b is alkoxy; R 2 A R 3 is alkyl; D* is hydrogen; and n is 0. In the embodiment, R 1a is hydrogen and R 1b is alkenyl; R 2 On the amino acid side Chain;R 3 is alkyl; D* is hydrogen; and n is 0. Hey, R 1a is hydrogen and R 1b is alkynyl; R 2 is an amino acid side chain; R 3is alkyl; D* is hydrogen; and n is 0. In another embodiment, R 1 a is hydrogen and R 1b is aryl; R 2 is an amino acid side chain; R 3 Is, Alki D* is hydrogen; and n is 0. In another embodiment, R 1a is hydrogen Yes and R 1b is arylalkyl; R 2 is an amino acid side chain; R 3 is an alkyl D* is hydrogen; and n is 0. In another embodiment, R 1a is hydrogen And R 1b is heteroaryl; R 2 is an amino acid side chain; R 3 is an alkyl D* is hydrogen; and n is 0. In another embodiment, R 1a is an alkylene wherein the alkylene further comprises R 3 4-, 5-, or 6-membered heterocyclyl and R 1b is hydrogen; R 2 is an amino acid side chain; R 3 is alkyl; D* is hydrogen; and n is 0. In another embodiment, R 1a is alkylene; wherein the alkylene further comprises R 3 to form a 4-, 5-, or 6-membered heterocyclyl S; and R 1b is alkyl; R 2 is an amino acid side chain; R 3 is alkyl; D* is , hydrogen; and n is 0. In another embodiment, R 1ais alkylene, wherein the alkylene further comprises R 3 to form a 4-, 5-, or 6-membered heterocyclyl; And R 1b is alkoxyl; R 2 is an amino acid side chain; R 3 is alkyl; D* is , hydrogen; and n is 0. In another embodiment, R 1a is alkylene, wherein the alkylene further comprises R 3 to form a 4-, 5-, or 6-membered heterocyclyl; And R 1b is alkenyl; R 2 is an amino acid side chain; R 3 is alkyl; D* is and n is 0. In another embodiment, R 1a is alkylene, wherein the alkylene further comprises R 3 to form a 4-, 5-, or 6-membered heterocyclyl; R 1b is alkynyl; R 2 is an amino acid side chain; R 3 is alkyl; D* is water and n is 0. In another embodiment, R 1a is alkylene, The alkylene further comprises R 3 to form a 4-, 5-, or 6-membered heterocyclyl; and R 1b is aryl; R 2 is an amino acid side chain; R 3 is alkyl; D* is hydrogen and n is 0. In another embodiment, R 1a is alkylene, where The alkylene may further include R 3 to form a 4-, 5-, or 6-membered heterocyclyl; and R1b is arylalkyl; R 2 is an amino acid side chain; R 3 is alkyl; D* is and n is 0. In another embodiment, R 1a is alkylene, wherein the alkylene further comprises R 3 to form a 4-, 5-, or 6-membered heterocyclyl; R 1b is heteroaryl; R 2 is an amino acid side chain; R 3 is alkyl; D* is , hydrogen; and n is 0. In another embodiment, R 1a is alkylene, wherein the alkylene further comprises R 3 to form a 4-, 5-, or 6-membered heterocyclyl; And R 1b is hydrogen; R 2 is hydrogen; R 3 is R 1a further linked to said 4, 5, or 6 membered is an alkylene group forming a heterocyclyl; D* is hydrogen; and n is 0. In any of the embodiments of paragraph R 4 is hydrogen. In any of the above, R 4 is alkyl.

[0073] In another embodiment, R 1a is alkylene, wherein the alkylene is further , R 3 to form a 4-, 5-, or 6-membered heterocyclyl; and R 1b is alkyl; R 2 is hydrogen; R 3 is R 1a to form said 4-, 5-, or 6-membered heterocyclyl. D* is hydrogen; and n is 0. In another embodiment, R 1a is alkylene, wherein the alkylene further comprises R 3 4, 5, or 6-membered bond and R 1b is alkoxyl; R 2 is hydrogen; R 3 is R 1 a is an alkylene which further binds to form said 4-, 5-, or 6-membered heterocyclyl; D* is , hydrogen; and n is 0. In another embodiment, R 1a is alkylene, wherein the alkylene further comprises R 3 to form a 4-, 5-, or 6-membered heterocyclyl; And R 1b is alkenyl; R 2 is hydrogen; R 3 is R 1a Further bind to the 4, 5, or is alkylene forming a 6-membered heterocyclyl; D* is hydrogen; and n is 0. In another embodiment, R 1a is alkylene, wherein the alkylene is further To, R 3 to form a 4-, 5-, or 6-membered heterocyclyl; and R 1b is alkynyl R 2 is hydrogen; R 3 is R 1a to form the 4-, 5-, or 6-membered heterocyclyl. D* is hydrogen; and n is 0. R 1a is alkylene, wherein the alkylene further comprises R 3 4, 5, or 6 forming a 1-membered heterocyclyl; and R 1b is aryl; R 2 is hydrogen; R 3 is R 1a is an alkylene which further binds to said 4-, 5-, or 6-membered heterocyclyl; D* is and n is 0. In another embodiment, R 1a is alkylene, wherein the alkylene further comprises R 3 to form a 4-, 5-, or 6-membered heterocyclyl; R 1b is arylalkyl; R 2 is hydrogen; R 3 is R 1a Further binding to the 4, 5 or alkylene forming a 6-membered heterocyclyl; D* is hydrogen; and n is 0 In another embodiment, R 1a is alkylene, where the alkylene is In addition, R 3 to form a 4-, 5-, or 6-membered heterocyclyl; and R 1b Hetero ants R 2 is hydrogen; R 3 is R 1a further linked to said 4, 5, or 6 membered heterocyclic D* is hydrogen; and n is 0. Hey, R 1a is alkylene, wherein the alkylene further comprises R 3 4, which is bonded to forming a 5- or 6-membered heterocyclyl; and R 1b is hydrogen; R 2 is an amino acid side chain R 3 is R 1a further attached to form said 4-, 5-, or 6-membered heterocyclyl; D* is hydrogen; and n is 0. In another embodiment, R 1a Alkire wherein the alkylene further comprises R 3 4-, 5-, or 6-membered heterocyclic R 1b is alkyl; R 2 is an amino acid side chain; R 3 is R 1a Nisara is an alkylene which is bonded to said 4-, 5-, or 6-membered heterocyclyl; D* is hydrogen. and n is 0. In another embodiment, R 1a is alkylene, where The alkylene may further include R 3 to form a 4-, 5-, or 6-membered heterocyclyl; and R 1b is alkoxyl; R 2 is an amino acid side chain; R 3 is R 1a Further binding to the 4, 5 or alkylene forming a 6-membered heterocyclyl; D* is hydrogen; and n is 0 In another embodiment, R 1a is alkylene, where the alkylene is In addition, R 3 to form a 4-, 5-, or 6-membered heterocyclyl; and R 1b is alkenyl ;R 2 is an amino acid side chain; R 3 is R 1a further linked to said 4, 5, or 6 membered heterocyclic is an alkylene group forming a cyclyl; D* is hydrogen; and n is 0. In any of the embodiments of the present invention, R 4 is hydrogen. In some cases, R 4 is alkyl.

[0074] In another embodiment, R 1a is alkylene, wherein the alkylene is further , R 3 to form a 4-, 5-, or 6-membered heterocyclyl; and R 1b is alkynyl; R 2 is an amino acid side chain; R 3 is R 1a further linked to said 4, 5, or 6 membered heterocyclyl D* is hydrogen; and n is 0. And R 1a is alkylene, wherein the alkylene further comprises R 3 4, 5 or a 6-membered heterocyclyl; and R 1b is aryl; R 2 is the amino acid side chain Yes;R 3 is R 1a which further binds to form said 4-, 5-, or 6-membered heterocyclyl. D* is hydrogen; and n is 0. In another embodiment, R 1a Is, Alki wherein the alkylene further comprises R 3 4, 5, or 6-membered heterocyclic Forms krill; and R 1b is arylalkyl; R 2 is an amino acid side chain; R 3 teeth, R 1a is an alkylene which is further bonded to form said 4-, 5-, or 6-membered heterocyclyl; D* is hydrogen; and n is 0. In another embodiment, R 1a is alkylene; wherein the alkylene further comprises R 3 to form a 4-, 5-, or 6-membered heterocyclyl S; and R1b is heteroaryl; R 2 is an amino acid side chain; R 3 is R 1a Further alkylene which combines with said 4-, 5-, or 6-membered heterocyclyl; D* is hydrogen. and n is 0. In another embodiment, R 1a is hydrogen and R 1b is hydrogen R 2 is hydrogen; R 3 is hydrogen; D* is acyl; and n is 0. In the embodiment, R 1a is hydrogen and R 1b is alkyl; R 2 is hydrogen; R 3 is hydrogen; D* is acyl; and n is 0. In another embodiment, R 1a teeth , hydrogen, and R 1b is alkoxy; R 2 is hydrogen; R 3 is hydrogen; D* is , acyl; and n is 0. In another embodiment, R 1a is hydrogen and R 1 b is alkenyl; R 2 is hydrogen; R 3 is hydrogen; D* is acyl; and n is 0. In another embodiment, R 1a is hydrogen and R 1b is alkynyl R 2 is hydrogen; R 3 is hydrogen; D* is acyl; and n is 0. In the embodiment, R 1a is hydrogen and R 1b is aryl; R 2 is hydrogen; R3 is hydrogen; D* is acyl; and n is 0. In another embodiment, R 1a teeth , hydrogen, and R 1b is arylalkyl; R 2 is hydrogen; R 3 is hydrogen D* is acyl; and n is 0. In another embodiment, R 1a is hydrogen , and R 1b is heteroaryl; R 2 is hydrogen; R 3 is hydrogen; D* is acyl and n is 0. In another embodiment, R 1a is alkylene, where The alkylene further comprises R 3 to form a 4-, 5-, or 6-membered heterocyclyl; and R 1 b is hydrogen; R 2 is hydrogen; R 3 is hydrogen; D* is acyl; and n is 0 In another embodiment, R 1a is alkylene, where the alkylene is In addition, R 3 to form a 4-, 5-, or 6-membered heterocyclyl; and R 1b is an alkyl Yes;R 2 is hydrogen; R 3 is hydrogen; D* is acyl; and n is 0. In an embodiment, R 1a is alkylene, wherein the alkylene further comprises R 3 To linked to form a 4-, 5-, or 6-membered heterocyclyl; and R 1b is alkoxyl; R 2 teeth , hydrogen; R 3is hydrogen; D* is acyl; and n is 0. In R 1a is alkylene, wherein the alkylene further comprises R 3 4 , 5, or 6 membered heterocyclyl; and R 1b is alkenyl; R 2 is hydrogen R 3 is hydrogen; D* is acyl; and n is 0. In any of the above, R 4 is hydrogen. In any of the embodiments of this paragraph, R 4 is alkyl.

[0075] In another embodiment, R 1a is alkylene, wherein the alkylene is further , R 3 to form a 4-, 5-, or 6-membered heterocyclyl; and R 1b is alkynyl; R 2 is hydrogen; R 3 is hydrogen; D* is acyl; and n is 0. In an embodiment, R 1a is alkylene, wherein the alkylene further comprises R 3 Combined to to form a 4-, 5-, or 6-membered heterocyclyl; and R 1b is aryl; R 2 is hydrogen Yes;R 3 is hydrogen; D* is acyl; and n is 0. , R 1a is alkylene, wherein the alkylene further comprises R 3 4, 5, or forms a six-membered heterocyclyl; and R 1b is arylalkyl; R 2is hydrogen ;R 3 is hydrogen; D* is acyl; and n is 0. In another embodiment, R 1a is alkylene, wherein the alkylene further comprises R 3 4, 5, or 6-membered bond and R 1b is heteroaryl; R 2 is hydrogen; R 3 teeth, D* is acyl; and n is 0. In another embodiment, R 1a Water Prime and R 1b is hydrogen; R 2 is an amino acid side chain; R 3 is hydrogen; D* is acyl; and n is 0. In another embodiment, R 1a is hydrogen and R 1b is alkyl; R 2 is an amino acid side chain; R 3 is hydrogen; D* is acyl; and n is 0. In another embodiment, R 1a is hydrogen and R 1b is an alkoxy ;R 2 is an amino acid side chain; R 3 is hydrogen; D* is acyl; and n is 0. In another embodiment, R 1a is hydrogen and R 1b is alkenyl; R 2 teeth , an amino acid side chain; R 3 is hydrogen; D* is acyl; and n is 0. In an embodiment, R 1a is hydrogen and R 1b is alkynyl; R 2 is an amino acid Side chain; R 3 is hydrogen; D* is acyl; and n is 0. Hey, R 1a is hydrogen and R 1b is aryl; R 2 is an amino acid side chain; R 3 is hydrogen; D* is acyl; and n is 0. In another embodiment, R 1a teeth , hydrogen, and R 1b is arylalkyl; R 2 is an amino acid side chain; R 3 teeth, D* is acyl; and n is 0. In another embodiment, R 1a Water Prime and R 1b is heteroaryl; R 2 is an amino acid side chain; R 3 is hydrogen D* is acyl; and n is 0. In another embodiment, R 1a Alkire wherein the alkylene further comprises R 3 4-, 5-, or 6-membered heterocyclic R 1b is hydrogen; R 2 is an amino acid side chain; R 3 is hydrogen; D* is acyl; and n is 0. In another embodiment, R 1a is an alkylene wherein the alkylene further comprises R 3 to form a 4-, 5-, or 6-membered heterocyclyl And R 1b is alkyl; R 2 is an amino acid side chain; R 3 is hydrogen; D* is acyl; and n is 0. In another embodiment, R 1ais alkylene, wherein the alkylene further comprises R 3 to form a 4-, 5-, or 6-membered heterocyclyl; And R 1b is alkoxyl; R 2 is an amino acid side chain; R 3 is hydrogen; D* is a and n is 0. In another embodiment, R 1a is alkylene, wherein the alkylene further comprises R 3 to form a 4-, 5-, or 6-membered heterocyclyl; R 1b is alkenyl; R 2 is an amino acid side chain; R 3 is hydrogen; D* is acyl and n is 0. In another embodiment, R 1a is alkylene, where The alkylene further comprises R 3 to form a 4-, 5-, or 6-membered heterocyclyl; and R 1 b is alkynyl; R 2 is an amino acid side chain; R 3 is hydrogen; D* is acyl and n is 0. In another embodiment, R 1a is alkylene, The alkylene may further include R 3 to form a 4-, 5-, or 6-membered heterocyclyl; and R 1b teeth , aryl; R 2 is an amino acid side chain; R 3 is hydrogen; D* is acyl; and n is 0. In any of the embodiments of this paragraph, R 4 is hydrogen. In any of the embodiments of the invention, R 4 is alkyl.

[0076] In another embodiment, R 1a is alkylene, wherein the alkylene is further , R 3 to form a 4-, 5-, or 6-membered heterocyclyl; and R 1b is aryl alkyl ;R 2 is an amino acid side chain; R 3 is hydrogen; D* is acyl; in another embodiment In R 1a is alkylene, wherein the alkylene further comprises R 3 4 , 5, or 6 membered heterocyclyl; and R 1b is heteroaryl; R 2 Ami R is an acid side chain; 3 is hydrogen; D* is acyl; and n is 0. In this regard, R 1a is hydrogen and R 1b is hydrogen; R 2 is hydrogen; R 3 Is, Al D* is acyl; and n is 0. In another embodiment, R 1a Water Prime and R 1b is alkyl; R 2 is hydrogen; R 3 is alkyl; D* is acyl; and n is 0. In another embodiment, R 1a is hydrogen and R 1b is alkoxy; R 2 is hydrogen; R 3 is alkyl; D* is acyl; In another embodiment, R 1a is hydrogen and R 1b is an alkenyl Yes;R 2 is hydrogen; R 3 is alkyl; D* is acyl; and n is 0. In another embodiment, R 1a is hydrogen and R 1b is alkynyl; R 2 is hydrogen ;R 3 is alkyl; D* is acyl; and n is 0. Hey, R 1a is hydrogen and R 1b is aryl; R 2 is hydrogen; R 3 Is, Al D* is acyl; and n is 0. In another embodiment, R 1a Water Prime and R 1b is arylalkyl; R 2 is hydrogen; R 3 is an alkyl D* is acyl; and n is 0. In another embodiment, R 1a is hydrogen , and R 1b is heteroaryl; R 2 is hydrogen; R 3 is alkyl; D* is a and n is 0. In another embodiment, R 1a is alkylene, wherein the alkylene further comprises R 3 to form a 4-, 5-, or 6-membered heterocyclyl; R 1b is hydrogen; R 2 is hydrogen; R 3 is alkyl; D* is acyl; In another embodiment, R 1a is alkylene, Killen further added that 3to form a 4-, 5-, or 6-membered heterocyclyl; and R 1b A RuKil is;R 2 is hydrogen; R 3 is alkyl; D* is acyl; and n is 0 In another embodiment, R 1a is alkylene, where the alkylene is In addition, R 3 to form a 4-, 5-, or 6-membered heterocyclyl; and R 1b is an alkoxy R 2 is hydrogen; R 3 is alkyl; D* is acyl; and n is 0. In another embodiment, R 1a is alkylene, wherein the alkylene is further To, R 3 to form a 4-, 5-, or 6-membered heterocyclyl; and R 1b is alkenyl R 2 is hydrogen; R 3 is alkyl; D* is acyl; and n is 0. In an embodiment of the invention, R 1a is alkylene, wherein the alkylene further comprises R 3 to form a 4-, 5-, or 6-membered heterocyclyl; and R 1b is alkynyl; R 2 teeth , hydrogen; R 3 is alkyl; D* is acyl; and n is 0. In an embodiment, R 1a is alkylene, wherein the alkylene further comprises R 3 Combined to to form a 4-, 5-, or 6-membered heterocyclyl; and R 1b is aryl; R 2 is hydrogen Yes;R 3is alkyl; D* is acyl; and n is 0. And R 1a is alkylene, wherein the alkylene further comprises R 3 4, 5 or a 6-membered heterocyclyl; and R 1b is arylalkyl; R 2 is hydrogen Yes;R 3 is alkyl; D* is acyl; and n is 0. And R 1a is alkylene, wherein the alkylene further comprises R 3 4, 5 or a 6-membered heterocyclyl; and R 1b is heteroaryl; R 2 is hydrogen R 3 is alkyl; D* is acyl; and n is 0. R 1a is hydrogen and R 1b is hydrogen; R 2 is an amino acid side chain; R 3 Is, Al D* is acyl; and n is 0. In another embodiment, R 1a Water Prime and R 1b is alkyl; R 2 is an amino acid side chain; R 3 is an alkyl D* is acyl; and n is 0. In any of the embodiments of this paragraph, , R 4 is hydrogen. In any of the embodiments of this paragraph, R 4 is an alkyl do.

[0077] In another embodiment, R 1a is hydrogen and R 1bis alkoxy; R 2 A R 3 is alkyl; D* is acyl; and n is 0. In an embodiment, R 1a is hydrogen and R 1b is alkenyl; R 2 is an amino acid Side chain; R 3 is alkyl; D* is acyl; and n is 0. In this regard, R 1a is hydrogen and R 1b is alkynyl; R 2 is the amino acid side chain Yes;R 3 is alkyl; D* is acyl; and n is 0. And R 1a is hydrogen and R 1b is aryl; R 2 is an amino acid side chain; R 3 teeth D* is acyl; and n is 0. In another embodiment, R 1a is hydrogen and R 1b is arylalkyl; R 2 is an amino acid side chain; R 3 teeth D* is acyl; and n is 0. In another embodiment, R 1a is hydrogen and R 1b is heteroaryl; R 2 is an amino acid side chain; R 3 teeth, D* is alkyl; D* is acyl; and n is 0. In another embodiment, R 1a teeth , alkylene, wherein the alkylene is further selected from the group consisting of R 3 4, 5, or 6-membered forming a heterocyclyl; and R 1b is hydrogen; R 2 is an amino acid side chain; R 3 Is, Al D* is acyl; and n is 0. In another embodiment, R 1a A alkylene, wherein the alkylene is further selected from the group consisting of R 3 4, 5, or 6-membered heterocyclic and R 1b is alkyl; R 2 is an amino acid side chain; R 3 Is, Al D* is acyl; and n is 0. In another embodiment, R 1a A alkylene, wherein the alkylene is further selected from the group consisting of R 3 4, 5, or 6-membered heterocyclic and R 1b is alkoxyl; R 2 is an amino acid side chain; R 3 teeth, D* is alkyl; D* is acyl; and n is 0. In another embodiment, R 1a teeth , alkylene, wherein the alkylene is further selected from the group consisting of R 3 4, 5, or 6-membered forming a heterocyclyl; and R 1b is alkenyl; R 2 is an amino acid side chain; R 3 teeth D* is acyl; and n is 0. In another embodiment, R 1a is alkylene, wherein the alkylene further comprises R 3 4, 5, or 6-membered bond and R 1b is alkynyl; R 2 is an amino acid side chain; R 3 is alkyl; D* is acyl; and n is 0. In another embodiment, R 1 a is alkylene, wherein the alkylene further comprises R 3 4, 5, or 6-membered bond and R 1b is aryl; R 2 is an amino acid side chain; R 3 teeth D* is acyl; and n is 0. In another embodiment, R 1a is alkylene, wherein the alkylene further comprises R 3 4, 5, or 6-membered bond and R 1b is arylalkyl; R 2 is the amino acid side chain Yes;R 3 is alkyl; D* is acyl; and n is 0. And R 1a is alkylene, wherein the alkylene further comprises R 3 4, 5 or a 6-membered heterocyclyl; and R 1b is heteroaryl; R 2 is an amino acid Side chain; R 3 is alkyl; D* is acyl; and n is 0. In this regard, R 1a is alkylene, wherein the alkylene further comprises R 3 Binds to forming a 4-, 5-, or 6-membered heterocyclyl; and R 1b is hydrogen; R 2 is hydrogen; R 3 is R 1a which further binds to form said 4-, 5-, or 6-membered heterocyclyl. D* is acyl; and n is 0. In any of the embodiments of this paragraph, , R 4 is hydrogen. In any of the embodiments of this paragraph, R 4 is an alkyl do.

[0078] In another embodiment, R 1a is alkylene, wherein the alkylene is further , R 3 to form a 4-, 5-, or 6-membered heterocyclyl; and R 1b is alkyl; R 2 is hydrogen; R 3 is R 1a to form said 4-, 5-, or 6-membered heterocyclyl. D* is acyl; and n is 0. In another embodiment, R 1 a is alkylene, wherein the alkylene further comprises R 3 4, 5, or 6-membered bond and R 1b is alkoxyl; R 2 is hydrogen; R 3 is R 1 a is an alkylene which further binds to form said 4-, 5-, or 6-membered heterocyclyl; D* is , acyl; and n is 0. In another embodiment, R 1a is an alkylene; wherein the alkylene further comprises R 3 to form a 4-, 5-, or 6-membered heterocyclyl S; and R 1b is alkenyl; R 2 is hydrogen; R 3 is R 1a Further binding to the 4, 5 or alkylene forming a 6-membered heterocyclyl; D* is acyl; and n is 0. In another embodiment, R 1a is alkylene, where the alkylene is In addition, R 3 to form a 4-, 5-, or 6-membered heterocyclyl; and R 1b is an alkynyl ;R 2 is hydrogen; R 3 is R 1a further bound to said 4-, 5-, or 6-membered heterocyclyl D* is acyl; and n is 0. And R 1a is alkylene, wherein the alkylene further comprises R 3 4, 5 or a 6-membered heterocyclyl; and R 1b is aryl; R 2 is hydrogen; R 3 is R 1a is an alkylene further attached to form said 4-, 5-, or 6-membered heterocyclyl; D* is acyl; and n is 0. In another embodiment, R 1a is an alkylene wherein the alkylene further comprises R 3 4-, 5-, or 6-membered heterocyclyl and R 1b is arylalkyl; R 2 is hydrogen; R 3 is R 1a Further alkylene which combines with said 4-, 5-, or 6-membered heterocyclyl; D* is acyl. and n is 0. In another embodiment, R 1a is alkylene, The alkylene may further include R 3to form a 4-, 5-, or 6-membered heterocyclyl; and R 1b teeth , heteroaryl; R 2 is hydrogen; R 3 is R 1a further linked to said 4, 5, or 6 membered is alkylene forming a heterocyclyl of the formula: D* is acyl; and n is 0. In another embodiment, R 1a is alkylene, wherein the alkylene further comprises R 3 to form a 4-, 5-, or 6-membered heterocyclyl; and R 1b is hydrogen; R 2 A R 3 is R 1a further attached to form said 4-, 5-, or 6-membered heterocyclyl D* is acyl; and n is 0. In another embodiment, R 1a is alkylene, wherein the alkylene further comprises R 3 4, 5, or 6 forming a 1-membered heterocyclyl; and R 1b is alkyl; R 2 is an amino acid side chain; R 3 is R 1a is an alkylene further attached to form said 4-, 5-, or 6-membered heterocyclyl; D* is acyl; and n is 0. In another embodiment, R 1a is an alkylene wherein the alkylene further comprises R 3 4-, 5-, or 6-membered heterocyclyl and R 1b is alkoxyl; R 2 is an amino acid side chain; R 3 is R 1a Nisara is an alkylene which is attached to said 4-, 5-, or 6-membered heterocyclyl; D* is an acyl and n is 0. In another embodiment, R 1a is alkylene, where The alkylene further comprises R 3 to form a 4-, 5-, or 6-membered heterocyclyl; and R 1 b is alkenyl; R 2 is an amino acid side chain; R 3 is R 1a Further bind to the 4, 5, or alkylene forming a 6-membered heterocyclyl; D* is acyl; and n is 0. In any of the embodiments of this paragraph, R 4 is hydrogen. In any of the embodiments, R 4 is alkyl.

[0079] In another embodiment, R 1a is alkylene, wherein the alkylene is further , R 3 to form a 4-, 5-, or 6-membered heterocyclyl; and R 1b is alkynyl; R 2 is an amino acid side chain; R 3 is R 1a further linked to said 4, 5, or 6 membered heterocyclyl D* is an alkylene group forming a ring; D* is acyl; and n is 0. Hey, R 1a is alkylene, wherein the alkylene further comprises R 3 4, which is bonded to forming a 5- or 6-membered heterocyclyl; and R 1b is aryl; R 2 is the amino acid side chain ;R 3 is R 1ato form said 4-, 5-, or 6-membered heterocyclyl. D* is acyl; and n is 0. In another embodiment, R 1a A alkylene, wherein the alkylene is further selected from the group consisting of R 3 4, 5, or 6-membered heterocyclic and R 1b is arylalkyl; R 2 is an amino acid side chain; R 3 is R 1a is an alkylene further attached to form said 4-, 5-, or 6-membered heterocyclyl; D* is acyl; and n is 0. In another embodiment, R 1a is an alkylene wherein the alkylene further comprises R 3 4-, 5-, or 6-membered heterocyclyl and R 1b is heteroaryl; R 2 is an amino acid side chain; R 3 is R 1a Nisa and D* is an alkylene which is bonded to said 4-, 5-, or 6-membered heterocyclyl; and n is 0. In another embodiment, R 1a is hydrogen and R 1b teeth, Hydrogen; R 2 is hydrogen; R 3 is hydrogen; D* is a residue of a biologically active compound; In another embodiment, R 1a is hydrogen and R 1b is an alkyl R 2 is hydrogen; R 3 is hydrogen; D* is a residue of a biologically active compound; and n is 0 In another embodiment, R 1a is hydrogen and R1b is alkoxy; R 2 is hydrogen; R 3 is hydrogen; D* is a residue of a biologically active compound; and n is 0. In another embodiment, R 1a is hydrogen and R 1b is alkenyl; R 2 teeth, Hydrogen; R 3 is hydrogen; D* is a residue of a biologically active compound; and n is 0. In another embodiment, R 1a is hydrogen and R 1b is alkynyl; R 2 is hydrogen ;R 3 is hydrogen; D* is a residue of a biologically active compound; and n is 0. In an embodiment, R 1a is hydrogen and R 1b is aryl; R 2 is hydrogen; R 3 is hydrogen; D* is a residue of a biologically active compound; and n is 0. In R 1a is hydrogen and R 1b is arylalkyl; R 2 is hydrogen; R 3 is hydrogen; D* is a residue of a biologically active compound; and n is 0. In R 1a is hydrogen and R 1b is heteroaryl; R 2 is hydrogen; R 3 is hydrogen; D* is a residue of a biologically active compound; and n is 0. Hey, R 1a is alkylene, wherein the alkylene further comprises R 3 4, which is bonded to forming a 5- or 6-membered heterocyclyl; and R 1b is hydrogen; R 2 is hydrogen; R 3 teeth, D* is a residue of a biologically active compound; and n is 0. R 1a is alkylene, wherein the alkylene further comprises R 3 4, 5, or a 6-membered heterocyclyl; and R 1b is alkyl; R 2 is hydrogen; R 3 teeth D* is a residue of a biologically active compound; and n is 0. In any of the embodiments, R 4 is hydrogen. In any of the embodiments of this paragraph, And R 4 is alkyl.

[0080] In another embodiment, R 1a is alkylene, wherein the alkylene is further , R 3 to form a 4-, 5-, or 6-membered heterocyclyl; and R 1b is an alkoxyl R 2 is hydrogen; R 3 is hydrogen; D* is a residue of a biologically active compound; and n is 0 In another embodiment, R 1a is alkylene, where the alkylene is In addition, R 3 to form a 4-, 5-, or 6-membered heterocyclyl; and R 1b is alkenyl ;R 2 is hydrogen; R 3 is hydrogen; D* is a residue of a biologically active compound; and n is 0. In another embodiment, R 1ais alkylene, where Ng further added that 3 to form a 4-, 5-, or 6-membered heterocyclyl; and R 1b Is, Alki Nil;R 2 is hydrogen; R 3 is hydrogen; D* is a residue of a biologically active compound; In another embodiment, R 1a is alkylene, Killen further added that 3 to form a 4-, 5-, or 6-membered heterocyclyl; and R 1b A Reel;R 2 is hydrogen; R 3 is hydrogen; D* is a residue of a biologically active compound; and n is 0. In another embodiment, R 1a is alkylene, Rukyren further added, 3 to form a 4-, 5-, or 6-membered heterocyclyl; and R 1b teeth, Arylalkyl; R 2 is hydrogen; R 3 is hydrogen; D* is the residue; and n is 0. In another embodiment, R 1a is alkylene, wherein the alkylene further comprises R 3 to form a 4-, 5-, or 6-membered heterocyclyl; R 1b is heteroaryl; R 2 is hydrogen; R 3 is hydrogen; D* is bioactive and n is 0. In another embodiment, R 1a is hydrogen, and R 1b is hydrogen; R 2 is an amino acid side chain; R3 is hydrogen; D* is a biologically active compound and n is 0. In another embodiment, R 1a is hydrogen and R 1b is alkyl; R 2 is an amino acid side chain; R 3 is hydrogen; D* is a bioactive compound and n is 0. In another embodiment, R 1a is hydrogen and R 1 b is alkoxy; R 2 is an amino acid side chain; R 3 is hydrogen; D* is bioactive and n is 0. In another embodiment, R 1a is hydrogen, and R 1b is alkenyl; R 2 is an amino acid side chain; R 3 is hydrogen; D* is bioactive and n is 0. In another embodiment, R 1a is hydrogen, R 1b is alkynyl; R 2 is an amino acid side chain; R 3 is hydrogen; D* is a physiological and n is 0. In another embodiment, R 1a is hydrogen, And R 1b is aryl; R 2 is an amino acid side chain; R 3 is hydrogen; D* is a physiological and n is 0. In another embodiment, R 1a is hydrogen, And R 1b is arylalkyl; R 2 is an amino acid side chain; R 3is hydrogen; D* is , a residue of a biologically active compound; and n is 0. In another embodiment, R 1a is hydrogen and R 1b is heteroaryl; R 2 is an amino acid side chain; R 3 is hydrogen D* is a residue of a biologically active compound; and n is 0. In either case, R 4 is hydrogen. In any of the embodiments of this paragraph, R 4 teeth , alkyl.

[0081] In another embodiment, R 1a is alkylene, wherein the alkylene is further , R 3 to form a 4-, 5-, or 6-membered heterocyclyl; and R 1b is hydrogen; R 2 teeth, is an amino acid side chain; R 3 is hydrogen; D* is a residue of a biologically active compound; and n is 0 In another embodiment, R 1a is alkylene, where the alkylene is In addition, R 3 to form a 4-, 5-, or 6-membered heterocyclyl; and R 1b is an alkyl Yes;R 2 is an amino acid side chain; R 3 is hydrogen; D* is a residue of a biologically active compound; and n is 0. In another embodiment, R 1a is alkylene, Lukiren further added, 3 to form a 4-, 5-, or 6-membered heterocyclyl; and R 1b teeth, Alkoxyl; R 2is an amino acid side chain; R 3 is hydrogen; D* is a bioactive compound and n is 0. In another embodiment, R 1a is an alkylene; wherein the alkylene further comprises R 3 to form a 4-, 5-, or 6-membered heterocyclyl S; and R 1b is alkenyl; R 2 is an amino acid side chain; R 3 is hydrogen; D* is is a residue of a biologically active compound; and n is 0. In another embodiment, R 1a Is, Alki wherein the alkylene further comprises R 3 4, 5, or 6-membered heterocyclic Forms krill; and R 1b is alkynyl; R 2 is an amino acid side chain; R 3 is hydrogen D* is a residue of a biologically active compound; and n is 0. 1 a is alkylene, wherein the alkylene further comprises R 3 4, 5, or 6-membered bond and R 1b is aryl; R 2 is an amino acid side chain; R 3 teeth D* is a residue of a biologically active compound; and n is 0. And R 1a is alkylene, wherein the alkylene further comprises R 3 4, 5 or a 6-membered heterocyclyl; and R 1b is arylalkyl; R 2 Amino R is an acid side chain; 3is hydrogen; D* is a residue of a biologically active compound; and n is 0. In another embodiment, R 1a is alkylene, wherein the alkylene is further , R 3 to form a 4-, 5-, or 6-membered heterocyclyl; and R 1b is a heteroaryl Yes;R 2 is an amino acid side chain; R 3 is hydrogen; D* is a residue of a biologically active compound; and n is 0. In another embodiment, R 1a is hydrogen and R 1b is hydrogen ;R 2 is hydrogen; R 3 is alkyl; D* is a residue of a biologically active compound; and n is , 0. In another embodiment, R 1a is hydrogen and R 1b is alkyl; R 2 is hydrogen; R 3 is alkyl; D* is a residue of a biologically active compound; and n is 0 In another embodiment, R 1a is hydrogen and R 1b is alkoxy; R 2 is hydrogen; R 3 is alkyl; D* is a residue of a biologically active compound; and n is 0 In another embodiment, R 1a is hydrogen and R 1b is alkenyl; R 2 is hydrogen; R 3 is alkyl; D* is a residue of a biologically active compound; and n is 0 In another embodiment, R 1a is hydrogen and R 1b is alkynyl; R 2 is hydrogen; R 3 is alkyl; D* is a residue of a biologically active compound; and n is 0 In another embodiment, R 1a is hydrogen and R 1b is aryl; R 2 teeth , hydrogen; R 3 is alkyl; D* is a residue of a biologically active compound; and n is 0. In any of the embodiments of this paragraph, R 4 is hydrogen. In any of the embodiments, R 4 is alkyl.

