Piperidinyl targeting compounds that selectively bind integrins

• US 20040224986A1
• Filed: 02/18/2004
• Published: 11/11/2004
• Est. Priority Date: 08/16/2002
• Status: Abandoned Application

• Current Assignee: Janssen Pharmaceutica NV (Johnson & Johnson)
• Original Assignee: Janssen Pharmaceutica NV (Johnson & Johnson)
• Inventors: Liu, Li, Ghosh, Shyamali, Maryanoff, Bruce E., De Corte, Bart, Kinney, William A.
• Application Number:
  US10/782,060
• Publication Number:
  US 20040224986A1
• Time in Patent Office: Days
• US Class Current: 514/326
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/4523 containing further heterocyclic ring systems
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61K 51/0455 having six-membered rings with one nitrogen as the only ring hetero atom
• CPC Class Codes: A61K 51/0459 having six-membered rings with two nitrogen atoms as the only ring hetero atoms, e.g. piperazine
• CPC Class Codes: A61P 13/12 of the kidneys
• CPC Class Codes: A61P 17/00 Drugs for dermatological disorders
• CPC Class Codes: A61P 17/06 Antipsoriatics
• CPC Class Codes: A61P 19/00 Drugs for skeletal disorders
• CPC Class Codes: A61P 19/02 for joint disorders, e.g. arthritis, arthrosis
• CPC Class Codes: A61P 19/10 for osteoporosis
• CPC Class Codes: A61P 27/00 Drugs for disorders of the senses
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: C07D 401/12 linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 401/14 containing three or more hetero rings
• CPC Class Codes: C07D 405/14 containing three or more hetero rings
• CPC Class Codes: C07D 471/04 Ortho-condensed systems
• CPC Class Codes: Y02P 20/582 Recycling of unreacted starting or intermediate materials

Abstract

The present invention relates to the synthesis and biological application of piperidinoyl carboxylic acid integrin antagonists affinity moiety of IFormula (I):

and Formula (II):

These affinity moieties maybe used with imaging agents or liposomes to target cells that express the α_vβ₃, α_vβ₅, or α_vβ₆ integrin receptors.

Claims

1. A targeting ligand having a formula selected from the group consisting of Formula (I):

2. The targeting ligand of claim 1 wherein W is selected from the group consisting of —

C_0-4alkyl(R₁) and —

C_0-4alkyl-aryl(R₁,R₈).

3. The targeting ligand of claim 1 wherein W is —

C_0-4alkyl(R₁) or —

C_0-4alkyl-phenyl(R₁,R₈).

4. The targeting ligand of claim 1 wherein R₁ is selected from the group consisting of —

N(R₄)(R₆), -heterocyclyl(R₈) and -heteroaryl(R₈).

5. The targeting ligand of claim 1 wherein R₁ is selected from the group consisting of —

N(R₄)(R₆), -dihydro-1H-pyrrolo[2,3-b]pyridinyl(R₈), -tetrahydropyrimidinyl(R₈), -tetrahydro-1,8-naphthyridinyl(R₈), -tetrahydro-1H-azepino[2,3-b]pyridinyl(R₈) and -pyridinyl(R₈).

6. The targeting ligand of claim 1 wherein R₁ is selected from the group consisting of —

N(R₄)(R₆), -tetrahydropyrimidinyl(R₈) and -tetrahydro-1,8-naphthyridinyl(R₈).

7. The targeting ligand of claim 1 wherein R_1a is selected from the group consisting of —

C(R₄)(═

N—

R₄), —

C(═

N—

R₄)—

N(R₄)₂, —

C(═

N—

R₄)—

N(R₄)(R₆), —

C(═

N—

R₄)—

N(R₄)—

C(═

O)—

R₄, —

C(═

N—

R₄)—

N(R₄)—

C(═

O)—

N(R₄)₂, —

C(═

N—

R₄)—

N(R₄)—

CO₂—

R₄, —

C(═

N—

R₄)—

N(R₄)—

SO₂—

C_1-4alkyl(R₇) and —

C(═

N—

R₄)—

N(R₄)—

SO₂—

N(R₄)₂.

8. The targeting ligand of claim 1 wherein R₄ is selected from the group consisting of hydrogen and —

C_1-4alkyl(R₇).

9. The targeting ligand of claim 1 wherein R₄ is hydrogen.

10. The targeting ligand of claim 1 wherein R₅ is selected from the group consisting of —

C(═

O)—

R₄, —

C(═

O)—

N(R₄)₂, —

C(═

O)-cycloalkyl(R₈), —

C(═

O)-heterocyclyl(R₈), —

C(═

O)-aryl(R₈), —

C(═

O)-heteroaryl(R₈), —

C(═

O)—

N(R₄)-cycloalkyl(R₈), —

C(═

O)—

N(R₄)-aryl(R₈), —

CO₂—

R₄, —

CO₂-cycloalkyl(R₉), —

CO₂-aryl(R₈), —

C(R₄)(═

N—

R₄), —

C(═

N—

R₄)—

N(R₄)₂, —

C(═

N—

R₄)—

N(R₄)(R₆), —

C(═

N—

R₄)—

N(R₄)—

C(═

O)—

R₄, —

C(═

N—

R₄)—

N(R₄)—

C(═

O)—

N(R₄)₂, —

C(═

N—

R₄)—

N(R₄)—

CO₂—

R₄, —

C(═

N—

R₄)—

N(R₄)—

SO₂—

C_1-4alkyl(R₇), —

C(═

N—

R₄)—

N(R₄)—

SO₂—

N(R₄)₂, —

N(R₄)—

C(R₄)(═

N—

R₄), —

N(R₄)—

C(═

N—

R₄)—

N(R₄)₂, —

N(R₄)—

C(═

N—

R₄)—

N(R₄)(R₆), —

N(R₄)—

C(═

N—

R₄)—

N(R₄)—

C(═

O)—

R₄, —

N(R₄)—

C(═

N—

R₄)—

N(R₄)—

C(═

O)—

N(R₄)₂, —

N(R₄)—

C(═

N—

R₄)—

N(R₄)—

CO₂—

R₄, —

N(R₄)—

C(═

N—

R₄)—

N(R₄)—

SO₂—

C_1-4alkyl(R₇), —

N(R₄)—

C(═

N—

R₄)—

N(R₄)—

SO₂—

N(R₄)₂, —

SO₂—

C_1-4alkyl(R₇), —

SO₂—

N(R₄)₂, —

SO₂-cycloalkyl(R₈) and —

SO₂-aryl(R₈).

11. The targeting ligand of claim 1 wherein R₅ is selected from the group consisting of —

C(═

O)—

R₄, —

C(═

O)—

N(R₄)₂, —

CO₂—

R₄, —

C(R₄)(═

N—

R₄), —

C(═

N—

R₄)—

N(R₄)₂, —

C(═

N—

R₄)—

N(R₄)(R₆), —

N(R₄)—

C(R₄)(═

N—

R₄), —

N(R₄)—

C(═

N—

R₄)—

N(R₄)₂, —

N(R₄)—

C(═

N—

R₄)—

N(R₄)(R₆), —

SO₂—

C_1-4alkyl(R₇) and —

SO₂—

N(R₄)₂.

12. The targeting ligand of claim 1 wherein R₆ is selected from the group consisting of -heterocyclyl(R₈) and -heteroaryl(R₈).

13. The targeting ligand of claim 1 wherein R₆ is selected from the group consisting of -dihydroimidazolyl(R₈), -tetrahydropyridinyl(R₈), -tetrahydropyrimidinyl(R₈) and -pyridinyl(R₈).

14. The targeting ligand of claim 1 wherein R₇ is one to two substituents independently selected from the group consisting of hydrogen, —

C_1-4alkoxy(R₉), —

NH₂, —

NH—

C_1-4alkyl(R₉), —

N(C_1-4alkyl(R₉))₂, —

C(═

O)H, —

C(═

O)—

C_1-4alkyl(R₉), —

C(═

O)—

NH₂, —

C(═

O)—

NH—

C_1-4alkyl(R₉), —

C(═

O)—

N(C_1-4alkyl(R₉))₂, —

C(═

O)—

NH-aryl(R₁₀), —

C(═

O)-cycloalkyl(R₁₀), —

C(═

O)-heterocyclyl(R₁₀), —

C(═

O)-aryl(R₁₀), —

C(═

O)-heteroaryl(R₁₀), —

CO₂H, —

CO₂—

C_1-4alkyl(R₉), —

CO₂-aryl(R₁₀), —

C(═

NH)—

NH₂, —

SH, —

S—

C_1-4alkyl(R₉), —

S—

C_1-4alkyl-S—

C_1-4alkyl(R₉), —

S—

C_1-4alkyl-C_1-4alkoxy(R₉), —

S—

C_1-4alkyl-NH—

C_1-4alkyl(R₉), —

SO₂—

C_1-4alkyl(R₉), —

SO₂—

NH₂, —

SO₂—

NH—

C_1-4alkyl(R₉), —

SO₂—

N(C₄alkyl(R₉))₂, —

SO₂-aryl(R₁₀), cyano, (halo)_1-3, hydroxy, nitro, oxo, -cycloalkyl(R₁₀), -heterocyclyl(R₁₀), -aryl(R₁₀) and -heteroaryl(R₁₀).

15. The targeting ligand of claim 1 wherein R₇ is one to two substituents independently selected from the group consisting of hydrogen, —

C_1-4alkoxy(R₉), —

NH₂, —

NH—

C_1-4alkyl(R₉), —

N(C_1-4alkyl(R₉))₂, (halo)_1-3, hydroxy and oxo.