[0082] In another embodiment, R 1a is hydrogen and R 1b is arylalkyl; R 2 is hydrogen; R 3 is alkyl; D* is a residue of a biologically active compound; and n is 0 In another embodiment, R 1a is hydrogen and R 1b is a heteroaryl ;R 2 is hydrogen; R 3 is alkyl; D* is a residue of a biologically active compound; and n is , 0. In another embodiment, R 1a is alkylene, where Furthermore, R 3 to form a 4-, 5-, or 6-membered heterocyclyl; and R 1b is hydrogen R 2 is hydrogen; R 3 is alkyl; D* is a residue of a biologically active compound; and n is 0. In another embodiment, R 1a is alkylene, where Ng further added that 3 to form a 4-, 5-, or 6-membered heterocyclyl; and R 1b Is, Alki R 2 is hydrogen; R 3 is alkyl; D* is a residue of a biologically active compound; and n is 0. In another embodiment, R 1a is alkylene, Rukyren further added, 3 to form a 4-, 5-, or 6-membered heterocyclyl; and R 1b teeth, Alkoxyl; R 2 is hydrogen; R 3 is an alkyl group; D* is a group of the biologically active compound residue; and n is 0. In another embodiment, R 1a is alkylene, wherein the alkylene further comprises R 3 to form a 4-, 5-, or 6-membered heterocyclyl; R 1b is alkenyl; R 2 is hydrogen; R 3 is alkyl; D* is bioactive and n is 0. In another embodiment, R 1a is an alkylene wherein the alkylene further comprises R 3 to form a 4-, 5-, or 6-membered heterocyclyl And R 1b is alkynyl; R 2 is hydrogen; R 3 is alkyl; D* is and n is 0. In another embodiment, R 1a Alkire wherein the alkylene further comprises R 3 4-, 5-, or 6-membered heterocyclic R 1bis aryl; R 2 is hydrogen; R 3 is alkyl; D* is a residue of a biologically active compound; and n is 0. In another embodiment, R 1a A alkylene, wherein the alkylene is further selected from the group consisting of R 3 4, 5, or 6-membered heterocyclic and R 1b is arylalkyl; R 2 is hydrogen; R 3 Is, Al D* is a residue of a biologically active compound; and n is 0. R 1a is alkylene, wherein the alkylene further comprises R 3 4, 5, or a 6-membered heterocyclyl; and R 1b is heteroaryl; R 2 is hydrogen ;R 3 is alkyl; D* is a residue of a biologically active compound; and n is 0. In the embodiment, R 1a is hydrogen and R 1b is hydrogen; R 2 is an amino acid side chain R 3 is alkyl; D* is a residue of a biologically active compound; and n is 0. In an embodiment, R 1a is hydrogen and R 1b is alkyl; R 2 On the amino acid side Chain;R 3 is alkyl; D* is a residue of a biologically active compound; and n is 0. In another embodiment, R 1a is hydrogen and R 1b is alkoxy; R 2 A R 3 is alkyl; D* is a residue of a biologically active compound; and n is 0. In another embodiment, R 1a is hydrogen and R 1b is alkenyl; R 2 is an amino acid side chain; R 3 is an alkyl; D* is a residue of a biologically active compound; and n is 0. In any of the embodiments of this paragraph, R 4 is hydrogen. In any of the embodiments of the invention, R 4 is alkyl.

[0083] In another embodiment, R 1a is hydrogen and R 1b is alkynyl; R 2 A R 3 is alkyl; D* is a residue of a biologically active compound; and n is 0. In another embodiment, R 1a is hydrogen and R 1b is aryl; R 2 teeth , an amino acid side chain; R 3 is alkyl; D* is a residue of a biologically active compound; and n is 0. In another embodiment, R 1a is hydrogen and R 1b is an aryl alkyl group. R 2 is an amino acid side chain; R 3 is alkyl; D* is the residue of a biologically active compound. group; and n is 0. In another embodiment, R 1a is hydrogen and R 1b teeth, Heteroaryl; R 2 is an amino acid side chain; R 3is alkyl; D* is a bioactive and n is 0. In another embodiment, R 1a is an alkylene wherein the alkylene further comprises R 3 4-, 5-, or 6-membered heterocyclyl and R 1b is hydrogen; R 2 is an amino acid side chain; R 3 is alkyl; D* is a residue of a biologically active compound; and n is 0. In another embodiment, R 1a A alkylene, wherein the alkylene is further selected from the group consisting of R 3 4, 5, or 6-membered heterocyclic and R 1b is alkyl; R 2 is an amino acid side chain; R 3 Is, Al D* is a residue of a biologically active compound; and n is 0. R 1a is alkylene, wherein the alkylene further comprises R 3 4, 5, or a 6-membered heterocyclyl; and R 1b is alkoxyl; R 2 is the amino acid side chain ;R 3 is alkyl; D* is a residue of a biologically active compound; and n is 0. In another embodiment, R 1a is alkylene, wherein the alkylene further comprises R 3 to form a 4-, 5-, or 6-membered heterocyclyl; and R 1b is alkenyl; R 2 is an amino acid side chain; R 3 is an alkyl; D* is a residue of a biologically active compound; In another embodiment, R 1a is alkylene, Killen further added that 3 to form a 4-, 5-, or 6-membered heterocyclyl; and R 1b A R is alkynyl; 2 is an amino acid side chain; R 3 is an alkyl group; D* is a bioactive group and n is 0. In another embodiment, R 1a is alkylene; wherein the alkylene further comprises R 3 to form a 4-, 5-, or 6-membered heterocyclyl S; and R 1b is aryl; R 2 is an amino acid side chain; R 3 is alkyl; D* is , a residue of a biologically active compound; and n is 0. In another embodiment, R 1a Is, Al alkylene, wherein the alkylene further comprises R 3 4, 5, or 6 membered heterocyclic Forming a cyclyl; and R 1b is arylalkyl; R 2 is an amino acid side chain; R 3 teeth , alkyl; D* is a residue of a biologically active compound; and n is 0. In R 1a is alkylene, wherein the alkylene further comprises R 3 4 , 5, or 6 membered heterocyclyl; and R 1b is heteroaryl; R 2 Ami R is an acid side chain; 3 is alkyl; D* is a residue of a biologically active compound; and n is 0 In another embodiment, R 1ais alkylene, where the alkylene is In addition, R 3 to form a 4-, 5-, or 6-membered heterocyclyl; and R 1b is hydrogen; R 2 is hydrogen; R 3 is R 1a further attached to form said 4-, 5-, or 6-membered heterocyclyl D* is a residue of a biologically active compound; and n is 0. In any of the above embodiments, R 4 is hydrogen. In either case, R 4 is alkyl.

[0084] In another embodiment, R 1a is alkylene, wherein the alkylene is further , R 3 to form a 4-, 5-, or 6-membered heterocyclyl; and R 1b is alkyl; R 2 is hydrogen; R 3 is R 1a to form said 4-, 5-, or 6-membered heterocyclyl. D* is a residue of a biologically active compound; and n is 0. In this regard, R 1a is alkylene, wherein the alkylene further comprises R 3 Binds to forming a 4-, 5-, or 6-membered heterocyclyl; and R 1b is alkoxyl; R 2 is hydrogen ;R 3 is R 1a to form said 4-, 5-, or 6-membered heterocyclyl. D* is a residue of a biologically active compound; and n is 0. R1a is alkylene, wherein the alkylene further comprises R 3 4, 5, or a 6-membered heterocyclyl; and R 1b is alkenyl; R 2 is hydrogen; R 3 is R 1a is an alkylene further attached to form said 4-, 5-, or 6-membered heterocyclyl; D* is a residue of a biologically active compound; and n is 0. In another embodiment, R 1a teeth , alkylene, wherein the alkylene is further selected from the group consisting of R 3 4, 5, or 6-membered forming a heterocyclyl; and R 1b is alkynyl; R 2 is hydrogen; R 3 is R 1a To is an alkylene which further binds to form said 4-, 5-, or 6-membered heterocyclyl; D* is and n is 0. In another embodiment, R 1a Alkire wherein the alkylene further comprises R 3 4-, 5-, or 6-membered heterocyclic R 1b is aryl; R 2 is hydrogen; R 3 is R 1a Further binding to D* is an alkylene which forms said 4-, 5-, or 6-membered heterocyclyl; and n is 0. In another embodiment, R 1a is alkylene, wherein the alkylene further comprises R 3 to form a 4-, 5-, or 6-membered heterocyclyl; And R 1b is arylalkyl; R2 is hydrogen; R 3 is R 1a Further binding to the 4 D* is an alkylene group forming a 5-, 5-, or 6-membered heterocyclyl; D* is the residue of a biologically active compound. group; and n is 0. In another embodiment, R 1a is alkylene, The alkylene further comprises R 3 to form a 4-, 5-, or 6-membered heterocyclyl; and R 1b is heteroaryl; R 2 is hydrogen; R 3 is R 1a Further bind to the 4, 5, or is an alkylene that forms a six-membered heterocyclyl; D* is a residue of a biologically active compound; and n is 0. In another embodiment, R 1a is alkylene, Rukyren further added, 3 to form a 4-, 5-, or 6-membered heterocyclyl; and R 1b teeth, Hydrogen; R 2 is an amino acid side chain; R 3 is R 1a further linked to said 4, 5, or 6 membered hydroxyl group is an alkylene that forms a terecyclyl; D* is a residue of a biologically active compound; and n is , 0. In another embodiment, R 1a is alkylene, where Furthermore, R 3 to form a 4-, 5-, or 6-membered heterocyclyl; and R 1b is an alkyl ;R 2 is an amino acid side chain; R 3 is R 1a further linked to said 4, 5, or 6 membered heterocyclic is an alkylene that forms a cyclyl; D* is a residue of a biologically active compound; and n is 0. In another embodiment, R 1a is alkylene, wherein the alkylene is Furthermore, R 3 to form a 4-, 5-, or 6-membered heterocyclyl; and R 1b is alkoxyl ;R 2 is an amino acid side chain; R 3 is R 1a further linked to said 4, 5, or 6 membered heterocyclic is an alkylene that forms a cyclyl; D* is a residue of a biologically active compound; and n is 0. In any of the embodiments of this paragraph, R 4 is hydrogen. In any of the embodiments, R 4 is alkyl.

[0085] In another embodiment, R 1a is alkylene, wherein the alkylene is further , R 3 to form a 4-, 5-, or 6-membered heterocyclyl; and R 1b is alkenyl; R 2 is an amino acid side chain; R 3 is R 1a further linked to said 4, 5, or 6 membered heterocyclyl D* is an alkylene group forming a ring; D* is a residue of a biologically active compound; and n is 0. In another embodiment, R 1a is alkylene, wherein the alkylene further comprises R 3 to form a 4-, 5-, or 6-membered heterocyclyl; and R 1b is alkynyl; R 2 is an amino acid side chain; R 3 is R 1afurther bound to said 4-, 5-, or 6-membered heterocyclyl D* is a residue of a biologically active compound; and n is 0. In an embodiment of the invention, R 1a is alkylene, wherein the alkylene further comprises R 3 to form a 4-, 5-, or 6-membered heterocyclyl; and R 1b is aryl; R 2 teeth, is an amino acid side chain; R 3 is R 1a to form the 4-, 5-, or 6-membered heterocyclyl. D* is a residue of a biologically active compound; and n is 0. In the embodiment, R 1a is alkylene, wherein the alkylene further comprises R 3 In conclusion combine with R to form a 4-, 5-, or 6-membered heterocyclyl; and R 1b is arylalkyl; R 2 is an amino acid side chain; R 3 is R 1a further bound to said 4-, 5-, or 6-membered heterocyclyl D* is a residue of a biologically active compound; and n is 0. In an embodiment of the invention, R 1a is alkylene, wherein the alkylene further comprises R 3 to form a 4-, 5-, or 6-membered heterocyclyl; and R 1b is heteroaryl; R 2 is an amino acid side chain; R 3 is R 1a further linked to said 4, 5, or 6 membered heterocyclyl D* is an alkylene group forming a ring; D* is a residue of a biologically active compound; and n is 0. In any of the embodiments of this paragraph, R4 is hydrogen. In any of the above cases, R 4 is alkyl.

[0086] In another embodiment, R 1a is hydrogen and R 1b is hydrogen; R 2 is hydrogen R 3 is hydrogen; D* is hydrogen; and n is 1. In another embodiment, R 1a is hydrogen and R 1b is alkyl; R 2 is hydrogen; R 3 is hydrogen; D* is , hydrogen; and n is 1. In another embodiment, R 1a is hydrogen and R 1b is alkoxy; R 2 is hydrogen; R 3 is hydrogen; D* is hydrogen; and n is , 1. In another embodiment, R 1a is hydrogen and R 1b is alkenyl; R 2 is hydrogen; R 3 is hydrogen; D* is hydrogen; and n is 1. In this regard, R 1a is hydrogen and R 1b is alkynyl; R 2 is hydrogen; R 3 teeth D* is hydrogen; and n is 1. In another embodiment, R 1a Water Prime and R 1b is aryl; R 2 is hydrogen; R 3 is hydrogen; D* is hydrogen and n is 1. In another embodiment, R1a is hydrogen and R 1b A R is aryl alkyl; 2 is hydrogen; R 3 is hydrogen; D* is hydrogen; and n is , 1. In another embodiment, R 1a is hydrogen and R 1b is a heteroaryl Yes;R 2 is hydrogen; R 3 is hydrogen; D* is hydrogen; and n is 1. In the embodiment, R 1a is alkylene, wherein the alkylene further comprises R 3 In conclusion combine with R to form a 4-, 5-, or 6-membered heterocyclyl; and R 1b is hydrogen; R 2 is hydrogen R 3 is hydrogen; D* is hydrogen; and n is 1. In another embodiment, R 1a is alkylene, wherein the alkylene further comprises R 3 4, 5, or 6-membered bond and R 1b is alkyl; R 2 is hydrogen; R 3 is hydrogen D* is hydrogen; and n is 1. In another embodiment, R 1a is an alkylene wherein the alkylene further comprises R 3 4, 5, or 6-membered heterocyclyl and R 1b is alkoxyl; R 2 is hydrogen; R 3 is hydrogen; D* is , hydrogen; and n is 1. In another embodiment, R 1a is alkylene, wherein the alkylene further comprises R 3 to form a 4-, 5-, or 6-membered heterocyclyl; And R 1b is alkenyl; R 2 is hydrogen; R 3 is hydrogen; D* is hydrogen; and n is 1. In another embodiment, R 1a is alkylene, Lukiren further added, 3 to form a 4-, 5-, or 6-membered heterocyclyl; and R 1b teeth, Alkynyl; R 2 is hydrogen; R 3 is hydrogen; D* is hydrogen; and n is 1 In another embodiment, R 1a is alkylene, wherein the alkylene is Furthermore, R 3 to form a 4-, 5-, or 6-membered heterocyclyl; and R 1b is an aryl R 2 is hydrogen; R 3 is hydrogen; D* is hydrogen; and n is 1. In an embodiment, R 1a is alkylene, wherein the alkylene further comprises R 3 Combined to to form a 4-, 5-, or 6-membered heterocyclyl; and R 1b is arylalkyl; R 2 teeth , hydrogen; R 3 is hydrogen; D* is hydrogen; and n is 1. Hey, R 1a is alkylene, wherein the alkylene further comprises R 3 4, which is bonded to forming a 5- or 6-membered heterocyclyl; and R 1b is heteroaryl; R 2 is hydrogen Yes;R 3 is hydrogen; D* is hydrogen; and n is 1. In another embodiment, R 1a is hydrogen and R 1b is hydrogen; R 2 is an amino acid side chain; R 3 is hydrogen D* is hydrogen; and n is 1. In another embodiment, R 1a is hydrogen, And R 1b is alkyl; R 2 is an amino acid side chain; R 3 is hydrogen; D* is hydrogen and n is 1. In another embodiment, R 1a is hydrogen and R 1b Is, Al Cox;R 2 is an amino acid side chain; R 3 is hydrogen; D* is hydrogen; and n is , 1. In another embodiment, R 1a is hydrogen and R 1b is alkenyl; R 2 is an amino acid side chain; R 3 is hydrogen; D* is hydrogen; and n is 1. In an embodiment of the invention, R 1a is hydrogen and R 1b is alkynyl; R 2 Amino R is an acid side chain; 3 is hydrogen; D* is hydrogen; and n is 1. Hey, R 1a is hydrogen and R 1b is aryl; R 2 is an amino acid side chain; R 3 is hydrogen; D* is hydrogen; and n is 1. In another embodiment, R 1a teeth, Hydrogen and R 1b is arylalkyl; R 2 is an amino acid side chain; R 3 Water D* is hydrogen; and n is 1. In another embodiment, R 1a is hydrogen Yes and R 1b is heteroaryl; R 2 is an amino acid side chain; R 3 is hydrogen; D* is hydrogen; and n is 1. In another embodiment, R 1a is an alkylene wherein the alkylene further comprises R 3 to form a 4-, 5-, or 6-membered heterocyclyl And R 1b is hydrogen; R 2 is an amino acid side chain; R 3 is hydrogen; D* is hydrogen and n is 1. In another embodiment, R 1a is alkylene, where The alkylene further comprises R 3 to form a 4-, 5-, or 6-membered heterocyclyl; and R 1 b is alkyl; R 2 is an amino acid side chain; R 3 is hydrogen; D* is hydrogen; and n is 1. In any of the embodiments of this paragraph, R 4 is hydrogen. In any of the embodiments of paragraph R 4 is alkyl.

[0087] In another embodiment, R 1a is alkylene, wherein the alkylene is further , R 3 to form a 4-, 5-, or 6-membered heterocyclyl; and R 1bis an alkoxyl R 2 is an amino acid side chain; R 3 is hydrogen; D* is hydrogen; and n is 1. In another embodiment, R 1a is alkylene, wherein the alkylene further comprises R 3 to form a 4-, 5-, or 6-membered heterocyclyl; and R 1b is alkenyl; R 2 is an amino acid side chain; R 3 is hydrogen; D* is hydrogen; and n is 1. In an embodiment, R 1a is alkylene, wherein the alkylene further comprises R 3 To linked to form a 4-, 5-, or 6-membered heterocyclyl; and R 1b is alkynyl; R 2 teeth, is an amino acid side chain; R 3 is hydrogen; D* is hydrogen; and n is 1. In an embodiment, R 1a is alkylene, wherein the alkylene further comprises R 3 Combined to to form a 4-, 5-, or 6-membered heterocyclyl; and R 1b is aryl; R 2 Amino R is an acid side chain; 3 is hydrogen; D* is hydrogen; and n is 1. Hey, R 1a is alkylene, wherein the alkylene further comprises R 3 4, which is bonded to forming a 5- or 6-membered heterocyclyl; and R 1b is arylalkyl; R 2 Ami R is an acid side chain; 3is hydrogen; D* is hydrogen; and n is 1. In R 1a is alkylene, wherein the alkylene further comprises R 3 4 , 5, or 6 membered heterocyclyl; and R 1b is heteroaryl; R 2 Ami R is an acid side chain; 3 is hydrogen; D* is hydrogen; and n is 1. In R 1a is hydrogen and R 1b is hydrogen; R 2 is hydrogen; R 3 Is, Alki D* is hydrogen; and n is 1. In another embodiment, R 1a is hydrogen Yes and R 1b is alkyl; R 2 is hydrogen; R 3 is alkyl; D* is hydrogen and n is 1. In another embodiment, R 1a is hydrogen and R 1b A R is alkoxy; 2 is hydrogen; R 3 is alkyl; D* is hydrogen; and n is 1 In another embodiment, R 1a is hydrogen and R 1b is alkenyl; R 2 is hydrogen; R 3 is alkyl; D* is hydrogen; and n is 1. In an embodiment, R 1a is hydrogen and R 1b is alkynyl; R 2 is hydrogen; R 3 is alkyl; D* is hydrogen; and n is 1. In another embodiment, R 1a is hydrogen and R 1b is aryl; R 2 is hydrogen; R 3 is alkyl; D* is hydrogen; and n is 1. In another embodiment, R 1a is hydrogen, and R 1b is arylalkyl; R 2 is hydrogen; R 3 is alkyl; D* is hydrogen and n is 1. In another embodiment, R 1a is hydrogen and R 1b Ha, Hete R is an aryl; 2 is hydrogen; R 3 is alkyl; D* is hydrogen; and n is , 1. In another embodiment, R 1a is alkylene, where Furthermore, R 3 to form a 4-, 5-, or 6-membered heterocyclyl; and R 1b is hydrogen R 2 is hydrogen; R 3 is alkyl; D* is hydrogen; and n is 1. In an embodiment, R 1a is alkylene, wherein the alkylene further comprises R 3 To linked to form a 4-, 5-, or 6-membered heterocyclyl; and R 1b is alkyl; R 2 Water R 3 is alkyl; D* is hydrogen; and n is 1. Hey, R 1a is alkylene, wherein the alkylene further comprises R 34, which is bonded to forming a 5- or 6-membered heterocyclyl; and R 1b is alkoxyl; R 2 is hydrogen R 3 is alkyl; D* is hydrogen; and n is 1. , R 1a is alkylene, wherein the alkylene further comprises R 3 4, 5, or forms a six-membered heterocyclyl; and R 1b is alkenyl; R 2 is hydrogen; R 3 teeth , alkyl; D* is hydrogen; and n is 1. In another embodiment, R 1a teeth , alkylene, wherein the alkylene is further selected from the group consisting of R 3 4, 5, or 6-membered forming a heterocyclyl; and R 1b is alkynyl; R 2 is hydrogen; R 3 Is, Alki D* is hydrogen; and n is 1. In any of the embodiments of this paragraph, And R 4 is hydrogen. In any of the embodiments of this paragraph, R 4 is an alkyl It is.

[0088] In another embodiment, R 1a is alkylene, wherein the alkylene is further , R 3 to form a 4-, 5-, or 6-membered heterocyclyl; and R 1b is aryl; R 2 is hydrogen; R 3 is alkyl; D* is hydrogen; and n is 1. In an embodiment, R 1ais alkylene, wherein the alkylene further comprises R 3 Combined to to form a 4-, 5-, or 6-membered heterocyclyl; and R 1b is arylalkyl; R 2 teeth , hydrogen; R 3 is alkyl; D* is hydrogen; and n is 1. In this regard, R 1a is alkylene, wherein the alkylene further comprises R 3 Binds to forming a 4-, 5-, or 6-membered heterocyclyl; and R 1b is heteroaryl; R 2 Water R 3 is alkyl; D* is hydrogen; and n is 1. Hey, R 1a is hydrogen and R 1b is hydrogen; R 2 is an amino acid side chain; R 3 teeth, D* is hydrogen; and n is 1. In another embodiment, R 1a teeth, Hydrogen and R 1b is alkyl; R 2 is an amino acid side chain; R 3 is an alkyl D* is hydrogen; and n is 1. In another embodiment, R 1a is hydrogen , and R 1b is alkoxy; R 2 is an amino acid side chain; R 3 is alkyl; D* is , hydrogen; and n is 1. In another embodiment, R 1a is hydrogen and R 1b is alkenyl; R 2 is an amino acid side chain; R 3is alkyl; D* is hydrogen and n is 1. In another embodiment, R 1a is hydrogen and R 1b Is, Al quinyl;R 2 is an amino acid side chain; R 3 is alkyl; D* is hydrogen; and n is 1. In another embodiment, R 1a is hydrogen and R 1b is an aryl ;R 2 is an amino acid side chain; R 3 is alkyl; D* is hydrogen; and n is 1. In another embodiment, R 1a is hydrogen and R 1b is arylalkyl; R 2 is an amino acid side chain; R 3 is alkyl; D* is hydrogen; and n is 1. In another embodiment, R 1a is hydrogen and R 1b is heteroaryl; R 2 teeth, is an amino acid side chain; R 3 is alkyl; D* is hydrogen; and n is 1. In an embodiment, R 1a is alkylene, wherein the alkylene further comprises R 3 To joined to form a 4-, 5-, or 6-membered heterocyclyl; and R 1b is hydrogen; R 2 Amino R is an acid side chain; 3 is alkyl; D* is hydrogen; and n is 1. In this regard, R 1a is alkylene, wherein the alkylene further comprises R 3 Binds to forming a 4-, 5-, or 6-membered heterocyclyl; and R 1b is alkyl; R 2 is an amino acid Side chain; R 3 is alkyl; D* is hydrogen; and n is 1. In R 1a is alkylene, wherein the alkylene further comprises R 3 4 , 5, or 6 membered heterocyclyl; and R 1b is alkoxyl; R 2 Amino R is an acid side chain; 3 is alkyl; D* is hydrogen; and n is 1. In this regard, R 1a is alkylene, wherein the alkylene further comprises R 3 Binds to forming a 4-, 5-, or 6-membered heterocyclyl; and R 1b is alkenyl; R 2 Amino R is an acid side chain; 3 is alkyl; D* is hydrogen; and n is 1. In this regard, R 1a is alkylene, wherein the alkylene further comprises R 3 Binds to forming a 4-, 5-, or 6-membered heterocyclyl; and R 1b is alkynyl; R 2 Amino R is an acid side chain; 3 is alkyl; D* is hydrogen; and n is 1. In any of the embodiments of the present invention, R 4 is hydrogen. In some cases, R 4 is alkyl.

[0089] In another embodiment, R 1ais alkylene, wherein the alkylene is further , R 3 to form a 4-, 5-, or 6-membered heterocyclyl; and R 1b is aryl; R 2 is an amino acid side chain; R 3 is alkyl; D* is hydrogen; and n is 1. In another embodiment, R 1a is alkylene, wherein the alkylene further comprises R 3 to form a 4-, 5-, or 6-membered heterocyclyl; and R 1b is an aryl alkyl R 2 is an amino acid side chain; R 3 is alkyl; D* is hydrogen; and n is 1. In another embodiment, R 1a is alkylene, wherein the alkylene is further To, R 3 to form a 4-, 5-, or 6-membered heterocyclyl; and R 1b is heteroaryl ;R 2 is an amino acid side chain; R 3 is alkyl; D* is hydrogen; and n is 1 In another embodiment, R 1a is alkylene, where the alkylene is In addition, R 3 to form a 4-, 5-, or 6-membered heterocyclyl; and R 1b is hydrogen; R 2 is hydrogen; R 3 is R 1a further attached to form said 4-, 5-, or 6-membered heterocyclyl D* is hydrogen; and n is 1. In another embodiment, R 1 ais alkylene, wherein the alkylene further comprises R 3 4, 5, or 6-membered bond and R 1b is alkyl; R 2 is hydrogen; R 3 is R 1a To is alkylene which further binds to form said 4-, 5-, or 6-membered heterocyclyl; D* is water. and n is 1. In another embodiment, R 1a is alkylene, The alkylene further comprises R 3 to form a 4-, 5-, or 6-membered heterocyclyl; and R 1b is alkoxyl; R 2 is hydrogen; R 3 is further R 1a 4, 5, or alkylene forming a 6-membered heterocyclyl; D* is hydrogen; and n is 1. In another embodiment, R 1a is alkylene, wherein the alkylene is further , R 3 to form a 4-, 5-, or 6-membered heterocyclyl; and R 1b is alkenyl; R 2 is hydrogen; R 3 is R 1a further attached to form said 4-, 5-, or 6-membered heterocyclyl D* is hydrogen; and n is 1. In another embodiment, R 1 a is alkylene, wherein the alkylene further comprises R 3 4, 5, or 6-membered bond and R 1b is alkynyl; R 2 is hydrogen; R 3 is R1a is an alkylene which further binds to said 4-, 5-, or 6-membered heterocyclyl; D* is and n is 1. In another embodiment, R 1a is alkylene, wherein the alkylene further comprises R 3 to form a 4-, 5-, or 6-membered heterocyclyl; R 1b is aryl; R 2 is hydrogen; R 3 is R 1a Further linked to the 4, 5, or 6 D* is hydrogen; and n is 1. In another embodiment, R 1a is alkylene, wherein the alkylene further comprises R 3 to form a 4-, 5-, or 6-membered heterocyclyl; and R 1b is an aryl alkyl R 2 is hydrogen; R 3 is R 1a to form the 4-, 5-, or 6-membered heterocyclyl. D* is hydrogen; and n is 1. In another embodiment, R 1a is alkylene, wherein the alkylene further comprises R 3 4, 5, or 6 forming a 1-membered heterocyclyl; and R 1b is heteroaryl; R 2 is hydrogen; R 3 teeth , R 1a is an alkylene further attached to form said 4-, 5-, or 6-membered heterocyclyl; * is hydrogen; and n is 1. In any of the embodiments of this paragraph, R 4 teeth , hydrogen. In any of the embodiments of this paragraph, R 4 is alkyl.

[0090] In another embodiment, R 1a is alkylene, wherein the alkylene is further , R 3 to form a 4-, 5-, or 6-membered heterocyclyl; and R 1b is hydrogen; R 2 teeth, is an amino acid side chain; R 3 is R 1a to form the 4-, 5-, or 6-membered heterocyclyl. D* is hydrogen; and n is 1. In another embodiment, R 1a is alkylene, wherein the alkylene further comprises R 3 4, 5, or 6 forming a 1-membered heterocyclyl; and R 1b is alkyl; R 2 is an amino acid side chain; R 3 is R 1a is an alkylene further attached to form said 4-, 5-, or 6-membered heterocyclyl; D* is hydrogen; and n is 1. In another embodiment, R 1a is an alkylene wherein the alkylene further comprises R 3 is bonded to a 4-, 5-, or 6-membered heterocyclyl Form; and R 1b is alkoxyl; R 2 is an amino acid side chain; R 3 is R 1a Furthermore are linked to form said 4-, 5-, or 6-membered heterocyclyl; D* is hydrogen. and n is 1. In another embodiment, R 1a is alkylene, The alkylene may further include R3 to form a 4-, 5-, or 6-membered heterocyclyl; and R 1b teeth , alkenyl; R 2 is an amino acid side chain; R 3 is R 1a Further bind to the 4, 5, or is alkylene forming a 6-membered heterocyclyl; D* is hydrogen; and n is 1. In another embodiment, R 1a is alkylene, wherein the alkylene is further To, R 3 to form a 4-, 5-, or 6-membered heterocyclyl; and R 1b is alkynyl R 2 is an amino acid side chain; R 3 is R 1a further linked to said 4, 5, or 6 membered heterocyclic D* is hydrogen; and n is 1. Hey, R 1a is alkylene, wherein the alkylene further comprises R 3 4, which is bonded to forming a 5- or 6-membered heterocyclyl; and R 1b is aryl; R 2 is the amino acid side chain ;R 3 is R 1a to form said 4-, 5-, or 6-membered heterocyclyl. D* is hydrogen; and n is 1. In another embodiment, R 1a Is, Al alkylene, wherein the alkylene further comprises R 3 4, 5, or 6 membered heterocyclic Forming a cyclyl; and R 1b is arylalkyl; R 2 is an amino acid side chain; R 3 teeth , R 1ais an alkylene further attached to form said 4-, 5-, or 6-membered heterocyclyl; * is hydrogen; and n is 1. In another embodiment, R 1a is an alkylene wherein the alkylene further comprises R 3 to form a 4-, 5-, or 6-membered heterocyclyl And R 1b is heteroaryl; R 2 is an amino acid side chain; R 3 is R 1a Furthermore are linked to form said 4-, 5-, or 6-membered heterocyclyl; D* is hydrogen. and n is 1. In another embodiment, R 1a is hydrogen and R 1b is hydrogen Yes;R 2 is hydrogen; R 3 is hydrogen; D* is acyl; and n is 1. In an embodiment, R 1a is hydrogen and R 1b is alkyl; R 2 is hydrogen; R 3 is hydrogen; D* is acyl; and n is 1. In another embodiment, R 1a is hydrogen and R 1b is alkoxy; R 2 is hydrogen; R 3 is hydrogen; D* is acyl; and n is 1. In another embodiment, R 1a is hydrogen, and R 1b is alkenyl; R 2 is hydrogen; R 3 is hydrogen; D* is acyl; In another embodiment, R 1a is hydrogen and R 1bis an alkynyl Yes;R 2 is hydrogen; R 3 is hydrogen; D* is acyl; and n is 1. In an embodiment, R 1a is hydrogen and R 1b is aryl; R 2 is hydrogen; R 3 is hydrogen; D* is acyl; and n is 1. In another embodiment, R 1a is hydrogen and R 1b is arylalkyl; R 2 is hydrogen; R 3 is hydrogen D* is acyl; and n is 1. In another embodiment, R 1a is hydrogen And R 1b is heteroaryl; R 2 is hydrogen; R 3 is hydrogen; D* is acyl and n is 1. In any of the embodiments of this paragraph, R 4 is hydrogen In any of the embodiments of this paragraph, R 4 is alkyl.

[0091] In another embodiment, R 1a is alkylene, wherein the alkylene is further , R 3 to form a 4-, 5-, or 6-membered heterocyclyl; and R 1b is hydrogen; R 2 teeth, Hydrogen; R 3 is hydrogen; D* is acyl; and n is 1. Hey, R 1a is alkylene, wherein the alkylene further comprises R 3 4, which is bonded to forming a 5- or 6-membered heterocyclyl; and R 1b is alkyl; R 2 is hydrogen; R 3 is hydrogen; D* is acyl; and n is 1. In another embodiment, R 1a teeth , alkylene, wherein the alkylene is further selected from the group consisting of R 3 4, 5, or 6-membered forming a heterocyclyl; and R 1b is alkoxyl; R 2 is hydrogen; R 3 is hydrogen D* is acyl; and n is 1. In another embodiment, R 1a Is, Alki wherein the alkylene further comprises R 3 4, 5, or 6-membered heterocyclic Forms krill; and R 1b is alkenyl; R 2 is hydrogen; R 3 is hydrogen; D* is acyl; and n is 1. In another embodiment, R 1a is an alkylene wherein the alkylene further comprises R 3 to form a 4-, 5-, or 6-membered heterocyclyl And R 1b is alkynyl; R 2 is hydrogen; R 3 is hydrogen; D* is acyl and n is 1. In another embodiment, R 1a is alkylene, where The alkylene further comprises R 3 to form a 4-, 5-, or 6-membered heterocyclyl; and R 1 b is aryl; R 2 is hydrogen; R 3is hydrogen; D* is acyl; and n is , 1. In another embodiment, R 1a is alkylene, where Furthermore, R 3 to form a 4-, 5-, or 6-membered heterocyclyl; and R 1b is an aryl R is alkyl; 2 is hydrogen; R 3 is hydrogen; D* is acyl; and n is 1 In another embodiment, R 1a is alkylene, wherein the alkylene is Furthermore, R 3 to form a 4-, 5-, or 6-membered heterocyclyl; and R 1b Heteroaryl R 2 is hydrogen; R 3 is hydrogen; D* is acyl; and n is 1. In another embodiment, R 1a is hydrogen and R 1b is hydrogen; R 2 On the amino acid side Chain;R 3 is hydrogen; D* is acyl; and n is 1. And R 1a is hydrogen and R 1b is alkyl; R 2 is an amino acid side chain; R 3 teeth is hydrogen; D* is acyl; and n is 1. In another embodiment, R 1a teeth, Hydrogen and R 1b is alkoxy; R 2 is an amino acid side chain; R 3 is hydrogen D* is acyl; and n is 1. In another embodiment, R 1a is hydrogen , and R 1bis alkenyl; R 2 is an amino acid side chain; R 3 is hydrogen; D* is a and n is 1. In another embodiment, R 1a is hydrogen and R 1b teeth , alkynyl; R 2 is an amino acid side chain; R 3 is hydrogen; D* is acyl; and n is 1. In another embodiment, R 1a is hydrogen and R 1b is an aryl Yes;R 2 is an amino acid side chain; R 3 is hydrogen; D* is acyl; and n is 1. In another embodiment, R 1a is hydrogen and R 1b is arylalkyl; R 2 is an amino acid side chain; R 3 is hydrogen; D* is acyl; and n is 1. In an embodiment of the invention, R 1a is hydrogen and R 1b is heteroaryl; R 2 A R 3 is hydrogen; D* is acyl; and n is 1. In any of the above embodiments, R 4 is hydrogen. In either case, R 4 is alkyl.

[0092] In another embodiment, R 1a is alkylene, wherein the alkylene is further , R 3 to form a 4-, 5-, or 6-membered heterocyclyl; and R 1b is hydrogen; R 2teeth, is an amino acid side chain; R 3 is hydrogen; D* is acyl; and n is 1. In the embodiment, R 1a is alkylene, wherein the alkylene further comprises R 3 In conclusion combine with R to form a 4-, 5-, or 6-membered heterocyclyl; and R 1b is alkyl; R 2 Ami R is an acid side chain; 3 is hydrogen; D* is acyl; and n is 1. In this regard, R 1a is alkylene, wherein the alkylene further comprises R 3 Binds to forming a 4-, 5-, or 6-membered heterocyclyl; and R 1b is alkoxyl; R 2 Ami R is an acid side chain; 3 is hydrogen; D* is acyl; and n is 1. In this regard, R 1a is alkylene, wherein the alkylene further comprises R 3 Binds to forming a 4-, 5-, or 6-membered heterocyclyl; and R 1b is alkenyl; R 2 Amino R is an acid side chain; 3 is hydrogen; D* is acyl; and n is 1. In R 1a is alkylene, wherein the alkylene further comprises R 3 4 , 5, or 6 membered heterocyclyl; and R 1b is alkynyl; R 2 is an amino acid Side chain; R 3 is hydrogen; D* is acyl; and n is 1. Hey, R1a is alkylene, wherein the alkylene further comprises R 3 4, which is bonded to forming a 5- or 6-membered heterocyclyl; and R 1b is aryl; R 2 is the amino acid side chain ;R 3 is hydrogen; D* is acyl; and n is 1. R 1a is alkylene, wherein the alkylene further comprises R 3 4, 5, or a 6-membered heterocyclyl; and R 1b is arylalkyl; R 2 is an amino acid Side chain; R 3 is hydrogen; D* is acyl; and n is 1. Hey, R 1a is alkylene, wherein the alkylene further comprises R 3 4, which is bonded to forming a 5- or 6-membered heterocyclyl; and R 1b is heteroaryl; R 2 Amino R is an acid side chain; 3 is hydrogen; D* is acyl; and n is 1. In R 1a is hydrogen and R 1b is hydrogen; R 2 is hydrogen; R 3 Is, Alki D* is acyl; and n is 1. In another embodiment, R 1a is hydrogen and R 1b is alkyl; R 2 is hydrogen; R 3 is alkyl; D* is a and n is 1. In another embodiment, R 1a is hydrogen and R1b teeth , alkoxy; R 2 is hydrogen; R 3 is alkyl; D* is acyl; and n is 1. In another embodiment, R 1a is hydrogen and R 1b is alkenyl R 2 is hydrogen; R 3 is alkyl; D* is acyl; and n is 1. In an embodiment of the invention, R 1a is hydrogen and R 1b is alkynyl; R 2 is hydrogen Yes;R 3 is alkyl; D* is acyl; and n is 1. And R 1a is hydrogen and R 1b is aryl; R 2 is hydrogen; R 3 Is, Alki D* is acyl; and n is 1. In another embodiment, R 1a is hydrogen and R 1b is arylalkyl; R 2 is hydrogen; R 3 is alkyl; D* is acyl; and n is 1. In another embodiment, R 1a is hydrogen, R 1b is heteroaryl; R 2 is hydrogen; R 3 is alkyl; D* is acyl and n is 1. In another embodiment, R 1a is alkylene, where The alkylene further comprises R 3 to form a 4-, 5-, or 6-membered heterocyclyl; and R 1 b is hydrogen; R 2 is hydrogen; R 3 is alkyl; D* is acyl; and n is , 1. In another embodiment, R 1a is alkylene, where Furthermore, R 3 to form a 4-, 5-, or 6-membered heterocyclyl; and R 1b is an alkyl ;R 2 is hydrogen; R 3 is alkyl; D* is acyl; and n is 1. In another embodiment, R 1a is alkylene, wherein the alkylene is further , R 3 to form a 4-, 5-, or 6-membered heterocyclyl; and R 1b is an alkoxyl R 2 is hydrogen; R 3 is alkyl; D* is acyl; and n is 1. In any of the embodiments of paragraph R 4 is hydrogen. In any of the above, R 4 is alkyl.

[0093] In another embodiment, R 1a is alkylene, wherein the alkylene is further , R 3 to form a 4-, 5-, or 6-membered heterocyclyl; and R 1b is alkenyl; R 2 is hydrogen; R 3 is alkyl; D* is acyl; and n is 1. In an embodiment, R 1a is alkylene, wherein the alkylene further comprises R 3 To joined to form a 4-, 5-, or 6-membered heterocyclyl; and R 1b is alkynyl; R 2 teeth, Hydrogen; R 3 is alkyl; D* is acyl; and n is 1. In this regard, R 1a is alkylene, wherein the alkylene further comprises R 3 Binds to forming a 4-, 5-, or 6-membered heterocyclyl; and R 1b is aryl; R 2 is hydrogen R 3 is alkyl; D* is acyl; and n is 1. R 1a is alkylene, wherein the alkylene further comprises R 3 4, 5, or a 6-membered heterocyclyl; and R 1b is arylalkyl; R 2 is hydrogen R 3 is alkyl; D* is acyl; and n is 1. R 1a is alkylene, wherein the alkylene further comprises R 3 4, 5, or a 6-membered heterocyclyl; and R 1b is heteroaryl; R 2 is hydrogen ;R 3 is alkyl; D* is acyl; and n is 1. , R 1a is hydrogen and R 1b is hydrogen; R 2 is an amino acid side chain; R 3 Is, Alki D* is acyl; and n is 1. In another embodiment, R 1ais hydrogen and R 1b is alkyl; R 2 is an amino acid side chain; R 3 is alkyl; D* is acyl; and n is 1. In another embodiment, R 1a is hydrogen, R 1b is alkoxy; R 2 is an amino acid side chain; R 3 is alkyl; D* is a and n is 1. In another embodiment, R 1a is hydrogen and R 1b teeth , alkenyl; R 2 is an amino acid side chain; R 3 is alkyl; D* is acyl and n is 1. In another embodiment, R 1a is hydrogen and R 1b Is, Al quinyl;R 2 is an amino acid side chain; R 3 is alkyl; D* is acyl; In another embodiment, R 1a is hydrogen and R 1b is an aryl R 2 is an amino acid side chain; R 3 is alkyl; D* is acyl; and n is 1. In another embodiment, R 1a is hydrogen and R 1b is arylalkyl ;R 2 is an amino acid side chain; R 3 is alkyl; D* is acyl; and n is 1. In another embodiment, R 1a is hydrogen and R 1b is heteroaryl; R 2 is an amino acid side chain; R 3 is alkyl; D* is acyl; and n is 1. In another embodiment, R 1a is alkylene, wherein the alkylene is further , R 3 to form a 4-, 5-, or 6-membered heterocyclyl; and R 1b is hydrogen; R 2 teeth, is an amino acid side chain; R 3 is alkyl; D* is acyl; and n is 1. In an embodiment of the invention, R 1a is alkylene, wherein the alkylene further comprises R 3 to form a 4-, 5-, or 6-membered heterocyclyl; and R 1b is alkyl; R 2 teeth, is an amino acid side chain; R 3 is alkyl; D* is acyl; and n is 1. In an embodiment of the invention, R 1a is alkylene, wherein the alkylene further comprises R 3 to form a 4-, 5-, or 6-membered heterocyclyl; and R 1b is alkoxyl; R 2 is an amino acid side chain; R 3 is alkyl; D* is acyl; and n is 1. In another embodiment, R 1a is alkylene, wherein the alkylene is further , R 3 to form a 4-, 5-, or 6-membered heterocyclyl; and R 1b is alkenyl; R 2 is an amino acid side chain; R 3 is alkyl; D* is acyl; and n is 1. In any of the embodiments of this paragraph, R 4 is hydrogen. In any of the embodiments, R 4 is alkyl.

[0094] In another embodiment, R 1a is alkylene, wherein the alkylene is further , R 3 to form a 4-, 5-, or 6-membered heterocyclyl; and R 1b is alkynyl; R 2 is an amino acid side chain; R 3 is alkyl; D* is acyl; and n is 1. In another embodiment, R 1a is alkylene, wherein the alkylene is further To, R 3 to form a 4-, 5-, or 6-membered heterocyclyl; and R 1b is aryl; R 2 is an amino acid side chain; R 3 is alkyl; D* is acyl; and n is 1. In another embodiment, R 1a is alkylene, wherein the alkylene is further To, R 3 to form a 4-, 5-, or 6-membered heterocyclyl; and R 1b is an aryl alkyl group. R 2 is an amino acid side chain; R 3 is alkyl; D* is acyl; and n is 1. In another embodiment, R 1a is alkylene, where Ng further added that 3 to form a 4-, 5-, or 6-membered heterocyclyl; and R 1b is hetero Aryl; R 2is an amino acid side chain; R 3 is alkyl; D* is acyl; and n is 1. In another embodiment, R 1a is alkylene, Lukiren further added, 3 to form a 4-, 5-, or 6-membered heterocyclyl; and R 1b teeth, Hydrogen; R 2 is hydrogen; R 3 is R 1a further linked to said 4, 5, or 6 membered heterocyclic D* is an alkylene forming an aryl; D* is acyl; and n is 1. In R 1a is alkylene, wherein the alkylene further comprises R 3 4 , 5, or 6 membered heterocyclyl; and R 1b is alkyl; R 2 is hydrogen; R 3 is R 1a which further binds to form said 4-, 5-, or 6-membered heterocyclyl. D* is acyl; and n is 1. In another embodiment, R 1a is an alkylene wherein the alkylene further comprises R 3 4, 5, or 6-membered heterocyclyl and R 1b is alkoxyl; R 2 is hydrogen; R 3 is R 1a Further binding to and D* is an alkylene group which forms the 4-, 5-, or 6-membered heterocyclyl; D* is an acyl group. and n is 1. In another embodiment, R 1a is alkylene, Lukiren further added, 3to form a 4-, 5-, or 6-membered heterocyclyl; and R 1b teeth, alkenyl; R 2 is hydrogen; R 3 is R 1a Further attached to said 4, 5, or 6 membered heterocyclic D* is an alkylene group forming a cyclocyclyl; D* is an acyl group; and n is 1. In the embodiment, R 1a is alkylene, wherein the alkylene further comprises R 3 In conclusion combine with R to form a 4-, 5-, or 6-membered heterocyclyl; and R 1b is alkynyl; R 2 Water R 3 is R 1a which further binds to form said 4-, 5-, or 6-membered heterocyclyl. D* is acyl; and n is 1. In another embodiment, R 1a teeth, alkylene, wherein the alkylene is further selected from the group consisting of R 3 4, 5, or 6-membered hexafluorophosphate Forming a tetracyclyl; and R 1b is aryl; R 2 is hydrogen; R 3 is R 1a Nisara is an alkylene which is attached to said 4-, 5-, or 6-membered heterocyclyl; D* is an acyl and n is 1. In any of the embodiments of this paragraph, R 4 is hydrogen In any of the embodiments of this paragraph, R 4 is alkyl.

[0095] In another embodiment, R 1a is alkylene, wherein the alkylene is further , R 3to form a 4-, 5-, or 6-membered heterocyclyl; and R 1b is aryl alkyl ;R 2 is hydrogen; R 3 is R 1a further bound to said 4-, 5-, or 6-membered heterocyclyl D* is an alkylene forming the formula: And R 1a is alkylene, wherein the alkylene further comprises R 3 4, 5 or a 6-membered heterocyclyl; and R 1b is heteroaryl; R 2 is hydrogen R 3 is R 1a further attached to form said 4-, 5-, or 6-membered heterocyclyl; D* is acyl; and n is 1. In another embodiment, R 1a Is, Alki wherein the alkylene further comprises R 3 4, 5, or 6-membered heterocyclic Forms krill; and R 1b is hydrogen; R 2 is an amino acid side chain; R 3 is R 1a Furthermore alkylene which are linked to form said 4-, 5-, or 6-membered heterocyclyl; D* is acyl. and n is 1. In another embodiment, R 1a is alkylene, where The alkylene may further include R 3 to form a 4-, 5-, or 6-membered heterocyclyl; and R 1b is alkyl; R 2 is an amino acid side chain; R 3 is R 1a Further bind to the 4, 5, or is alkylene forming a 6-membered heterocyclyl; D* is acyl; and n is 1. In another embodiment, R 1a is alkylene, wherein the alkylene is Furthermore, R 3 to form a 4-, 5-, or 6-membered heterocyclyl; and R 1b is alkoxyl ;R 2 is an amino acid side chain; R 3 is R 1a further linked to said 4, 5, or 6 membered heterocyclic is an alkylene forming a cyclyl; D* is acyl; and n is 1. In an embodiment, R 1a is alkylene, wherein the alkylene further comprises R 3 Combined to to form a 4-, 5-, or 6-membered heterocyclyl; and R 1b is alkenyl; R 2 Ami R is an acid side chain; 3 is R 1a to form said 4-, 5-, or 6-membered heterocyclyl. D* is acyl; and n is 1. In another embodiment, R 1 a is alkylene, wherein the alkylene further comprises R 3 4, 5, or 6-membered bond and R 1b is alkynyl; R 2 is an amino acid side chain; R 3 is R 1a is an alkylene further attached to form said 4-, 5-, or 6-membered heterocyclyl; D* is acyl; and n is 1. In another embodiment, R 1a is an alkylene wherein the alkylene further comprises R 34-, 5-, or 6-membered heterocyclyl and R 1b is aryl; R 2 is an amino acid side chain; R 3 is R 1a Further alkylene which combines with said 4-, 5-, or 6-membered heterocyclyl; D* is acyl. and n is 1. In another embodiment, R 1a is alkylene, The alkylene may further include R 3 to form a 4-, 5-, or 6-membered heterocyclyl; and R 1b teeth , arylalkyl; R 2 is an amino acid side chain; R 3 is R 1a 4, which is further bonded to is alkylene forming a 5- or 6-membered heterocyclyl; D* is acyl; and n is , 1. In another embodiment, R 1a is alkylene, where Furthermore, R 3 to form a 4-, 5-, or 6-membered heterocyclyl; and R 1b Heteroa Reel;R 2 is an amino acid side chain; R 3 is R 1a further linked to said 4, 5, or 6 membered is alkylene forming a heterocyclyl; D* is acyl; and n is 1. In an embodiment of the invention, R 1a is hydrogen and R 1b is hydrogen; R 2 is hydrogen; R 3 is hydrogen; D* is a residue of a biologically active compound; and n is 1. Hey, R 1a is hydrogen and R 1b is alkyl; R2 is hydrogen; R 3 is hydrogen D* is a residue of a biologically active compound; and n is 1. In any of the above, R 4 is hydrogen. In any of the embodiments of this paragraph, R 4 is alkyl.

[0096] In another embodiment, R 1a is hydrogen and R 1b is alkoxy; R 2 Water R 3 is hydrogen; D* is a residue of a biologically active compound; and n is 1. In an embodiment of the invention, R 1a is hydrogen and R 1b is alkenyl; R 2 is hydrogen Yes;R 3 is hydrogen; D* is a residue of a biologically active compound; and n is 1. In the embodiment, R 1a is hydrogen and R 1b is alkynyl; R 2 is hydrogen; R 3 is hydrogen; D* is a residue of a biologically active compound; and n is 1. In R 1a is hydrogen and R 1b is aryl; R 2 is hydrogen; R 3 Water D* is a residue of a biologically active compound; and n is 1. , R 1a is hydrogen and R 1b is arylalkyl; R 2 is hydrogen; R 3 Water D* is a residue of a biologically active compound; and n is 1. , R 1a is hydrogen and R 1b is heteroaryl; R 2 is hydrogen; R 3 is hydrogen D* is a residue of a biologically active compound; and n is 1. In another embodiment, R 1a is alkylene, wherein the alkylene further comprises R 3 4, 5, or 6 forming a 1-membered heterocyclyl; and R 1b is hydrogen; R 2 is hydrogen; R 3 is hydrogen D* is a residue of a biologically active compound; and n is 1. 1a is alkylene, wherein the alkylene further comprises R 3 4, 5, or 6-membered bond and R 1b is alkyl; R 2 is hydrogen; R 3 is hydrogen D* is a residue of a biologically active compound; and n is 1. In another embodiment, R 1 a is alkylene, wherein the alkylene further comprises R 3 4, 5, or 6-membered bond and R 1b is alkoxyl; R 2 is hydrogen; R 3 Water D* is a residue of a biologically active compound; and n is 1. , R 1a is alkylene, wherein the alkylene further comprises R 3 4, 5, or forms a six-membered heterocyclyl; and R 1b is alkenyl; R 2 is hydrogen; R 3 teeth is hydrogen; D* is a residue of a biologically active compound; and n is 1. And R 1a is alkylene, wherein the alkylene further comprises R 3 4, 5 or a 6-membered heterocyclyl; and R 1b is alkynyl; R 2 is hydrogen; R 3 is hydrogen; D* is a residue of a biologically active compound; and n is 1. In R 1a is alkylene, wherein the alkylene further comprises R 3 4 , 5, or 6 membered heterocyclyl; and R 1b is aryl; R 2 is hydrogen; R 3 is hydrogen; D* is a residue of a biologically active compound; and n is 1. In R 1a is alkylene, wherein the alkylene further comprises R 3 4 , 5, or 6 membered heterocyclyl; and R 1b is arylalkyl; R 2 Water R 3 is hydrogen; D* is a residue of a biologically active compound; and n is 1. In an embodiment of the invention, R 1a is alkylene, wherein the alkylene further comprises R 3 to form a 4-, 5-, or 6-membered heterocyclyl; and R 1b is heteroaryl; R 2is hydrogen; R 3 is hydrogen; D* is a residue of a biologically active compound; and n is 1 In any of the embodiments of this paragraph, R 4 is hydrogen. In any of the embodiments, R 4 is alkyl.

[0097] In another embodiment, R 1a is hydrogen and R 1b is hydrogen; R 2 is an amino acid Side chain; R 3 is hydrogen; D* is a residue of a biologically active compound; and n is 1. In another embodiment, R 1a is hydrogen and R 1b is alkyl; R 2 Amino R is an acid side chain; 3 is hydrogen; D* is a residue of a biologically active compound; and n is 1. In another embodiment, R 1a is hydrogen and R 1b is alkoxy; R 2 A R 3 is hydrogen; D* is a residue of a biologically active compound; and n is 1 In another embodiment, R 1a is hydrogen and R 1b is alkenyl; R 2 teeth , an amino acid side chain; R 3 is hydrogen; D* is a residue of a biologically active compound; and n is 1. In another embodiment, R 1a is hydrogen and R 1b is alkynyl; R 2 is an amino acid side chain; R 3 is hydrogen; D* is a residue of a biologically active compound; and n is , 1. In another embodiment, R 1a is hydrogen and R 1b is aryl; R 2 is an amino acid side chain; R 3 is hydrogen; D* is a residue of a biologically active compound; and n is , 1. In another embodiment, R 1a is hydrogen and R 1b is aryl alkyl ;R 2 is an amino acid side chain; R 3 is hydrogen; D* is the residue of a biologically active compound. and n is 1. In another embodiment, R 1a is hydrogen and R 1b is hetero Aryl; R 2 is an amino acid side chain; R 3 is hydrogen; D* is the residue; and n is 1. In another embodiment, R 1a is alkylene, wherein the alkylene further comprises R 3 to form a 4-, 5-, or 6-membered heterocyclyl; R 1b is hydrogen; R 2 is an amino acid side chain; R 3 is hydrogen; D* is a bioactive compound and n is 1. In another embodiment, R 1a is an alkylene; wherein the alkylene further comprises R 3 to form a 4-, 5-, or 6-membered heterocyclyl S; and R 1b is alkyl; R 2 is an amino acid side chain; R 3 is hydrogen; D* is and n is 1. In another embodiment, R 1aAlkire wherein the alkylene further comprises R 3 4-, 5-, or 6-membered heterocyclic R 1b is alkoxyl; R 2 is an amino acid side chain; R 3 is hydrogen D* is a residue of a biologically active compound; and n is 1. In another embodiment, R 1 a is alkylene, wherein the alkylene further comprises R 3 4, 5, or 6-membered bond and R 1b is alkenyl; R 2 is an amino acid side chain; R 3 is hydrogen; D* is a residue of a biologically active compound; and n is 1. Hey, R 1a is alkylene, wherein the alkylene further comprises R 3 4, which is bonded to forming a 5- or 6-membered heterocyclyl; and R 1b is alkynyl; R 2 On the amino acid side Chain;R 3 is hydrogen; D* is a residue of a biologically active compound; and n is 1. In an embodiment of the invention, R 1a is alkylene, wherein the alkylene further comprises R 3 to form a 4-, 5-, or 6-membered heterocyclyl; and R 1b is aryl; R 2 teeth, is an amino acid side chain; R 3 is hydrogen; D* is a residue of a biologically active compound; and n is 1 In another embodiment, R 1a is alkylene, where the alkylene is In addition, R 3 to form a 4-, 5-, or 6-membered heterocyclyl; and R 1b is an aryl RuKil is;R 2 is an amino acid side chain; R 3 is hydrogen; D* is the residue of a biologically active compound. group; and n is 1. In any of the embodiments of this paragraph, R 4 is hydrogen In any of the embodiments of this paragraph, R 4 is alkyl.

[0098] In another embodiment, R 1a is alkylene, wherein the alkylene is further , R 3 to form a 4-, 5-, or 6-membered heterocyclyl; and R 1b is a heteroaryl Yes;R 2 is an amino acid side chain; R 3 is hydrogen; D* is a residue of a biologically active compound; and n is 1. In another embodiment, R 1a is hydrogen and R 1b is hydrogen ;R 2 is hydrogen; R 3 is alkyl; D* is a residue of a biologically active compound; and n is , 1. In another embodiment, R 1a is hydrogen and R 1b is alkyl; R 2 is hydrogen; R 3 is alkyl; D* is a residue of a biologically active compound; and n is 1 In another embodiment, R 1a is hydrogen and R 1b is alkoxy; R 2 is hydrogen; R 3is alkyl; D* is a residue of a biologically active compound; and n is 1 In another embodiment, R 1a is hydrogen and R 1b is alkenyl; R 2 is hydrogen; R 3 is alkyl; D* is a residue of a biologically active compound; and n is 1 In another embodiment, R 1a is hydrogen and R 1b is alkynyl; R 2 is hydrogen; R 3 is alkyl; D* is a residue of a biologically active compound; and n is 1 In another embodiment, R 1a is hydrogen and R 1b is aryl; R 2 teeth , hydrogen; R 3 is alkyl; D* is a residue of a biologically active compound; and n is 1 and In another embodiment, R 1a is hydrogen and R 1b is arylalkyl ;R 2 is hydrogen; R 3 is alkyl; D* is a residue of a biologically active compound; and n is , 1. In another embodiment, R 1a is hydrogen and R 1b is a heteroaryl Yes;R 2 is hydrogen; R 3 is an alkyl; D* is a residue of a biologically active compound; and n is 1. In another embodiment, R 1a is alkylene, Len further added, 3 to form a 4-, 5-, or 6-membered heterocyclyl; and R 1b is hydrogen ;R2 is hydrogen; R 3 is an alkyl; D* is a residue of a biologically active compound; In another embodiment, R 1a is alkylene, Killen further added that 3 to form a 4-, 5-, or 6-membered heterocyclyl; and R 1b A RuKil is;R 2 is hydrogen; R 3 is an alkyl; D* is the residue of a biologically active compound and n is 1. In another embodiment, R 1a is alkylene, where The alkylene may further include R 3 to form a 4-, 5-, or 6-membered heterocyclyl; and R 1b is alkoxyl; R 2 is hydrogen; R 3 is an alkyl group; D* is a bioactive group and n is 1. In another embodiment, R 1a is an alkylene; wherein the alkylene further comprises R 3 to form a 4-, 5-, or 6-membered heterocyclyl S; and R 1b is alkenyl; R 2 is hydrogen; R 3 is alkyl; D* is physiological is a residue of an active compound; and n is 1. In another embodiment, R 1a is an alkylene wherein the alkylene further comprises R 3 4, 5, or 6-membered heterocyclyl and R 1b is alkynyl; R 2 is hydrogen; R 3 is alkyl; D* is a residue of a biologically active compound; and n is 1. In another embodiment, R 1a A alkylene, wherein the alkylene is further selected from the group consisting of R 3 4, 5, or 6-membered heterocyclic and R 1b is aryl; R 2 is hydrogen; R 3 is an alkyl D* is a residue of a biologically active compound; and n is 1. In either case, R 4 is hydrogen. In any of the embodiments of this paragraph, R 4 teeth , alkyl.

[0099] In another embodiment, R 1a is alkylene, wherein the alkylene is further , R 3 to form a 4-, 5-, or 6-membered heterocyclyl; and R 1b is aryl alkyl ;R 2 is hydrogen; R 3 is an alkyl; D* is a residue of a biologically active compound; In another embodiment, R 1a is alkylene, Killen further added that 3 to form a 4-, 5-, or 6-membered heterocyclyl; and R 1b Ha, He R 2 is hydrogen; R 3 is an alkyl group; D* is a group of the biologically active compound residue; and n is 1. In another embodiment, R 1a is hydrogen and R 1b teeth , hydrogen; R 2 is an amino acid side chain; R 3is an alkyl; D* is a biologically active compound and n is 1. In another embodiment, R 1a is hydrogen and R 1b is alkyl; R 2 is an amino acid side chain; R 3 is alkyl; D* is bioactive and n is 1. In another embodiment, R 1a is hydrogen, R 1b is alkoxy; R 2 is an amino acid side chain; R 3 is alkyl; D* is and n is 1. In another embodiment, R 1a is hydrogen And R 1b is alkenyl; R 2 is an amino acid side chain; R 3 is alkyl; D* is a residue of a biologically active compound; and n is 1. In another embodiment, R 1a Water Prime and R 1b is alkynyl; R 2 is an amino acid side chain; R 3 is an alkyl D* is a residue of a biologically active compound; and n is 1. In another embodiment, R 1 a is hydrogen and R 1b is aryl; R 2 is an amino acid side chain; R 3 Is, Alki D* is a residue of a biologically active compound; and n is 1. , R 1a is hydrogen and R 1b is arylalkyl; R 2 is an amino acid side chain; R3 is alkyl; D* is a residue of a biologically active compound; and n is 1. In an embodiment, R 1a is hydrogen and R 1b is heteroaryl; R 2 is an amino acid Side chain; R 3 is alkyl; D* is a residue of a biologically active compound; and n is 1. In another embodiment, R 1a is alkylene, wherein the alkylene is further To, R 3 to form a 4-, 5-, or 6-membered heterocyclyl; and R 1b is hydrogen; R 2 teeth , an amino acid side chain; R 3 is alkyl; D* is a residue of a biologically active compound; and n is 1. In another embodiment, R 1a is alkylene, where Ng further added that 3 to form a 4-, 5-, or 6-membered heterocyclyl; and R 1b Is, Alki R 2 is an amino acid side chain; R 3 is alkyl; D* is the residue of a biologically active compound. group; and n is 1. In another embodiment, R 1a is alkylene, The alkylene further comprises R 3 to form a 4-, 5-, or 6-membered heterocyclyl; and R 1b is alkoxyl; R 2 is an amino acid side chain; R 3 is alkyl; D* is and n is 1. In another embodiment, R 1a Alkire wherein the alkylene further comprises R3 4-, 5-, or 6-membered heterocyclic R 1b is alkenyl; R 2 is an amino acid side chain; R 3 is an alkyl D* is a residue of a biologically active compound; and n is 1. In another embodiment, R 1a is alkylene, wherein the alkylene further comprises R 3 4, 5, or 6 forming a 1-membered heterocyclyl; and R 1b is alkynyl; R 2 is an amino acid side chain; R 3 is alkyl; D* is a residue of a biologically active compound; and n is 1. In any of the above embodiments, R 4 is hydrogen. In either case, R 4 is alkyl.

[0100] In another embodiment, R 1a is alkylene, wherein the alkylene is further , R 3 to form a 4-, 5-, or 6-membered heterocyclyl; and R 1b is aryl; R 2 is an amino acid side chain; R 3 is an alkyl; D* is a residue of a biologically active compound; In another embodiment, R 1a is alkylene, Killen further added that 3 to form a 4-, 5-, or 6-membered heterocyclyl; and R 1b A R is aryl alkyl; 2 is an amino acid side chain; R 3 is alkyl; D* is a bioactive and n is 1. In another embodiment, R 1a is an alkylene wherein the alkylene further comprises R 3 4-, 5-, or 6-membered heterocyclyl and R 1b is heteroaryl; R 2 is an amino acid side chain; R 3 is an alkyl D* is a residue of a biologically active compound; and n is 1. In another embodiment, R 1a is alkylene, wherein the alkylene further comprises R 3 4, 5, or 6 forming a 1-membered heterocyclyl; and R 1b is hydrogen; R 2 is hydrogen; R 3 is R 1a Nisa and D* is an alkylene which is attached to said 4-, 5-, or 6-membered heterocyclyl; is a residue of an active compound; and n is 1. In another embodiment, R 1a is an alkylene wherein the alkylene further comprises R 3 4, 5, or 6-membered heterocyclyl and R 1b is alkyl; R 2 is hydrogen; R 3 is R 1a Further combining with D* is an alkylene group forming a 4-, 5-, or 6-membered heterocyclyl; residue; and n is 1. In another embodiment, R 1a is alkylene, wherein the alkylene further comprises R 3 to form a 4-, 5-, or 6-membered heterocyclyl; R 1b is alkoxyl; R2 is hydrogen; R 3 is R 1a Further bind to the 4, 5, or is an alkylene that forms a six-membered heterocyclyl; D* is a residue of a biologically active compound; and n is 1. In another embodiment, R 1a is alkylene, Rukyren further added, 3 to form a 4-, 5-, or 6-membered heterocyclyl; and R 1b teeth, alkenyl; R 2 is hydrogen; R 3 is R 1a Further attached to said 4, 5, or 6 membered heterocyclic D* is a residue of a biologically active compound; and n is 1. In another embodiment, R 1a is alkylene, where the alkylene is In addition, R 3 to form a 4-, 5-, or 6-membered heterocyclyl; and R 1b is an alkynyl ;R 2 is hydrogen; R 3 is R 1a further bound to said 4-, 5-, or 6-membered heterocyclyl D* is a residue of a biologically active compound; and n is 1. In an embodiment of the invention, R 1a is alkylene, wherein the alkylene further comprises R 3 to form a 4-, 5-, or 6-membered heterocyclyl; and R 1b is aryl; R 2 teeth, Hydrogen; R 3 is R 1a which further binds to form said 4-, 5-, or 6-membered heterocyclyl. D* is a residue of a biologically active compound; and n is 1. Hey, R 1a is alkylene, wherein the alkylene further comprises R 3 4, which is bonded to forming a 5- or 6-membered heterocyclyl; and R 1b is arylalkyl; R 2 is hydrogen ;R 3 is R 1a to form said 4-, 5-, or 6-membered heterocyclyl. D* is a residue of a biologically active compound; and n is 1. R 1a is alkylene, wherein the alkylene further comprises R 3 4, 5, or a 6-membered heterocyclyl; and R 1b is heteroaryl; R 2 is hydrogen ;R 3 is R 1a which further binds to form said 4-, 5-, or 6-membered heterocyclyl; D* is a residue of a biologically active compound; and n is 1. In either case, R 4 is hydrogen. In any of the embodiments of this paragraph, R 4 is alkyl.

[0101] In another embodiment, R 1a is alkylene, wherein the alkylene is further , R 3 to form a 4-, 5-, or 6-membered heterocyclyl; and R 1b is hydrogen; R 2 teeth, is an amino acid side chain; R 3 is R 1a to form the 4-, 5-, or 6-membered heterocyclyl. D* is a residue of a biologically active compound; and n is 1. In the embodiment, R 1a is alkylene, wherein the alkylene further comprises R 3 In conclusion combine with R to form a 4-, 5-, or 6-membered heterocyclyl; and R 1b is alkyl; R 2 Ami R is an acid side chain; 3 is R 1a to form said 4-, 5-, or 6-membered heterocyclyl. D* is a residue of a biologically active compound; and n is 1. In this regard, R 1a is alkylene, wherein the alkylene further comprises R 3 Binds to forming a 4-, 5-, or 6-membered heterocyclyl; and R 1b is alkoxyl; R 2 Ami R is an acid side chain; 3 is R 1a to form said 4-, 5-, or 6-membered heterocyclyl. D* is a residue of a biologically active compound; and n is 1. In this regard, R 1a is alkylene, wherein the alkylene further comprises R 3 Binds to forming a 4-, 5-, or 6-membered heterocyclyl; and R 1b is alkenyl; R 2 Amino R is an acid side chain; 3 is R 1a further attached to form said 4-, 5-, or 6-membered heterocyclyl is alkylene; D* is a residue of a biologically active compound; and n is 1. In R 1a is alkylene, wherein the alkylene further comprises R3 4 , 5, or 6 membered heterocyclyl; and R 1b is alkynyl; R 2 is an amino acid Side chain; R 3 is R 1a which further binds to form said 4-, 5-, or 6-membered heterocyclyl. D* is a residue of a biologically active compound; and n is 1. Hey, R 1a is alkylene, wherein the alkylene further comprises R 3 4, which is bonded to forming a 5- or 6-membered heterocyclyl; and R 1b is aryl; R 2 is the amino acid side chain ;R 3 is R 1a to form said 4-, 5-, or 6-membered heterocyclyl. D* is a residue of a biologically active compound; and n is 1. R 1a is alkylene, wherein the alkylene further comprises R 3 4, 5, or a 6-membered heterocyclyl; and R 1b is arylalkyl; R 2 is an amino acid Side chain; R 3 is R 1a which further binds to form said 4-, 5-, or 6-membered heterocyclyl. D* is a residue of a biologically active compound; and n is 1. Hey, R 1a is alkylene, wherein the alkylene further comprises R 3 4, which is bonded to forming a 5- or 6-membered heterocyclyl; and R 1b is heteroaryl; R 2 Amino R is an acid side chain; 3 is R 1a further attached to form said 4-, 5-, or 6-membered heterocyclyl is alkylene; D* is a residue of a biologically active compound; and n is 1. In any of the embodiments, R 4 is hydrogen. In R 4 is alkyl.