16. The targeting ligand of claim 1 wherein R₇ is hydrogen.

17. The targeting ligand of claim 1 wherein R₈ is one to four substituents independently selected from the group consisting of hydrogen, —

C_1-4alkyl(R₉), —

C(═

O)H, —

C(═

O)—

C_1-4alkyl(R₉), —

C(═

O)—

NH₂, —

C(═

O)—

NH—

C₄alkyl(R₉), —

C(═

O)—

N(C_1-4alkyl(R₉))₂, —

C(═

O)—

NH-aryl(R₁₀), —

C(═

O)-cycloalkyl(R₁₀), —

C(═

O)-heterocyclyl(R₁₀), —

C(═

O)-aryl(R₁₀), —

C(═

O)-heteroaryl(R₁₀), —

CO₂H, —

CO₂—

C_1-4alkyl(R₉), —

CO₂-aryl(R₁₀), —

C(═

NH)—

NH₂, —

SO₂—

C_1-4alkyl(R₉), —

SO₂—

NH₂, —

SO₂—

NH—

C_1-4alkyl(R₉), —

SO₂—

N(C_1-4alkyl(R₉))₂, —

SO₂-aryl(R₁₀), -cycloalkyl(R₁₀) and -aryl(R₁₀) when attached to a nitrogen atom; and

, wherein R₈ is one to four substituents independently selected from the group consisting of hydrogen, —

C_1-4alkyl(R₉), —

C_1-4alkoxy(R₉), —

O-cycloalkyl(R₁₀), —

O-aryl(R₁₀), —

C(═

O)H, —

C(═

O)—

C_1-4alkyl(R₉), —

C(═

O)—

NH₂, —

C(═

O)—

NH—

C_1-4alkyl(R₉), —

C(═

O)—

N(C_1-4alkyl-R₁₁)₂, —

C(═

O)—

NH-aryl(R₁₀), —

C(═

O)-cycloalkyl(R₁₀), —

C(═

O)-heterocyclyl(R₁₀), —

C(═

O)-aryl(R₁₀), —

C(═

O)-heteroaryl(R₁₀), —

CO₂H, —

CO₂—

C_1-4alkyl(R₉), —

CO₂-aryl(R₁₀), —

C(═

NH)—

NH₂, —

SO₂—

C_1-4alkyl(R₉), —

SO₂—

NH₂, —

SO₂—

NH—

C_1-4alkyl(R₉), —

SO₂—

N(C_1-4alkyl(R₉))₂, —

SO₂-aryl(R₁₀), —

SH, —

S—

C_1-4alkyl(R₉), —

S—

C_1-4alkyl-S—

C_1-4alkyl(R₉), —

S—

C_1-4alkyl-C_1-4alkoxy(R₉), —

S—

C_1-4alkyl-NH—

C_1-4alkyl(R₉), —

NH₂, —

NH—

C_1-4alkyl(R₉), —

N(C_1-4alkyl(R₉))₂, cyano, halo, hydroxy, nitro, oxo, -cycloalkyl(R₁₀), -heterocyclyl(R₁₀), -aryl(R₁₀) and -heteroaryl(R₁₀) when attached to a carbon atom.

18. The targeting ligand of claim 1 wherein R₈ is one to four substituents independently selected from the group consisting of hydrogen, —

C_1-4alkyl(R₉), —

C(═

O)H, —

C(═

O)—

NH₂, —

C(═

O)—

NH—

C_1-4alkyl(R₉), —

C(═

O)—

N(C_1-4alkyl(R₉))₂, —

CO₂H, —

CO₂—

C_1-4alkyl(R₉) and —

SO₂—

NH₂ when attached to a nitrogen atom; and

, wherein R₈ is one to four substituents independently selected from the group consisting of hydrogen, —

C_1-4alkyl(R₉), —

C_1-4alkoxy(R₉), —

O-aryl(R₁₀), —

C(═

O)H, —

C(═

O)—

NH₂, —

C(═

O)—

NH—

C_1-4alkyl(R₉), —

C(═

O)—

N(C_1-4alkyl(R₉))₂, —

CO₂H, —

CO₂—

C_1-4alkyl(R₉), —

SO₂—

NH₂, —

NH₂, —

NH—

C_1-4alkyl(R₉), —

N(C_1-4alkyl(R₉))₂, cyano, halo, hydroxy, nitro and oxo when attached to a carbon atom.

19. The targeting ligand of claim 1 wherein R₈ is one to four substituents independently selected from the group consisting of hydrogen and —

C_1-4alkyl(R₉) when attached to a nitrogen atom; and

, wherein R₈ is one to four substituents independently selected from the group consisting of hydrogen, —

C_1-4alkyl(R₉), —

C_1-4alkoxy(R₉), —

O-aryl(R₁₀), —

NH₂, —

NH—

C_1-4alkyl(R₉), —

N(C_1-4alkyl(R₉))₂, halo, hydroxy and oxo when attached to a carbon atom.

20. The targeting ligand of claim 1 wherein R₈ is one to four substituents independently selected from the group consisting of hydrogen and —

C_1-4alkyl(R₉) when attached to a nitrogen atom; and

, wherein R₈ is one to four substituents independently selected from the group consisting of hydrogen, —

C_1-4alkyl(R₉), —

C_1-4alkoxy(R₉), —

O-aryl(R₁₀) and hydroxy when attached to a carbon atom.

21. The targeting ligand of claim 1 wherein R₉ is selected from the group consisting of hydrogen, —

C_1-4alkoxy, —

NH₂, —

NH—

C_1-4alkyl, —

N(C_1-4alkyl)₂, —

C(═

O)H, —

C(═

O)—

NH₂, —

C(═

O)—

NH—

C_1-4alkyl, —

C(═

O)—

N(C_1-4alkyl)₂, —

CO₂H, —

CO₂—

C_1-4alkyl, —

SO₂—

C_1-4alkyl, —

SO₂—

NH₂, —

SO₂—

NH—

C_1-4alkyl, —

SO₂—

N(C_1-4alkyl)₂, cyano, (halo)_1-3, hydroxy, nitro and oxo.

22. The targeting ligand of claim 1 wherein R₉ is selected from the group consisting of hydrogen, —

C_1-4alkoxy, —

NH₂, —

NH—

C_1-4alkyl, —

N(C_1-4alkyl)₂, —

C(═

O)H, —

CO₂H, —

C(═

O)—

C_1-4alkoxy, (halo)_1-3, hydroxy and oxo.

23. The targeting ligand of claim 1 wherein R₉ is selected from the group consisting of hydrogen, —

C_1-4alkoxy, —

NH₂, —

NH—

C_1-4alkyl, —

N(C_1-4alkyl)₂, (halo)_1-3 and hydroxy.

24. The targeting ligand claim 1 wherein R₁₀ is one to four substituents independently selected from the group consisting of hydrogen, —

C_1-4alkyl, —

C(═

O)H, —

C(═

O)—

C_1-4alkyl, —

C(═

O)—

NH₂, —

C(═

O)—

NH—

C_1-4alkyl, —

C(═

O)—

N(C_1-4alkyl)₂, —

CO₂H, —

CO₂—

C_1-4alkyl, —

SO₂—

C_1-4alkyl, —

SO₂—

NH₂, —

SO₂—

NH—

C_1-4alkyl and —

SO₂—

N(C_1-4alkyl)₂ when attached to a nitrogen atom; and

, wherein R₁₀ is one to four substituents independently selected from the group consisting of hydrogen, —

C_1-4alkyl, —

C_1-4alkoxy, —

C(═

O)H, —

C(═

O)—

C_1-4alkyl, —

C(═

O)—

NH₂, —

C(═

O)—

NH—

C_1-4alkyl, —

C(═

O)—

N(C_1-4alkyl)₂, —

CO₂H, —

CO₂—

C_1-4alkyl, —

SO₂—

C_1-4alkyl, —

SO₂—

NH₂, —

SO₂—

NH—

C_1-4alkyl, —

SO₂—

N(C_1-4alkyl)₂, —

NH₂, —

NH—

C_1-4alkyl, —

N(C_1-4alkyl)₂, cyano, halo, hydroxy, nitro and oxo when attached to a carbon atom.

25. The targeting ligand of claim 1 wherein (R₁₀)₁₄ is selected from the group consisting of hydrogen, —

C_1-4alkyl, —

C_1-4alkoxy, —

C(═

O)H, —

C(═

O)—

C_1-4alkyl, —

CO₂H, —

CO₂—

C_1-4alkyl, —

NH₂, —

NH—

C_1-4alkyl, —

N(C_1-4alkyl)₂, halo, hydroxy, nitro and oxo when attached to a carbon atom.

26. The targeting ligand of claim 1 wherein R₁₀ is hydrogen.

27. The targeting ligand of claim 1 wherein R_2a is selected from the group consisting of —

C_1-4alkyl (R₇)(R₁₁), —

C_2-4alkenyl(R₇)(R₁₁), —

C_2-4alkynyl(R₇)(R₁₁), -cycloalkyl(R₇)(R₁₁), -heterocyclyl(R₈)(R₁₂), -aryl(R₈)(R₁₂), and -heteroaryl(R₈)(R₁₂).

28. The targeting ligand of claim 1 wherein R_2a is selected from the group consisting of -cycloalkyl(R₇)(R₁₁), -heterocyclyl(R₈)(R₁₂), -aryl(R₈)(R₁₂), and -heteroaryl(R₈)(R₁₁).

29. The targeting ligand of claim 1 wherein R_2a is selected from the group consisting of -cycloalkyl(R₇)(R₁₁), -heterocyclyl(R₈)(R₁₂), -phenyl(R₈)(R₁₂), -naphthalenyl(R₈)(R₁₂), and -heteroaryl(R₈)(R₁₁).

30. The targeting ligand claim 1 wherein R_2a is selected from the group consisting of -tetrahydropyrimidinyl(R₈)(R₁₂), -1,3-benzodioxolyl(R₈)(R₁₂), -dihydrobenzofuranyl(R₈)(R₁₂), -tetrahydroquinolinyl(R₈)(R₁₂), -phenyl(R₈)(R₁₂), -naphthalenyl(R₈)(R₁₂), -pyridinyl(R₈)(R₁₂), -pyrimidinyl(R₈)(R₁₂), and -quinolinyl(R₈)(R₁₂).

31. The targeting ligand of claim 1 wherein R₁₁ is selected from the group consisting of —

C_1-8alkyl(R₁₄), —

O—

C_1-8alkyl(R₁₄), —

NH—

C_1-8alkyl(R₁₄), —

S—

C_1-8alkyl(R₁₄), —

C(═

O)C_1-8alkyl(R₁₄), —

O—

C(═

O)C_1-8alkyl(R₁₄), —

NH—

C(═

O)C_1-8alkyl(R₁₄), —

C(═

O)OC_1-8alkyl(R₁₄), —

C(═

O)NHC_1-8alkyl(R₁₄), —

O—

C(═

O)OC_1-8alkyl(R₁₄), —

O—

C(═

O)NHC_1-8alkyl(R₁₄), —

O—

C(═

O)C_1-8alkylC(═

O)(R₁₄), —

NH—

C(═

O)C_1-8alkylC(═

O)(R₁₄), —

C(═

O)OC_1-8alkylC(═

O)(R₁₄), —

O—

C(═

O)OC_1-8alkylC(═

O)(R₁₄), —

NH—

C(═

O)OC_1-8alkylC(═

O)(R₁₄), —

C(═

O)NHC_1-8alkylC(═

O)(R₁₄), —

O—

C(═

O)NHC_1-8alkylC(═

O)(R₁₄), —

NH—

C(═

O)NHC_1-8alkylC(═

O)(R₁₄), —

SCH₂CH₂O(CH₂CH₂O)_rCH₂CH₂(R₁₄), —

NHCH₂CH₂O(CH₂CH₂O)_rCH₂C(═

O)(R₁₄), —

SO₂NHCH₂CH₂O(CH₂CH₂O)_rCH₂CH₂(R₁₄), —

C(═

O)CH₂O(CH₂CH₂O)_rCH₂C(═

O)(R₁₄), —

OC(═

O)OCH₂CH₂O(CH₂CH₂O)_rCH₂C(═

O)(R₁₄), —

OC(═

O)NHCH₂CH₂O(CH₂CH₂O)_rCH₂C(═

O)(R₁₄), —

NHC(═

O)NHCH₂CH₂O(CH₂CH₂O)_rCH₂C(═

O)(R₁₄), and —

SO₂NHCH₂CH₂O(CH₂CH₂O)_rCH₂C(═

O)(R₁₄).

32. The targeting ligand of claim 1 wherein R₁₁ is selected from the group consisting of —

C_1-8alkyl(R₁₄), —

O—

C_1-8alkyl(R₁₄), —

NH—

C_1-8alkyl(R₁₄), —

S—

C_1-8alkyl(R₁₄), —

C(═

O)C_1-8alkyl(R₁₄), —

O—

C(═

O)C_1-8alkyl(R₁₄), —

NH—

C(═

O)C_1-8alkyl(R₁₄), —

C(═

O)OC_1-8alkyl(R₁₄), —

C(═

O)NHC_1-8alkyl(R₁₄), —

O—

C(═

O)OC_1-8alkyl(R₁₄), —

O—

C(═

O)NHC_1-8alkyl(R₁₄), —

O—

C(═

O)C_1-8alkylC(═

O)(R₁₄), —

NH—

C(═

O)C_1-8alkylC(═

O)(R₁₄), —

C(═

O)OC_1-8alkylC(═

O)(R₁₄), —

O—

C(═

O)OC_1-8alkylC(═

O)(R₁₄), —

NH—

C(═

O)OC_1-8alkylC(═

O)(R₁₄), —

C(═

O)NHC_1-8alkylC(═

O)(R₁₄), —

O—

C(═

O)NHC_1-8alkylC(═

O)(R₁₄), and —

NH—

C(═

O)NHC_1-8alkylC(═

O)(R₁₄).

33. The targeting ligand of claim 1 wherein R₁₂ is selected from the group consisting of —

C_1-6alkyl(R₁₄), —

O—

C_1-6alkyl(R₁₄), —

NH—

C₄alkyl(R₁₄), —

S—

C_1-6alkyl(R₁₄), —

CH₂O—

C_1-6alkyl(R₁₄), —

CH₂NH—

C_1-6alkyl(R₁₄), —

CH₂S—

C_1-6alkyl(R₁₄), —

C(═

O)C_1-6alkyl(R₁₄), —

O—

C(═

O)C_1-6alkyl(R₁₄), —

NH—

C(═

O)C_1-8alkyl(R₁₄), —

CH₂O—

C(═

O)C_1-8alkyl(R₁₄), —

CH₂NH—

C(═

O)C_1-6alkyl(R₁₄), —

C(═

O)OC_1-6alkyl(R₁₄), —

C(═

O)NHC_1-6alkyl(R₁₄), —

O—

C(═

O)OC_1-6alkyl(R₁₄), —

O—

C(═

O)NHC_1-6alkyl(R₁₄), —

NH—

C(═

O)OC_1-6alkyl(R₁₄), —

NH—

C(═

O)NHC_1-6alkyl(R₁₄), —

NH—

C(═

O)C_1-6alkylC(═

O)(R₁₄), —

CH₂O—

C(═

O)C_1-8alkylC(═

O)(R₁₄), —

NH—

C(═

O)NHC_1-8alkylC(═

O)(R₁₄), —

CH₂O—

C(═

O)NHC_1-8alkylC(═

O)(R₁₄), —

CH₂NH—

C(═

O)NHC_1-8alkylC(═

O)(R₁₄), —

OCH₂CH₂O(CH₂CH₂O)_rCH₂CH₂(R₁₄), —

NHCH₂CH₂O(CH₂CH₂O)_rCH₂CH₂(R₁₄), —

SCH₂CH₂O(CH₂CH₂O)_rCH₂CH₂(R₁₄), —

OCH₂CH₂O(CH₂CH₂O)_rCH₂C(═

O)(R₁₄), —

NHCH₂CH₂O(CH₂CH₂O)_rCH₂C(═

O)(R₁₄), —

OC(═

O)NHCH₂CH₂O(CH₂CH₂O)_rCH₂CH₂(R₁₄), —

NH(C═

O)CH₂O(CH₂CH₂O)_rCH₂CH₂(R₁₄), —

NHC(═

O)OCH₂CH₂O(CH₂CH₂O)_rCH₂CH₂(R₁₄), —

NHC(═

O)NHCH₂CH₂O(CH₂CH₂O)_rCH₂CH₂(R₁₄), —

SO₂CH₂CH₂O(CH₂CH₂O)_rCH₂CH₂(R₁₄), —

SO₂NHCH₂CH₂O(CH₂CH₂O)_rCH₂CH₂(R₁₄), —

CH₂OCH₂CH₂O(CH₂CH₂O)_rCH₂CH₂(R₁₄), —

CH₂NHCH₂CH₂O(CH₂CH₂O)_rCH₂CH₂(R₁₄), —

CH₂SCH₂CH₂O(CH₂CH₂O)_rCH₂CH₂(R₁₄), —

CH₂OCH₂CH₂O(CH₂CH₂O)_rCH₂C(═

O)(R₁₄), —

OC(═

O)NHCH₂CH₂O(CH₂CH₂O)_rCH₂C(═

O)(R₁₄), —

NH(C═

O)CH₂O(CH₂CH₂O)_rCH₂C(═

O)(R₁₄), —

NHC(═

O)OCH₂CH₂O(CH₂CH₂O)_rCH₂C(═

O)(R₁₄), —

NHC(═

O)NHCH₂CH₂O(CH₂CH₂O)_rCH₂C(═

O)(R₁₄), —

CH₂C(═

O)CH₂O(CH₂CH₂O)_rCH₂C(═

O)(R₁₄), —

CH₂NH(C═

O)CH₂O(CH₂CH₂O)_rCH₂C(═

O)(R₁₄), —

CH₂NHC(═

O)OCH₂CH₂O(CH₂CH₂O)_rCH₂C(═

O)(R₁₄), and —

CH₂NHC(═

O)NHCH₂CH₂O(CH₂CH₂O)_rCH₂C(═

O)(R₁₄).

34. The targeting ligand of claim 1 wherein q is 1, 2 or 3.

35. The targeting ligand claim 1 wherein Z is selected from the group consisting of hydroxy, —

NH₂, —

NH—

C_1-8alkyl, —

N(C_1-8alkyl)₂, —

O—

C_1-8alkyl, —

O—

C_1-8alkyl-OH, —

O—

C_1-8alkylC_1-4alkoxy, —

O—

C_1-8alkylcarbonylC_1-4alkyl, —

O—

C_1-8alkyl-CO₂H, —

O—

C_1-8alkyl-C(O)O—

C_1-6alkyl, C_1-8alkyl-OC(O)—

C_1-6alkyl, —

O—

C_1-8alkyl-NH₂, —

O—

C_1-8alkyl-NH—

C_1-8alkyl, —

O—

C_1-8alkyl-N(C_1-8alkyl)₂, —

O—

C_1-8alkylamide, C_1-8alkyl-C(O)—

NH—

C_1-8alkyl, —

O—

C_1-8alkyl-C(O)—

N(C_1-8alkyl)₂ and —

NHC(O)C_1-8alkyl.

36. The targeting ligand of claim 1 wherein the targeting ligand is conjugated to an radioactive element.

37. The targeting ligand of claim 1 wherein the targeting ligand is conjugated to an imagining agent.

38. The targeting ligand of claim 37 wherein the imagining agent is selected from the group consisting of ⁹⁹Tc, ¹²⁵I, ¹⁸F, ¹¹C, and ⁶⁴Cu.

39. A targeting ligand of Formula (I):

40. A targeting conjugate having a formula selected from the group consisting of

41. The targeting conjugate of claim 40 wherein W is selected from the group consisting of —

C_0-4alkyl(R₁) and —

C_0-4alkyl-aryl(R₁,R₈).

42. The targeting conjugate of claim 40 wherein W is —

C_0-4alkyl(R₁) or —

C_0-4alkyl-phenyl(R₁,R₈).

43. The targeting conjugate of claim 40 wherein R₁ is selected from the group consisting of —

N(R₄)(R₆), -heterocyclyl(R₈) and -heteroaryl(R₉).

44. The targeting conjugate of claim 40 wherein R₁ is selected from the group consisting of —

N(R₄)(R₆), -dihydro-1H-pyrrolo[2,3-b]pyridinyl(R₈), -tetrahydropyrimidinyl(R₈), -tetrahydro-1,8-naphthyridinyl(R₈), -tetrahydro-1H-azepino[2,3-b]pyridinyl(R₈) and -pyridinyl(R₈).

45. The targeting conjugate of claim 40 wherein R₁ is selected from the group consisting of —

N(R₄)(R₆), -tetrahydropyrimidinyl(R₈) and -tetrahydro-1,8-naphthyridinyl(R₈).

46. The targeting conjugate of claim 40 wherein R_1a is selected from the group consisting of —

C(R₄)(═

N—

R₄), —

C(═

N—

R₄)—

N(R₄)₂, —

C(═

N—

R₄)—

N(R₄)(R₆), —

C(═

N—

R₄)—

N(R₄)—

C(═

O)—

R₄, —

C(═

N—

R₄)—

N(R₄)—

C(═

O)—

N(R₄)₂, —

C(═

N—

R₄)—

N(R₄)—

CO₂—

R₄, —

C(═

N—

R₄)—

N(R₄)—

SO₂—

C_1-4alkyl(R₇) and —

C(═

N—

R₄)—

N(R₄)—

SO₂—

N(R₄)₂.