[0102] In another embodiment, R 1a is hydrogen and R 1b is hydrogen; R 2 is hydrogen R 3 is hydrogen; D* is hydrogen; and n is 2. In another embodiment, R 1a is hydrogen and R 1b is alkyl; R 2 is hydrogen; R 3 is hydrogen; D* is , hydrogen; and n is 2. In another embodiment, R 1a is hydrogen and R 1b is alkoxy; R 2 is hydrogen; R 3 is hydrogen; D* is hydrogen; and n is , 2. In another embodiment, R 1a is hydrogen and R 1b is alkenyl; R 2 is hydrogen; R 3 is hydrogen; D* is hydrogen; and n is 2. In this regard, R 1a is hydrogen and R 1b is alkynyl; R 2 is hydrogen; R 3 teeth D* is hydrogen; and n is 2. In another embodiment, R 1a Water Prime and R 1b is aryl; R 2 is hydrogen; R 3 is hydrogen; D* is hydrogen and n is 2. In another embodiment, R 1a is hydrogen and R 1b A R is aryl alkyl; 2 is hydrogen; R 3 is hydrogen; D* is hydrogen; and n is , 2. In another embodiment, R 1a is hydrogen and R 1b is a heteroaryl Yes;R 2 is hydrogen; R 3 is hydrogen; D* is hydrogen; and n is 2. In the embodiment, R 1a is alkylene, wherein the alkylene further comprises R 3 In conclusion combine with R to form a 4-, 5-, or 6-membered heterocyclyl; and R 1b is hydrogen; R 2 is hydrogen R 3 is hydrogen; D* is hydrogen; and n is 2. In another embodiment, R 1a is alkylene, wherein the alkylene further comprises R 3 4, 5, or 6-membered bond and R 1b is alkyl; R 2 is hydrogen; R 3 is hydrogen D* is hydrogen; and n is 2. In another embodiment, R 1a is an alkylene wherein the alkylene further comprises R 34, 5, or 6-membered heterocyclyl and R 1b is alkoxyl; R 2 is hydrogen; R 3 is hydrogen; D* is , hydrogen; and n is 2. In another embodiment, R 1a is alkylene, wherein the alkylene further comprises R 3 to form a 4-, 5-, or 6-membered heterocyclyl; And R 1b is alkenyl; R 2 is hydrogen; R 3 is hydrogen; D* is hydrogen; and n is 2. In another embodiment, R 1a is alkylene, Lukiren further added, 3 to form a 4-, 5-, or 6-membered heterocyclyl; and R 1b teeth, Alkynyl; R 2 is hydrogen; R 3 is hydrogen; D* is hydrogen; and n is 2 In another embodiment, R 1a is alkylene, wherein the alkylene is Furthermore, R 3 to form a 4-, 5-, or 6-membered heterocyclyl; and R 1b is an aryl R 2 is hydrogen; R 3 is hydrogen; D* is hydrogen; and n is 2. In an embodiment, R 1a is alkylene, wherein the alkylene further comprises R 3 Combined to to form a 4-, 5-, or 6-membered heterocyclyl; and R 1b is arylalkyl; R 2 teeth , hydrogen; R 3is hydrogen; D* is hydrogen; and n is 2. Hey, R 1a is alkylene, wherein the alkylene further comprises R 3 4, which is bonded to forming a 5- or 6-membered heterocyclyl; and R 1b is heteroaryl; R 2 is hydrogen Yes;R 3 is hydrogen; D* is hydrogen; and n is 2. In another embodiment, R 1a is hydrogen and R 1b is hydrogen; R 2 is an amino acid side chain; R 3 is hydrogen D* is hydrogen; and n is 2. In another embodiment, R 1a is hydrogen, And R 1b is alkyl; R 2 is an amino acid side chain; R 3 is hydrogen; D* is hydrogen In another embodiment, R 1a is hydrogen and R 1b is alkoxy; R 2 teeth, is an amino acid side chain; R 3 is hydrogen; D* is hydrogen; and n is 2. In any of the above embodiments, R 4 is hydrogen. In either case, R 4 is alkyl.

[0103] In another embodiment, R 1a is hydrogen and R 1b is alkenyl; R 2 A R 3 is hydrogen; D* is hydrogen; and n is 2. In this regard, R 1a is hydrogen and R 1b is alkynyl; R 2 is the amino acid side chain Yes;R 3 is hydrogen; D* is hydrogen; and n is 2. In another embodiment, R 1a is hydrogen and R 1b is aryl; R 2 is an amino acid side chain; R 3 is hydrogen D* is hydrogen; and n is 2. In another embodiment, R 1a is hydrogen And R 1b is arylalkyl; R 2 is an amino acid side chain; R 3 is hydrogen; D* is hydrogen; and n is 2. In another embodiment, R 1a is hydrogen, and R 1b is heteroaryl; R 2 is an amino acid side chain; R 3 is hydrogen; D* is hydrogen and n is 2. In another embodiment, R 1a is alkylene, where The alkylene further comprises R 3 to form a 4-, 5-, or 6-membered heterocyclyl; and R 1 b is hydrogen; R 2 is an amino acid side chain; R 3 is hydrogen; D* is hydrogen; and n is 2. In another embodiment, R 1a is alkylene, where Ng further added that 3 to form a 4-, 5-, or 6-membered heterocyclyl; and R 1b Is, Alki R 2is an amino acid side chain; R 3 is hydrogen; D* is hydrogen; and n is 2 In another embodiment, R 1a is alkylene, wherein the alkylene is Furthermore, R 3 to form a 4-, 5-, or 6-membered heterocyclyl; and R 1b is alkoxyl ;R 2 is an amino acid side chain; R 3 is hydrogen; D* is hydrogen; and n is 2. In another embodiment, R 1a is alkylene, wherein the alkylene is further To, R 3 to form a 4-, 5-, or 6-membered heterocyclyl; and R 1b is alkenyl R 2 is an amino acid side chain; R 3 is hydrogen; D* is hydrogen; and n is 2. In another embodiment, R 1a is alkylene, wherein the alkylene further comprises R 3 to form a 4-, 5-, or 6-membered heterocyclyl; and R 1b is alkynyl; R 2 is an amino acid side chain; R 3 is hydrogen; D* is hydrogen; and n is 2. In an embodiment, R 1a is alkylene, wherein the alkylene further comprises R 3 To linked to form a 4-, 5-, or 6-membered heterocyclyl; and R 1b is aryl; R 2 A R 3 is hydrogen; D* is hydrogen; and n is 2. In this regard, R 1ais alkylene, wherein the alkylene further comprises R 3 Binds to forming a 4-, 5-, or 6-membered heterocyclyl; and R 1b is arylalkyl; R 2 teeth, is an amino acid side chain; R 3 is hydrogen; D* is hydrogen; and n is 2. In an embodiment, R 1a is alkylene, wherein the alkylene further comprises R 3 Combined to to form a 4-, 5-, or 6-membered heterocyclyl; and R 1b is heteroaryl; R 2 teeth, is an amino acid side chain; R 3 is hydrogen; D* is hydrogen; and n is 2. In an embodiment, R 1a is hydrogen and R 1b is hydrogen; R 2 is hydrogen; R 3 A D* is hydrogen; and n is 2. In another embodiment, R 1a Water Prime and R 1b is alkyl; R 2 is hydrogen; R 3 is alkyl; D* is and n is 2. In another embodiment, R 1a is hydrogen and R 1b teeth , alkoxy; R 2 is hydrogen; R 3 is alkyl; D* is hydrogen; and n is 2. In another embodiment, R 1a is hydrogen and R 1b is alkenyl R 2 is hydrogen; R 3is alkyl; D* is hydrogen; and n is 2. In an embodiment, R 1a is hydrogen and R 1b is alkynyl; R 2 is hydrogen R 3 is alkyl; D* is hydrogen; and n is 2. In any of the above cases, R 4 is hydrogen. In any of the embodiments of this paragraph , R 4 is alkyl.

[0104] In another embodiment, R 1a is hydrogen and R 1b is aryl; R 2 is hydrogen ;R 3 is alkyl; D* is hydrogen; and n is 2. And R 1a is hydrogen and R 1b is arylalkyl; R 2 is hydrogen; R 3 teeth , alkyl; D* is hydrogen; and n is 2. In another embodiment, R 1a teeth , hydrogen, and R 1b is heteroaryl; R 2 is hydrogen; R 3 is an alkyl D* is hydrogen; and n is 2. In another embodiment, R 1a is an alkylene wherein the alkylene further comprises R 3 4, 5, or 6-membered heterocyclyl and R 1b is hydrogen; R 2 is hydrogen; R 3 is alkyl; D* is water and n is 2. In another embodiment, R 1a is alkylene, The alkylene further comprises R 3 to form a 4-, 5-, or 6-membered heterocyclyl; and R 1b is alkyl; R 2 is hydrogen; R 3 is alkyl; D* is hydrogen; or In another embodiment, R 1a is alkylene, Killen further added that 3 to form a 4-, 5-, or 6-membered heterocyclyl; and R 1b A R is alkoxyl; 2 is hydrogen; R 3 is alkyl; D* is hydrogen; and n is , 2. In another embodiment, R 1a is alkylene, where Furthermore, R 3 to form a 4-, 5-, or 6-membered heterocyclyl; and R 1b Is Arken R 2 is hydrogen; R 3 is alkyl; D* is hydrogen; and n is 2 In another embodiment, R 1a is alkylene, wherein the alkylene is further , R 3 to form a 4-, 5-, or 6-membered heterocyclyl; and R 1b is alkynyl; R 2 is hydrogen; R 3 is alkyl; D* is hydrogen; and n is 2. In the embodiment, R 1a is alkylene, wherein the alkylene further comprises R 3 In conclusion combine with R to form a 4-, 5-, or 6-membered heterocyclyl; and R 1b is aryl; R 2 is hydrogen ;R 3 is alkyl; D* is hydrogen; and n is 2. And R 1a is alkylene, wherein the alkylene further comprises R 3 4, 5 or a 6-membered heterocyclyl; and R 1b is arylalkyl; R 2 is hydrogen Yes;R 3 is alkyl; D* is hydrogen; and n is 2. R 1a is alkylene, wherein the alkylene further comprises R 3 4, 5, or a 6-membered heterocyclyl; and R 1b is heteroaryl; R 2 is hydrogen ;R 3 is alkyl; D* is hydrogen; and n is 2. In another embodiment, R 1a is hydrogen and R 1b is hydrogen; R 2 is an amino acid side chain; R 3 is an alkyl D* is hydrogen; and n is 2. In another embodiment, R 1a is hydrogen And R 1b is alkyl; R 2 is an amino acid side chain; R 3 is alkyl; D* is , hydrogen; and n is 2. In another embodiment, R 1a is hydrogen and R 1b is alkoxy; R 2 is an amino acid side chain; R 3is alkyl; D* is hydrogen and n is 2. In another embodiment, R 1a is hydrogen and R 1b Is, Al Kenyl;R 2 is an amino acid side chain; R 3 is alkyl; D* is hydrogen; and n is 2. In another embodiment, R 1a is hydrogen and R 1b is alkynyl R 2 is an amino acid side chain; R 3 is alkyl; D* is hydrogen; and n is 2. In another embodiment, R 1a is hydrogen and R 1b is aryl; R 2 A R 3 is alkyl; D* is hydrogen; and n is 2. In any of the embodiments of the graph, R 4 is hydrogen. In either case, R 4 is alkyl.

[0105] In another embodiment, R 1a is hydrogen and R 1b is arylalkyl; R 2 is an amino acid side chain; R 3 is alkyl; D* is hydrogen; and n is 2. In another embodiment, R 1a is hydrogen and R 1b is heteroaryl; R 2 teeth, is an amino acid side chain; R 3 is alkyl; D* is hydrogen; and n is 2. In an embodiment, R 1ais alkylene, wherein the alkylene further comprises R 3 To linked to form a 4-, 5-, or 6-membered heterocyclyl; and R 1b is hydrogen; R 2 Amino R is an acid side chain; 3 is alkyl; D* is hydrogen; and n is 2. In this regard, R 1a is alkylene, wherein the alkylene further comprises R 3 Binds to forming a 4-, 5-, or 6-membered heterocyclyl; and R 1b is alkyl; R 2 is an amino acid Side chain; R 3 is alkyl; D* is hydrogen; and n is 2. In R 1a is alkylene, wherein the alkylene further comprises R 3 4 , 5, or 6 membered heterocyclyl; and R 1b is alkoxyl; R 2 Amino R is an acid side chain; 3 is alkyl; D* is hydrogen; and n is 2. In this regard, R 1a is alkylene, wherein the alkylene further comprises R 3 Binds to forming a 4-, 5-, or 6-membered heterocyclyl; and R 1b is alkenyl; R 2 Amino R is an acid side chain; 3 is alkyl; D* is hydrogen; and n is 2. In this regard, R 1a is alkylene, wherein the alkylene further comprises R 3 Binds to forming a 4-, 5-, or 6-membered heterocyclyl; and R1b is alkynyl; R 2 Amino R is an acid side chain; 3 is alkyl; D* is hydrogen; and n is 2. In this regard, R 1a is alkylene, wherein the alkylene further comprises R 3 Binds to forming a 4-, 5-, or 6-membered heterocyclyl; and R 1b is aryl; R 2 is an amino acid Side chain; R 3 is alkyl; D* is hydrogen; and n is 2. In R 1a is alkylene, wherein the alkylene further comprises R 3 4 , 5, or 6 membered heterocyclyl; and R 1b is arylalkyl; R 2 A R 3 is alkyl; D* is hydrogen; and n is 2. In the embodiment, R 1a is alkylene, wherein the alkylene further comprises R 3 In conclusion combine with R to form a 4-, 5-, or 6-membered heterocyclyl; and R 1b is heteroaryl; R 2 teeth , an amino acid side chain; R 3 is alkyl; D* is hydrogen; and n is 2. In an embodiment of the invention, R 1a is alkylene, wherein the alkylene further comprises R 3 to form a 4-, 5-, or 6-membered heterocyclyl; and R 1b is hydrogen; R 2 is hydrogen ;R 3 is R 1ato form said 4-, 5-, or 6-membered heterocyclyl. D* is hydrogen; and n is 2. In another embodiment, R 1a Is, Al alkylene, wherein the alkylene further comprises R 3 4, 5, or 6 membered heterocyclic Forming a cyclyl; and R 1b is alkyl; R 2 is hydrogen; R 3 is R 1a Further alkylene which combines with said 4-, 5-, or 6-membered heterocyclyl; D* is hydrogen. and n is 2. In another embodiment, R 1a is alkylene, Lukiren further added, 3 to form a 4-, 5-, or 6-membered heterocyclyl; and R 1b teeth, Alkoxyl; R 2 is hydrogen; R 3 is R 1a further linked to said 4, 5, or 6 membered hydroxyl group D* is hydrogen; and n is 2. In the embodiment, R 1a is alkylene, wherein the alkylene further comprises R 3 In conclusion combine with R to form a 4-, 5-, or 6-membered heterocyclyl; and R 1b is alkenyl; R 2 Water R 3 is R 1a which further binds to form said 4-, 5-, or 6-membered heterocyclyl. xylene; D* is hydrogen; and n is 2. Any of the embodiments of this paragraph In R 4 is hydrogen. In any of the embodiments of this paragraph, R 4 Is, Al It's a kill.

[0106] In another embodiment, R 1a is alkylene, wherein the alkylene is further , R 3 to form a 4-, 5-, or 6-membered heterocyclyl; and R 1b is alkynyl; R 2 is hydrogen; R 3 is R 1a further attached to form said 4-, 5-, or 6-membered heterocyclyl D* is hydrogen; and n is 2. In another embodiment, R 1 a is alkylene, wherein the alkylene further comprises R 3 4, 5, or 6-membered bond and R 1b is aryl; R 2 is hydrogen; R 3 is R 1a To is alkylene which further binds to form said 4-, 5-, or 6-membered heterocyclyl; D* is water. and n is 2. In another embodiment, R 1a is alkylene, The alkylene further comprises R 3 to form a 4-, 5-, or 6-membered heterocyclyl; and R 1b is arylalkyl; R 2 is hydrogen; R 3 is R 1a Further bind to the 4, 5, or alkylene forming a 6-membered heterocyclyl; D* is hydrogen; and n is 2. In another embodiment, R 1a is alkylene, wherein the alkylene is Furthermore, R 3to form a 4-, 5-, or 6-membered heterocyclyl; and R 1b Heteroaryl R 2 is hydrogen; R 3 is R 1a further linked to said 4, 5, or 6 membered heterocyclyl D* is hydrogen; and n is 2. And R 1a is alkylene, wherein the alkylene further comprises R 3 4, 5 or a 6-membered heterocyclyl; and R 1b is hydrogen; R 2 is the amino acid side chain ;R 3 is R 1a which further binds to form said 4-, 5-, or 6-membered heterocyclyl; D* is hydrogen; and n is 2. In another embodiment, R 1a is an alkylene wherein the alkylene further comprises R 3 4, 5, or 6-membered heterocyclyl and R 1b is alkyl; R 2 is an amino acid side chain; R 3 is R 1a Furthermore are linked to form said 4-, 5-, or 6-membered heterocyclyl; D* is hydrogen. and n is 2. In another embodiment, R 1a is alkylene, The alkylene may further include R 3 to form a 4-, 5-, or 6-membered heterocyclyl; and R 1b teeth , alkoxyl; R 2 is an amino acid side chain; R 3 is R 1a Further bind to the 4, 5, or alkylene forming a 6-membered heterocyclyl; D* is hydrogen; and n is 2. In another embodiment, R 1a is alkylene, wherein the alkylene is Furthermore, R 3 to form a 4-, 5-, or 6-membered heterocyclyl; and R 1b is an alkenyl Yes;R 2 is an amino acid side chain; R 3 is R 1a further linked to said 4, 5, or 6 membered heterocyclic D* is hydrogen; and n is 2. In R 1a is alkylene, wherein the alkylene further comprises R 3 4 , 5, or 6 membered heterocyclyl; and R 1b is alkynyl; R 2 is an amino acid Side chain; R 3 is R 1a which further binds to form said 4-, 5-, or 6-membered heterocyclyl. D* is hydrogen; and n is 2. In another embodiment, R 1a teeth, alkylene, wherein the alkylene is further selected from the group consisting of R 3 4, 5, or 6-membered hexafluorophosphate Forming a tetracyclyl; and R 1b is aryl; R 2 is an amino acid side chain; R 3 is R 1 a is an alkylene which further binds to form said 4-, 5-, or 6-membered heterocyclyl; D* is , hydrogen; and n is 2. In any of the embodiments of this paragraph, R 4 teeth, In any of the embodiments of this paragraph, R4 is alkyl.

[0107] In another embodiment, R 1a is alkylene, wherein the alkylene is further , R 3 to form a 4-, 5-, or 6-membered heterocyclyl; and R 1b is aryl alkyl ;R 2 is an amino acid side chain; R 3 is R 1a further linked to said 4, 5, or 6 membered heterocyclic is an alkylene group forming a cyclyl; D* is hydrogen; and n is 2. In this regard, R 1a is alkylene, wherein the alkylene further comprises R 3 Binds to forming a 4-, 5-, or 6-membered heterocyclyl; and R 1b is heteroaryl; R 2 A R 3 is R 1a further attached to form said 4-, 5-, or 6-membered heterocyclyl D* is hydrogen; and n is 2. In another embodiment, R 1 a is hydrogen and R 1b is hydrogen; R 2 is hydrogen; R 3 is hydrogen; D* is acyl; and n is 2. In another embodiment, R 1a is hydrogen and R 1b is alkyl; R 2 is hydrogen; R 3 is hydrogen; D* is acyl; and n is , 2. In another embodiment, R 1a is hydrogen and R 1b is alkoxy; R 2 is hydrogen; R 3 is hydrogen; D* is acyl; and n is 2. In an embodiment, R 1a is hydrogen and R 1b is alkenyl; R 2 is hydrogen; R 3 is hydrogen; D* is acyl; and n is 2. In another embodiment, R 1a teeth , hydrogen, and R 1b is alkynyl; R 2 is hydrogen; R 3 is hydrogen; D* is , acyl; and n is 2. In another embodiment, R 1a is hydrogen and R 1 b is aryl; R 2 is hydrogen; R 3 is hydrogen; D* is acyl; and n is , 2. In another embodiment, R 1a is hydrogen and R 1b is aryl alkyl ;R 2 is hydrogen; R 3 is hydrogen; D* is acyl; and n is 2. In an embodiment of the invention, R 1a is hydrogen and R 1b is heteroaryl; R 2 Water R 3 is hydrogen; D* is acyl; and n is 2. And R 1a is alkylene, wherein the alkylene further comprises R 3 4, 5 or a 6-membered heterocyclyl; and R 1b is hydrogen; R 2 is hydrogen; R3 teeth, D* is acyl; and n is 2. In another embodiment, R 1a A alkylene, wherein the alkylene is further selected from the group consisting of R 3 4, 5, or 6-membered heterocyclic and R 1b is alkyl; R 2 is hydrogen; R 3 is hydrogen; D * is acyl; and n is 2. In another embodiment, R 1a is an alkylene wherein the alkylene further comprises R 3 is bonded to a 4-, 5-, or 6-membered heterocyclyl Form; and R 1b is alkoxyl; R 2 is hydrogen; R 3 is hydrogen; D* is a and n is 2. In another embodiment, R 1a is alkylene, wherein the alkylene further comprises R 3 to form a 4-, 5-, or 6-membered heterocyclyl; R 1b is alkenyl; R 2 is hydrogen; R 3 is hydrogen; D* is acyl; and n is 2. In another embodiment, R 1a is alkylene, Lukiren further added, 3 to form a 4-, 5-, or 6-membered heterocyclyl; and R 1b teeth, Alkynyl; R 2 is hydrogen; R 3 is hydrogen; D* is acyl; and n is 2 In another embodiment, R 1a is alkylene, where the alkylene is In addition, R 3 to form a 4-, 5-, or 6-membered heterocyclyl; and R 1b is an aryl Yes;R 2 is hydrogen; R 3 is hydrogen; D* is acyl; and n is 2. In an embodiment, R 1a is alkylene, wherein the alkylene further comprises R 3 To linked to form a 4-, 5-, or 6-membered heterocyclyl; and R 1b is arylalkyl; R 2 is hydrogen; R 3 is hydrogen; D* is acyl; and n is 2. In any of the above embodiments, R 4 is hydrogen. In either case, R 4 is alkyl.

[0108] In another embodiment, R 1a is alkylene, wherein the alkylene is further , R 3 to form a 4-, 5-, or 6-membered heterocyclyl; and R 1b is a heteroaryl Yes;R 2 is hydrogen; R 3 is hydrogen; D* is acyl; and n is 2. In an embodiment, R 1a is hydrogen and R 1b is hydrogen; R 2 is the amino acid side chain Yes;R 3 is hydrogen; D* is acyl; and n is 2. , R 1a is hydrogen and R 1b is alkyl; R 2 is an amino acid side chain; R3 Water D* is acyl; and n is 2. In another embodiment, R 1a is hydrogen and R 1b is alkoxy; R 2 is an amino acid side chain; R 3 is hydrogen; D* is acyl; and n is 2. In another embodiment, R 1a is hydrogen, and R 1b is alkenyl; R 2 is an amino acid side chain; R 3 is hydrogen; D* is acyl and n is 2. In another embodiment, R 1a is hydrogen and R 1b Is, Al quinyl;R 2 is an amino acid side chain; R 3 is hydrogen; D* is acyl; and n is 2. In another embodiment, R 1a is hydrogen and R 1b is aryl; R 2 is an amino acid side chain; R 3 is hydrogen; D* is acyl; and n is 2. In another embodiment, R 1a is hydrogen and R 1b is arylalkyl; R 2 teeth , an amino acid side chain; R 3 is hydrogen; D* is acyl; and n is 2. In an embodiment, R 1a is hydrogen and R 1b is heteroaryl; R 2 Ami R is an acid side chain; 3 is hydrogen; D* is acyl; and n is 2. In this regard, R1a is alkylene, wherein the alkylene further comprises R 3 Binds to forming a 4-, 5-, or 6-membered heterocyclyl; and R 1b is hydrogen; R 2 is the amino acid side chain ;R 3 is hydrogen; D* is acyl; and n is 2. R 1a is alkylene, wherein the alkylene further comprises R 3 4, 5, or a 6-membered heterocyclyl; and R 1b is alkyl; R 2 is an amino acid side chain R 3 is hydrogen; D* is acyl; and n is 2. In another embodiment, R 1a is alkylene, wherein the alkylene further comprises R 3 4, 5, or 6 forming a 1-membered heterocyclyl; and R 1b is alkoxyl; R 2 is an amino acid side chain R 3 is hydrogen; D* is acyl; and n is 2. In another embodiment, R 1a is alkylene, wherein the alkylene further comprises R 3 4, 5, or 6 forming a 1-membered heterocyclyl; and R 1b is alkenyl; R 2 is an amino acid side chain; R 3 is hydrogen; D* is acyl; and n is 2. In another embodiment, R 1a is alkylene, wherein the alkylene further comprises R 3 4, 5, or 6-membered bond and R1b is alkynyl; R 2 is an amino acid side chain; R 3 is hydrogen; D* is acyl; and n is 2. In another embodiment, R 1a teeth , alkylene, wherein the alkylene is further selected from the group consisting of R 3 4, 5, or 6-membered forming a heterocyclyl; and R 1b is aryl; R 2 is an amino acid side chain; R 3 teeth, D* is acyl; and n is 2. In another embodiment, R 1a A alkylene, wherein the alkylene is further selected from the group consisting of R 3 4, 5, or 6-membered heterocyclic and R 1b is arylalkyl; R 2 is an amino acid side chain; R 3 is hydrogen; D* is acyl; and n is 2. In another embodiment, R 1a teeth , alkylene, wherein the alkylene is further selected from the group consisting of R 3 4, 5, or 6-membered forming a heterocyclyl; and R 1b is heteroaryl; R 2 is an amino acid side chain; R 3 is hydrogen; D* is acyl; and n is 2. In either case, R 4 is hydrogen. In any of the embodiments of this paragraph, R 4 teeth , alkyl.

[0109] In another embodiment, R 1a is hydrogen and R 1b is hydrogen; R2 is hydrogen R 3 is alkyl; D* is acyl; and n is 2. R 1a is hydrogen and R 1b is alkyl; R 2 is hydrogen; R 3 is an alkyl D* is acyl; and n is 2. In another embodiment, R 1a is hydrogen Yes and R 1b is alkoxy; R 2 is hydrogen; R 3 is alkyl; D* is a and n is 2. In another embodiment, R 1a is hydrogen and R 1b teeth , alkenyl; R 2 is hydrogen; R 3 is alkyl; D* is acyl; and n is 2. In another embodiment, R 1a is hydrogen and R 1b is alkynyl R 2 is hydrogen; R 3 is alkyl; D* is acyl; and n is 2. In an embodiment of the invention, R 1a is hydrogen and R 1b is aryl; R 2 is hydrogen R 3 is alkyl; D* is acyl; and n is 2. R 1a is hydrogen and R 1b is arylalkyl; R 2 is hydrogen; R 3 teeth, D* is alkyl; D* is acyl; and n is 2. In another embodiment, R1a teeth , hydrogen, and R 1b is heteroaryl; R 2 is hydrogen; R 3 is an alkyl D* is acyl; and n is 2. In another embodiment, R 1a Alkire wherein the alkylene further comprises R 3 4-, 5-, or 6-membered heterocyclic R 1b is hydrogen; R 2 is hydrogen; R 3 is alkyl; D* is acyl; and n is 2. In another embodiment, R 1a is alkylene, wherein the alkylene further comprises R 3 to form a 4-, 5-, or 6-membered heterocyclyl; And R 1b is alkyl; R 2 is hydrogen; R 3 is alkyl; D* is acyl and n is 2. In another embodiment, R 1a is alkylene, The alkylene may further include R 3 to form a 4-, 5-, or 6-membered heterocyclyl; and R 1b teeth , alkoxyl; R 2 is hydrogen; R 3 is alkyl; D* is acyl; In another embodiment, R 1a is alkylene, Killen further added that 3 to form a 4-, 5-, or 6-membered heterocyclyl; and R 1b A R is alkenyl; 2 is hydrogen; R 3is alkyl; D* is acyl; and n is , 2. In another embodiment, R 1a is alkylene, where Furthermore, R 3 to form a 4-, 5-, or 6-membered heterocyclyl; and R 1b Alkini R 2 is hydrogen; R 3 is alkyl; D* is acyl; and n is 2. In another embodiment, R 1a is alkylene, wherein the alkylene is further To, R 3 to form a 4-, 5-, or 6-membered heterocyclyl; and R 1b is aryl; R 2 is hydrogen; R 3 is alkyl; D* is acyl; and n is 2. In an embodiment, R 1a is alkylene, wherein the alkylene further comprises R 3 To linked to form a 4-, 5-, or 6-membered heterocyclyl; and R 1b is arylalkyl; R 2 is hydrogen; R 3 is alkyl; D* is acyl; and n is 2. In an embodiment, R 1a is alkylene, wherein the alkylene further comprises R 3 To linked to form a 4-, 5-, or 6-membered heterocyclyl; and R 1b is heteroaryl; R 2 is hydrogen; R 3 is alkyl; D* is acyl; and n is 2. In the embodiment, R 1a is hydrogen and R 1bis hydrogen; R 2 is an amino acid side chain R 3 is alkyl; D* is acyl; and n is 2. R 1a is hydrogen and R 1b is alkyl; R 2 is an amino acid side chain; R 3 teeth, D* is alkyl; D* is acyl; and n is 2. In another embodiment, R 1a teeth , hydrogen, and R 1b is alkoxy; R 2 is an amino acid side chain; R 3 Is, Alki D* is acyl; and n is 2. In another embodiment, R 1a is hydrogen and R 1b is alkenyl; R 2 is an amino acid side chain; R 3 is an alkyl D* is acyl; and n is 2. In any of the embodiments of this paragraph, , R 4 is hydrogen. In any of the embodiments of this paragraph, R 4 is an alkyl do.

[0110] In another embodiment, R 1a is hydrogen and R 1b is alkynyl; R 2 A R 3 is alkyl; D* is acyl; and n is 2. In an embodiment, R 1a is hydrogen and R 1b is aryl; R 2 On the amino acid side Chain;R 3is alkyl; D* is acyl; and n is 2. In R 1a is hydrogen and R 1b is arylalkyl; R 2 On the amino acid side Chain;R 3 is alkyl; D* is acyl; and n is 2. In R 1a is hydrogen and R 1b is heteroaryl; R 2 is the amino acid side chain ;R 3 is alkyl; D* is acyl; and n is 2. Hey, R 1a is alkylene, wherein the alkylene further comprises R 3 4, which is bonded to forming a 5- or 6-membered heterocyclyl; and R 1b is hydrogen; R 2 is an amino acid side chain R 3 is alkyl; D* is acyl; and n is 2. R 1a is alkylene, wherein the alkylene further comprises R 3 4, 5, or a 6-membered heterocyclyl; and R 1b is alkyl; R 2 is an amino acid side chain R 3 is alkyl; D* is acyl; and n is 2. R 1a is alkylene, wherein the alkylene further comprises R 3 4, 5, or a 6-membered heterocyclyl; and R 1b is alkoxyl; R 2 is the amino acid side chain ;R 3is alkyl; D* is acyl; and n is 2. Hey, R 1a is alkylene, wherein the alkylene further comprises R 3 4, which is bonded to forming a 5- or 6-membered heterocyclyl; and R 1b is alkenyl; R 2 On the amino acid side Chain;R 3 is alkyl; D* is acyl; and n is 2. In R 1a is alkylene, wherein the alkylene further comprises R 3 4 , 5, or 6 membered heterocyclyl; and R 1b is alkynyl; R 2 is an amino acid Side chain; R 3 is alkyl; D* is acyl; and n is 2. In this regard, R 1a is alkylene, wherein the alkylene further comprises R 3 Binds to forming a 4-, 5-, or 6-membered heterocyclyl; and R 1b is aryl; R 2 is an amino acid Side chain; R 3 is alkyl; D* is acyl; and n is 2. In this regard, R 1a is alkylene, wherein the alkylene further comprises R 3 Binds to forming a 4-, 5-, or 6-membered heterocyclyl; and R 1b is arylalkyl; R 2 teeth, is an amino acid side chain; R 3 is alkyl; D* is acyl; and n is 2. In an embodiment of the invention, R 1ais alkylene, wherein the alkylene further comprises R 3 to form a 4-, 5-, or 6-membered heterocyclyl; and R 1b is heteroaryl; R 2 is an amino acid side chain; R 3 is alkyl; D* is acyl; and n is 2. In another embodiment, R 1a is alkylene, wherein the alkylene is further To, R 3 to form a 4-, 5-, or 6-membered heterocyclyl; and R 1b is hydrogen; R 2 teeth , hydrogen; R 3 is R 1a further attached to form said 4-, 5-, or 6-membered heterocyclyl D* is alkylene; D* is acyl; and n is 2. In another embodiment, R 1a is alkylene, wherein the alkylene further comprises R 3 4, 5, or 6-membered bond and R 1b is alkyl; R 2 is hydrogen; R 3 is R 1a To is an alkylene which further binds to form said 4-, 5-, or 6-membered heterocyclyl; D* is and n is 2. In any of the embodiments of this paragraph, R 4 Water In any of the embodiments of this paragraph, R 4 is alkyl.