47. The targeting conjugate of claim 40 wherein R₄ is selected from the group consisting of hydrogen and —

C_1-4alkyl(R₇).

48. The targeting conjugate of claim 40 wherein R₄ is hydrogen.

49. The targeting conjugate of claim 40 wherein R₅ is selected from the group consisting of —

C(═

O)—

R₄, —

C(═

O)—

N(R₄)₂, —

C(═

O)-cycloalkyl(R₈), —

C(═

O)-heterocyclyl(R₉), —

C(═

O)-aryl(R₈), —

C(═

O)-heteroaryl(R₈), —

C(═

O)—

N(R₄)-cycloalkyl(R₈), —

C(═

O)—

N(R₄)-aryl(R₉), —

CO₂—

R₄, —

CO₂-cycloalkyl(R₈), —

CO₂-aryl(R₈), —

C(R₄)(═

N—

R₄), —

C(═

N—

R₄)—

N(R₄)₂, —

C(═

N—

R₄)—

N(R₄)(R₆), —

C(═

N—

R₄)—

N(R₄)—

C(═

O)—

R₄, —

C(═

N—

R₄)—

N(R₄)—

C(═

O)—

N(R₄)₂, —

C(═

N—

R₄)—

N(R₄)—

CO₂—

R₄, —

C(═

N—

R₄)—

N(R₄)—

SO₂—

C_1-4alkyl(R₇), —

C(═

N—

R₄)—

N(R₄)—

SO₂—

N(R₄)₂, —

N(R₄)—

C(R₄)(═

N—

R₄), —

N(R₄)—

C(═

N—

R₄)—

N(R₄)₂, —

N(R₄)—

C(═

N—

R₄)—

N(R₄)(R₆), —

N(R₄)—

C(═

N—

R₄)—

N(R₄)—

C(═

O)—

R₄, —

N(R₄)—

C(═

N—

R₄)—

N(R₄)—

C(═

O)—

N(R₄)₂, —

N(R₄)—

C(═

N—

R₄)—

N(R₄)—

CO₂—

R₄, —

N(R₄)—

C(═

N—

R₄)—

N(R₄)—

SO₂—

C_1-4alkyl(R₇), —

N(R₄)—

C(═

N—

R₄)—

N(R₄)—

SO₂—

N(R₄)₂, —

SO₂—

C_1-4alkyl(R₇), —

SO₂—

N(R₄)₂, —

SO₂-cycloalkyl(R₈) and —

SO₂-aryl(R₈).

50. The targeting conjugate of claim 40 wherein R₅ is selected from the group consisting of —

C(═

O)—

R₄, —

C(═

O)—

N(R₄)₂, —

CO₂—

R₄, —

C(R₄)(═

N—

R₄), —

C(═

N—

R₄)—

N(R₄)₂, —

C(═

N—

R₄)—

N(R₄)(R₆), —

N(R₄)—

C(R₄)(═

N—

R₄), —

N(R₄)—

C(═

N—

R₄)—

N(R₄)₂, —

N(R₄)—

C(═

N—

R₄)—

N(R₄)(R₆), —

SO₂—

C_1-4alkyl(R₇) and —

SO₂—

N(R₄)₂.

51. The targeting conjugate of claim 40 wherein R₆ is selected from the group consisting of -heterocyclyl(R₈) and -heteroaryl(R₈).

52. The targeting conjugate of claim 40 wherein R₆ is selected from the group consisting of -dihydroimidazolyl(R₈), -tetrahydropyridinyl(R₈), -tetrahydropyrimidinyl(R₈) and -pyridinyl(R₈).

53. The targeting conjugate of claim 40 wherein R₇ is one to two substituents independently selected from the group consisting of hydrogen, —

C_1-4alkoxy(R₉), —

NH₂, —

NH—

C_1-4alkyl(R₉), —

N(C_1-4alkyl(R₉))₂, —

C(═

O)H, —

C(═

O)—

C_1-4alkyl(R₉), —

C(═

O)—

NH₂, —

C(═

O)—

NH—

C_1-4alkyl(R₉), —

C(═

O)—

N(C_1-4alkyl(R₉))₂, —

C(═

O)—

NH-aryl(R₁₀), —

C(═

O)-cycloalkyl(R₁₀), —

C(═

O)-heterocyclyl(R₁₀), —

C(═

O)-aryl(R₁₀), —

C(═

O)-heteroaryl(R₁₀), —

CO₂H, —

CO₂—

C_1-4alkyl(R₉), —

CO₂-aryl(R₁₀), —

C(═

NH)—

NH₂, —

SH, —

S—

C_1-4alkyl(R₉), —

S—

C_1-4alkyl-S—

C_1-4alkyl(R₉), —

S—

C_1-4alkyl-C_1-4alkoxy(R₉), —

S—

C_1-4alkyl-NH—

C_1-4alkyl(R₉), —

SO₂—

C_1-4alkyl(R₉), —

SO₂—

NH₂, —

SO₂—

NH—

C_1-4alkyl(R₉), —

SO₂—

N(C_1-4alkyl(R₉))₂, —

SO₂-aryl(R₁₀), cyano, (halo)_1-3, hydroxy, nitro, oxo, -cycloalkyl(R₁₀), -heterocyclyl(R₁₀), -aryl(R₁₀) and -heteroaryl(R₁₀).

54. The targeting conjugate of claim 40 wherein R₇ is one to two substituents independently selected from the group consisting of hydrogen, —

C_1-4alkoxy(R₉), —

NH₂, —

NH—

C_1-4alkyl(R₉), —

N(C_1-4alkyl(R₉))₂, (halo)₁₃, hydroxy and oxo.

55. The targeting conjugate of claim 40 wherein R₇ is hydrogen.

56. The targeting conjugate of claim 40 wherein R₈ is one to four substituents independently selected from the group consisting of hydrogen, —

C_1-4alkyl(R₉), —

C(═

O)H, —

C(═

O)—

C₄alkyl(R₉), —

C(═

O)—

NH₂, —

C(═

O)—

NH—

C_1-4alkyl(R₉), —

C(═

O)—

N(C_1-4alkyl(R₉))₂, —

C(═

O)—

NH-aryl(R₁₀), —

C(═

O)-cycloalkyl(R₁₀), —

C(═

O)-heterocyclyl(R₁₀), —

C(═

O)-aryl(R₁₀), —

C(═

O)-heteroaryl(R₁₀), —

CO₂H, —

CO₂—

C_1-4alkyl(R₉), —

CO₂-aryl(R₁₀), —

C(═

NH)—

NH₂, —

SO₂—

C_1-4alkyl(R₉), —

SO₂—

NH₂, —

SO₂—

NH—

C_1-4alkyl(R₉), —

SO₂—

N(C_1-4alkyl(R₉))₂, —

SO₂-aryl(R₁₀), -cycloalkyl(R₁₀) and -aryl(R₁₀) when attached to a nitrogen atom; and

, wherein R₈ is one to four substituents independently selected from the group consisting of hydrogen, —

C_1-4alkyl(R₉), —

C_1-4alkoxy(R₉), —

O-cycloalkyl(R₁₀), —

O-aryl(R₁₀), —

C(═

O)H, —

C(═

O)—

C_1-4alkyl(R₉), —

C(═

O)—

NH₂, —

C(═

O)—

NH—

C_1-4alkyl(R₉), —

C(═

O)—

N(C_1-4alkyl-R₁₁)₂, —

C(═

O)—

NH-aryl(R₁₀), —

C(═

O)-cycloalkyl(R_1a), —

C(═

O)-heterocyclyl(R₁₀), —

C(═

O)-aryl(R₁₀), —

C(═

O)-heteroaryl(R₁₀), —

CO₂H, —

CO₂—

C_1-4alkyl(R₉), —

CO₂-aryl(R₁₀), —

C(═

NH)—

NH₂, —

SO₂—

C_1-4alkyl(R₉), —

SO₂—

NH₂, —

SO₂—

NH—

C_1-4alkyl(R₉), —

SO₂—

N(C_1-4alkyl(R₉))₂, —

SO₂-aryl(R₁₀), —

SH, —

S—

C_1-4alkyl(R₉), —

S—

C_1-4alkyl-S—

C_1-4alkyl(R₉), —

S—

C_1-4alkyl-C_1-4alkoxy(R₉), —

S—

C_1-4alkyl-NH—

C_1-4alkyl(R₉), —

NH₂, —

NH—

C_1-4alkyl(R₉), —

N(C_1-4alkyl(R₉))₂, cyano, halo, hydroxy, nitro, oxo, -cycloalkyl(R₁₀), -heterocyclyl(R₁₀), -aryl(R₁₀) and -heteroaryl(R₁₀) when attached to a carbon atom.

57. The targeting conjugate of claim 40 wherein R₈ is one to four substituents independently selected from the group consisting of hydrogen, —

C_1-4alkyl(R₉), —

C(═

O)H, —

C(═

O)—

NH₂, —

C(═

O)—

NH—

C_1-4alkyl(R₉), —

C(═

O)—

N(C_1-4alkyl(R₉))₂, —

CO₂H, —

CO₂—

C_1-4alkyl(R₉) and —

SO₂—

NH₂ when attached to a nitrogen atom; and

, wherein R₈ is one to four substituents independently selected from the group consisting of hydrogen, —

C_1-4alkyl(R₉), —

C_1-4alkoxy(R₉), —

O-aryl(R₁₀), —

C(═

O)H, —

C(═

O)—

NH₂, —

C(═

O)—

NH—

C_1-4alkyl(R₉), —

C(═

O)—

N(C_1-4alkyl(R₉))₂, —

CO₂H, —

CO₂—

C_1-4alkyl(R₉), —

SO₂—

NH₂, —

NH₂, —

NH—

C_1-4alkyl(R₉), —

N(C_1-4alkyl(R₉))₂, cyano, halo, hydroxy, nitro and oxo when attached to a carbon atom.

58. The targeting conjugate of claim 40 wherein R₈ is one to four substituents independently selected from the group consisting of hydrogen and —

C_1-4alkyl(R₉) when attached to a nitrogen atom; and

, wherein R₈ is one to four substituents independently selected from the group consisting of hydrogen, —

C_1-4alkyl(R₉), —

C_1-4alkoxy(R₉), —

O-aryl(R_1a), —

NH₂, —

NH—

C_1-4alkyl(R₉), —

N(C_1-4alkyl(R₉))₂, halo, hydroxy and oxo when attached to a carbon atom.

59. The targeting conjugate of claim 40 wherein R₈ is one to four substituents independently selected from the group consisting of hydrogen and —

C_1-4alkyl(R₉) when attached to a nitrogen atom; and

, wherein R₈ is one to four substituents independently selected from the group consisting of hydrogen, —

C_1-4alkyl(R₉), —

C_1-4alkoxy(R₉), —

O-aryl(R₁₀) and hydroxy when attached to a carbon atom.

60. The targeting conjugate of claim 40 wherein R₉ is selected from the group consisting of hydrogen, —

C_1-4alkoxy, —

NH₂, —

NH—

C_1-4alkyl, —

N(C_1-4alkyl)₂, —

C(═

O)H, —

C(═

O)—

NH₂, —

C(═

O)—

NH—

C_1-4alkyl, —

C(═

O)—

N(C_1-4alkyl)₂, —

CO₂H, —

CO₂—

C_1-4alkyl, —

SO₂—

C_1-4alkyl, —

SO₂—

NH₂, —

SO₂—

NH—

C_1-4alkyl, —

SO₂—

N(C_1-4alkyl)₂, cyano, (halo)_1-3, hydroxy, nitro and oxo.

61. The targeting conjugate of claim 40 wherein R₉ is selected from the group consisting of hydrogen, —

C_1-4alkoxy, —

NH₂, —

NH—

C_1-4alkyl, —

N(C_1-4alkyl)₂, —

C(═

O)H, —

CO₂H, —

C(═

O)—

C_1-4alkoxy, (halo)_1-3, hydroxy and oxo.

62. The targeting conjugate of claim 40 wherein R₉ is selected from the group consisting of hydrogen, —

C_1-4alkoxy, —

NH₂, —

NH—

C_1-4alkyl, —

N(C_1-4alkyl)₂, (halo)_1-3 and hydroxy.

63. The targeting conjugate claim 40 wherein R₁₀ is one to four substituents independently selected from the group consisting of hydrogen, —

C_1-4alkyl, —

C(═

O)H, —

C(═

O)—

C_1-4alkyl, —

C(═

O)—

NH₂, —

C(═

O)—

NH—

C_1-4alkyl, —

C(═

O)—

N(C_1-4alkyl)₂, —

CO₂H, —

CO₂—

C_1-4alkyl, —

SO₂—

C_1-4alkyl, —

SO₂—

NH₂, —

SO₂—

NH—

C_1-4alkyl and —

SO₂—

N(C_1-4alkyl)₂ when attached to a nitrogen atom; and

, wherein R₁₀ is one to four substituents independently selected from the group consisting of hydrogen, —

C_1-4alkyl, —

C_1-4alkoxy, —

C(═

O)H, —

C(═

O)—

C_1-4alkyl, —

C(═

O)—

NH₂, —

C(═

O)—

NH—

C_1-4alkyl, —

C(═

O)—

N(C_1-4alkyl)₂, —

CO₂H, —

CO₂—

C_1-4alkyl, —

SO₂—

C_1-4alkyl, —

SO₂—

NH₂, —

SO₂—

NH—

C_1-4alkyl, —

SO₂—

N(C_1-4alkyl)₂, —

NH₂, —

NH—

C_1-4alkyl, —

N(C_1-4alkyl)₂, cyano, halo, hydroxy, nitro and oxo when attached to a carbon atom.

64. The targeting conjugate of claim 40 wherein (R₁₀)_1-4 is selected from the group consisting of hydrogen, —

C_1-4alkyl, —

C_1-4alkoxy, —

C(═

O)H, —

C(═

O)—

C_1-4alkyl, —

CO₂H, —

CO₂—

C_1-4alkyl, —

NH₂, —

NH—

C_1-4alkyl, —

N(C_1-4alkyl)₂, halo, hydroxy, nitro and oxo when attached to a carbon atom.

65. The targeting conjugate of claim 40 wherein R₁₀ is hydrogen.

66. The targeting conjugate of claim 40 wherein R_2a is selected from the group consisting of —

C_1-4alkyl (R₇)(R₁₁), —

C_2-4alkenyl(R₇)(R₁₁), —

C_2-4alkynyl(R₇)(R₁₁), -cycloalkyl(R₇)(R₁₁), -heterocyclyl(R₈)(R₁₂), -aryl(R₈)(R₁₂), and -heteroaryl(R₈)(R₁₂).

67. The targeting conjugate of claim 40 wherein R_2a is selected from the group consisting of -cycloalkyl(R₇)(R₁₁), -heterocyclyl(R₈)(R₁₂), -aryl(R₈)(R₁₂), and -heteroaryl(R₈)(R₁₁).

68. The targeting conjugate of claim 40 wherein R_2a is selected from the group consisting of -cycloalkyl(R₇)(R₁₁), -heterocyclyl(R₈)(R₁₂), -phenyl(R₈)(R₁₂), -naphthalenyl(R₈)(R₁₂), and -heteroaryl(R₈)(R₁₁).

69. The targeting conjugate claim 40 wherein R_2a is selected from the group consisting of -tetrahydropyrimidinyl(R₈)(R₁₂), -1,3-benzodioxolyl(R₈)(R₁₂), -dihydrobenzofuranyl(R₈)(R₁₂), -tetrahydroquinolinyl(R₈)(R₁₂), -phenyl(R₈)(R₁₂), -naphthalenyl(R₈)(R₁₂), -pyridinyl(R₈)(R₁₂), -pyrimidinyl(R₈)(R₁₂), and -quinolinyl(R₈)(R₁₂).

70. The targeting conjugate of claim 40 wherein R₁₁ is selected from the group consisting of —

C_1-8alkyl(R₁₃), —

O—

C_1-8alkyl(R₁₃), —

NH—

C_1-8alkyl(R₁₃), —

S—

C_1-8alkyl(R₁₃), —

C(═

O)C_1-8alkyl(R₁₃), —

O—

C(═

O)C_1-8alkyl(R₁₃), —

NH—

C(═

O)C_1-8alkyl(R₁₃), —

C(═

O)OC_1-8alkyl(R₁₃), —

C(═

O)NHC_1-8alkyl(R₁₃), —

O—

C(═

O)OC_1-8alkyl(R₁₃), —

O—

C(═

O)NHC_1-8alkyl(R₁₃), —

O—

C(═

O)C_1-8alkylC(═

O)(R₁₃), —

NH—

C(═

O)C_1-8alkylC(═

O)(R₁₃), —

C(═

O)OC_1-8alkylC(═

O)(R₁₃), —

O—

C(═

O)OC_1-8alkylC(═

O)(R₁₃), —

NH—

C(═

O)OC_1-8alkylC(═

O)(R₁₃), —

C(═

O)NHC_1-8alkylC(═

O)(R₁₃), —

O—

C(═

O)NHC_1-8alkylC(═

O)(R₁₃), —

NH—

C(═

O)NHC_1-8alkylC(═

O)(R₁₃), —

SCH₂CH₂O(CH₂CH₂O)_rCH₂CH₂(R₁₃), —

NHCH₂CH₂O(CH₂CH₂O)_rCH₂C(═

O)(R₁₃), —

SO₂NHCH₂CH₂O(CH₂CH₂O)_rCH₂CH₂(R₁₃), —

C(═

O)CH₂O(CH₂CH₂O)_rCH₂C(═

O)(R₁₃), —

OC(═

O)OCH₂CH₂O(CH₂CH₂O)_rCH₂C(═

O)(R₁₃), —

OC(═

O)NHCH₂CH₂O(CH₂CH₂O)_rCH₂C(═

O)(R₁₃), —

NHC(═

O)NHCH₂CH₂O(CH₂H₂O)_rCH₂C(═

O)(R₁₃), and —

SO₂NHCH₂CH₂O(CH₂CH₂O)_rCH₂C(═

O)(R₁₃).

71. The targeting conjugate of claim 40 wherein R₁₁ is selected from the group consisting of —

C_1-8alkyl(R₁₃), —

O—

C_1-8alkyl(R₁₃), —

NH—

C_1-8alkyl(R₁₃), —

S—

C_1-8alkyl(R₁₃), —

C(═

O)C_1-8alkyl(R₁₃), —

O—

C(═

O)C_1-8alkyl(R₁₃), —

NH—

C(═

O)C_1-8alkyl(R₁₃), —

C(═

O)OC_1-8alkyl(R₁₃), —

C(═

O)NHC_1-8alkyl(R₁₃), —

O—

C(═

O)OC_1-8alkyl(R₁₃), —

O—

C(═

O)NHC_1-8alkyl(R₁₃), —

O—

C(═

O)C_1-8alkylC(═

O)(R₁₃), —

NH—

C(═

O)C_1-8alkylC(═

O)(R₁₃), —

C(═

O)OC_1-8alkylC(═

O)(R₁₃), —

O—

C(═

O)OC_1-8alkylC(═

O)(R₁₃), —

NH—

C(═

O)OC_1-8alkylC(═

O)(R₁₃), —

C(═

O)NHC_1-8alkylC(═

O)(R₁₃), —

O—

C(═

O)NHC_1-8alkylC(═

O)(R₁₃), and —

NH—

C(═

O)NHC_1-8alkylC(═

O)(R₁₃).