[0111] In another embodiment, R 1a is alkylene, wherein the alkylene is further , R 3to form a 4-, 5-, or 6-membered heterocyclyl; and R 1b is an alkoxyl R 2 is hydrogen; R 3 is R 1a to form the 4-, 5-, or 6-membered heterocyclyl. D* is acyl; and n is 2. , R 1a is alkylene, wherein the alkylene further comprises R 3 4, 5, or forms a six-membered heterocyclyl; and R 1b is alkenyl; R 2 is hydrogen; R 3 teeth , R 1a is an alkylene further attached to form said 4-, 5-, or 6-membered heterocyclyl; * is acyl; and n is 2. In another embodiment, R 1a is an alkylene wherein the alkylene further comprises R 3 is bonded to a 4-, 5-, or 6-membered heterocyclyl Form; and R 1b is alkynyl; R 2 is hydrogen; R 3 is R 1a Further binding to the 4 D* is acyl; and n is an alkylene group forming a 5-, 5-, or 6-membered heterocyclyl; is 2. In another embodiment, R 1a is alkylene, where Ng further added that 3 to form a 4-, 5-, or 6-membered heterocyclyl; and R 1b Ali R 2 is hydrogen; R 3 is R 1a further linked to said 4, 5, or 6 membered heterocyclyl D* is an alkylene group forming a ring; D* is acyl; and n is 2. Hey, R 1a is alkylene, wherein the alkylene further comprises R 3 4, which is bonded to forming a 5- or 6-membered heterocyclyl; and R 1b is arylalkyl; R 2 is hydrogen ;R 3 is R 1a to form said 4-, 5-, or 6-membered heterocyclyl. D* is aryl; D* is acyl; and n is 2. In another embodiment, R 1a A alkylene, wherein the alkylene is further selected from the group consisting of R 3 4, 5, or 6-membered heterocyclic and R 1b is heteroaryl; R 2 is hydrogen; R 3 is R 1a To is an alkylene which further binds to form said 4-, 5-, or 6-membered heterocyclyl; D* is and n is 2. In another embodiment, R 1a is alkylene, wherein the alkylene further comprises R 3 to form a 4-, 5-, or 6-membered heterocyclyl; R 1b is hydrogen; R 2 is an amino acid side chain; R 3 is R 1a Further bind to the 4, 5, or is alkylene forming a 6-membered heterocyclyl; D* is acyl; and n is 2. In another embodiment, R 1a is alkylene, wherein the alkylene is Furthermore, R 3 to form a 4-, 5-, or 6-membered heterocyclyl; and R1b is an alkyl R 2 is an amino acid side chain; R 3 is R 1a further linked to said 4, 5, or 6 membered heterocyclic D* is an alkylene forming an aryl; D* is acyl; and n is 2. In R 1a is alkylene, wherein the alkylene further comprises R 3 4 , 5, or 6 membered heterocyclyl; and R 1b is alkoxyl; R 2 Amino R is an acid side chain; 3 is R 1a further attached to form said 4-, 5-, or 6-membered heterocyclyl D* is alkylene; D* is acyl; and n is 2. In another embodiment, R 1a is alkylene, wherein the alkylene further comprises R 3 4, 5, or 6-membered bond and R 1b is alkenyl; R 2 is an amino acid side chain; R 3 is R 1a is an alkylene further attached to form said 4-, 5-, or 6-membered heterocyclyl; D* is acyl; and n is 2. In another embodiment, R 1a is an alkylene wherein the alkylene further comprises R 3 4-, 5-, or 6-membered heterocyclyl and R 1b is alkynyl; R 2 is an amino acid side chain; R 3 is R 1a Furthermore alkylene which are linked to form said 4-, 5-, or 6-membered heterocyclyl; D* is acyl. and n is 2. In any of the embodiments of this paragraph, R 4 is hydrogen In any of the embodiments of this paragraph, R 4 is alkyl.

[0112] In another embodiment, R 1a is alkylene, wherein the alkylene is further , R 3 to form a 4-, 5-, or 6-membered heterocyclyl; and R 1b is aryl; R 2 is an amino acid side chain; R 3 is R 1a further bound to said 4-, 5-, or 6-membered heterocyclyl D* is an alkylene forming the formula: And R 1a is alkylene, wherein the alkylene further comprises R 3 4, 5 or a 6-membered heterocyclyl; and R 1b is arylalkyl; R 2 Amino R is an acid side chain; 3 is R 1a further attached to form said 4-, 5-, or 6-membered heterocyclyl D* is alkylene; D* is acyl; and n is 2. In another embodiment, R 1a is alkylene, wherein the alkylene further comprises R 3 4, 5, or 6-membered bond and R 1b is heteroaryl; R 2 is an amino acid side chain R 3 is R 1a further attached to form said 4-, 5-, or 6-membered heterocyclyl; D* is acyl; and n is 2. In another embodiment, R 1a is hydrogen Yes and R 1b is hydrogen; R 2 is hydrogen; R 3 is hydrogen; D* is a bioactive compound and n is 2. In another embodiment, R 1a is hydrogen and R 1 b is alkyl; R 2 is hydrogen; R 3 is hydrogen; D* is a residue of a biologically active compound and n is 2. In another embodiment, R 1a is hydrogen and R 1b A R is alkoxy; 2 is hydrogen; R 3 is hydrogen; D* is the residue of a biologically active compound. and n is 2. In another embodiment, R 1a is hydrogen and R 1b Is, Arke Nil;R 2 is hydrogen; R 3 is hydrogen; D* is a residue of a biologically active compound; In another embodiment, R 1a is hydrogen and R 1b is an alkynyl Yes;R 2 is hydrogen; R 3 is hydrogen; D* is a residue of a biologically active compound; and n is , 2. In another embodiment, R 1a is hydrogen and R 1b is aryl; R 2 is hydrogen; R 3 is hydrogen; D* is a residue of a biologically active compound; and n is 2. In another embodiment, R1a is hydrogen and R 1b is arylalkyl; R 2 is hydrogen; R 3 is hydrogen; D* is a residue of a biologically active compound; and n is 2. In another embodiment, R 1a is hydrogen and R 1b is heteroaryl; R 2 is hydrogen; R 3 is hydrogen; D* is a residue of a biologically active compound; and n is 2. In another embodiment, R 1a is alkylene, wherein the alkylene is further To, R 3 to form a 4-, 5-, or 6-membered heterocyclyl; and R 1b is hydrogen; R 2 teeth , hydrogen; R 3 is hydrogen; D* is a residue of a biologically active compound; and n is 2. In another embodiment, R 1a is alkylene, wherein the alkylene is further , R 3 to form a 4-, 5-, or 6-membered heterocyclyl; and R 1b is alkyl; R 2 is hydrogen; R 3 is hydrogen; D* is a residue of a biologically active compound; and n is 2. In another embodiment, R 1a is alkylene, wherein the alkylene is further To, R 3 to form a 4-, 5-, or 6-membered heterocyclyl; and R 1b is an alkoxy group. Yes;R 2 is hydrogen; R 3 is hydrogen; D* is a residue of a biologically active compound; and n is , 2. In any of the embodiments of this paragraph, R 4 is hydrogen. In any of the above embodiments, R 4 is alkyl.

[0113] In another embodiment, R 1a is alkylene, wherein the alkylene is further , R 3 to form a 4-, 5-, or 6-membered heterocyclyl; and R 1b is alkenyl; R 2 is hydrogen; R 3 is hydrogen; D* is a residue of a biologically active compound; and n is 2 In another embodiment, R 1a is alkylene, wherein the alkylene is Furthermore, R 3 to form a 4-, 5-, or 6-membered heterocyclyl; and R 1b is an alkynyl Yes;R 2 is hydrogen; R 3 is hydrogen; D* is a residue of a biologically active compound; and n is , 2. In another embodiment, R 1a is alkylene, where Furthermore, R 3 to form a 4-, 5-, or 6-membered heterocyclyl; and R 1b is an aryl ;R 2 is hydrogen; R 3 is hydrogen; D* is a residue of a biologically active compound; and n is 2. In another embodiment, R 1a is alkylene, where Ng further added that 3 to form a 4-, 5-, or 6-membered heterocyclyl; and R 1b Ali R is alkyl; 2is hydrogen; R 3 is hydrogen; D* is the residue of a biologically active compound and n is 2. In another embodiment, R 1a is alkylene, where The alkylene may further include R 3 to form a 4-, 5-, or 6-membered heterocyclyl; and R 1b is heteroaryl; R 2 is hydrogen; R 3 is hydrogen; D* is a biologically active compound and n is 2. In another embodiment, R 1a is hydrogen and R 1b is hydrogen; R 2 is an amino acid side chain; R 3 is hydrogen; D* is the residue; and n is 2. In another embodiment, R 1a is hydrogen and R 1b teeth , alkyl; R 2 is an amino acid side chain; R 3 is hydrogen; D* is a biologically active compound and n is 2. In another embodiment, R 1a is hydrogen and R 1b is alkoxy; R 2 is an amino acid side chain; R 3 is hydrogen; D* is bioactive and n is 2. In another embodiment, R 1a is hydrogen, and R 1b is alkenyl; R 2 is an amino acid side chain; R 3 is hydrogen; D* is bioactive and n is 2. In another embodiment, R 1a is hydrogen, R1b is alkynyl; R 2 is an amino acid side chain; R 3 is hydrogen; D* is a physiological and n is 2. In another embodiment, R 1a is hydrogen, And R 1b is aryl; R 2 is an amino acid side chain; R 3 is hydrogen; D* is a physiological and n is 2. In another embodiment, R 1a is hydrogen, And R 1b is arylalkyl; R 2 is an amino acid side chain; R 3 is hydrogen; D* is , a residue of a biologically active compound; and n is 2. In another embodiment, R 1a is hydrogen and R 1b is heteroaryl; R 2 is an amino acid side chain; R 3 is hydrogen D* is a residue of a biologically active compound; and n is 2. In another embodiment, R 1a is alkylene, wherein the alkylene further comprises R 3 4, 5, or 6-membered bond and R 1b is hydrogen; R 2 is an amino acid side chain; R 3 Water D* is a residue of a biologically active compound; and n is 2. In any of the above cases, R 4 is hydrogen. In any of the embodiments of this paragraph , R 4 is alkyl.

[0114] In another embodiment, R1a is alkylene, wherein the alkylene is further , R 3 to form a 4-, 5-, or 6-membered heterocyclyl; and R 1b is alkyl; R 2 is an amino acid side chain; R 3 is hydrogen; D* is a residue of a biologically active compound; and n is , 2. In another embodiment, R 1a is alkylene, where Furthermore, R 3 to form a 4-, 5-, or 6-membered heterocyclyl; and R 1b Alcoki Sil;R 2 is an amino acid side chain; R 3 is hydrogen; D* is a residue of a biologically active compound and n is 2. In another embodiment, R 1a is alkylene, where The alkylene further comprises R 3 to form a 4-, 5-, or 6-membered heterocyclyl; and R 1 b is alkenyl; R 2 is an amino acid side chain; R 3 is hydrogen; D* is bioactive and n is 2. In another embodiment, R 1a is an alkylene wherein the alkylene further comprises R 3 to form a 4-, 5-, or 6-membered heterocyclyl And R 1b is alkynyl; R 2 is an amino acid side chain; R 3 is hydrogen; D* is , a residue of a biologically active compound; and n is 2. In another embodiment, R 1a Is, Al alkylene, wherein the alkylene further comprises R3 4, 5, or 6 membered heterocyclic Forming a cyclyl; and R 1b is aryl; R 2 is an amino acid side chain; R 3 is hydrogen D* is a residue of a biologically active compound; and n is 2. In another embodiment, R 1 a is alkylene, wherein the alkylene further comprises R 3 4, 5, or 6-membered bond and R 1b is arylalkyl; R 2 is the amino acid side chain Yes;R 3 is hydrogen; D* is a residue of a biologically active compound; and n is 2. In the embodiment, R 1a is alkylene, wherein the alkylene further comprises R 3 In conclusion combine with R to form a 4-, 5-, or 6-membered heterocyclyl; and R 1b is heteroaryl; R 2 teeth , an amino acid side chain; R 3 is hydrogen; D* is a residue of a biologically active compound; and n is 2. In another embodiment, R 1a is hydrogen and R 1b is hydrogen; R 2 Water R 3 is alkyl; D* is a residue of a biologically active compound; and n is 2. In another embodiment, R 1a is hydrogen and R 1b is alkyl; R 2 is hydrogen ;R 3 is alkyl; D* is a residue of a biologically active compound; and n is 2. In another embodiment, R1a is hydrogen and R 1b is alkoxy; R 2 is hydrogen ;R 3 is alkyl; D* is a residue of a biologically active compound; and n is 2. In another embodiment, R 1a is hydrogen and R 1b is alkenyl; R 2 is hydrogen ;R 3 is alkyl; D* is a residue of a biologically active compound; and n is 2. In another embodiment, R 1a is hydrogen and R 1b is alkynyl; R 2 is hydrogen ;R 3 is alkyl; D* is a residue of a biologically active compound; and n is 2. In another embodiment, R 1a is hydrogen and R 1b is aryl; R 2 is hydrogen Yes;R 3 is alkyl; D* is a residue of a biologically active compound; and n is 2. In an embodiment of the invention, R 1a is hydrogen and R 1b is arylalkyl; R 2 teeth, Hydrogen; R 3 is alkyl; D* is a residue of a biologically active compound; and n is 2. In another embodiment, R 1a is hydrogen and R 1b is heteroaryl; R 2 is hydrogen; R 3 is alkyl; D* is a residue of a biologically active compound; and n is 2 In another embodiment, R 1a is alkylene, where the alkylene is In addition, R 3 to form a 4-, 5-, or 6-membered heterocyclyl; and R 1b is hydrogen; R 2 is hydrogen; R 3 is alkyl; D* is a residue of a biologically active compound; and n is 2. In any of the embodiments of this paragraph, R 4 is hydrogen. In any of the embodiments of the present invention, R 4 is alkyl.

[0115] In another embodiment, R 1a is alkylene, wherein the alkylene is further , R 3 to form a 4-, 5-, or 6-membered heterocyclyl; and R 1b is alkyl; R 2 is hydrogen; R 3 is alkyl; D* is a residue of a biologically active compound; and n is 2 In another embodiment, R 1a is alkylene, where the alkylene is In addition, R 3 to form a 4-, 5-, or 6-membered heterocyclyl; and R 1b is an alkoxy R 2 is hydrogen; R 3 is alkyl; D* is a residue of a biologically active compound; and n is 2. In another embodiment, R 1a is alkylene, Rukyren further added, 3 to form a 4-, 5-, or 6-membered heterocyclyl; and R 1b teeth, alkenyl; R 2 is hydrogen; R 3 is alkyl; D* is the residue of a biologically active compound. group; and n is 2. In another embodiment, R 1a is alkylene, The alkylene further comprises R 3 to form a 4-, 5-, or 6-membered heterocyclyl; and R 1b is alkynyl; R 2 is hydrogen; R 3 is an alkyl group; D* is a bioactive group and n is 2. In another embodiment, R 1a is alkylene; wherein the alkylene further comprises R 3 to form a 4-, 5-, or 6-membered heterocyclyl S; and R 1b is aryl; R 2 is hydrogen; R 3 is alkyl; D* is a bioactive and n is 2. In another embodiment, R 1a is an alkylene wherein the alkylene further comprises R 3 4-, 5-, or 6-membered heterocyclyl and R 1b is arylalkyl; R 2 is hydrogen; R 3 is an alkyl D* is a residue of a biologically active compound; and n is 2. In another embodiment, R 1a teeth , alkylene, wherein the alkylene is further selected from the group consisting of R 3 4, 5, or 6-membered forming a heterocyclyl; and R 1b is heteroaryl; R 2 is hydrogen; R 3 A D* is a residue of a biologically active compound; and n is 2. And R 1a is hydrogen and R1b is hydrogen; R 2 is an amino acid side chain; R 3 A D* is a residue of a biologically active compound; and n is 2. And R 1a is hydrogen and R 1b is alkyl; R 2 is an amino acid side chain; R 3 teeth , alkyl; D* is a residue of a biologically active compound; and n is 2. In R 1a is hydrogen and R 1b is alkoxy; R 2 is an amino acid side chain R 3 is alkyl; D* is a residue of a biologically active compound; and n is 2. In an embodiment, R 1a is hydrogen and R 1b is alkenyl; R 2 is an amino acid Side chain; R 3 is alkyl; D* is a residue of a biologically active compound; and n is 2. In another embodiment, R 1a is hydrogen and R 1b is alkynyl; R 2 teeth, is an amino acid side chain; R 3 is alkyl; D* is a residue of a biologically active compound; and n is , 2. In another embodiment, R 1a is hydrogen and R 1b is aryl; R 2 is an amino acid side chain; R 3 is an alkyl; D* is a residue of a biologically active compound; In another embodiment, R 1a is hydrogen and R 1b is aryl Kill;R 2 is an amino acid side chain; R 3 is an alkyl group; D* is a group of the biologically active compound residue; and n is 2. In another embodiment, R 1a is hydrogen and R 1b teeth , heteroaryl; R 2 is an amino acid side chain; R 3 is alkyl; D* is physiological is a residue of an active compound; and n is 2. In any of the embodiments of this paragraph R 4 is hydrogen. In any of the embodiments of this paragraph, R 4 is an alkyl be.

[0116] In another embodiment, R 1a is alkylene, wherein the alkylene is further , R 3 to form a 4-, 5-, or 6-membered heterocyclyl; and R 1b is hydrogen; R 2 teeth, is an amino acid side chain; R 3 is alkyl; D* is a residue of a biologically active compound; and n is , 2. In another embodiment, R 1a is alkylene, where Furthermore, R 3 to form a 4-, 5-, or 6-membered heterocyclyl; and R 1b is an alkyl ;R 2 is an amino acid side chain; R 3 is an alkyl; D* is a residue of a biologically active compound and n is 2. In another embodiment, R 1a is alkylene, where The alkylene further comprises R 3to form a 4-, 5-, or 6-membered heterocyclyl; and R 1 b is alkoxyl; R 2 is an amino acid side chain; R 3 is alkyl; D* is physiological is a residue of an active compound; and n is 2. In another embodiment, R 1a is an alkylene wherein the alkylene further comprises R 3 4, 5, or 6-membered heterocyclyl and R 1b is alkenyl; R 2 is an amino acid side chain; R 3 is an alkyl D* is a residue of a biologically active compound; and n is 2. In another embodiment, R 1 a is alkylene, wherein the alkylene further comprises R 3 4, 5, or 6-membered bond and R 1b is alkynyl; R 2 is an amino acid side chain; R 3 is alkyl; D* is a residue of a biologically active compound; and n is 2. In this regard, R 1a is alkylene, wherein the alkylene further comprises R 3 Binds to forming a 4-, 5-, or 6-membered heterocyclyl; and R 1b is aryl; R 2 is an amino acid Side chain; R 3 is alkyl; D* is a residue of a biologically active compound; and n is 2. In another embodiment, R 1a is alkylene, wherein the alkylene is further To, R 3to form a 4-, 5-, or 6-membered heterocyclyl; and R 1b is an aryl alkyl group. R 2 is an amino acid side chain; R 3 is alkyl; D* is the residue of a biologically active compound. group; and n is 2. In another embodiment, R 1a is alkylene, The alkylene further comprises R 3 to form a 4-, 5-, or 6-membered heterocyclyl; and R 1b is heteroaryl; R 2 is an amino acid side chain; R 3 is alkyl; D* is and n is 2. In another embodiment, R 1a Is, Alki wherein the alkylene further comprises R 3 4, 5, or 6-membered heterocyclic Forms krill; and R 1b is hydrogen; R 2 is hydrogen; R 3 is R 1a Further combining with D* is an alkylene group forming a 4-, 5-, or 6-membered heterocyclyl; residue; and n is 2. In another embodiment, R 1a is alkylene, wherein the alkylene further comprises R 3 to form a 4-, 5-, or 6-membered heterocyclyl; R 1b is alkyl; R 2 is hydrogen; R 3 is R 1a Further linked to the 4, 5, or 6 D* is a residue of a biologically active compound; In another embodiment, R 1ais alkylene, Killen further added that 3 to form a 4-, 5-, or 6-membered heterocyclyl; and R 1b A R is alkoxyl; 2 is hydrogen; R 3 is R 1a Further attached to said 4, 5, or 6 membered heterocyclic D* is a residue of a biologically active compound; and n is 2 In any of the embodiments of this paragraph, R 4 is hydrogen. In any of the embodiments, R 4 is alkyl.

[0117] In another embodiment, R 1a is alkylene, wherein the alkylene is further , R 3 to form a 4-, 5-, or 6-membered heterocyclyl; and R 1b is alkenyl; R 2 is hydrogen; R 3 is R 1a further attached to form said 4-, 5-, or 6-membered heterocyclyl D* is a residue of a biologically active compound; and n is 2. In an embodiment, R 1a is alkylene, wherein the alkylene further comprises R 3 Combined to to form a 4-, 5-, or 6-membered heterocyclyl; and R 1b is alkynyl; R 2 is hydrogen ;R 3 is R 1a to form said 4-, 5-, or 6-membered heterocyclyl. D* is a residue of a biologically active compound; and n is 2. R1a is alkylene, wherein the alkylene further comprises R 3 4, 5, or a 6-membered heterocyclyl; and R 1b is aryl; R 2 is hydrogen; R 3 teeth , R 1a is an alkylene further attached to form said 4-, 5-, or 6-membered heterocyclyl; * is a residue of a biologically active compound; and n is 2. In another embodiment, R 1a teeth, alkylene, wherein the alkylene is further selected from the group consisting of R 3 4, 5, or 6-membered hexafluorophosphate Forming a tetracyclyl; and R 1b is arylalkyl; R 2 is hydrogen; R 3 is R 1 a is an alkylene which further binds to form said 4-, 5-, or 6-membered heterocyclyl; D* is , a residue of a biologically active compound; and n is 2. In another embodiment, R 1a Is, Al alkylene, wherein the alkylene further comprises R 3 4, 5, or 6 membered heterocyclic Forming a cyclyl; and R 1b is heteroaryl; R 2 is hydrogen; R 3 is R 1a Nisa and D* is an alkylene which is attached to said 4-, 5-, or 6-membered heterocyclyl; is a residue of an active compound; and n is 2. In another embodiment, R 1a is an alkylene wherein the alkylene further comprises R 3 4, 5, or 6-membered heterocyclyl and R 1bis hydrogen; R 2 is an amino acid side chain; R 3 is R 1a Further binding to D* is an alkylene which combines with the aryl group to form said 4-, 5-, or 6-membered heterocyclyl; and n is 2. In another embodiment, R 1a is an alkylene; wherein the alkylene further comprises R 3 to form a 4-, 5-, or 6-membered heterocyclyl S; and R 1b is alkyl; R 2 is an amino acid side chain; R 3 is R 1a Further combining with D* is an alkylene group forming a 4-, 5-, or 6-membered heterocyclyl; residue; and n is 2. In another embodiment, R 1a is alkylene, wherein the alkylene further comprises R 3 to form a 4-, 5-, or 6-membered heterocyclyl; R 1b is alkoxyl; R 2 is an amino acid side chain; R 3 is R 1a It further binds to the D* is an alkylene group forming a 4-, 5-, or 6-membered heterocyclyl; D* is the residue of a biologically active compound. group; and n is 2. In another embodiment, R 1a is alkylene, The alkylene further comprises R 3 to form a 4-, 5-, or 6-membered heterocyclyl; and R 1b is alkenyl; R 2 is an amino acid side chain; R 3 is R 1a Further binding to the 4, 5 or alkylene forming a 6-membered heterocyclyl; D* is a residue of a biologically active compound. and n is 2. In any of the embodiments of this paragraph, R 4 is hydrogen In any of the embodiments of this paragraph, R 4 is alkyl.

[0118] In another embodiment, R 1a is alkylene, wherein the alkylene is further , R 3 to form a 4-, 5-, or 6-membered heterocyclyl; and R 1b is alkynyl; R 2 is an amino acid side chain; R 3 is R 1a further linked to said 4, 5, or 6 membered heterocyclyl D* is an alkylene group forming a ring; D* is a residue of a biologically active compound; and n is 2. In another embodiment, R 1a is alkylene, wherein the alkylene further comprises R 3 to form a 4-, 5-, or 6-membered heterocyclyl; and R 1b is aryl; R 2 teeth , an amino acid side chain; R 3 is R 1a further attached to said 4-, 5-, or 6-membered heterocyclyl D* is a residue of a biologically active compound; and n is 2. In an embodiment, R 1a is alkylene, wherein the alkylene further comprises R 3 To linked to form a 4-, 5-, or 6-membered heterocyclyl; and R 1b is arylalkyl; R 2 is an amino acid side chain; R 3 is R 1afurther linked to said 4, 5, or 6 membered heterocyclyl D* is an alkylene group forming a ring; D* is a residue of a biologically active compound; and n is 2. In another embodiment, R 1a is alkylene, wherein the alkylene further comprises R 3 to form a 4-, 5-, or 6-membered heterocyclyl; and R 1b is a heteroaryl ;R 2 is an amino acid side chain; R 3 is R 1a further linked to said 4, 5, or 6 membered heterocyclyl D* is an alkylene group forming a ring; D* is a residue of a biologically active compound; and n is 2. In any of the embodiments of this paragraph, R 4 is hydrogen. In any of the above cases, R 4 is alkyl.

[0119] In another embodiment, R 1a is hydrogen and R 1b is hydrogen; R 2 is hydrogen R 3 is hydrogen; D* is hydrogen; and n is 3. In another embodiment, R 1a is hydrogen and R 1b is alkyl; R 2 is hydrogen; R 3 is hydrogen; D* is , hydrogen; and n is 3. In another embodiment, R 1a is hydrogen and R 1b is alkoxy; R 2 is hydrogen; R 3 is hydrogen; D* is hydrogen; and n is , 3. In another embodiment, R 1a is hydrogen and R1b is alkenyl; R 2 is hydrogen; R 3 is hydrogen; D* is hydrogen; and n is 3. In this regard, R 1a is hydrogen and R 1b is alkynyl; R 2 is hydrogen; R 3 teeth D* is hydrogen; and n is 3. In another embodiment, R 1a Water Prime and R 1b is aryl; R 2 is hydrogen; R 3 is hydrogen; D* is hydrogen and n is 3. In another embodiment, R 1a is hydrogen and R 1b A R is aryl alkyl; 2 is hydrogen; R 3 is hydrogen; D* is hydrogen; and n is , 3. In another embodiment, R 1a is hydrogen and R 1b is a heteroaryl Yes;R 2 is hydrogen; R 3 is hydrogen; D* is hydrogen; and n is 3. In the embodiment, R 1a is alkylene, wherein the alkylene further comprises R 3 In conclusion combine with R to form a 4-, 5-, or 6-membered heterocyclyl; and R 1b is hydrogen; R 2 is hydrogen R 3 is hydrogen; D* is hydrogen; and n is 3. In another embodiment, R 1a is alkylene, wherein the alkylene further comprises R 3 4, 5, or 6-membered bond and R 1b is alkyl; R 2 is hydrogen; R 3 is hydrogen D* is hydrogen; and n is 3. In another embodiment, R 1a is an alkylene wherein the alkylene further comprises R 3 4, 5, or 6-membered heterocyclyl and R 1b is alkoxyl; R 2 is hydrogen; R 3 is hydrogen; D* is , hydrogen; and n is 3. In another embodiment, R 1a is alkylene, wherein the alkylene further comprises R 3 to form a 4-, 5-, or 6-membered heterocyclyl; And R 1b is alkenyl; R 2 is hydrogen; R 3 is hydrogen; D* is hydrogen; and n is 3. In another embodiment, R 1a is alkylene, Rukyren further added, 3 to form a 4-, 5-, or 6-membered heterocyclyl; and R 1b teeth, Alkynyl; R 2 is hydrogen; R 3 is hydrogen; D* is hydrogen; and n is 3 In another embodiment, R 1a is alkylene, wherein the alkylene is Furthermore, R 3 to form a 4-, 5-, or 6-membered heterocyclyl; and R 1b is an aryl R 2 is hydrogen; R 3is hydrogen; D* is hydrogen; and n is 3. In an embodiment, R 1a is alkylene, wherein the alkylene further comprises R 3 Combined to to form a 4-, 5-, or 6-membered heterocyclyl; and R 1b is arylalkyl; R 2 teeth , hydrogen; R 3 is hydrogen; D* is hydrogen; and n is 3. Hey, R 1a is alkylene, wherein the alkylene further comprises R 3 4, which is bonded to forming a 5- or 6-membered heterocyclyl; and R 1b is heteroaryl; R 2 is hydrogen Yes;R 3 is hydrogen; D* is hydrogen; and n is 3. In another embodiment, R 1a is hydrogen and R 1b is hydrogen; R 2 is an amino acid side chain; R 3 is hydrogen D* is hydrogen; and n is 3. In another embodiment, R 1a is hydrogen, And R 1b is alkyl; R 2 is an amino acid side chain; R 3 is hydrogen; D* is hydrogen and n is 3. In another embodiment, R 1a is hydrogen and R 1b Is, Al Cox;R 2 is an amino acid side chain; R 3 is hydrogen; D* is hydrogen; and n is , 3. In another embodiment, R 1a is hydrogen and R 1b is alkenyl; R 2 is an amino acid side chain; R 3 is hydrogen; D* is hydrogen; and n is 3. In an embodiment of the invention, R 1a is hydrogen and R 1b is alkynyl; R 2 Amino R is an acid side chain; 3 is hydrogen; D* is hydrogen; and n is 3. Hey, R 1a is hydrogen and R 1b is aryl; R 2 is an amino acid side chain; R 3 is hydrogen; D* is hydrogen; and n is 3. In another embodiment, R 1a teeth, Hydrogen and R 1b is arylalkyl; R 2 is an amino acid side chain; R 3 Water D* is hydrogen; and n is 3. In another embodiment, R 1a is hydrogen Yes and R 1b is heteroaryl; R 2 is an amino acid side chain; R 3 is hydrogen; D* is hydrogen; and n is 3. In another embodiment, R 1a is an alkylene wherein the alkylene further comprises R 3 to form a 4-, 5-, or 6-membered heterocyclyl And R 1b is hydrogen; R 2 is an amino acid side chain; R 3 is hydrogen; D* is hydrogen and n is 3. In another embodiment, R 1a is alkylene, where The alkylene further comprises R 3to form a 4-, 5-, or 6-membered heterocyclyl; and R 1 b is alkyl; R 2 is an amino acid side chain; R 3 is hydrogen; D* is hydrogen; and n is 3. In another embodiment, R 1a is alkylene, Lukiren further added, 3 to form a 4-, 5-, or 6-membered heterocyclyl; and R 1b teeth, Alkoxyl; R 2 is an amino acid side chain; R 3 is hydrogen; D* is hydrogen; or n is 3. In another embodiment, R 1a is alkylene, Killen further added that 3 to form a 4-, 5-, or 6-membered heterocyclyl; and R 1b A R is alkenyl; 2 is an amino acid side chain; R 3 is hydrogen; D* is hydrogen; and n is 3. In any of the embodiments of this paragraph, R 4 is hydrogen. In any of the embodiments of the graph, R 4 is alkyl.

[0120] In another embodiment, R 1a is alkylene, wherein the alkylene is further , R 3 to form a 4-, 5-, or 6-membered heterocyclyl; and R 1b is alkynyl; R 2 is an amino acid side chain; R 3 is hydrogen; D* is hydrogen; and n is 3. In an embodiment of the invention, R 1ais alkylene, wherein the alkylene further comprises R 3 to form a 4-, 5-, or 6-membered heterocyclyl; and R 1b is aryl; R 2 teeth, is an amino acid side chain; R 3 is hydrogen; D* is hydrogen; and n is 3. In an embodiment, R 1a is alkylene, wherein the alkylene further comprises R 3 Combined to to form a 4-, 5-, or 6-membered heterocyclyl; and R 1b is arylalkyl; R 2 teeth , an amino acid side chain; R 3 is hydrogen; D* is hydrogen; and n is 3. In the embodiment, R 1a is alkylene, wherein the alkylene further comprises R 3 In conclusion combine with R to form a 4-, 5-, or 6-membered heterocyclyl; and R 1b is heteroaryl; R 2 teeth , an amino acid side chain; R 3 is hydrogen; D* is hydrogen; and n is 3. In the embodiment, R 1a is hydrogen and R 1b is hydrogen; R 2 is hydrogen; R 3 teeth, D* is hydrogen; and n is 3. In another embodiment, R 1a teeth, Hydrogen and R 1b is alkyl; R 2 is hydrogen; R 3 is alkyl; D* is , hydrogen; and n is 3. In another embodiment, R 1a is hydrogen and R 1b is alkoxy; R 2 is hydrogen; R 3 is alkyl; D* is hydrogen; and n is 3. In another embodiment, R 1a is hydrogen and R 1b is alkenyl R 2 is hydrogen; R 3 is alkyl; D* is hydrogen; and n is 3. In an embodiment, R 1a is hydrogen and R 1b is alkynyl; R 2 is hydrogen R 3 is alkyl; D* is hydrogen; and n is 3. , R 1a is hydrogen and R 1b is aryl; R 2 is hydrogen; R 3 is an alkyl D* is hydrogen; and n is 3. In another embodiment, R 1a is hydrogen , and R 1b is arylalkyl; R 2 is hydrogen; R 3 is alkyl; D* is and n is 3. In another embodiment, R 1a is hydrogen and R 1b teeth , heteroaryl; R 2 is hydrogen; R 3 is alkyl; D* is hydrogen; or n is 3. In another embodiment, R 1a is alkylene, Killen further added that 3 to form a 4-, 5-, or 6-membered heterocyclyl; and R 1b Water R2 is hydrogen; R 3 is alkyl; D* is hydrogen; and n is 3. In another embodiment, R 1a is alkylene, wherein the alkylene is further , R 3 to form a 4-, 5-, or 6-membered heterocyclyl; and R 1b is alkyl; R 2 is hydrogen; R 3 is alkyl; D* is hydrogen; and n is 3. In an embodiment, R 1a is alkylene, wherein the alkylene further comprises R 3 Combined to to form a 4-, 5-, or 6-membered heterocyclyl; and R 1b is alkoxyl; R 2 Water R 3 is alkyl; D* is hydrogen; and n is 3. Hey, R 1a is alkylene, wherein the alkylene further comprises R 3 4, which is bonded to forming a 5- or 6-membered heterocyclyl; and R 1b is alkenyl; R 2 is hydrogen; R 3 is alkyl; D* is hydrogen; and n is 3. In another embodiment, R 1 a is alkylene, wherein the alkylene further comprises R 3 4, 5, or 6-membered bond and R 1b is alkynyl; R 2 is hydrogen; R 3 Is, Al D* is hydrogen; and n is 3. Hey, R 4 is hydrogen. In any of the embodiments of this paragraph, R 4 Is, Alki It is.