72. The targeting conjugate of claim 40 wherein R₁₂ is selected from the group consisting of —

C_1-6alkyl(R₁₃), —

O—

C_1-6alkyl(R₁₃), —

NH—

C_1-4alkyl(R₁₃), —

S—

C_1-6alkyl(R₁₃), —

CH₂O—

C_1-8alkyl(R₁₃), —

CH₂NH—

C_1-6alkyl(R₁₃), —

CH₂S—

C_1-6alkyl(R₁₃), —

C(═

O)C_1-6alkyl(R₁₃), —

O—

C(═

O)C_1-6alkyl(R₁₃), —

NH—

C(═

O)C_1-8alkyl(R₁₃), —

CH₂O—

C(═

O)C_1-8alkyl(R₁₃), —

CH₂NH—

C(═

O)C_1-6alkyl(R₁₃), —

C(═

O)OC_1-6alkyl(R₁₃), —

C(═

O)NHC_1-6alkyl(R₁₃), —

O—

C(═

O)OC_1-6alkyl(R₁₃), —

O—

C(═

O)NHC_1-6alkyl(R₁₃), —

NH—

C(═

O)OC_1-6alkyl(R₁₃), —

NH—

C(═

O)NHC_1-6alkyl(R₁₃), —

NH—

C(═

O)C_1-6alkylC(═

O)(R₁₃), —

CH₂O—

C(═

O)C_1-8alkylC(═

O)(R₁₃), —

NH—

C(═

O)NHC_1-8alkylC(═

O)(R₁₃), —

CH₂O—

C(═

O)NHC_1-8alkylC(═

O)(R₁₃), —

CH₂NH—

C(═

O)NHC_1-8alkylC(═

O)(R₁₃), —

OCH₂CH₂O(CH₂CH₂O)_rCH₂CH₂(R₁₃), —

NHCH₂CH₂O(CH₂CH₂O)_rCH₂CH₂(R₁₃), —

SCH₂CH₂O(CH₂CH₂O)_rCH₂CH₂(R₁₃), —

OCH₂CH₂O(CH₂CH₂O)_rCH₂C(═

O)(R₁₃), —

NHCH₂CH₂O(CH₂CH₂O)_rCH₂C(═

O)(R₁₃), —

OC(═

O)NHCH₂CH₂O(CH₂CH₂O)_rCH₂CH₂(R₁₃), —

NH(C═

O)CH₂O(CH₂CH₂O)_rCH₂CH₂(R₁₃), —

NHC(═

O)OCH₂CH₂O(CH₂CH₂O)_rCH₂CH₂(R₁₃), —

NHC(═

O)NHCH₂CH₂O(CH₂CH₂O)_rCH₂CH₂(R₁₃), —

SO₂CH₂CH₂O(CH₂CH₂O)_rCH₂CH₂(R₁₃), —

SO₂NHCH₂CH₂O(CH₂CH₂O)_rCH₂CH₂(R₁₃), —

CH₂OCH₂CH₂O(CH₂CH₂O)_rCH₂CH₂(R₁₃), —

CH₂NHCH₂CH₂O(CH₂CH₂O)_rCH₂CH₂(R₁₃), —

CH₂SCH₂CH₂O(CH₂CH₂O)_rCH₂CH₂(R₁₃), —

CH₂OCH₂CH₂O(CH₂CH₂O)_rCH₂C(═

O)(R₁₃), —

OC(═

O)NHCH₂CH₂O(CH₂CH₂O)_rCH₂C(═

O)(R₁₃), —

NH(C═

O)CH₂O(CH₂CH₂₂O)_rCH₂C(═

O)(R₁₃), —

NHC(═

O)OCH₂CH₂O(CH₂CH₂O)_rCH₂C(═

O)(R₁₃), —

NHC(═

O)NHCH₂CH₂O(CH₂CH₂O)_rCH₂C(═

O)(R₁₃), —

CH₂C(═

O)CH₂O(CH₂CH₂O)_rCH₂C(═

O)(R₁₃), —

CH₂NH(C═

O)CH₂O(CH₂CH₂O)_rCH₂C(═

O)(R₁₃), —

CH₂NHC(═

O)OCH₂CH₂O(CH₂CH₂O)_rCH₂C(═

O)(R₁₃), and —

CH₂NHC(═

O)NHCH₂CH₂O(CH₂CH₂O)_rCH₂C(═

O)(R₁₃);

wherein when R₁₁ or R₁₂ terminates with a —

C(═

O)—

, R₁₃ is selected from the group consisting of

73. The targeting conjugate of claim 40 wherein R₁₂ is selected from the group consisting of —

CH₂O—

C_1-6alkyl(R₁₃), —

CH₂NH—

C_1-6alkyl(R₁₃), —

CH₂S—

C_1-6alkyl(R₁₃), —

NH—

C(═

O)C_1-8alkyl(R₁₃), —

CH₂NH—

C(═

O)C_1-6alkyl(R₁₃), —

NH—

C(═

O)NHC_1-6alkyl(R₁₃), —

NH—

C(═

O)C_1-6alkylC(═

O)(R₁₃), —

OCH₂CH₂O(CH₂CH₂O)_rCH₂CH₂(R₁₃), —

NHCH₂CH₂O(CH₂CH₂O)_rCH₂CH₂(R₁₃), —

OCH₂CH₂O(CH₂CH₂O)_rCH₂C(═

O)(R₁₃), —

NH(C═

O)CH₂O(CH₂CH₂O)_rCH₂CH₂(R₁₃), —

CH₂OCH₂CH₂O(CH₂CH₂O)_rCH₂CH₂(R₁₃), —

CH₂NHCH₂CH₂O(CH₂CH₂O)_rCH₂CH₂(R₁₃), —

CH₂SCH₂CH₂O(CH₂CH₂O)_rCH₂CH₂(R₁₃), —

NH(C═

O)CH₂O(CH₂CH₂O)_rCH₂C(═

O)(R₁₃), and —

CH₂NH(C═

O)CH₂O(CH₂CH₂O)_rCH₂C(═

O)(R₁₃).

wherein when R₁₁ or R₁₂ terminates with a —

C(═

O)—

, R₁₃ is selected from the group consisting of

74. The targeting conjugate of claim 40 wherein said —

O—

(CH₂CH₂O—

)_p—

or

75. The targeting conjugate of claim 40 wherein wherein Q and Q¹ of substituents R₁₂ and R₁₃ are the same within a given compound and are selected from the group consisting of the C_1-5 saturated chain of palmitoic acid,

the C_1-7 saturated chain of stearoic acid, and the C₁₇ mono-unsaturated chain of oleoic acid.

76. The targeting conjugate of claim 40 wherein

W is preferably is selected from the group consisting of —

C_0-4alkyl(R₁), —

C_1-4alkyl(R_1a), —

C_0-4alkyl-aryl(R₁,R₈), —

C_0-4alkyl-heterocyclyl(R₁,R₈), —

C_0-4alkoxy(R₁), —

C_0-4alkoxy-aryl(R₁,R₈), and —

C_0-4alkoxy-heterocyclyl(R₁,R₈);

R₁ is —

N(R₄)(R₆), -heterocyclyl(R₈) or -heteroaryl(R₈);

R_1a is —

C(R₄)(═

N—

R₄), —

C(═

N—

R₄)—

N(R₄)₂, —

C(═

N—

R₄)—

N(R₄)(R₆), —

C(═

N—

R₄)—

N(R₄)—

C(═

O)—

R₄, —

C(═

N—

R₄)—

N(R₄)—

C(═

O)—

N(R₄)₂, —

C(═

N—

R₄)—

N(R₄)—

CO₂—

R₄, —

C(═

N—

R₄)—

N(R₄)—

SO₂—

C_1-4alkyl(R₇) or —

C(═

N—

R₄)—

N(R₄)—

SO₂—

N(R₄)₂;

R₄ is hydrogen or —

C_1-4alkyl(R₇);

R₅ is —

C(═

O)—

R₄, —

C(═

O)—

N(R₄)₂, —

C(═

O)-cycloalkyl(R₈), —

C(═

O)-heterocyclyl(R₈), —

C(═

O)-aryl(R₈), —

C(═

O)-heteroaryl(R₈), —

C(═

O)—

N(R₄)-cycloalkyl(R₈), —

C(═

O)—

N(R₄)-aryl(R₈), —

CO₂—

R₄, —

CO₂-cycloalkyl(R₈), —

CO₂-aryl(R₈), —

C(R₄)(═

N—

R₄), —

C(═

N—

R₄)—

N(R₄)₂, —

C(═

N—

R₄)—

N(R₄)(R₆), —

C(═

N—

R₄)—

N(R₄)—

C(═

O)—

R₄, —

C(═

N—

R₄)—

N(R₄)—

C(═

O)—

N(R₄)₂, —

C(═

N—

R₄)—

N(R₄)—

CO₂—

R₄, —

C(═

N—

R₄)—

N(R₄)—

SO₂—

C_1-4alkyl(R₇), —

C(═

N—

R₄)—

N(R₄)—

SO₂—

N(R₄)₂, —

N(R₄)—

C(R₄)(═

N—

R₄), —

N(R₄)—

C(═

N—

R₄)—

N(R₄)₂, —

N(R₄)—

C(═

N—

R₄)—

N(R₄)(R₆), —

N(R₄)—

C(═

N—

R₄)—

N(R₄)—

C(═

O)—

R₄, —

N(R₄)—

C(═

N—

R₄)—

N(R₄)—

C(═

O)—

N(R₄)₂, —

N(R₄)—

C(═

N—

R₄)—

N(R₄)—

CO₂—

R₄, —

N(R₄)—

C(═

N—

R₄)—

N(R₄)—

SO₂—

C_1-4alkyl(R₇), —

N(R₄)—

C(═

N—

R₄)—

N(R₄)—

SO₂—

N(R₄)₂, —

SO₂—

C_1-4alkyl(R₇), —

SO₂—

N(R₄)₂, —

SO₂-cycloalkyl(R₈) or —

SO₂-aryl(R₈);

R₆ is -heterocyclyl(R₈) or -heteroaryl(R₈);

R₇ is one to two substituents independently selected from hydrogen, —

C_1-4alkoxy(R₉), —

NH₂, —

NH—

C_1-4alkyl(R₉), —

N(C_1-4alkyl(R₉))₂, —

C(═

O)H, —

C(═

O)—

C_1-4alkyl(R₉), —

C(═

O)—

NH₂, —

C(═

O)—

NH—

C_1-4alkyl(R₉), —

C(═

O)—

N(C_1-4alkyl(R₉))₂, —

C(═

O)—

NH-aryl(R₁₀), —

C(═

O)-cycloalkyl(R₁₀), —

C(═

O)-heterocyclyl(R₁₀), —

C(═

O)-aryl(R₁₀), —

C(═

O)-heteroaryl(R₁₀), —

CO₂H, —

CO₂—

C_1-4alkyl(R₉), —

CO₂-aryl(R₁₀), —

C(═

NH)—

NH₂, —

SH, —

S—

C_1-4alkyl(R₉), —

S—

C_1-4alkyl-S—

C_1-4alkyl(R₉), —

S—

C_1-4alkyl-C_1-4alkoxy(R₉), —

S—

C_1-4alkyl-NH—

C_1-4alkyl(R₉), —

SO₂—

C_1-4alkyl(R₉), —

SO₂—

NH₂, —

SO₂—

NH—

C_1-4alkyl(R₉), —

SO₂—

N(C_1-4alkyl(R₉))₂, —

SO₂-aryl(R₁₀), cyano, (halo)-3, hydroxy, nitro, oxo, -cycloalkyl(R₁₀), -heterocyclyl(R₁₀), -aryl(R₁₀) or -heteroaryl(R₁₀);

R₈ is one to four substituents independently selected from hydrogen, —

C_1-4alkyl(R₉), —

C(═

O)H, —

C(═

O)—

NH₂, —

C(═

O)—

NH—

C_1-4alkyl(R₉), —

C(═

O)—

N(C_1-4alkyl(R₉))₂, —

CO₂H, —

CO₂—

C_1-4alkyl(R₉) or —

SO₂—

NH₂ when attached to a nitrogen atom; and

, wherein R₈ is one to four substituents independently selected from hydrogen, —

C_1-4alkyl(R₉), —

C_1-4alkoxy(R₉), —

O-aryl(R₁₀), —

C(═

O)H, —

C(═

O)—

NH₂, —

C(═

O)—

NH—

C_1-4alkyl(R₉), —

C(═

O)—

N(C_1-4alkyl(R₉))₂, —

CO₂H, —

CO₂—

C_1-4alkyl(R₉), —

SO₂—

NH₂, —

NH₂, —

NH—

C_1-4alkyl(R₉), —

N(C_1-4alkyl(R₉))₂, cyano, halo, hydroxy, nitro or oxo when attached to a carbon atom;

R₉ is hydrogen, —

C_1-4alkoxy, —

NH₂, —

NH—

C_1-4alkyl, —

N(C_1-4alkyl)₂, —

C(═

O)H, —

C(═

O)—

NH₂, —

C(═

O)—

NH—

C_1-4alkyl, —

C(═

O)—

N(C_1-4alkyl)₂, —

CO₂H, —

CO₂—

C_1-4alkyl, —

SO₂—

C_1-4alkyl, —

SO₂—

NH₂, —

SO₂—

NH—

C_1-4alkyl, —

SO₂—

N(C_1-4alkyl)₂, cyano, (halo)_1-3, hydroxy, nitro or oxo;

R₁₀ is one to four substituents independently selected from hydrogen, —

C_1-4alkyl, —

C(═

O)H, —

C(═

O)—

C_1-4alkyl, —

C(═

O)—

NH₂, —

C(═

O)—

NH—

C_1-4alkyl, —

C(═

O)—

N(C_1-4alkyl)₂, —

CO₂H, —

CO₂—

C_1-4alkyl, —

SO₂—

C_1-4alkyl, —

SO₂—

NH₂, —

SO₂—

NH—

C_1-4alkyl or —

SO₂—

N(C_1-4alkyl)₂ when attached to a nitrogen atom; and

, wherein R₁₀ is one to four substituents independently selected from hydrogen, —

C_1-4alkyl, —

C_1-4alkoxy, —

C(═

O)H, —

C(═

O)—

C_1-4alkyl, —

C(═

O)—

NH₂, —

C(═

O)—

NH—

C_1-4alkyl, —

C(═

O)—

N(C_1-4alkyl)₂, —

CO₂H, —

CO₂—

C_1-4alkyl, —

SO₂—

C_1-4alkyl, —

SO₂—

NH₂, —

SO₂—

NH—

C_1-4alkyl, —

SO₂—

N(C_1-4alkyl)₂, —

NH₂, —

NH—

C_1-4alkyl, —

N(C_1-4alkyl)₂, cyano, halo, hydroxy, nitro or oxo when attached to a carbon atom;

R_2a is -cycloalkyl(R₈)(R₁₁), -heterocyclyl(R₈)(R₁₂), -aryl(R₈)(R₁₂) or -heteroaryl(R₈)(R₁₂);

q is 1, 2 or 3.

R₁₁ is selected from the group consisting of —

C_1-8alkyl(R₁₃), —

O—

C_1-8alkyl(R₁₃), —

NH—

C_1-8alkyl(R₁₃), —

S—

C_1-8alkyl(R₁₃), —

C(═

O)C_1-8alkyl(R₁₃), —

O—

C(═

O)C_1-8alkyl(R₁₃), —

NH—

C(═

O)C_1-8alkyl(R₁₃), —

C(═

O)OC_1-8alkyl(R₁₃), —

C(═

O)NHC_1-8alkyl(R₁₃), —

O—

C(═

O)OC_1-8alkyl(R₁₃), —

O—

C(═

O)NHC_1-8alkyl(R₁₃), —

O—

C(═

O)C_1-8alkylC(═

O)(R₁₃), —

NH—

C(═

O)C_1-8alkylC(═

O)(R₁₃), —

C(═

O)OC_1-8alkylC(═

O)(R₁₃), —

O—

C(═

O)OC_1-8alkylC(═

O)(R₁₃), —

NH—

C(═

O)OC_1-8alkylC(═

O)(R₁₃), —

C(═

O)NHC_1-8alkylC(═

O)(R₁₃), —

O—

C(═

O)NHC_1-8alkylC(═

O)(R₁₃), —

NH—

C(═

O)NHC_1-8alkylC(═

O)(R₁₃), —

SCH₂CH₂O(CH₂CH₂O)_rCH₂CH₂(R₁₃), —

NHCH₂CH₂O(CH₂CH₂O)_rCH₂C(═

O)(R₁₃), —

SO₂NHCH₂CH₂O(CH₂CH₂O)_rCH₂CH₂(R₁₃), —

C(═

O)CH₂O(CH₂CH₂O)_rCH₂C(═

O)(R₁₃), —

OC(═

O)OCH₂CH₂O(CH₂CH₂O)_rCH₂C(═

O)(R₁₃), —

OC(═

O)NHCH₂CH₂O(CH₂CH₂O)_rCH₂C(═

O)(R₁₃), —

NHC(═

O)NHCH₂CH₂O(CH₂CH₂O)_rCH₂C(═

O)(R₁₃), and —

SO₂NHCH₂CH₂O(CH₂CH₂O)_rCH₂C(═

O)(R₁₃);

R₁₂ is selected from the group consisting of —

C_1-6alkyl(R₁₃), —

O—

C_1-6alkyl(R₁₃), —

NH—

C_1-4alkyl(R₁₃), —

S—

C_1-6alkyl(R₁₃), —

CH₂O—

C_1-6alkyl(R₁₃), —

CH₂NH—

C_1-6alkyl(R₁₃), —

CH₂S—

C_1-6alkyl(R₁₃), —

C(═

O)C₁₆alkyl(R₁₃), —

O—

C(═

O)C_1-6alkyl(R₁₃), —

NH—

C(═

O)C_1-8alkyl(R₁₃), —

CH₂O—

C(═

O)C_1-8alkyl(R₁₃), —

CH₂NH—

C(═

O)C_1-6alkyl(R₁₃), —

C(═

O)OC_1-6alkyl(R₁₃), —

C(═

O)NHC_1-6alkyl(R₁₃), —

O—

C(═

O)OC_1-6alkyl(R₁₃), —

O—

C(═

O)NHC_1-6alkyl(R₁₃), —

NH—

C(═

O)OC_1-6alkyl(R₁₃), —

NH—

C(═

O)NHC_1-6alkyl(R₁₃), —

NH—

C(═

O)C_1-6alkylC(═

O)(R₁₃), —

CH₂O—

C(═

O)C_1-8alkylC(═

O)(R₁₃), —

NH—

C(═

O)NHC_1-8alkylC(═

O)(R₁₃), —

CH₂O—

C(═

O)NHC_1-8alkylC(═

O)(R₁₃), —

CH₂NH—

C(═

O)NHC_1-8alkylC(═

O)(R₁₃), —

OCH₂CH₂O(CH₂CH₂O)_rCH₂CH₂(R₁₃), —

NHCH₂CH₂O(CH₂CH₂O)_rCH₂CH₂(R₁₃), —

SCH₂CH₂O(CH₂CH₂O)_rCH₂CH₂(R₁₃), —

OCH₂CH₂O(CH₂CH₂O)_rCH₂C(═

O)(R)

     3), —

NHCH₂CH₂O(CH₂CH₂O)_rCH₂C(═

O)(R₁₃), —

OC(═

O)NHCH₂CH₂O(CH₂CH₂O)_rCH₂CH₂(R₁₃), —

NH(C═

O)CH₂O(CH₂CH₂O)_rCH₂CH₂(R₁₃), —

NHC(═

O)OCH₂CH₂O(CH₂CH₂O)_rCH₂CH₂(R₁₃), —

NHC(═

O)NHCH₂CH₂O(CH₂CH₂O)_rCH₂CH₂(R₁₃), —

SO₂CH₂CH₂O(CH₂CH₂O)_rCH₂CH₂(R₁₃), —

SO₂NHCH₂CH₂O(CH₂CH₂O)_rCH₂CH₂(R₁₃), —

CH₂OCH₂CH₂O(CH₂CH₂O)_rCH₂CH₂(R₁₃), —

CH₂NHCH₂CH₂O(CH₂CH₂O)_rCH₂CH₂(R₁₃), —

CH₂SCH₂CH₂O(CH₂CH₂O)_rCH₂CH₂(R₁₃), —

CH₂OCH₂CH₂O(CH₂CH₂O)_rCH₂C(═

O)(R₁₃), —

OC(═

O)NHCH₂CH₂O(CH₂CH₂O)_rCH₂C(═

O)(R₁₃), —

NH(C═

O)CH₂O(CH₂CH₂O)_rCH₂C(═

O)(R₁₃), —

NHC(═

O)OCH₂CH₂O(CH₂CH₂O)_rCH₂C(═

O)(R₁₃), —

NHC(═

O)NHCH₂CH₂O(CH₂CH₂O)_rCH₂C(═

O)(R₁₃), —

CH₂C(═

O)CH₂O(CH₂CH₂O)_rCH₂C(═

O)(R₁₃), —

CH₂NH(C═

O)CH₂O(CH₂CH₂O)_rCH₂C(═

O)(R₁₃), —

CH₂NHC(═

O)OCH₂CH₂O(CH₂CH₂O)_rCH₂C(═

O)(R₁₃), and —

CH₂NHC(═

O)NHCH₂CH₂O(CH₂CH₂O)_rCH₂C(═

O)(R₁₃);

wherein when R₁₁ or R₁₂ terminates with a —

C(═

O)—

, R₁₃ is selected from the group consisting of

 

and when R₁₁ or R₁₂ does not terminate with a —

C(═

O)—

, R₁₃ is selected from the group consisting of

said —

O—

(CH₂CH₂O—

)_p—

or

 

of R₁₂ and R₁₃ is a polyethylene glycol (PEG) polymer ranging in molecular weight from 750 to 5000 daltons;

r is an integer from 0 to 8;

Q and Q¹ of substituents R₁₂ and R₁₃ are the same within a given compound and are selected from the group consisting of

the C₁₁ saturated chain of lauric acid,

the C₁₅ saturated chain of palmitoic acid,

the C₁₇ saturated chain of stearoic acid,

the C₁₇ mono-unsaturated chain of oleoic acid, and

the C₁₇ di-unsaturated chain of linoleic acid;

Z is selected from the group consisting of hydroxy, —

NH₂, —

NH—

C_1-8alkyl, —

N(C_1-8alkyl)₂, —

O—

C_1-8alkyl, —

O—

C_1-8alkyl-OH, —

O—

C_1-8alkylC_1-4alkoxy, —

O—

C_1-8alkylcarbonylC_1-4alkyl, —

O—

C_1-8alkyl-CO₂H, —

O—

C_1-8alkyl-C(O)O—

C_1-6alkyl, —

O—

C_1-8alkyl-O—

C(O)C_1-8alkyl, —

O—

C_1-8alkyl-NH₂, —

O—

C_1-8alkyl-NH—

C_1-8alkyl, —

O—

C_1-8alkyl-N(C_1-8alkyl)₂, —

O—

C_1-8alkylamide —

O—

C_1-8alkyl-C(O)—

NH—

C_1-8alkyl, —

O—

C_1-8alkyl-C(O)—

N(C_1-8alkyl)₂ and —

NHC(O)C_1-8alkyl.