[0121] In another embodiment, R 1a is alkylene, wherein the alkylene is further , R 3 to form a 4-, 5-, or 6-membered heterocyclyl; and R 1b is aryl; R 2 is hydrogen; R 3 is alkyl; D* is hydrogen; and n is 3. In an embodiment, R 1a is alkylene, wherein the alkylene further comprises R 3 Combined to to form a 4-, 5-, or 6-membered heterocyclyl; and R 1b is arylalkyl; R 2 teeth , hydrogen; R 3 is alkyl; D* is hydrogen; and n is 3. In this regard, R 1a is alkylene, wherein the alkylene further comprises R 3 Binds to forming a 4-, 5-, or 6-membered heterocyclyl; and R 1b is heteroaryl; R 2 Water R 3 is alkyl; D* is hydrogen; and n is 3. Hey, R 1a is hydrogen and R 1b is hydrogen; R 2 is an amino acid side chain; R 3 teeth, D* is hydrogen; and n is 3. In another embodiment, R 1a teeth, Hydrogen and R 1bis alkyl; R 2 is an amino acid side chain; R 3 is an alkyl D* is hydrogen; and n is 3. In another embodiment, R 1a is hydrogen , and R 1b is alkoxy; R 2 is an amino acid side chain; R 3 is alkyl; D* is , hydrogen; and n is 3. In another embodiment, R 1a is hydrogen and R 1b is alkenyl; R 2 is an amino acid side chain; R 3 is alkyl; D* is hydrogen and n is 3. In another embodiment, R 1a is hydrogen and R 1b Is, Al quinyl;R 2 is an amino acid side chain; R 3 is alkyl; D* is hydrogen; and n is 3. In another embodiment, R 1a is hydrogen and R 1b is an aryl ;R 2 is an amino acid side chain; R 3 is alkyl; D* is hydrogen; and n is 3. In another embodiment, R 1a is hydrogen and R 1b is arylalkyl; R 2 is an amino acid side chain; R 3 is alkyl; D* is hydrogen; and n is 3. In another embodiment, R 1a is hydrogen and R 1b is heteroaryl; R 2 teeth, is an amino acid side chain; R 3is alkyl; D* is hydrogen; and n is 3. In an embodiment, R 1a is alkylene, wherein the alkylene further comprises R 3 To linked to form a 4-, 5-, or 6-membered heterocyclyl; and R 1b is hydrogen; R 2 Amino R is an acid side chain; 3 is alkyl; D* is hydrogen; and n is 3. In this regard, R 1a is alkylene, wherein the alkylene further comprises R 3 Binds to forming a 4-, 5-, or 6-membered heterocyclyl; and R 1b is alkyl; R 2 is an amino acid Side chain; R 3 is alkyl; D* is hydrogen; and n is 3. In R 1a is alkylene, wherein the alkylene further comprises R 3 4 , 5, or 6 membered heterocyclyl; and R 1b is alkoxyl; R 2 Amino R is an acid side chain; 3 is alkyl; D* is hydrogen; and n is 3. In this regard, R 1a is alkylene, wherein the alkylene further comprises R 3 Binds to forming a 4-, 5-, or 6-membered heterocyclyl; and R 1b is alkenyl; R 2 Amino R is an acid side chain; 3 is alkyl; D* is hydrogen; and n is 3. In this regard, R 1ais alkylene, wherein the alkylene further comprises R 3 Binds to forming a 4-, 5-, or 6-membered heterocyclyl; and R 1b is alkynyl; R 2 Amino R is an acid side chain; 3 is alkyl; D* is hydrogen; and n is 3. In this regard, R 1a is alkylene, wherein the alkylene further comprises R 3 Binds to forming a 4-, 5-, or 6-membered heterocyclyl; and R 1b is aryl; R 2 is an amino acid Side chain; R 3 is alkyl; D* is hydrogen; and n is 3. In any of the embodiments, R 4 is hydrogen. In R 4 is alkyl.

[0122] In another embodiment, R 1a is alkylene, wherein the alkylene is further , R 3 to form a 4-, 5-, or 6-membered heterocyclyl; and R 1b is aryl alkyl ;R 2 is an amino acid side chain; R 3 is alkyl; D* is hydrogen; and n is 3 In another embodiment, R 1a is alkylene, where the alkylene is In addition, R 3 to form a 4-, 5-, or 6-membered heterocyclyl; and R 1b Hetero ants R 2 is an amino acid side chain; R 3is alkyl; D* is hydrogen; and n is 3. In another embodiment, R 1a is alkylene, where Ng further added that 3 to form a 4-, 5-, or 6-membered heterocyclyl; and R 1b is hydrogen Yes;R 2 is hydrogen; R 3 is R 1a further attached to said 4-, 5-, or 6-membered heterocyclyl D* is hydrogen; and n is 3. , R 1a is alkylene, wherein the alkylene further comprises R 3 4, 5, or forms a six-membered heterocyclyl; and R 1b is alkyl; R 2 is hydrogen; R 3 is R 1a is an alkylene which further binds to form said 4-, 5-, or 6-membered heterocyclyl; D* is , hydrogen; and n is 3. In another embodiment, R 1a is alkylene, wherein the alkylene further comprises R 3 to form a 4-, 5-, or 6-membered heterocyclyl; And R 1b is alkoxyl; R 2 is hydrogen; R 3 is R 1a Further bind to the 4, 5, or alkylene forming a 6-membered heterocyclyl; D* is hydrogen; and n is 3. In another embodiment, R 1a is alkylene, wherein the alkylene is Furthermore, R 3 to form a 4-, 5-, or 6-membered heterocyclyl; and R 1bis an alkenyl Yes;R 2 is hydrogen; R 3 is R 1a further attached to said 4-, 5-, or 6-membered heterocyclyl D* is hydrogen; and n is 3. , R 1a is alkylene, wherein the alkylene further comprises R 3 4, 5, or forms a six-membered heterocyclyl; and R 1b is alkynyl; R 2 is hydrogen; R 3 teeth , R 1a is an alkylene further attached to form said 4-, 5-, or 6-membered heterocyclyl; * is hydrogen; and n is 3. In another embodiment, R 1a is an alkylene wherein the alkylene further comprises R 3 to form a 4-, 5-, or 6-membered heterocyclyl And R 1b is aryl; R 2 is hydrogen; R 3 is R 1a Further binding to the 4, 5 or alkylene forming a 6-membered heterocyclyl; D* is hydrogen; and n is 3 In another embodiment, R 1a is alkylene, where the alkylene is In addition, R 3 to form a 4-, 5-, or 6-membered heterocyclyl; and R 1b is an aryl RuKil is;R 2 is hydrogen; R 3 is R 1a further linked to said 4, 5, or 6 membered heterocyclic D* is hydrogen; and n is 3. In R 1a is alkylene, wherein the alkylene further comprises R 3 4 , 5, or 6 membered heterocyclyl; and R 1b is heteroaryl; R 2 is hydrogen ;R 3 is R 1a to form said 4-, 5-, or 6-membered heterocyclyl. D* is hydrogen; and n is 3. In another embodiment, R 1a Is, Al alkylene, wherein the alkylene further comprises R 3 4, 5, or 6 membered heterocyclic Forming a cyclyl; and R 1b is hydrogen; R 2 is an amino acid side chain; R 3 is R 1a Nisara is an alkylene which is bonded to said 4-, 5-, or 6-membered heterocyclyl; D* is hydrogen. and n is 3. In any of the embodiments of this paragraph, R 4 is hydrogen In any of the embodiments of this paragraph, R 4 is alkyl.

[0123] In another embodiment, R 1a is alkylene, wherein the alkylene is further , R 3 to form a 4-, 5-, or 6-membered heterocyclyl; and R 1b is alkyl; R 2 is an amino acid side chain; R 3 is R 1a further bound to said 4-, 5-, or 6-membered heterocyclyl D* is hydrogen; and n is 3. R 1ais alkylene, wherein the alkylene further comprises R 3 4, 5, or a 6-membered heterocyclyl; and R 1b is alkoxyl; R 2 is the amino acid side chain ;R 3 is R 1a to form said 4-, 5-, or 6-membered heterocyclyl. D* is hydrogen; and n is 3. In another embodiment, R 1a Is, Al alkylene, wherein the alkylene further comprises R 3 4, 5, or 6 membered heterocyclic Forming a cyclyl; and R 1b is alkenyl; R 2 is an amino acid side chain; R 3 is R 1a is an alkylene which further binds to said 4-, 5-, or 6-membered heterocyclyl; D* is hydrogen; and n is 3. In another embodiment, R 1a is alkylene, wherein the alkylene further comprises R 3 to form a 4-, 5-, or 6-membered heterocyclyl; R 1b is alkynyl; R 2 is an amino acid side chain; R 3 is R 1a Further binding to the 4 , 5, or 6-membered heterocyclyl; D* is hydrogen; and n is , 3. In another embodiment, R 1a is alkylene, where Furthermore, R 3 to form a 4-, 5-, or 6-membered heterocyclyl; and R 1b is an aryl ;R 2 is an amino acid side chain; R3 is R 1a further linked to said 4, 5, or 6 membered heterocyclic is an alkylene group forming a cyclyl; D* is hydrogen; and n is 3. In this regard, R 1a is alkylene, wherein the alkylene further comprises R 3 Binds to forming a 4-, 5-, or 6-membered heterocyclyl; and R 1b is arylalkyl; R 2 teeth, is an amino acid side chain; R 3 is R 1a to form the 4-, 5-, or 6-membered heterocyclyl. D* is hydrogen; and n is 3. In another embodiment, R 1a is alkylene, wherein the alkylene further comprises R 3 4, 5, or 6 forming a 1-membered heterocyclyl; and R 1b is heteroaryl; R 2 is the amino acid side chain Yes;R 3 is R 1a which further binds to form said 4-, 5-, or 6-membered heterocyclyl. D* is hydrogen; and n is 3. In another embodiment, R 1a is hydrogen Yes and R 1b is hydrogen; R 2 is hydrogen; R 3 is hydrogen; D* is acyl and n is 3. In another embodiment, R 1a is hydrogen and R 1b is an alkyl ;R 2 is hydrogen; R 3 is hydrogen; D* is acyl; and n is 3. In an embodiment of the invention, R 1ais hydrogen and R 1b is alkoxy; R 2 is hydrogen Yes;R 3 is hydrogen; D* is acyl; and n is 3. , R 1a is hydrogen and R 1b is alkenyl; R 2 is hydrogen; R 3 is hydrogen D* is acyl; and n is 3. In another embodiment, R 1a is hydrogen , and R 1b is alkynyl; R 2 is hydrogen; R 3 is hydrogen; D* is acyl and n is 3. In another embodiment, R 1a is hydrogen and R 1b Ali R 2 is hydrogen; R 3 is hydrogen; D* is acyl; and n is 3. In another embodiment, R 1a is hydrogen and R 1b is arylalkyl; R 2 teeth , hydrogen; R 3 is hydrogen; D* is acyl; and n is 3. In R 1a is hydrogen and R 1b is heteroaryl; R 2 is hydrogen; R 3 is hydrogen; D* is acyl; and n is 3. In either case, R 4 is hydrogen. In any of the embodiments of this paragraph, R 4 teeth, It is an alkyl.

[0124] In another embodiment, R 1a is alkylene, wherein the alkylene is further , R 3 to form a 4-, 5-, or 6-membered heterocyclyl; and R 1b is hydrogen; R 2 teeth, Hydrogen; R 3 is hydrogen; D* is acyl; and n is 3. Hey, R 1a is alkylene, wherein the alkylene further comprises R 3 4, which is bonded to forming a 5- or 6-membered heterocyclyl; and R 1b is alkyl; R 2 is hydrogen; R 3 is hydrogen; D* is acyl; and n is 3. In another embodiment, R 1a teeth , alkylene, wherein the alkylene is further selected from the group consisting of R 3 4, 5, or 6-membered forming a heterocyclyl; and R 1b is alkoxyl; R 2 is hydrogen; R 3 is hydrogen D* is acyl; and n is 3. In another embodiment, R 1a Is, Alki wherein the alkylene further comprises R 3 4, 5, or 6-membered heterocyclic Forms krill; and R 1b is alkenyl; R 2 is hydrogen; R 3 is hydrogen; D* is acyl; and n is 3. In another embodiment, R 1a is an alkylene wherein the alkylene further comprises R 3 to form a 4-, 5-, or 6-membered heterocyclyl And R 1b is alkynyl; R 2 is hydrogen; R 3 is hydrogen; D* is acyl and n is 3. In another embodiment, R 1a is alkylene, where The alkylene further comprises R 3 to form a 4-, 5-, or 6-membered heterocyclyl; and R 1 b is aryl; R 2 is hydrogen; R 3 is hydrogen; D* is acyl; and n is , 3. In another embodiment, R 1a is alkylene, where Furthermore, R 3 to form a 4-, 5-, or 6-membered heterocyclyl; and R 1b is an aryl R is alkyl; 2 is hydrogen; R 3 is hydrogen; D* is acyl; and n is 3. In another embodiment, R 1a is alkylene, wherein the alkylene is Furthermore, R 3 to form a 4-, 5-, or 6-membered heterocyclyl; and R 1b Heteroaryl R 2 is hydrogen; R 3 is hydrogen; D* is acyl; and n is 3. In another embodiment, R 1a is hydrogen and R 1b is hydrogen; R 2 On the amino acid side Chain;R 3 is hydrogen; D* is acyl; and n is 3. And R 1a is hydrogen and R 1bis alkyl; R 2 is an amino acid side chain; R 3 teeth is hydrogen; D* is acyl; and n is 3. In another embodiment, R 1a teeth, Hydrogen and R 1b is alkoxy; R 2 is an amino acid side chain; R 3 is hydrogen D* is acyl; and n is 3. In another embodiment, R 1a is hydrogen , and R 1b is alkenyl; R 2 is an amino acid side chain; R 3 is hydrogen; D* is a and n is 3. In another embodiment, R 1a is hydrogen and R 1b teeth , alkynyl; R 2 is an amino acid side chain; R 3 is hydrogen; D* is acyl; and n is 3. In another embodiment, R 1a is hydrogen and R 1b is an aryl Yes;R 2 is an amino acid side chain; R 3 is hydrogen; D* is acyl; and n is 3. In another embodiment, R 1a is hydrogen and R 1b is arylalkyl; R 2 is an amino acid side chain; R 3 is hydrogen; D* is acyl; and n is 3. In an embodiment of the invention, R 1a is hydrogen and R 1b is heteroaryl; R 2 A R 3is hydrogen; D* is acyl; and n is 3. In an embodiment, R 1a is alkylene, wherein the alkylene further comprises R 3 Combined to to form a 4-, 5-, or 6-membered heterocyclyl; and R 1b is hydrogen; R 2 On the amino acid side Chain;R 3 is hydrogen; D* is acyl; and n is 3. And R 1a is alkylene, wherein the alkylene further comprises R 3 4, 5 or a 6-membered heterocyclyl; and R 1b is alkyl; R 2 is the amino acid side chain Yes;R 3 is hydrogen; D* is acyl; and n is 3. In any of the above cases, R 4 is hydrogen. In any of the embodiments of this paragraph , R 4 is alkyl.

[0125] In another embodiment, R 1a is alkylene, wherein the alkylene is further , R 3 to form a 4-, 5-, or 6-membered heterocyclyl; and R 1b is an alkoxyl R 2 is an amino acid side chain; R 3 is hydrogen; D* is acyl; and n is 3 In another embodiment, R 1a is alkylene, wherein the alkylene is further , R 3 to form a 4-, 5-, or 6-membered heterocyclyl; and R 1b is alkenyl; R 2 is an amino acid side chain; R 3 is hydrogen; D* is acyl; and n is 3. In another embodiment, R 1a is alkylene, wherein the alkylene further comprises R 3 to form a 4-, 5-, or 6-membered heterocyclyl; and R 1b is alkynyl; R 2 is an amino acid side chain; R 3 is hydrogen; D* is acyl; and n is 3. In an embodiment of the invention, R 1a is alkylene, wherein the alkylene further comprises R 3 to form a 4-, 5-, or 6-membered heterocyclyl; and R 1b is aryl; R 2 teeth, is an amino acid side chain; R 3 is hydrogen; D* is acyl; and n is 3. In the embodiment, R 1a is alkylene, wherein the alkylene further comprises R 3 In conclusion combine with R to form a 4-, 5-, or 6-membered heterocyclyl; and R 1b is arylalkyl; R 2 is an amino acid side chain; R 3 is hydrogen; D* is acyl; and n is 3. In an embodiment of the invention, R 1a is alkylene, wherein the alkylene further comprises R 3 to form a 4-, 5-, or 6-membered heterocyclyl; and R 1b is heteroaryl; R 2 is an amino acid side chain; R 3 is hydrogen; D* is acyl; and n is 3. In another embodiment, R 1a is hydrogen and R 1b is hydrogen; R 2 is hydrogen; R 3 is alkyl; D* is acyl; and n is 3. In another embodiment, R 1a is hydrogen and R 1b is alkyl; R 2 is hydrogen; R 3 is an alkyl D* is acyl; and n is 3. In another embodiment, R 1a is hydrogen , and R 1b is alkoxy; R 2 is hydrogen; R 3 is alkyl; D* is acyl and n is 3. In another embodiment, R 1a is hydrogen and R 1b A R is alkenyl; 2 is hydrogen; R 3 is alkyl; D* is acyl; and n is , 3. In another embodiment, R 1a is hydrogen and R 1b is alkynyl; R 2 is hydrogen; R 3 is alkyl; D* is acyl; and n is 3. In an embodiment, R 1a is hydrogen and R 1b is aryl; R 2 is hydrogen; R 3 is alkyl; D* is acyl; and n is 3. In another embodiment, R 1a is hydrogen and R 1b is arylalkyl; R 2 is hydrogen; R3 Is, Al D* is acyl; and n is 3. In another embodiment, R 1a Water Prime and R 1b is heteroaryl; R 2 is hydrogen; R 3 is alkyl; D* is acyl; and n is 3. In another embodiment, R 1a is an alkylene wherein the alkylene further comprises R 3 is bonded to a 4-, 5-, or 6-membered heterocyclyl Form; and R 1b is hydrogen; R 2 is hydrogen; R 3 is alkyl; D* is acyl and n is 3. In another embodiment, R 1a is alkylene, where The alkylene further comprises R 3 to form a 4-, 5-, or 6-membered heterocyclyl; and R 1 b is alkyl; R 2 is hydrogen; R 3 is alkyl; D* is acyl; n is 3. In another embodiment, R 1a is alkylene, Killen further added that 3 to form a 4-, 5-, or 6-membered heterocyclyl; and R 1b A R is alkoxyl; 2 is hydrogen; R 3 is alkyl; D* is acyl; and n is 3. In another embodiment, R 1a is alkylene, where Ng further added that 3to form a 4-, 5-, or 6-membered heterocyclyl; and R 1b Is, Arke Nil;R 2 is hydrogen; R 3 is alkyl; D* is acyl; and n is 3. In any of the embodiments of this paragraph, R 4 is hydrogen. In any of the embodiments, R 4 is alkyl.

[0126] In another embodiment, R 1a is alkylene, wherein the alkylene is further , R 3 to form a 4-, 5-, or 6-membered heterocyclyl; and R 1b is alkynyl; R 2 is hydrogen; R 3 is alkyl; D* is acyl; and n is 3. In an embodiment, R 1a is alkylene, wherein the alkylene further comprises R 3 To linked to form a 4-, 5-, or 6-membered heterocyclyl; and R 1b is aryl; R 2 Water R 3 is alkyl; D* is acyl; and n is 3. In R 1a is alkylene, wherein the alkylene further comprises R 3 4 , 5, or 6 membered heterocyclyl; and R 1b is arylalkyl; R 2 Water R 3 is alkyl; D* is acyl; and n is 3. In R 1ais alkylene, wherein the alkylene further comprises R 3 4 , 5, or 6 membered heterocyclyl; and R 1b is heteroaryl; R 2 is hydrogen ;R 3 is alkyl; D* is acyl; and n is 3. Hey, R 1a is hydrogen and R 1b is hydrogen; R 2 is an amino acid side chain; R 3 teeth, D* is alkyl; D* is acyl; and n is 3. In another embodiment, R 1a teeth , hydrogen, and R 1b is alkyl; R 2 is an amino acid side chain; R 3 is an alkyl D* is acyl; and n is 3. In another embodiment, R 1a is hydrogen Yes and R 1b is alkoxy; R 2 is an amino acid side chain; R 3 is alkyl; D* is acyl; and n is 3. In another embodiment, R 1a is hydrogen, R 1b is alkenyl; R 2 is an amino acid side chain; R 3 is alkyl; D* is a and n is 3. In another embodiment, R 1a is hydrogen and R 1b teeth , alkynyl; R 2 is an amino acid side chain; R 3 is alkyl; D* is acyl and n is 3. In another embodiment, R 1ais hydrogen and R 1b Yes, ants R 2 is an amino acid side chain; R 3 is alkyl; D* is acyl; and n is 3. In another embodiment, R 1a is hydrogen and R 1b is an aryl alkyl group. R 2 is an amino acid side chain; R 3 is alkyl; D* is acyl; and n is 3. In another embodiment, R 1a is hydrogen and R 1b is heteroaryl ;R 2 is an amino acid side chain; R 3 is alkyl; D* is acyl; and n is , 3. In another embodiment, R 1a is alkylene, where Furthermore, R 3 to form a 4-, 5-, or 6-membered heterocyclyl; and R 1b is hydrogen R 2 is an amino acid side chain; R 3 is alkyl; D* is acyl; and n is 3. In another embodiment, R 1a is alkylene, wherein the alkylene is Furthermore, R 3 to form a 4-, 5-, or 6-membered heterocyclyl; and R 1b is an alkyl R 2 is an amino acid side chain; R 3 is alkyl; D* is acyl; and n is 3. In another embodiment, R 1a is alkylene, wherein the alkylene is Furthermore, R 3to form a 4-, 5-, or 6-membered heterocyclyl; and R 1b is alkoxyl ;R 2 is an amino acid side chain; R 3 is alkyl; D* is acyl; and n is , 3. In another embodiment, R 1a is alkylene, where Furthermore, R 3 to form a 4-, 5-, or 6-membered heterocyclyl; and R 1b Is Arken R 2 is an amino acid side chain; R 3 is alkyl; D* is acyl; and n is 3. In another embodiment, R 1a is alkylene, where Ng further added that 3 to form a 4-, 5-, or 6-membered heterocyclyl; and R 1b Is, Alki Nil;R 2 is an amino acid side chain; R 3 is alkyl; D* is acyl; and n is 3. In any of the embodiments of this paragraph, R 4 is hydrogen. In any of the embodiments of the graph, R 4 is alkyl.

[0127] In another embodiment, R 1a is alkylene, wherein the alkylene is further , R 3 to form a 4-, 5-, or 6-membered heterocyclyl; and R 1b is aryl; R 2 is an amino acid side chain; R 3 is alkyl; D* is acyl; and n is 3. In another embodiment, R 1ais alkylene, wherein the alkylene is further , R 3 to form a 4-, 5-, or 6-membered heterocyclyl; and R 1b is aryl alkyl ;R 2 is an amino acid side chain; R 3 is alkyl; D* is acyl; and n is , 3. In another embodiment, R 1a is alkylene, where Furthermore, R 3 to form a 4-, 5-, or 6-membered heterocyclyl; and R 1b Heteroa Reel;R 2 is an amino acid side chain; R 3 is alkyl; D* is acyl; n is 3. In another embodiment, R 1a is alkylene, Killen further added that 3 to form a 4-, 5-, or 6-membered heterocyclyl; and R 1b Water R 2 is hydrogen; R 3 is R 1a further linked to said 4, 5, or 6 membered heterocyclyl D* is an alkylene group forming an alkyl group; D* is acyl; and n is 3. Hey, R 1a is alkylene, wherein the alkylene further comprises R 3 4, which is bonded to forming a 5- or 6-membered heterocyclyl; and R 1b is alkyl; R 2 is hydrogen; R 3 is R 1a is an alkylene further attached to form said 4-, 5-, or 6-membered heterocyclyl; D* is acyl; and n is 3. In another embodiment, R1a is an alkylene wherein the alkylene further comprises R 3 4-, 5-, or 6-membered heterocyclyl and R 1b is alkoxyl; R 2 is hydrogen; R 3 is R 1a Further binding to is alkylene which forms said 4-, 5-, or 6-membered heterocyclyl; D* is acyl; and n is 3. In another embodiment, R 1a is alkylene, Lukiren further added, 3 to form a 4-, 5-, or 6-membered heterocyclyl; and R 1b teeth, alkenyl; R 2 is hydrogen; R 3 is R 1a Further attached to said 4, 5, or 6 membered heterocyclic D* is an alkylene group forming a cyclocyclyl; D* is an acyl group; and n is 3. In the embodiment, R 1a is alkylene, wherein the alkylene further comprises R 3 In conclusion combine with R to form a 4-, 5-, or 6-membered heterocyclyl; and R 1b is alkynyl; R 2 Water R 3 is R 1a which further binds to form said 4-, 5-, or 6-membered heterocyclyl. D* is acyl; and n is 3. In another embodiment, R 1a teeth, alkylene, wherein the alkylene is further selected from the group consisting of R 3 4, 5, or 6-membered hexafluorophosphate Forming a tetracyclyl; and R 1b is aryl; R 2 is hydrogen; R 3is R 1a Nisara is an alkylene which is attached to said 4-, 5-, or 6-membered heterocyclyl; D* is an acyl and n is 3. In another embodiment, R 1a is alkylene, where The alkylene further comprises R 3 to form a 4-, 5-, or 6-membered heterocyclyl; and R 1 b is arylalkyl; R 2 is hydrogen; R 3 is R 1a Further bind to the 4, 5, or is alkylene forming a 6-membered heterocyclyl; D* is acyl; and n is 3. In another embodiment, R 1a is alkylene, wherein the alkylene is Furthermore, R 3 to form a 4-, 5-, or 6-membered heterocyclyl; and R 1b Heteroaryl R 2 is hydrogen; R 3 is R 1a further linked to said 4, 5, or 6 membered heterocyclyl D* is an alkylene group forming an alkyl group; D* is acyl; and n is 3. In any of the embodiments, R 4 is hydrogen. Hey, R 4 is alkyl.

[0128] In another embodiment, R 1a is alkylene, wherein the alkylene is further , R 3 to form a 4-, 5-, or 6-membered heterocyclyl; and R 1b is hydrogen; R 2 teeth, is an amino acid side chain; R3 is R 1a to form the 4-, 5-, or 6-membered heterocyclyl. D* is acyl; and n is 3. , R 1a is alkylene, wherein the alkylene further comprises R 3 4, 5, or forms a six-membered heterocyclyl; and R 1b is alkyl; R 2 is the amino acid side chain ;R 3 is R 1a which further binds to form said 4-, 5-, or 6-membered heterocyclyl; D* is acyl; and n is 3. In another embodiment, R 1a Alkire wherein the alkylene further comprises R 3 4-, 5-, or 6-membered heterocyclic R 1b is alkoxyl; R 2 is an amino acid side chain; R 3 is R 1a To is an alkylene which further binds to form said 4-, 5-, or 6-membered heterocyclyl; D* is and n is 3. In another embodiment, R 1a is alkylene, wherein the alkylene further comprises R 3 to form a 4-, 5-, or 6-membered heterocyclyl; R 1b is alkenyl; R 2 is an amino acid side chain; R 3 is R 1a Further binding to the 4 D* is acyl; and n is an alkylene group forming a 5-, 5-, or 6-membered heterocyclyl; is 3. In another embodiment, R 1ais alkylene, where Ng further added that 3 to form a 4-, 5-, or 6-membered heterocyclyl; and R 1b Is, Alki Nil;R 2 is an amino acid side chain; R 3 is R 1a further linked to said 4, 5, or 6 membered hydroxyl group is an alkylene forming a terecyclyl; D* is acyl; and n is 3. In an embodiment, R 1a is alkylene, wherein the alkylene further comprises R 3 To joined to form a 4-, 5-, or 6-membered heterocyclyl; and R 1b is aryl; R 2 A R 3 is R 1a further attached to form said 4-, 5-, or 6-membered heterocyclyl D* is acyl; and n is 3. In another embodiment, R 1a is alkylene, wherein the alkylene further comprises R 3 4, 5, or 6 forming a 1-membered heterocyclyl; and R 1b is arylalkyl; R 2 is the amino acid side chain ;R 3 is R 1a to form said 4-, 5-, or 6-membered heterocyclyl. D* is acyl; and n is 3. In another embodiment, R 1a A alkylene, wherein the alkylene is further selected from the group consisting of R 3 4, 5, or 6-membered heterocyclic and R 1b is heteroaryl; R 2 is an amino acid side chain; R3 teeth , R 1a is an alkylene further attached to form said 4-, 5-, or 6-membered heterocyclyl; * is acyl; and n is 3. In another embodiment, R 1a is hydrogen, R 1b is hydrogen; R 2 is hydrogen; R 3 is hydrogen; D* is a residue of a biologically active compound and n is 3. In another embodiment, R 1a is hydrogen and R 1b A RuKil is;R 2 is hydrogen; R 3 is hydrogen; D* is a residue of a biologically active compound; and n is 3. In another embodiment, R 1a is hydrogen and R 1b is an alkoxy ;R 2 is hydrogen; R 3 is hydrogen; D* is a residue of a biologically active compound; and n is 3. In another embodiment, R 1a is hydrogen and R 1b is alkenyl R 2 is hydrogen; R 3 is hydrogen; D* is a residue of a biologically active compound; and n is 3 In another embodiment, R 1a is hydrogen and R 1b is alkynyl; R 2 is hydrogen; R 3 is hydrogen; D* is a residue of a biologically active compound; and n is 3. In any of the embodiments of this paragraph, R 4 is hydrogen. In any of the embodiments, R 4 is alkyl.

[0129] In another embodiment, R 1a is hydrogen and R 1b is aryl; R 2 is hydrogen ;R 3 is hydrogen; D* is a residue of a biologically active compound; and n is 3. In an embodiment, R 1a is hydrogen and R 1b is arylalkyl; R 2 Water R 3 is hydrogen; D* is a residue of a biologically active compound; and n is 3. In an embodiment of the invention, R 1a is hydrogen and R 1b is heteroaryl; R 2 Water R 3 is hydrogen; D* is a residue of a biologically active compound; and n is 3. In an embodiment of the invention, R 1a is alkylene, wherein the alkylene further comprises R 3 to form a 4-, 5-, or 6-membered heterocyclyl; and R 1b is hydrogen; R 2 is hydrogen ;R 3 is hydrogen; D* is a residue of a biologically active compound; and n is 3. In an embodiment, R 1a is alkylene, wherein the alkylene further comprises R 3 To joined to form a 4-, 5-, or 6-membered heterocyclyl; and R 1b is alkyl; R 2 Water R 3 is hydrogen; D* is a residue of a biologically active compound; and n is 3. In an embodiment of the invention, R 1ais alkylene, wherein the alkylene further comprises R 3 to form a 4-, 5-, or 6-membered heterocyclyl; and R 1b is alkoxyl; R 2 is hydrogen; R 3 is hydrogen; D* is a residue of a biologically active compound; and n is 3. In another embodiment, R 1a is alkylene, wherein the alkylene is further To, R 3 to form a 4-, 5-, or 6-membered heterocyclyl; and R 1b is alkenyl R 2 is hydrogen; R 3 is hydrogen; D* is a residue of a biologically active compound; and n is 3 In another embodiment, R 1a is alkylene, where the alkylene is In addition, R 3 to form a 4-, 5-, or 6-membered heterocyclyl; and R 1b is an alkynyl ;R 2 is hydrogen; R 3 is hydrogen; D* is a residue of a biologically active compound; and n is 3. In another embodiment, R 1a is alkylene, where Ng further added that 3 to form a 4-, 5-, or 6-membered heterocyclyl; and R 1b Ali R 2 is hydrogen; R 3 is hydrogen; D* is a residue of a biologically active compound; and n is 3. In another embodiment, R 1a is alkylene, Len further added, 3to form a 4-, 5-, or 6-membered heterocyclyl; and R 1b Yes, ants R is alkyl; 2 is hydrogen; R 3 is hydrogen; D* is a residue of a biologically active compound and n is 3. In another embodiment, R 1a is alkylene, where The alkylene further comprises R 3 to form a 4-, 5-, or 6-membered heterocyclyl; and R 1 b is heteroaryl; R 2 is hydrogen; R 3 is hydrogen; D* is a biologically active compound and n is 3. In another embodiment, R 1a is hydrogen and R 1b is hydrogen; R 2 is an amino acid side chain; R 3 is hydrogen; D* is the residue; and n is 3. In another embodiment, R 1a is hydrogen and R 1b teeth , alkyl; R 2 is an amino acid side chain; R 3 is hydrogen; D* is a biologically active compound and n is 3. In another embodiment, R 1a is hydrogen and R 1b is alkoxy; R 2 is an amino acid side chain; R 3 is hydrogen; D* is bioactive and n is 3. In any of the embodiments of this paragraph, R 4 is hydrogen. In any of the embodiments of this paragraph, R 4 is alkyl.

[0130] In another embodiment, R 1a is hydrogen and R 1b is alkenyl; R 2 A R 3 is hydrogen; D* is a residue of a biologically active compound; and n is 3. In another embodiment, R 1a is hydrogen and R 1b is alkynyl; R 2 teeth , an amino acid side chain; R 3 is hydrogen; D* is a residue of a biologically active compound; and n is 3. In another embodiment, R 1a is hydrogen and R 1b is aryl; R 2 teeth , an amino acid side chain; R 3 is hydrogen; D* is a residue of a biologically active compound; and n is 3. In another embodiment, R 1a is hydrogen and R 1b is an aryl alkyl Yes;R 2 is an amino acid side chain; R 3 is hydrogen; D* is a residue of a biologically active compound; and n is 3. In another embodiment, R 1a is hydrogen and R 1b Hetero ants R 2 is an amino acid side chain; R 3 is hydrogen; D* is a residue of a biologically active compound and n is 3. In another embodiment, R 1a is alkylene, where The alkylene further comprises R 3 to form a 4-, 5-, or 6-membered heterocyclyl; and R 1 b is hydrogen; R2 is an amino acid side chain; R 3 is hydrogen; D* is the residue; and n is 3. In another embodiment, R 1a is alkylene, wherein the alkylene further comprises R 3 to form a 4-, 5-, or 6-membered heterocyclyl; R 1b is alkyl; R 2 is an amino acid side chain; R 3 is hydrogen; D* is bioactive and n is 3. In another embodiment, R 1a is an alkylene wherein the alkylene further comprises R 3 is bonded to a 4-, 5-, or 6-membered heterocyclyl Form; and R 1b is alkoxyl; R 2 is an amino acid side chain; R 3 is hydrogen; D * is a residue of a biologically active compound; and n is 3. In another embodiment, R 1a teeth, alkylene, wherein the alkylene is further selected from the group consisting of R 3 4, 5, or 6-membered hexafluorophosphate Forming a tetracyclyl; and R 1b is alkenyl; R 2 is an amino acid side chain; R 3 teeth, is hydrogen; D* is a residue of a biologically active compound; and n is 3. R 1a is alkylene, wherein the alkylene further comprises R 3 4, 5, or a 6-membered heterocyclyl; and R 1b is alkynyl; R 2 is the amino acid side chain Yes;R 3is hydrogen; D* is a residue of a biologically active compound; and n is 3. In the embodiment, R 1a is alkylene, wherein the alkylene further comprises R 3 In conclusion combine with R to form a 4-, 5-, or 6-membered heterocyclyl; and R 1b is aryl; R 2 Ami R is an acid side chain; 3 is hydrogen; D* is a residue of a biologically active compound; and n is 3. In another embodiment, R 1a is alkylene, wherein the alkylene is further To, R 3 to form a 4-, 5-, or 6-membered heterocyclyl; and R 1b is an aryl alkyl group. R 2 is an amino acid side chain; R 3 is hydrogen; D* is the residue of a biologically active compound and n is 3. In another embodiment, R 1a is alkylene, where The alkylene may further include R 3 to form a 4-, 5-, or 6-membered heterocyclyl; and R 1b is heteroaryl; R 2 is an amino acid side chain; R 3 is hydrogen; D* is a physiological and n is 3. In any of the embodiments of this paragraph, , R 4 is hydrogen. In any of the embodiments of this paragraph, R 4 is an alkyl do.

[0131] In another embodiment, R 1a is hydrogen and R 1b is hydrogen; R 2 is hydrogen R3 is alkyl; D* is a residue of a biologically active compound; and n is 3. In an embodiment, R 1a is hydrogen and R 1b is alkyl; R 2 is hydrogen; R 3 is alkyl; D* is a residue of a biologically active compound; and n is 3. In an embodiment, R 1a is hydrogen and R 1b is alkoxy; R 2 is hydrogen; R 3 is alkyl; D* is a residue of a biologically active compound; and n is 3. In this regard, R 1a is hydrogen and R 1b is alkenyl; R 2 is hydrogen; R 3 teeth is alkyl; D* is a residue of a biologically active compound; and n is 3. In R 1a is hydrogen and R 1b is alkynyl; R 2 is hydrogen; R 3 teeth, D* is a residue of a biologically active compound; and n is 3. Hey, R 1a is hydrogen and R 1b is aryl; R 2 is hydrogen; R 3 Is, Al D* is a residue of a biologically active compound; and n is 3. R 1a is hydrogen and R 1b is arylalkyl; R 2 is hydrogen; R 3 teeth, D* is a residue of a biologically active compound; and n is 3. Hey, R 1a is hydrogen and R 1b is heteroaryl; R 2 is hydrogen; R 3 teeth is alkyl; D* is a residue of a biologically active compound; and n is 3. In R 1a is alkylene, wherein the alkylene further comprises R 3 4 , 5, or 6 membered heterocyclyl; and R 1b is hydrogen; R 2 is hydrogen; R 3 teeth is alkyl; D* is a residue of a biologically active compound; and n is 3. In R 1a is alkylene, wherein the alkylene further comprises R 3 4 , 5, or 6 membered heterocyclyl; and R 1b is alkyl; R 2 is hydrogen; R 3 is alkyl; D* is a residue of a biologically active compound; and n is 3. In an embodiment, R 1a is alkylene, wherein the alkylene further comprises R 3 Combined to to form a 4-, 5-, or 6-membered heterocyclyl; and R 1b is alkoxyl; R 2 Water R 3 is alkyl; D* is a residue of a biologically active compound; and n is 3. In another embodiment, R 1a is alkylene, wherein the alkylene is further , R 3to form a 4-, 5-, or 6-membered heterocyclyl; and R 1b is alkenyl; R 2 is hydrogen; R 3 is alkyl; D* is a residue of a biologically active compound; and n is 3. In another embodiment, R 1a is alkylene, where the alkylene is In addition, R 3 to form a 4-, 5-, or 6-membered heterocyclyl; and R 1b is an alkynyl ;R 2 is hydrogen; R 3 is an alkyl; D* is a residue of a biologically active compound; n is 3. In another embodiment, R 1a is alkylene, Killen further added that 3 to form a 4-, 5-, or 6-membered heterocyclyl; and R 1b A Reel;R 2 is hydrogen; R 3 is an alkyl; D* is the residue of a biologically active compound and n is 3. In another embodiment, R 1a is alkylene, where The alkylene may further include R 3 to form a 4-, 5-, or 6-membered heterocyclyl; and R 1b is arylalkyl; R 2 is hydrogen; R 3 is alkyl; D* is bioactive and n is 3. In any of the embodiments of this paragraph, R 4 is hydrogen. In any of the embodiments of this paragraph, R 4 is an alkyl .

[0132] In another embodiment, R 1a is alkylene, wherein the alkylene is further , R 3 to form a 4-, 5-, or 6-membered heterocyclyl; and R 1b is a heteroaryl Yes;R 2 is hydrogen; R 3 is an alkyl; D* is a residue of a biologically active compound; and n is 3. In another embodiment, R 1a is hydrogen and R 1b is hydrogen; R 2 is an amino acid side chain; R 3 is an alkyl; D* is a residue of a biologically active compound; n is 3. In another embodiment, R 1a is hydrogen and R 1b is an alkyl R 2 is an amino acid side chain; R 3 is an alkyl; D* is a residue of a biologically active compound. and n is 3. In another embodiment, R 1a is hydrogen and R 1b , Arco It is kisi;R 2 is an amino acid side chain; R 3 is an alkyl group; D* is a group of the biologically active compound residue; and n is 3. In another embodiment, R 1a is hydrogen and R 1b teeth , alkenyl; R 2 is an amino acid side chain; R 3 is alkyl; D* is bioactive and n is 3. In another embodiment, R 1a is hydrogen, R 1b is alkynyl; R 2 is an amino acid side chain; R3 is alkyl; D* is and n is 3. In another embodiment, R 1a is hydrogen And R 1b is aryl; R 2 is an amino acid side chain; R 3 is alkyl; D* is , a residue of a biologically active compound; and n is 3. In another embodiment, R 1a is hydrogen and R 1b is arylalkyl; R 2 is an amino acid side chain; R 3 Is, Alki D* is a residue of a biologically active compound; and n is 3. , R 1a is hydrogen and R 1b is heteroaryl; R 2 is an amino acid side chain; R 3 is alkyl; D* is a residue of a biologically active compound; and n is 3. In this regard, R 1a is alkylene, wherein the alkylene further comprises R 3 Binds to forming a 4-, 5-, or 6-membered heterocyclyl; and R 1b is hydrogen; R 2 is the amino acid side chain ;R 3 is alkyl; D* is a residue of a biologically active compound; and n is 3. In another embodiment, R 1a is alkylene, wherein the alkylene further comprises R 3 to form a 4-, 5-, or 6-membered heterocyclyl; and R 1b is alkyl; R 2 teeth , an amino acid side chain; R 3is alkyl; D* is a residue of a biologically active compound; and n is 3. In another embodiment, R 1a is alkylene, where Ng further added that 3 to form a 4-, 5-, or 6-membered heterocyclyl; and R 1b Alco xyl; R 2 is an amino acid side chain; R 3 is an alkyl; D* is a biologically active compound and n is 3. In another embodiment, R 1a is alkylene, wherein the alkylene further comprises R 3 to form a 4-, 5-, or 6-membered heterocyclyl; And R 1b is alkenyl; R 2 is an amino acid side chain; R 3 is alkyl; D* is is a residue of a biologically active compound; and n is 3. In another embodiment, R 1a Is, Alki wherein the alkylene further comprises R 3 4, 5, or 6-membered heterocyclic Forms krill; and R 1b is alkynyl; R 2 is an amino acid side chain; R 3 Is, Alki D* is a residue of a biologically active compound; and n is 3. , R 1a is alkylene, wherein the alkylene further comprises R 3 4, 5, or forms a six-membered heterocyclyl; and R 1b is aryl; R 2 is the amino acid side chain ;R 3 is alkyl; D* is a residue of a biologically active compound; and n is 3. In any of the embodiments of the graph, R 4 is hydrogen. In either case, R 4 is alkyl.

[0133] In another embodiment, R 1a is alkylene, wherein the alkylene is further , R 3 to form a 4-, 5-, or 6-membered heterocyclyl; and R 1b is aryl alkyl ;R 2 is an amino acid side chain; R 3 is an alkyl; D* is a residue of a biologically active compound and n is 3. In another embodiment, R 1a is alkylene, where The alkylene further comprises R 3 to form a 4-, 5-, or 6-membered heterocyclyl; and R 1 b is heteroaryl; R 2 is an amino acid side chain; R 3 is alkyl; D* is and n is 3. In another embodiment, R 1a Alkire wherein the alkylene further comprises R 3 4-, 5-, or 6-membered heterocyclic R 1b is hydrogen; R 2 is hydrogen; R 3 is R 1a Further binding to the 4 D* is an alkylene group forming a 5-, 5-, or 6-membered heterocyclyl; D* is the residue of a biologically active compound. group; and n is 3. In another embodiment, R 1a is alkylene, The alkylene further comprises R3 to form a 4-, 5-, or 6-membered heterocyclyl; and R 1b is alkyl; R 2 is hydrogen; R 3 is R 1a further linked to said 4, 5, or 6 membered D* is a residue of a biologically active compound; and n is 3. In another embodiment, R 1a is alkylene, Len further added, 3 to form a 4-, 5-, or 6-membered heterocyclyl; and R 1b Is, Al Coxyl; R 2 is hydrogen; R 3 is R 1a further linked to said 4, 5, or 6 membered heterocyclic is an alkylene that forms a cyclyl; D* is a residue of a biologically active compound; and n is 3. In another embodiment, R 1a is alkylene, wherein the alkylene is Furthermore, R 3 to form a 4-, 5-, or 6-membered heterocyclyl; and R 1b is an alkenyl Yes;R 2 is hydrogen; R 3 is R 1a further attached to said 4-, 5-, or 6-membered heterocyclyl D* is a residue of a biologically active compound; and n is 3. In an embodiment, R 1a is alkylene, wherein the alkylene further comprises R 3 To linked to form a 4-, 5-, or 6-membered heterocyclyl; and R 1b is alkynyl; R 2 teeth, Hydrogen; R 3 is R 1awhich further binds to form said 4-, 5-, or 6-membered heterocyclyl. D* is a residue of a biologically active compound; and n is 3. Hey, R 1a is alkylene, wherein the alkylene further comprises R 3 4, which is bonded to forming a 5- or 6-membered heterocyclyl; and R 1b is aryl; R 2 is hydrogen; R 3 is R 1a is an alkylene further attached to form said 4-, 5-, or 6-membered heterocyclyl; D* is a residue of a biologically active compound; and n is 3. In another embodiment, R 1a teeth , alkylene, wherein the alkylene is further selected from the group consisting of R 3 4, 5, or 6-membered forming a heterocyclyl; and R 1b is arylalkyl; R 2 is hydrogen; R 3 teeth, R 1a is an alkylene which is further bonded to form said 4-, 5-, or 6-membered heterocyclyl; D* is a residue of a biologically active compound; and n is 3. In another embodiment, R 1a A alkylene, wherein the alkylene is further selected from the group consisting of R 3 4, 5, or 6-membered heterocyclic and R 1b is heteroaryl; R 2 is hydrogen; R 3 is R 1a To is an alkylene which further binds to form said 4-, 5-, or 6-membered heterocyclyl; D* is and n is 3. In any of the embodiments of this paragraph, And R 4is hydrogen. In any of the embodiments of this paragraph, R 4 is an alkyl It is.

[0134] In another embodiment, R 1a is alkylene, wherein the alkylene is further , R 3 to form a 4-, 5-, or 6-membered heterocyclyl; and R 1b is hydrogen; R 2 teeth, is an amino acid side chain; R 3 is R 1a to form the 4-, 5-, or 6-membered heterocyclyl. D* is a residue of a biologically active compound; and n is 3. In the embodiment, R 1a is alkylene, wherein the alkylene further comprises R 3 In conclusion combine with R to form a 4-, 5-, or 6-membered heterocyclyl; and R 1b is alkyl; R 2 Ami R is an acid side chain; 3 is R 1a to form said 4-, 5-, or 6-membered heterocyclyl. D* is a residue of a biologically active compound; and n is 3. In this regard, R 1a is alkylene, wherein the alkylene further comprises R 3 Binds to forming a 4-, 5-, or 6-membered heterocyclyl; and R 1b is alkoxyl; R 2 Ami R is an acid side chain; 3 is R 1a to form said 4-, 5-, or 6-membered heterocyclyl. D* is a residue of a biologically active compound; and n is 3. In this regard, R1a is alkylene, wherein the alkylene further comprises R 3 Binds to forming a 4-, 5-, or 6-membered heterocyclyl; and R 1b is alkenyl; R 2 Amino R is an acid side chain; 3 is R 1a further attached to form said 4-, 5-, or 6-membered heterocyclyl is alkylene; D* is a residue of a biologically active compound; and n is 3. In R 1a is alkylene, wherein the alkylene further comprises R 3 4 , 5, or 6 membered heterocyclyl; and R 1b is alkynyl; R 2 is an amino acid Side chain; R 3 is R 1a which further binds to form said 4-, 5-, or 6-membered heterocyclyl. D* is a residue of a biologically active compound; and n is 3. Hey, R 1a is alkylene, wherein the alkylene further comprises R 3 4, which is bonded to forming a 5- or 6-membered heterocyclyl; and R 1b is aryl; R 2 is the amino acid side chain ;R 3 is R 1a to form said 4-, 5-, or 6-membered heterocyclyl. D* is a residue of a biologically active compound; and n is 3. R 1a is alkylene, wherein the alkylene further comprises R 3 4, 5, or a 6-membered heterocyclyl; and R 1bis arylalkyl; R 2 is an amino acid Side chain; R 3 is R 1a which further binds to form said 4-, 5-, or 6-membered heterocyclyl. D* is a residue of a biologically active compound; and n is 3. Hey, R 1a is alkylene, wherein the alkylene further comprises R 3 4, which is bonded to forming a 5- or 6-membered heterocyclyl; and R 1b is heteroaryl; R 2 Amino R is an acid side chain; 3 is R 1a further attached to form said 4-, 5-, or 6-membered heterocyclyl is alkylene; D* is a residue of a biologically active compound; and n is 3. In any of the embodiments, R 4 is hydrogen. In R 4 is alkyl.

[0135] In another embodiment, R 1a is hydrogen and R 1b is hydrogen; R 2 is hydrogen R 3 is hydrogen; D* is hydrogen; and n is 4. In another embodiment, R 1a is hydrogen and R 1b is alkyl; R 2 is hydrogen; R 3 is hydrogen; D* is , hydrogen; and n is 4. In another embodiment, R 1a is hydrogen and R 1b is alkoxy; R 2 is hydrogen; R3 is hydrogen; D* is hydrogen; and n is , 4. In another embodiment, R 1a is hydrogen and R 1b is alkenyl; R 2 is hydrogen; R 3 is hydrogen; D* is hydrogen; and n is 4. In this regard, R 1a is hydrogen and R 1b is alkynyl; R 2 is hydrogen; R 3 teeth D* is hydrogen; and n is 4. In another embodiment, R 1a Water Prime and R 1b is aryl; R 2 is hydrogen; R 3 is hydrogen; D* is hydrogen and n is 4. In another embodiment, R 1a is hydrogen and R 1b A R is aryl alkyl; 2 is hydrogen; R 3 is hydrogen; D* is hydrogen; and n is , 4. In another embodiment, R 1a is hydrogen and R 1b is a heteroaryl Yes;R 2 is hydrogen; R 3 is hydrogen; D* is hydrogen; and n is 4. In the embodiment, R 1a is alkylene, wherein the alkylene further comprises R 3 In conclusion combine with R to form a 4-, 5-, or 6-membered heterocyclyl; and R 1b is hydrogen; R 2 is hydrogen R 3is hydrogen; D* is hydrogen; and n is 4. In another embodiment, R 1a is alkylene, wherein the alkylene further comprises R 3 4, 5, or 6-membered bond and R 1b is alkyl; R 2 is hydrogen; R 3 is hydrogen D* is hydrogen; and n is 4. In another embodiment, R 1a is an alkylene wherein the alkylene further comprises R 3 4, 5, or 6-membered heterocyclyl and R 1b is alkoxyl; R 2 is hydrogen; R 3 is hydrogen; D* is , hydrogen; and n is 4. In another embodiment, R 1a is alkylene, wherein the alkylene further comprises R 3 to form a 4-, 5-, or 6-membered heterocyclyl; And R 1b is alkenyl; R 2 is hydrogen; R 3 is hydrogen; D* is hydrogen; and n is 4. In another embodiment, R 1a is alkylene, Rukyren further added, 3 to form a 4-, 5-, or 6-membered heterocyclyl; and R 1b teeth, Alkynyl; R 2 is hydrogen; R 3 is hydrogen; D* is hydrogen; and n is 4 In another embodiment, R 1a is alkylene, wherein the alkylene is Furthermore, R 3to form a 4-, 5-, or 6-membered heterocyclyl; and R 1b is an aryl R 2 is hydrogen; R 3 is hydrogen; D* is hydrogen; and n is 4. In an embodiment, R 1a is alkylene, wherein the alkylene further comprises R 3 Combined to to form a 4-, 5-, or 6-membered heterocyclyl; and R 1b is arylalkyl; R 2 teeth , hydrogen; R 3 is hydrogen; D* is hydrogen; and n is 4. Hey, R 1a is alkylene, wherein the alkylene further comprises R 3 4, which is bonded to forming a 5- or 6-membered heterocyclyl; and R 1b is heteroaryl; R 2 is hydrogen Yes;R 3 is hydrogen; D* is hydrogen; and n is 4. In another embodiment, R 1a is hydrogen and R 1b is hydrogen; R 2 is an amino acid side chain; R 3 is hydrogen D* is hydrogen; and n is 4. In another embodiment, R 1a is hydrogen, And R 1b is alkyl; R 2 is an amino acid side chain; R 3 is hydrogen; D* is hydrogen and n is 4. In another embodiment, R 1a is hydrogen and R 1b Is, Al Cox;R 2 is an amino acid side chain; R 3is hydrogen; D* is hydrogen; and n is , 4. In another embodiment, R 1a is hydrogen and R 1b is alkenyl; R 2 is an amino acid side chain; R 3 is hydrogen; D* is hydrogen; and n is 4. In an embodiment of the invention, R 1a is hydrogen and R 1b is alkynyl; R 2 Amino R is an acid side chain; 3 is hydrogen; D* is hydrogen; and n is 4. In any of the embodiments, R 4 is hydrogen. Hey, R 4 is alkyl.

[0136] In another embodiment, R 1a is hydrogen and R 1b is aryl; R 2 Ami R is an acid side chain; 3 is hydrogen; D* is hydrogen; in another embodiment, R 1a Water Prime and R 1b is arylalkyl; R 2 is an amino acid side chain; R 3 is hydrogen D* is hydrogen; and n is 4. In another embodiment, R 1a is hydrogen And R 1b is heteroaryl; R 2 is an amino acid side chain; R 3 is hydrogen; D* is hydrogen; and n is 4. In another embodiment, R 1a is an alkylene; wherein the alkylene further comprises R3 to form a 4-, 5-, or 6-membered heterocyclyl S; and R 1b is hydrogen; R 2 is an amino acid side chain; R 3 is hydrogen; D* is hydrogen and n is 4. In another embodiment, R 1a is alkylene, where The alkylene may further include R 3 to form a 4-, 5-, or 6-membered heterocyclyl; and R 1b is alkyl; R 2 is an amino acid side chain; R 3 is hydrogen; D* is hydrogen; or n is 4. In another embodiment, R 1a is alkylene, Killen further added that 3 to form a 4-, 5-, or 6-membered heterocyclyl; and R 1b A R is alkoxyl; 2 is an amino acid side chain; R 3 is hydrogen; D* is hydrogen; and n is 4. In another embodiment, R 1a is alkylene, Len further added, 3 to form a 4-, 5-, or 6-membered heterocyclyl; and R 1b Is, Al Kenyl;R 2 is an amino acid side chain; R 3 is hydrogen; D* is hydrogen; and n is , 4. In another embodiment, R 1a is alkylene, where Furthermore, R 3 to form a 4-, 5-, or 6-membered heterocyclyl; and R 1b Alkini R 2is an amino acid side chain; R 3 is hydrogen; D* is hydrogen; and n is 4 In another embodiment, R 1a is alkylene, wherein the alkylene is Furthermore, R 3 to form a 4-, 5-, or 6-membered heterocyclyl; and R 1b is an aryl R 2 is an amino acid side chain; R 3 is hydrogen; D* is hydrogen; and n is 4. In another embodiment, R 1a is alkylene, wherein the alkylene further comprises R 3 to form a 4-, 5-, or 6-membered heterocyclyl; and R 1b is an aryl alkyl R 2 is an amino acid side chain; R 3 is hydrogen; D* is hydrogen; and n is 4. In another embodiment, R 1a is alkylene, wherein the alkylene further comprises R 3 to form a 4-, 5-, or 6-membered heterocyclyl; and R 1b is a heteroaryl ;R 2 is an amino acid side chain; R 3 is hydrogen; D* is hydrogen; and n is 4. In an embodiment of the invention, R 1a is hydrogen and R 1b is hydrogen; R 2 is hydrogen; R 3 is alkyl; D* is hydrogen; and n is 4. In another embodiment, R 1a is hydrogen and R 1b is alkyl; R 2 is hydrogen; R 3is alkyl; D* is hydrogen; and n is 4. In another embodiment, R 1a is hydrogen, and R 1b is alkoxy; R 2 is hydrogen; R 3 is alkyl; D* is hydrogen; and n is 4. In another embodiment, R 1a is hydrogen and R 1b is alkenyl ;R 2 is hydrogen; R 3 is alkyl; D* is hydrogen; and n is 4. In another embodiment, R 1a is hydrogen and R 1b is alkynyl; R 2 is hydrogen ;R 3 is alkyl; D* is hydrogen; and n is 4. And R 1a is hydrogen and R 1b is aryl; R 2 is hydrogen; R 3 Is, Alki D* is hydrogen; and n is 4. In any of the embodiments of this paragraph, And R 4 is hydrogen. In any of the embodiments of this paragraph, R 4 is an alkyl It is.

[0137] In another embodiment, R 1a is hydrogen and R 1b is arylalkyl; R 2 is hydrogen; R 3 is alkyl; D* is hydrogen; and n is 4. In an embodiment, R 1a is hydrogen and R 1bis heteroaryl; R 2 is hydrogen R 3 is alkyl; D* is hydrogen; and n is 4. , R 1a is alkylene, wherein the alkylene further comprises R 3 4, 5, or forms a six-membered heterocyclyl; and R 1b is hydrogen; R 2 is hydrogen; R 3 Is, Al D* is hydrogen; and n is 4. In another embodiment, R 1a Is, Al alkylene, wherein the alkylene further comprises R 3 4, 5, or 6 membered heterocyclic Forming a cyclyl; and R 1b is alkyl; R 2 is hydrogen; R 3 is an alkyl D* is hydrogen; and n is 4. In another embodiment, R 1a is an alkylene wherein the alkylene further comprises R 3 is bonded to a 4-, 5-, or 6-membered heterocyclyl Form; and R 1b is alkoxyl; R 2 is hydrogen; R 3 is alkyl; D* is , hydrogen; and n is 4. In another embodiment, R 1a is alkylene, wherein the alkylene further comprises R 3 to form a 4-, 5-, or 6-membered heterocyclyl; And R 1b is alkenyl; R 2 is hydrogen; R 3 is alkyl; D* is hydrogen. and n is 4. In another embodiment, R1a is alkylene, The alkylene may further include R 3 to form a 4-, 5-, or 6-membered heterocyclyl; and R 1b teeth , alkynyl; R 2 is hydrogen; R 3 is alkyl; D* is hydrogen; and n is 4. In another embodiment, R 1a is alkylene, where Ng further added that 3 to form a 4-, 5-, or 6-membered heterocyclyl; and R 1b Ali R 2 is hydrogen; R 3 is alkyl; D* is hydrogen; and n is 4 In another embodiment, R 1a is alkylene, wherein the alkylene is further , R 3 to form a 4-, 5-, or 6-membered heterocyclyl; and R 1b is aryl alkyl ;R 2 is hydrogen; R 3 is alkyl; D* is hydrogen; and n is 4. In another embodiment, R 1a is alkylene, wherein the alkylene further comprises R 3 to form a 4-, 5-, or 6-membered heterocyclyl; and R 1b is a heteroaryl ;R 2 is hydrogen; R 3 is alkyl; D* is hydrogen; and n is 4. In the embodiment, R 1a is hydrogen and R 1b is hydrogen; R 2 is an amino acid side chain R 3is alkyl; D* is hydrogen; and n is 4. , R 1a is hydrogen and R 1b is alkyl; R 2 is an amino acid side chain; R 3 A D* is hydrogen; and n is 4. In another embodiment, R 1a Water Prime and R 1b is alkoxy; R 2 is an amino acid side chain; R 3 is an alkyl D* is hydrogen; and n is 4. In another embodiment, R 1a is hydrogen , and R 1b is alkenyl; R 2 is an amino acid side chain; R 3 is alkyl; D* is , hydrogen; and n is 4. In another embodiment, R 1a is hydrogen and R 1b is alkynyl; R 2 is an amino acid side chain; R 3 is alkyl; D* is hydrogen and n is 4. In another embodiment, R 1a is hydrogen and R 1b Yes, ants R 2 is an amino acid side chain; R 3 is alkyl; D* is hydrogen; and n is 4. In another embodiment, R 1a is hydrogen and R 1b is an aryl alkyl group. R 2 is an amino acid side chain; R 3 is alkyl; D* is hydrogen; and n is , 4. In another embodiment, R 1ais hydrogen and R 1b is a heteroaryl Yes;R 2 is an amino acid side chain; R 3 is alkyl; D* is hydrogen; and n is 4. In any of the embodiments of this paragraph, R 4 is hydrogen. In any of the embodiments, R 4 is alkyl.

[0138] In another embodiment, R 1a is alkylene, wherein the alkylene is further , R 3 to form a 4-, 5-, or 6-membered heterocyclyl; and R 1b is hydrogen; R 2 teeth, is an amino acid side chain; R 3 is alkyl; D* is hydrogen; and n is 4. In an embodiment, R 1a is alkylene, wherein the alkylene further comprises R 3 To linked to form a 4-, 5-, or 6-membered heterocyclyl; and R 1b is alkyl; R 2 A R 3 is alkyl; D* is hydrogen; and n is 4. In the embodiment, R 1a is alkylene, wherein the alkylene further comprises R 3 In conclusion combine with R to form a 4-, 5-, or 6-membered heterocyclyl; and R 1b is alkoxyl; R 2 teeth, is an amino acid side chain; R 3 is alkyl; D* is hydrogen; and n is 4. In an embodiment, R 1ais alkylene, wherein the alkylene further comprises R 3 To joined to form a 4-, 5-, or 6-membered heterocyclyl; and R 1b is alkenyl; R 2 teeth, is an amino acid side chain; R 3 is alkyl; D* is hydrogen; and n is 4. In an embodiment, R 1a is alkylene, wherein the alkylene further comprises R 3 To joined to form a 4-, 5-, or 6-membered heterocyclyl; and R 1b is alkynyl; R 2 teeth, is an amino acid side chain; R 3 is alkyl; D* is hydrogen; and n is 4. In an embodiment, R 1a is alkylene, wherein the alkylene further comprises R 3 To joined to form a 4-, 5-, or 6-membered heterocyclyl; and R 1b is aryl; R 2 A R 3 is alkyl; D* is hydrogen; and n is 4. In the embodiment, R 1a is alkylene, wherein the alkylene further comprises R 3 In conclusion combine with R to form a 4-, 5-, or 6-membered heterocyclyl; and R 1b is arylalkyl; R 2 is an amino acid side chain; R 3 is alkyl; D* is hydrogen; and n is 4. In another embodiment, R 1a is alkylene, wherein the alkylene further comprises R 3 to form a 4-, 5-, or 6-membered heterocyclyl; and R1b is a heteroaryl ;R 2 is an amino acid side chain; R 3 is alkyl; D* is hydrogen; and n is 4 In another embodiment, R 1a is alkylene, wherein the alkylene is further , R 3 to form a 4-, 5-, or 6-membered heterocyclyl; and R 1b is hydrogen; R 2 teeth, Hydrogen; R 3 is R 1a which further binds to form said 4-, 5-, or 6-membered heterocyclyl. D* is hydrogen; and n is 4. In another embodiment, R 1a teeth, alkylene, wherein the alkylene is further selected from the group consisting of R 3 4, 5, or 6-membered hexafluorophosphate Forming a tetracyclyl; and R 1b is alkyl; R 2 is hydrogen; R 3 is R 1a Nisara is an alkylene which is bonded to said 4-, 5-, or 6-membered heterocyclyl; D* is hydrogen. and n is 4. In another embodiment, R 1a is alkylene, where The alkylene may further include R 3 to form a 4-, 5-, or 6-membered heterocyclyl; and R 1b is alkoxyl; R 2 is hydrogen; R 3 is R 1a further linked to said 4, 5, or 6 membered D* is hydrogen; and n is 4. In an embodiment of the invention, R 1ais alkylene, wherein the alkylene further comprises R 3 to form a 4-, 5-, or 6-membered heterocyclyl; and R 1b is alkenyl; R 2 teeth , hydrogen; R 3 is R 1a further attached to form said 4-, 5-, or 6-membered heterocyclyl is alkylene; D* is hydrogen; and n is 4. In another embodiment, R 1a teeth , alkylene, wherein the alkylene is further selected from the group consisting of R 3 4, 5, or 6-membered forming a heterocyclyl; and R 1b is alkynyl; R 2 is hydrogen; R 3 is R 1a To is alkylene which further binds to form said 4-, 5-, or 6-membered heterocyclyl; D* is water. and n is 4. In any of the embodiments of this paragraph, R 4 is hydrogen In any of the embodiments of this paragraph, R 4 is alkyl.

[0139] In another embodiment, R 1a is alkylene, wherein the alkylene is further , R 3 to form a 4-, 5-, or 6-membered heterocyclyl; and R 1b is aryl; R 2 is hydrogen; R 3 is R 1a to form said 4-, 5-, or 6-membered heterocyclyl. D* is hydrogen; and n is 4. In another embodiment, R 1a is alkylene, wherein the alkylene further comprises R3 4, 5, or 6-membered bond and R 1b is arylalkyl; R 2 is hydrogen; R 3 teeth , R 1a is an alkylene further attached to form said 4-, 5-, or 6-membered heterocyclyl; * is hydrogen; and n is 4. In another embodiment, R 1a is an alkylene wherein the alkylene further comprises R 3 to form a 4-, 5-, or 6-membered heterocyclyl And R 1b is heteroaryl; R 2 is hydrogen; R 3 is R 1a Further combining with is an alkylene which forms the 4-, 5-, or 6-membered heterocyclyl; D* is hydrogen; and n is 4. In another embodiment, R 1a is alkylene, where Ng further added that 3 to form a 4-, 5-, or 6-membered heterocyclyl; and R 1b is hydrogen Yes;R 2 is an amino acid side chain; R 3 is R 1a further linked to said 4, 5, or 6 membered heterocyclic is an alkylene forming a aryl group; D* is hydrogen; and n is 4. In R 1a is alkylene, wherein the alkylene further comprises R 3 4 , 5, or 6 membered heterocyclyl; and R 1b is alkyl; R 2 On the amino acid side Chain;R 3 is R 1awhich further binds to form said 4-, 5-, or 6-membered heterocyclyl. D* is hydrogen; and n is 4. In another embodiment, R 1a A alkylene, wherein the alkylene is further selected from the group consisting of R 3 4, 5, or 6-membered heterocyclic and R 1b is alkoxyl; R 2 is an amino acid side chain; R 3 teeth, R 1a is an alkylene which is further bonded to form said 4-, 5-, or 6-membered heterocyclyl; D* is hydrogen; and n is 4. In another embodiment, R 1a is an alkylene; wherein the alkylene further comprises R 3 to form a 4-, 5-, or 6-membered heterocyclyl S; and R 1b is alkenyl; R 2 is an amino acid side chain; R 3 is R 1a Further binding to forming said 4-, 5-, or 6-membered heterocyclyl; D* is hydrogen; n is 4. In another embodiment, R 1a is alkylene, Killen further added that 3 to form a 4-, 5-, or 6-membered heterocyclyl; and R 1b A R is alkynyl; 2 is an amino acid side chain; R 3 is R 1a further linked to said 4, 5, or 6 membered D* is hydrogen; and n is 4. In an embodiment of the invention, R 1a is alkylene, wherein the alkylene further comprises R 3 to form a 4-, 5-, or 6-membered heterocyclyl; and R 1b is aryl; R 2 teeth, is an amino acid side chain; R 3 is R 1a to form the 4-, 5-, or 6-membered heterocyclyl. D* is hydrogen; and n is 4. In another embodiment, R 1a is alkylene, wherein the alkylene further comprises R 3 4, 5, or 6 forming a 1-membered heterocyclyl; and R 1b is arylalkyl; R 2 is the amino acid side chain ;R 3 is R 1a to form said 4-, 5-, or 6-membered heterocyclyl. D* is hydrogen; and n is 4. In another embodiment, R 1a Is, Al alkylene, wherein the alkylene further comprises R 3 4, 5, or 6 membered heterocyclic Forming a cyclyl; and R 1b is heteroaryl; R 2 is an amino acid side chain; R 3 teeth, R 1a is an alkylene which is further bonded to form said 4-, 5-, or 6-membered heterocyclyl; D* is hydrogen; and n is 4. In any of the embodiments of this paragraph, R 4 teeth , hydrogen. In any of the embodiments of this paragraph, R 4 is alkyl.

[0140] In another embodiment, R 1a is hydrogen and R 1b is hydrogen; R 2 is hydrogen R 3 is hydrogen; D* is acyl; and n is 4. In another embodiment, R 1a is hydrogen and R 1b is alkyl; R 2 is hydrogen; R 3 is hydrogen; D* is acyl; and n is 4. In another embodiment, R 1a is hydrogen, and R 1b is alkoxy; R 2 is hydrogen; R 3 is hydrogen; D* is acyl; n is 4. In another embodiment, R 1a is hydrogen and R 1b is an alkenyl Yes;R 2 is hydrogen; R 3 is hydrogen; D* is acyl; and n is 4. In an embodiment, R 1a is hydrogen and R 1b is alkynyl; R 2 is hydrogen R 3 is hydrogen; D* is acyl; and n is 4. In another embodiment, R 1a is hydrogen and R 1b is aryl; R 2 is hydrogen; R 3 is hydrogen; D* is acyl; and n is 4. In another embodiment, R 1a is hydrogen, and R 1b is arylalkyl; R 2 is hydrogen; R 3 is hydrogen; D* is acyl and n is 4. In another embodiment, R 1a is hydrogen and R 1bis hetero Aryl; R 2 is hydrogen; R 3 is hydrogen; D* is acyl; and n is 4. In another embodiment, R 1a is alkylene, wherein the alkylene is Furthermore, R 3 to form a 4-, 5-, or 6-membered heterocyclyl; and R 1b is hydrogen; R 2 is hydrogen; R 3 is hydrogen; D* is acyl; and n is 4. In this regard, R 1a is alkylene, wherein the alkylene further comprises R 3 Binds to forming a 4-, 5-, or 6-membered heterocyclyl; and R 1b is alkyl; R 2 is hydrogen R 3 is hydrogen; D* is acyl; and n is 4. In another embodiment, R 1a is alkylene, wherein the alkylene further comprises R 3 4, 5, or 6 forming a 1-membered heterocyclyl; and R 1b is alkoxyl; R 2 is hydrogen; R 3 teeth, D* is acyl; and n is 4. In another embodiment, R 1a A alkylene, wherein the alkylene is further selected from the group consisting of R 3 4, 5, or 6-membered heterocyclic and R 1b is alkenyl; R 2 is hydrogen; R 3 is hydrogen D* is acyl; and n is 4. In another embodiment, R1a is an alkylene wherein the alkylene further comprises R 3 4-, 5-, or 6-membered heterocyclyl and R 1b is alkynyl; R 2 is hydrogen; R 3 is hydrogen; D* is a and n is 4. In another embodiment, R 1a is alkylene, wherein the alkylene further comprises R 3 to form a 4-, 5-, or 6-membered heterocyclyl; R 1b is aryl; R 2 is hydrogen; R 3 is hydrogen; D* is acyl; n is 4. In another embodiment, R 1a is alkylene, Killen further added that 3 to form a 4-, 5-, or 6-membered heterocyclyl; and R 1b A R is aryl alkyl; 2 is hydrogen; R 3 is hydrogen; D* is acyl; and n is 4. In another embodiment, R 1a is alkylene, where Ng further added that 3 to form a 4-, 5-, or 6-membered heterocyclyl; and R 1b is hetero Aryl; R 2 is hydrogen; R 3 is hydrogen; D* is acyl; and n is 4. In another embodiment, R 1a is hydrogen and R 1b is hydrogen; R 2 Ami R is an acid side chain; 3is hydrogen; D* is acyl; and n is 4. In this regard, R 1a is hydrogen and R 1b is alkyl; R 2 is an amino acid side chain R 3 is hydrogen; D* is acyl; and n is 4. In any of the above, R 4 is hydrogen. In any of the embodiments of this paragraph, R 4 is alkyl.

[0141] In another embodiment, R 1a is hydrogen and R 1b is alkoxy; R 2 A R 3 is hydrogen; D* is acyl; and n is 4. In an embodiment,...

Claims

1. A compound having the structure: or a pharma- ceutical acceptable salt thereof 【Chemistry 1】 (In the ceremony R 1a and R 1b are independently hydrogen, alkyl, alkoxy, alkenyl, alkynyl, aryl, aryl, arylalkyl, heteroaryl, alkylene, or heteroalkylene; So, R 1a When is alkylene or heteroalkylene, the alkylene or heteroa Lukiren further added, 3 to form a 3-, 4-, 5-, 6-, 7-, or 8-membered heterocyclyl; R 2 is hydrogen, alkylene, heteroalkylene, or an amino acid side chain, where R 2 but When it is an alkylene or a heteroalkylene, the alkylene or the heteroalkylene may be Furthermore, R 3 to form a 4-, 5-, or 6-membered heterocyclyl; R 3 is hydrogen, alkyl, alkylene, or heteroalkylene, where R 3 But, When the alkylene or heteroalkylene is an alkylene or heteroalkylene, the alkylene or heteroalkylene may further include , R 1a or R 2 to form said 3-, 4-, 5-, 6-, 7-, or 8-membered heterocyclyl; R 4 is hydrogen or alkyl; R 5 is oxygen, NR 6 or sulfur; R 6 is hydrogen or alkyl; D* is an acyl or bioactive group containing hydroxyl, amino, or thiol. is a residue of a compound; and where n is 0, 1, 2, 3, 4, 5, or 6.

2. 2. The compound of claim 1, having the structure: 【Chemistry 2】 (In the ceremony R 1a and R 1b are independently hydrogen, alkyl, alkoxy, alkenyl, alkynyl, aryl, aryl, arylalkyl, heteroaryl, alkylene, or heteroalkylene; So, R 1a When is alkylene or heteroalkylene, the alkylene or heteroa Lukiren further added, 3 to form a 4-, 5-, or 6-membered heterocyclyl; R 2 is hydrogen, alkylene, heteroalkylene, or an amino acid side chain, where R 2 but When it is an alkylene or a heteroalkylene, the alkylene or the heteroalkylene may be Furthermore, R 3 to form a 4-, 5-, or 6-membered heterocyclyl; R 3 is hydrogen, alkyl, alkylene, or heteroalkylene, where R 3 But, A When the alkylene or heteroalkylene is an alkylene or heteroalkylene, the alkylene or heteroalkylene may further include , R 1a or R 2 to form said 4-, 5-, or 6-membered heterocyclyl; R 4 is hydrogen or alkyl; R 5 is oxygen, NR 6 or sulfur; R 6 is hydrogen or alkyl; D* is an acyl or bioactive group containing hydroxyl, amino, or thiol. is a residue of a compound; and where n is 0, 1, 2, 3, 4, or 5.

3. 3. The compound of claim 2, having the structure: 【Chemistry 3】 (In the ceremony R 1a and R 1b are independently hydrogen, alkyl, alkoxy, alkenyl, alkynyl, aryl, aryl, arylalkyl, heteroaryl, or alkylene, where R 1a But, When the alkylene is an alkylene, the alkylene may further include R 3 4, 5, or 6-membered heterocyclyl Form a loop; R 2 is hydrogen or an amino acid side chain; R 3 is hydrogen, alkyl, or alkylene, where R 3 is an alkylene The alkylene further comprises R 1a to form said 4-, 5-, or 6-membered heterocyclyl; D* is an acyl or hydroxyl-containing residue of a biologically active compound; and where n is 0, 1, 2, 3, 4, or 5.

4. The compound of claim 2 having the structure: 【Chemistry 4】 。

5. R 1a and R 1b The compound of any one of claims 1 to 4, wherein each is hydrogen.

6. The compound of any one of claims 1 to 5, wherein n is 2.

7. n is 2 and R 2 is hydrogen or methyl. Compound.

8. n is 2, R 2 is hydrogen or methyl, R 3 is hydrogen and D* is hydroxyl The compound of any one of claims 1 to 7, which is a residue of a biologically active compound that contains a sil.

9. below: 【Chemistry 5】 9. The compound of claim 8, selected from the group consisting of: or a pharma- ceutically acceptable salt thereof.

10. 6. The compound of claim 5, wherein n is 1.

11. R 2 is hydrogen, methyl, or -CH 2 11. The compound of claim 10, wherein said compound is Ph.

12. R 3 The compound of claim 11, wherein is hydrogen.

13. 13. The compound of claim 12, wherein D* is a residue of a hydroxyl-containing biologically active compound.

14. below: 【Chemistry 6】 14. The compound of claim 13, selected from the group consisting of: or a pharma- ceutically acceptable salt thereof.

15. R 2 11. The compound of claim 10, wherein is hydrogen or methyl.

16. R 3 16. The compound of claim 15, wherein is alkyl.

17. 17. The compound of claim 16, wherein D* is a residue of a hydroxyl-containing biologically active compound.

18. below 【Chemistry 7】 18. The compound of claim 17, selected from the group consisting of:

19. R 1a is alkyl or arylalkyl, and R 1b is hydrogen, Compound.

20. 20. The compound of claim 19, wherein n is 1.

21. R 2 21. The compound of claim 20, wherein is hydrogen.

22. R 3 22. The compound of claim 21, wherein is hydrogen.

23. 23. The compound of claim 22, wherein D* is a residue of a hydroxyl-containing biologically active compound.

24. below 【Chemistry 8】 24. The compound of claim 23, selected from the group consisting of: or a pharma- ceutically acceptable salt thereof.

25. R 1a is alkylene, wherein the alkylene further comprises R 3 4, 5, or 6-membered forming a heterocyclyl of; R 1b is hydrogen; and R 3 But R 1a which further binds to form said 4-, 5-, or 6-membered heterocyclyl; be, The compound of claim 2.

26. 26. The compound of claim 25, wherein n is 1.

27. R 2 27. The compound of claim 26, wherein is hydrogen.

28. 28. The compound of claim 27, wherein D* is a residue of a hydroxyl-containing biologically active compound.

29. below 【Chemistry 9】 29. The compound of claim 28, selected from the group consisting of: or a pharma- ceutically acceptable salt thereof.

30. The following 【Chemistry 10】 11. The compound of claim 10, wherein

31. below 【Chemistry 11】 6. The compound of claim 5, selected from the group consisting of:

32. R 2 is alkylene, wherein the alkylene further comprises R 3 6-membered heterocycle forming a cyclocyclyl; and R 3 is alkylene, wherein the alkylene further comprises R 2 6-membered hexafluorophenyl 11. The compound of claim 10, which forms a telocyclyl.

33. 33. The compound of claim 32, wherein D* is a residue of a hydroxyl-containing biologically active compound.

34. The following 【Chemistry 12】 34. The compound of claim 33, which is: or a pharma- ceutically acceptable salt thereof.

35. A compound having the structure: 【Chemistry 13】 (In the ceremony L is a linker comprising a site reactive with an antibody or antigen-binding fragment thereof; R 1a and R 1b are independently hydrogen, alkyl, alkoxy, alkenyl, alkynyl, aryl, aryl, arylalkyl, heteroaryl, alkylene, or heteroalkylene; So, R 1a When is alkylene or heteroalkylene, the alkylene or heteroalkylene The alkylene may further include R 3 to form a 3-, 4-, 5-, 6-, 7-, or 8-membered heterocyclyl; R 2 is hydrogen, alkylene, heteroalkylene, or an amino acid side chain, where R 2 but When it is an alkylene or a heteroalkylene, the alkylene or the heteroalkylene may be Furthermore, R 3 to form a 4-, 5-, or 6-membered heterocyclyl; R 3 is hydrogen, alkyl, alkylene, or heteroalkylene, where R 3 But, A When the alkylene or heteroalkylene is an alkylene or heteroalkylene, the alkylene or heteroalkylene may further include , R 1a or R 2 to form said 3-, 4-, 5-, 6-, 7-, or 8-membered heterocyclyl; R 4 is hydrogen or alkyl; R 5 is oxygen, NR 6 or sulfur; R 6 is hydrogen or alkyl; D* is an acyl or bioactive group containing hydroxyl, amino, or thiol. is a residue of a compound; and where n is 0, 1, 2, 3, 4, 5, or 6.

36. When D* is a residue of a biologically active compound containing hydroxyl, amino, or thiol, The physiologically active compound or a residue thereof is an anti-inflammatory physiologically active compound or a residue thereof. Item 36. The compound according to item 35.

37. 37. The compound of claim 36, wherein the anti-inflammatory bioactive compound is a steroid or a residue thereof. thing.

38. 37. The method of claim 36, wherein the anti-inflammatory bioactive compound is an LXR agonist or a residue thereof. compound.

39. 36. The compound of claim 35, having the structure: 【Chemistry 14】 (In the ceremony L is a linker comprising a site reactive with an antibody or antigen-binding fragment thereof; R 1a and R 1b are independently hydrogen, alkyl, alkoxy, alkenyl, alkynyl, aryl, aryl, arylalkyl, heteroaryl, alkylene, or heteroalkylene; So, R 1a When is alkylene or heteroalkylene, the alkylene or heteroalkylene The alkylene may further include R 3 to form a 4-, 5-, or 6-membered heterocyclyl; R 2 is hydrogen, alkylene, heteroalkylene, or an amino acid side chain, where R 2 but When it is an alkylene or a heteroalkylene, the alkylene or the heteroalkylene may be Furthermore, R 3 to form a 4-, 5-, or 6-membered heterocyclyl; R 3 is hydrogen, alkyl, alkylene, or heteroalkylene, where R 3 But, A When the alkylene or heteroalkylene is an alkylene or heteroalkylene, the alkylene or heteroalkylene may further include , R 1a or R 2 to form said 4-, 5-, or 6-membered heterocyclyl; R 4 is hydrogen or alkyl; R 5 is oxygen, NR 6 or sulfur; R 6 is hydrogen or alkyl; D* is an acyl or bioactive group containing hydroxyl, amino, or thiol. is a residue of a compound; and where n is 0, 1, 2, 3, 4, 5, or 6.

40. 40. The compound of claim 39, having the structure: or a pharma- ceutically acceptable salt thereof. 【Chemistry 15】 (In the ceremony L is a linker comprising a site reactive with an antibody or antigen-binding fragment thereof; R 1a and R 1b are independently hydrogen, alkyl, alkoxy, alkenyl, alkynyl, aryl, aryl, arylalkyl, heteroaryl, or alkylene, where R 1a But, When the alkylene is an alkylene, the alkylene may further include R 3 4, 5, or 6-membered heterocyclyl Form a loop; R 2 is hydrogen or an amino acid side chain; R 3 is hydrogen, alkyl, or alkylene, where R 3 is an alkylene The alkylene further comprises R 1a to form said 4-, 5-, or 6-membered heterocyclyl; D* is an acyl or hydroxyl-containing residue of a biologically active compound; and where n is 0, 1, 2, 3, 4, 5, or 6.

41. 40. The compound of claim 39, having the structure: or a pharma- ceutically acceptable salt thereof. 【Chemistry 16】 (In the ceremony L is a linker comprising a site reactive with an antibody or antigen-binding fragment thereof; R 1a and R 1b are independently hydrogen, alkyl, alkoxy, alkenyl, alkynyl, aryl, aryl, arylalkyl, heteroaryl, or alkylene, where R 1a But, When the alkylene is alkylene, the alkylene may further include R 3 4, 5, or 6-membered heterocyclyl Form a loop; R 2 is hydrogen or an amino acid side chain; R 3 is hydrogen, alkyl, or alkylene, where R 3 is an alkylene The alkylene further comprises R 1a to form said 4-, 5-, or 6-membered heterocyclyl; D* is an acyl or hydroxyl-containing residue of a biologically active compound; and where n is 0, 1, 2, 3, 4, 5, or 6.

42. The linker is 【Chemistry 17】 The compound of any one of claims 35 to 41, further comprising:

43. The following 【Chemistry 18】 40. The compound of claim 39, which is: (In the ceremony SP 1 and SP 2 is a spacer group, if present, where SP 1 The antibody or further comprising a site reactive with an antigen-binding fragment of each AA is an amino acid; and and p is an integer from 1 to 10.

44. SP 1 44. The compound of claim 43, wherein comprises a reactive group that comprises an alkyne.

45. 45. The compound of claim 44, wherein the alkyne is capable of participating in a 1,3-cycloaddition reaction.

46. The alkyne undergoes a 1,3-cycloaddition reaction with an azide to give the regioisomeric 1,2,3-triazolate. wherein the azide comprises an azide-functionalized linking agent. Item 36. The compound according to item 35.

47. SP 2 but, 【Chemistry 19】 44. The compound of claim 43, comprising:

48. SP 2 but, 【Chemistry 20】 and R 2 44. The compound of claim 43, wherein is hydrogen or alkyl.

49. The alkyne undergoes a 1,3-cycloaddition reaction with an azide to give the regioisomeric 1,2,3-triazolate. and the azide comprises an azide-functionalized linking agent and is capable of forming a aryl moiety, 2 but, 【Chemistry 21】 47. The compound of claim 46, comprising:

50. The alkyne undergoes a 1,3-cycloaddition reaction with an azide to give the regioisomeric 1,2,3-triazolate. The azide can form a aryl moiety, the azide comprising an azide-functionalized linking agent, SP 2 but, ​ Contains and R 2 47. The compound of claim 46, wherein is hydrogen or alkyl.

51. R 1a and R 1b is hydrogen; R 2 is hydrogen or methyl; R 3 is hydrogen; and n is 2; 44. The compound of claim 43.

52. 52. The compound of claim 51, wherein D* is a residue of a hydroxyl-containing biologically active compound.

53. below 【Chemistry 23】 53. The compound of claim 52, selected from the group consisting of:

54. R 1a and R 1b is hydrogen; R 2 is hydrogen, methyl, or -CH 2 Ph; R 3 is hydrogen or alkyl; and n is 1, 44. The compound of claim 43.

55. 55. The compound of claim 54, wherein D* is a residue of a hydroxyl-containing biologically active compound.

56. below 【Chemistry 24】 【change】 【change】 【change】 【change】 【change】 56. The compound of claim 55, selected from the group consisting of:

57. R 1a and R 1b is hydrogen; R 2 is hydrogen; R 3 is alkyl; and n is 1, 44. The compound of claim 43.

58. 58. The compound of claim 57, wherein D* is a residue of a hydroxyl-containing biologically active compound.

59. below 【Chemistry 25】 59. The compound of claim 58 having the structure: or a pharma- ceutically acceptable salt thereof.

60. R 1a is alkyl or arylalkyl; R 1b is hydrogen; R 2 is hydrogen; R 3 is hydrogen; and n is 1, 44. The compound of claim 43.

61. 61. The compound of claim 60, wherein D* is a residue of a hydroxyl-containing biologically active compound.

62. below 【Chemistry 26】 62. The compound of claim 61, selected from the group consisting of:

63. R 1a But further R 3 is linked to form a 4-, 5-, or 6-membered heterocyclyl. the law of nature; R 1b is hydrogen; R 2 is hydrogen; R 3 But R 1a which further binds to form said 4-, 5-, or 6-membered heterocyclyl; Yes; and n is 1, 44. The compound of claim 43.

64. 64. The compound of claim 63, wherein D* is a residue of a hydroxyl-containing biologically active compound.

65. below 【Chemistry 27】 65. The compound of claim 64, selected from the group consisting of: or a pharma- ceutically acceptable salt thereof.

66. below 【Chemistry 28】 65. The compound of claim 64 having the structure: or a pharma- ceutically acceptable salt thereof.

67. R 1a and R 1b is hydrogen; R 2 is hydrogen; R 3 is hydrogen; and n is 1, 40. The compound of claim 39.

68. 68. The compound of claim 67, wherein D* is a residue of a hydroxyl-containing biologically active compound.

69. below 【Chemical 29】 69. The compound of claim 68 having the structure: or a pharma- ceutically acceptable salt thereof.

70. R 1a and R 1b is hydrogen; R 2 is hydrogen or -CH 2 Ph; R 3 is hydrogen; and n is 4; 40. The compound of claim 39.

71. 71. The compound of claim 70, wherein D* is a residue of a hydroxyl-containing biologically active compound.

72. below 【Chemistry 30】 72. The compound of claim 71, selected from the group consisting of:

73. R 1a and R 1b is hydrogen; R 3 is hydrogen; and n is 0, 42. The compound of claim 41.

74. 74. The compound of claim 73, wherein D* is a residue of a hydroxyl-containing biologically active compound.

75. below 【Chemistry 31】 75. The compound of claim 74, selected from the group consisting of:

76. R 1a and R 1b is hydrogen; R 2 is hydrogen; R 3 is alkyl; R 4 is alkyl; and n is 1, 58. The compound of claim 57.

77. 77. The compound of claim 76, wherein D* is a residue of a hydroxyl-containing biologically active compound.

78. The following structure: 【Chemistry 32】 78. The compound of claim 77, having the formula:

79. R 1a and R 1b is hydrogen; R 2 is hydrogen or -CH 2 OH; R 3 is hydrogen; and n is 6; 40. The compound of claim 39.

80. 80. The compound of claim 79, wherein D* is a residue of a hydroxyl-containing biologically active compound.

81. The following structure: 【Chemical 33】 81. The compound of claim 80, having the formula:

82. R 1a and R 1b is hydrogen; R 2 is alkylene, wherein the alkylene further comprises R 3 6-membered heterocycle Forming rocyclyl; R 3 is alkylene, wherein the alkylene further comprises R 2 6-membered hexafluorophenyl forming a terecyclyl; and n is 1, 44. The compound of claim 43.

83. 83. The compound of claim 82, wherein D* is a residue of a hydroxyl-containing biologically active compound.

84. The following 【Chemical 34】 84. The compound of claim 83, which is: or a pharma- ceutically acceptable salt thereof.

85. The following 【Chemistry 35】 54. The compound of claim 53, which is: or a pharma- ceutically acceptable salt thereof.

86. The following 【Chemical 36】 54. The compound of claim 53, which is: or a pharma- ceutically acceptable salt thereof.

87. The following 【Chemical 37】 66. The compound of claim 65, which is: or a pharma- ceutically acceptable salt thereof.

88. The following 【Chemical Formula 38】 57. The compound of claim 56, which is: or a pharma- ceutically acceptable salt thereof.

89. The following 【Chemical 39】 57. The compound of claim 56, which is: or a pharma- ceutically acceptable salt thereof.

90. A compound having the structure 【Chemistry 40】 (In the formula, L is a linker; BA is a binder; R 1a and R 1b are independently hydrogen, alkyl, alkoxy, alkenyl, alkynyl, aryl, aryl, arylalkyl, heteroaryl, alkylene, or heteroalkylene; So, R 1a When is alkylene or heteroalkylene, the alkylene or heteroa Lukiren further added, 3 to form a 3-, 4-, 5-, 6-, 7-, or 8-membered heterocyclyl; R 2 is hydrogen, alkylene, heteroalkylene, or an amino acid side chain, where R 2 but When it is an alkylene or a heteroalkylene, the alkylene or the heteroalkylene may be Furthermore, R 3 to form a 4-, 5-, or 6-membered heterocyclyl; R 3 is hydrogen, alkyl, alkylene, or heteroalkylene, where R 3 But, When the alkylene or heteroalkylene is an alkylene or heteroalkylene, the alkylene or heteroalkylene may further include , R 1a or R 2 to form said 3-, 4-, 5-, 6-, 7-, or 8-membered heterocyclyl; R 4 is hydrogen or alkyl; R 5 is oxygen, NR 6 or sulfur; R 6 is hydrogen or alkyl; D* is a residue of a bioactive compound containing a hydroxyl, amino, or thiol; n is 0, 1, 2, 3, 4, 5, or 6; and and k is an integer from 1 to 30.

91. D* is a residue of an anti-inflammatory bioactive compound containing hydroxyl, amino, or thiol. The compound of claim 90.

92. 92. The compound of claim 91, wherein the anti-inflammatory bioactive compound is a steroid or a residue thereof. thing.

93. 92. The method of claim 91, wherein the anti-inflammatory bioactive compound is an LXR agonist or a residue thereof. compound.

94. A compound having the structure 【Chemistry 41】 (In the formula, L is a linker; BA is a binder; R 1a and R 1b are independently hydrogen, alkyl, alkoxy, alkenyl, alkynyl, aryl, aryl, arylalkyl, heteroaryl, alkylene, or heteroalkylene; So, R 1a When is alkylene or heteroalkylene, the alkylene or heteroa Lukiren further added, 3 to form a 3-, 4-, 5-, 6-, 7-, or 8-membered heterocyclyl; R 2 is hydrogen, alkylene, heteroalkylene, or an amino acid side chain, where R 2 but When it is an alkylene or a heteroalkylene, the alkylene or the heteroalkylene may be Furthermore, R 3 to form a 4-, 5-, or 6-membered heterocyclyl; R 3 is hydrogen, alkyl, alkylene, or heteroalkylene, where R 3 But, When the alkylene or heteroalkylene is an alkylene or heteroalkylene, the alkylene or heteroalkylene may further include , R 1a or R 2 to form said 3-, 4-, 5-, 6-, 7-, or 8-membered heterocyclyl; R 4 is hydrogen or alkyl; R 5 is oxygen, NR 6 or sulfur; R 6 is hydrogen or alkyl; D* is the residue of an anti-inflammatory bioactive compound that contains a hydroxyl, amino, or thiol. the law of nature; n is 0, 1, 2, 3, 4, 5, or 6; and and k is an integer from 1 to 30.

95. 94. The compound of claim 93, wherein D* is a residue of a steroid containing a hydroxyl, amino, or thiol. The compound described.

96. A compound having the structure 【Chemistry 42】 (In the formula, L is 【Chemistry 43】 is a linker comprising: BA is a binder; R 1a and R 1b are independently hydrogen, alkyl, alkoxy, alkenyl, alkynyl, aryl, aryl, arylalkyl, heteroaryl, alkylene, or heteroalkylene; So, R 1a When is alkylene or heteroalkylene, the alkylene or heteroa Lukiren further added, 3 to form a 3-, 4-, 5-, 6-, 7-, or 8-membered heterocyclyl; R 2 is hydrogen, alkylene, heteroalkylene, or an amino acid side chain, where R 2 but When it is an alkylene or a heteroalkylene, the alkylene or the heteroalkylene may be Furthermore, R 3 to form a 4-, 5-, or 6-membered heterocyclyl; R 3 is hydrogen, alkyl, alkylene, or heteroalkylene, where R 3 But, A When the alkylene or heteroalkylene is an alkylene or heteroalkylene, the alkylene or heteroalkylene may further include , R 1a or R 2 to form said 3-, 4-, 5-, 6-, 7-, or 8-membered heterocyclyl; R 4 is hydrogen or alkyl; R 5 is oxygen, NR 6 or sulfur; R 6 is hydrogen or alkyl; D* is a residue of a bioactive compound containing a hydroxyl, amino, or thiol; n is 0, 1, 2, 3, 4, 5, or 6; and and k is an integer from 1 to 30.

97. L, 【Chemistry 44】 and R 2 97. The compound of claim 96, wherein is hydrogen.

98. A compound having the structure 【Chemistry 45】 (In the formula, L is a linker; BA is a binder; R 1a and R 1b are independently hydrogen, alkyl, alkoxy, alkenyl, alkynyl, aryl, aryl, arylalkyl, heteroaryl, alkylene, or heteroalkylene; So, R 1a When is alkylene or heteroalkylene, the alkylene or heteroa Lukiren further added, 3 to form a 3-, 4-, 5-, 6-, 7-, or 8-membered heterocyclyl; R 2 is hydrogen, alkylene, heteroalkylene, or an amino acid side chain, where R 2 but When it is an alkylene or a heteroalkylene, the alkylene or the heteroalkylene may be Furthermore, R 3 to form a 4-, 5-, or 6-membered heterocyclyl; R 3 is hydrogen, alkyl, alkylene, or heteroalkylene, where R 3 But, When the alkylene or heteroalkylene is an alkylene or heteroalkylene, the alkylene or heteroalkylene may further include , R 1a or R 2 to form said 3-, 4-, 5-, 6-, 7-, or 8-membered heterocyclyl; R 4 is hydrogen or alkyl; R 5 is oxygen, NR 6 or sulfur; R 6 is hydrogen or alkyl; D* is a residue of a bioactive compound containing a hydroxyl, amino, or thiol; n is 0, 1, 2, 3, 4, 5, or 6; Here, the conjugation of L to BA can be via a click chemistry residue, an amide residue, and a residue containing two cysteine ​​residues of a single BA chemically bonded to L. and and k is an integer from 1 to 30.

99. The compound of claim 90 having the structure: 【Chemistry 46】 (In the formula, L is a linker; BA is a binder; R 1a and R 1b are independently hydrogen, alkyl, alkoxy, alkenyl, alkynyl, aryl, aryl, arylalkyl, heteroaryl, alkylene, or heteroalkylene; So, R 1a When is alkylene or heteroalkylene, the alkylene or heteroa Lukiren further added, 3 to form a 4-, 5-, or 6-membered heterocyclyl; R 2 is hydrogen, alkylene, heteroalkylene, or an amino acid side chain, where R 2 but When it is an alkylene or a heteroalkylene, the alkylene or the heteroalkylene may be Furthermore, R 3 to form a 4-, 5-, or 6-membered heterocyclyl; R 3 is hydrogen, alkyl, alkylene, or heteroalkylene, where R 3 But, When the alkylene or heteroalkylene is an alkylene or heteroalkylene, the alkylene or heteroalkylene may further include , R 1a or R 2 to form said 4-, 5-, or 6-membered heterocyclyl; R 4 is hydrogen or alkyl; R 5 is oxygen, NR 6 or sulfur; R 6 is hydrogen or alkyl; D* is a residue of a bioactive compound containing a hydroxyl, amino, or thiol; n is 0, 1, 2, 3, 4, 5, or 6; and and k is an integer from 1 to 30.

100. 99. The compound of claim 99 having the structure: 【Chemistry 47】 (In the formula, L is a linker; BA is a binder; R 1a and R 1b are independently hydrogen, alkyl, alkoxy, alkenyl, alkynyl, aryl, aryl, arylalkyl, heteroaryl, or alkylene, where R 1a But, When the alkylene is alkylene, the alkylene may further include R 3 4, 5, or 6-membered heterocyclyl Form a loop; R 2 is hydrogen or an amino acid side chain; R 3 is hydrogen, alkyl, or alkylene, where R 3 is an alkylene The alkylene further comprises R 1a to form said 4-, 5-, or 6-membered heterocyclyl; D* is a residue of a hydroxyl-containing bioactive compound; n is 0, 1, 2, 3, 4, 5, or 6; and and k is an integer from 1 to 30.

101. 99. The compound of claim 99 having the structure: 【Chemistry 48】 (In the formula, L is a linker; BA is a binder; R 1a and R 1b are independently hydrogen, alkyl, alkoxy, alkenyl, alkynyl, aryl, aryl, arylalkyl, heteroaryl, or alkylene, where R 1a But, When the alkylene is an alkylene, the alkylene may further include R 3 4, 5, or 6-membered heterocyclyl Form a loop; R 2 is hydrogen or an amino acid side chain; R 3 is hydrogen, alkyl, or alkylene, where R 3 is an alkylene The alkylene further comprises R 1a to form said 4-, 5-, or 6-membered heterocyclyl; D* is a residue of a hydroxyl-containing bioactive compound; n is 0, 1, 2, 3, 4, 5, or 6; and and k is an integer from 1 to 30.

102. The linker is 【Chemistry 49】 The compound of any one of claims 90 to 101, comprising:

103. 99. The compound of claim 99, which is 【Chemistry 50】 (In the formula, SP 1 and SP 2 is a spacer group, if present, where SP 1 The antibody or further comprising a site reactive with an antigen-binding fragment of each AA is an amino acid; and and p is an integer from 1 to 10.

104. SP 1 104. The compound of claim 103, wherein comprises a reactive group that comprises an alkyne.

105. The compound of claim 104, wherein the alkyne is capable of participating in a 1,3-cycloaddition reaction. 。

106. The alkyne is capable of participating in a 1,3-cycloaddition reaction with the linking agent, 106. The compound of claim 105, which is an azide-functionalized linking agent.

107. SP 2 but, 【Chemistry 51】 104. The compound of claim 103, comprising:

108. SP 2 but, 【Chemistry 52】 Contains and R 2 104. The compound of claim 103, wherein is hydrogen or alkyl.

109. The alkyne is capable of participating in a 1,3-cycloaddition reaction with the linking agent, , an azide-functionalized linking agent, and SP 2 but, 【Chemistry 53】 107. The compound of claim 106, comprising:

110. The alkyne is capable of participating in a 1,3-cycloaddition reaction with the linking agent, , an azide-functionalized coupling agent, SP 2 but, 【Chemical 54】 Contains and R 2 is hydrogen or alkyl.

111. The binder is of formula H 2 10. The antibody according to claim 10, wherein the antibody is modified with a primary amine compound according to N-LL-X. Compound 3 (Wherein, LL is a divalent polyethylene glycol (PEG) group; -(CH 2 ) n -; -(CH 2 CH 2 O) n -(CH 2 ) p -; -(CH 2 ) n -N(H)C(O)-(CH 2 ) m -; -(CH 2 CH 2 O) n -N(H)C(O)-(CH 2 CH 2 O) m -(CH 2 ) p -; -(CH 2 ) n -C(O)N(H)-(CH 2 ) m -; -(CH 2 CH 2 O) n -C(O)N(H)-(CH 2 CH 2 O) m -(CH 2 ) p -; -(CH 2 ) n -N(H)C(O)-(CH 2 CH 2 O) m -(CH 2 ) p -; -(CH 2 CH 2 O) n -N(H)C(O)-(CH 2 ) m -; -(CH 2 ) n -C(O)N(H)-(CH 2 CH 2 O) m -(CH 2 ) p -; and -(CH 2 CH 2 O) n -C(O)N(H)-(CH 2 ) m - (In the formula, n is an integer selected from 1 to 12; m is an integer selected from 0 to 12; p is an integer selected from 0 to 2. and X is -SH, -N 3 , -C≡CH, -C(O)H, tetrazole, 【Chemistry 55】 (selected from the group consisting of:

112. The binder has the following structure: 【Chemistry 56】 The compound of claim 111, which is an antibody modified with a primary amine having the formula:

113. below 【Chemistry 57】 【change】 【change】 【change】 【change】 【change】 【change】 【change】 【change】 【change】 【change】 【change】 【change】 【change】 【change】 【change】 【change】 【change】 【change】 【change】 【change】 【change】 【change】 【change】 【change】 【change】 【change】 【change】 (wherein k is 1, 2, 3, or 4).

113. The compound of claim 112, selected from the group consisting of:

114. below 【Chemistry 58】 【change】 【change】 (wherein z is 1, 2, 3, or 4).

91. The compound of claim 90, selected from the group consisting of:

115. An antibody-drug conjugate comprising an antibody or an antigen-binding fragment thereof, 40. The antibody-drug, wherein the antigen-binding fragment is conjugated to the compound of claim 2 or 39. Material conjugates.

116. The conjugated compound is 【Chemistry 59】 【change】 【change】 【change】 The antibody-drug conjugate of claim 115, selected from the group consisting of:

117. 100. The compound of claim 99, wherein the BA is an antibody or an antigen-binding fragment thereof.

118. The BA contains at least one glutamine residue that is used for conjugation.

118. The compound of claim 117, which is a transglutaminase-modified antibody or an antigen-binding fragment thereof. 。

119. The BA contains at least two glutamine residues that are used for conjugation.

118. The compound of claim 117, which is a transglutaminase-modified antibody or an antigen-binding fragment thereof. 。

120. The BA contains at least four glutamine residues that are used for conjugation.

118. The compound of claim 117, which is a transglutaminase-modified antibody or an antigen-binding fragment thereof. 。

121. BA is a transglutaminase-modified antibody or an antigen-binding fragment thereof, and the conjugate and k is 2. The compound of claim 120, wherein the substitution is at two Q295 residues; and k is 2.

122. BA is a transglutaminase-modified antibody or an antigen-binding fragment thereof, and the conjugate and k is 4. The compound described in 0.

123. A compound according to any one of claims 1 to 122, and a pharma- ceutically acceptable excipient or carrier; or a pharmaceutical composition comprising a diluent.

124. Diseases, disorders, or conditions associated with glucocorticoid receptor signaling in a subject A method for treating a subject, comprising administering to said subject an effective amount of a compound according to any one of claims 1 to 123. The method comprises administering a compound or pharmaceutical composition.

125. 125. The method of claim 124, wherein the disease, disorder, or condition is an inflammatory disease, disorder, or condition. How to.

126. side effects associated with administration of an unconjugated steroid payload of the compound, 126. The method of claim 124 or 125, wherein the

127. Methods for treating dyslipidemia, metabolic disease, inflammation, or neurodegenerative disease in a subject administering to said subject an effective amount of a compound or pharmaceutical composition according to any one of claims 1 to 126 The method comprising administering.

128. A method for treating dyslipidemia in a subject, comprising administering to the subject an effective amount of any one of claims 1 to 10.

27. The method comprising administering a compound or pharmaceutical composition according to any one of claims 27 to a patient.

129. A method for treating a metabolic disorder in a subject, comprising administering to the subject an effective amount of any one of claims 1 to 10.

28. The method comprising administering a compound or pharmaceutical composition according to any one of claims 27 to a patient.

130. A method for treating inflammation in a subject, comprising administering to the subject an effective amount of any of claims 1 to 129. The method comprises administering a compound or pharmaceutical composition according to any one of claims 1 to 4.

131. A method for treating a neurodegenerative disease in a subject, comprising administering to the subject an effective amount of claim 1. The method comprises administering a compound or pharmaceutical composition according to any one of claims 1 to 130.

132. An antibody-drug conjugate comprising contacting a binding agent with a compound of claim 39. Method for preparing the compound.

133. The following structure: 【Chemistry 60】 3. The compound of claim 2, having the formula:

134. The following structure: 【Chemistry 61】 3. The compound of claim 2, having the formula:

135. The following structure: 【Chemistry 62】 3. The compound of claim 2, having the formula:

136. The following structure: 【Chemistry 63】 3. The compound of claim 2, having the formula:

137. The following structure: 【Chemistry 64】 40. The compound of claim 39, having the formula:

138. The following structure: 【Chemistry 65】 40. The compound of claim 39, having the formula:

139. The following structure: 【Chemistry 66】 40. The compound of claim 39, having the formula:

140. The following structure: 【Chemistry 67】 40. The compound of claim 39, having the formula:

141. The following structure: 【Chemistry 68】 100. The compound of claim 99, having the formula:

142. The following structure: 【Chemistry 69】 100. The compound of claim 99, having the formula:

143. The following structure: 【Chemistry 70】 100. The compound of claim 99, having the formula:

144. The following structure: 【Chemistry 71】 100. The compound of claim 99, having the formula:

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