77. The targeting conjugate of claim 40 wherein

W is preferably —

C_0-4alkyl(R₁) or —

C_0-4alkyl-phenyl(R₁,R₈);

R₁ is —

N(R₄)(R₆), -tetrahydropyrimidinyl(R₈) or -tetrahydro-1,8-naphthyridinyl(R₈);

R_1a is —

C(R₄)(═

N—

R₄), —

C(═

N—

R₄)—

N(R₄)₂, —

C(═

N—

R₄)—

N(R₄)(R₆), —

C(═

N—

R₄)—

N(R₄)—

C(═

O)—

R₄, —

C(═

N—

R₄)—

N(R₄)—

C(═

O)—

N(R₄)₂, —

C(═

N—

R₄)—

N(R₄)—

CO₂—

R₄, —

C(═

N—

R₄)—

N(R₄)—

SO₂—

C_1-4alkyl(R₇) or —

C(═

N—

R₄)—

N(R₄)—

SO₂—

N(R₄)₂;

R₄ is hydrogen;

R₅ is —

C(═

O)—

R₄, —

C(═

O)—

N(R₄)₂, —

CO₂—

R₄, —

C(R₄)(═

N—

R₄), —

C(═

N—

R₄)—

N(R₄)₂, —

C(═

N—

R₄)—

N(R₄)(R₆), —

N(R₄)—

C(R₄)(═

N—

R₄), —

N(R₄)—

C(═

N—

R₄)—

N(R₄)₂, —

N(R₄)—

C(═

N—

R₄)—

N(R₄)(R₆), —

SO₂—

C_1-4alkyl(R₇) or —

SO₂—

N(R₄)₂;

R₆ is -dihydroimidazolyl(R₈), -tetrahydropyridinyl(R₈), -tetrahydropyrimidinyl(R₈) or -pyridinyl(R₈);

R₇ is hydrogen;

R₈ is one to four substituents independently selected from hydrogen or —

C_1-4alkyl(R₉) when attached to a nitrogen atom; and

, wherein R₈ is one to four substituents independently selected from hydrogen, —

C_1-4alkyl(R₉), —

C_1-4alkoxy(R₉)-O-aryl(R₁₀) or hydroxy when attached to a carbon atom;

R₉ is hydrogen, —

C_1-4alkoxy, —

NH₂, —

NH—

C_1-4alkyl, —

N(C_1-4alkyl)₂, (halo)_1-3 or hydroxy;

R₁₀ is hydrogen;

R_2a is -tetrahydropyrimidinyl(R₈)(R₁₂), -1,3-benzodioxolyl(R₈)(R₁₂), -dihydrobenzofuranyl(R₈)(R₁₂), -tetrahydroquinolinyl(R₈)(R₁₂), -phenyl(R₈)(R₁₂), -naphthalenyl(R₈)(R₁₂), -pyridinyl(R₈)(R₁₂), -pyrimidinyl(R₈)(R₁₂) or -quinolinyl(R₈)(R₁₂);

q is 1 or 2;

R₁₂ is selected from the group consisting of

—

CH₂—

O—

(CH₂)₄(R₁₃)—

,

—

CH₂—

NH—

(CH₂)₄(R₁₃)—

,

—

CH₂—

S—

(CH₂)₄(R₁₃)—

,

—

CH₂—

O—

(CH₂)₆(R₁₃)—

,

—

CH₂—

NH—

(CH₂)₆(R₁₃)—

,

—

CH₂—

S—

(CH₂)₆(R₁₃)—

,

—

NH—

C(═

O)—

(CH₂)₄(R₁₃)—

,

—

NH—

C(═

O)—

(CH₂)₇(R₁₃)—

,

—

NH—

C(═

O)NH—

(CH₂)₃(R₁₃)—

,

—

NH—

C(═

O)NH—

(CH₂)₆(R₁₃)—

,

—

CH₂NH—

C(═

O)NH—

(CH₂)₂(R₁₃)—

,

—

CH₂NH—

C(═

O)NH—

(CH₂)₅(R₁₃)—

,

—

NHC(═

O)—

(CH₂)₂—

C(═

O)(R₁₃)—

,

—

NHC(═

O)—

(CH₂)₃—

C(═

O)(R₁₃)—

,

—

NHC(═

O)—

(CH₂)₄—

C(═

O)(R₁₃)—

,

—

OCH₂CH₂OCH₂CH₂(R₁₃)—

,

—

NHCH₂CH₂OCH₂CH₂(R₁₃)—

,

—

OCH₂CH₂OCH₂CH₂OCH₂CH₂(R₁₃)—

,

—

NHCH₂CH₂OCH₂CH₂OCH₂CH₂(R₁₃)—

,

—

OCH₂CH₂OCH₂C(═

O)(R₁₃)—

,

—

OCH₂CH₂OCH₂CH₂OCH₂C(═

O)(R₁₃)—

,

—

NHC(═

O)CH₂OCH₂CH₂(R₁₃)—

,

—

NHC(═

O)CH₂OCH₂CH₂OCH₂CH₂(R₁₃)—

,

—

CH₂OCH₂CH₂OCH₂CH₂(R₁₃)—

,

—

CH₂NHCH₂CH₂OCH₂CH₂(R₁₃)—

,

—

CH₂SCH₂CH₂OCH₂CH₂(R₁₃)—

,

—

CH₂OCH₂CH₂OCH₂CH₂OCH₂CH₂(R₁₃)—

,

—

CH₂NHCH₂CH₂OCH₂CH₂OCH₂CH₂(R₁₃)—

,

—

CH₂SCH₂CH₂OCH₂CH₂OCH₂CH₂(R₁₃)—

,

—

CH₂NHC(═

O)CH₂OCH₂C(═

O)(R₁₃)—

, and

—

NHC(═

O)CH₂OCH₂C(═

O)(R₁₃)—

;

wherein when R₁₁ or R₁₂ terminates with a —

C(═

O)—

, R₁₃ is selected from the group consisting of

and when R₁₁ or R₁₂ does not terminate with a —

C(═

O)—

, R₁₃ is selected from the group consisting of

wherein said —

O—

(CH₂CH₂O—

)_p—

or

 

of R₁₂ and R₁₃ is a polyethylene glycol (PEG) polymer selected from 2000 (PEG

     2000), 3400 (PEG 3400), or 5000 (PEG

     5000) Daltons;

r is an integer from 0 to 8;

Q and Q¹ of substituents R₁₂ and R₁₃ are the same within a given compound and is the C_1-7 saturated chain of stearoic acid;

Z is selected from the group consisting of hydroxy, —

NH₂, —

NH—

C_1-8alkyl, —

N(C_1-8alkyl)₂, —

O—

C_1-8alkyl, —

O—

C_1-8alkyl-OH, —

O—

C_1-8alkylC_1-4alkoxy, —

O—

C_1-8alkylcarbonylC_1-4alkyl, —

O—

C_1-8alkyl-CO₂H, —

O—

C_1-8alkyl-C(O)O—

C_1-6alkyl, —

O—

C_1-8alkyl-O—

C(O)C_1-8alkyl, —

O—

C_1-8alkyl-NH₂, —

O—

C_1-8alkyl-NH—

C_1-8alkyl, —

O—

C_1-8alkyl-N(C_1-8alkyl)₂, —

O—

C_1-8alkylamide —

O—

C_1-8alkyl-C(O)—

NH—

C_1-8alkyl, —

O—

C_1-8alkyl-C(O)—

N(C_1-8alkyl)₂ and —

NHC(O)C_1-8alkyl.

78. A therapeutic liposome composition sensitized to a target cell, comprising

(i) a liposomal composition composed of pre-formed liposomes having an entrapped therapeutic agent;

and

(ii) a plurality of targeting conjugates, each conjugate composed of (a) a lipid having a polar head group and a hydrophobic tail, (b) a hydrophilic polymer having a proximal end and a distal end, where the polymer is attached at its proximal end to the head group of the lipid, and (c) a targeting ligand attached to the distal end of the polymer.

79. The liposome of claim 78 wherein the targeting conjugate has a formula selected from the group consisting of Formula (I):

80. The liposome of claim 79 wherein R₁₂ is selected from the group consisting of —

C_1-6alkyl(R₁₃), —

O—

C_1-6alkyl(R₁₃), —

NH—

C_1-4alkyl(R₁₃), —

S—

C_1-6alkyl(R₁₃), —

CH₂O—

C_1-6alkyl(R₁₃), —

CH₂NH—

C_1-6alkyl(R₁₃), —

CH₂S—

C_1-6alkyl(R₁₃), —

C(═

O)C_1-6alkyl(R₁₃), —

O—

C(═

O)C_1-6alkyl(R₁₃), —

NH—

C(═

O)C_1-8alkyl(R₁₃), —

CH₂O—

C(═

O)C_1-8alkyl(R₁₃), —

CH₂NH—

C(═

O)C_1-6alkyl(R₁₃), —

C(═

O)OC_1-6alkyl(R₁₃), —

C(═

O)NHC_1-6alkyl(R₁₃), —

O—

C(═

O)OC_1-6alkyl(R₁₃), —

O—

C(═

O)NHC_1-6alkyl(R₁₃), —

NH—

C(═

O)OC_1-6alkyl(R₁₃), —

NH—

C(═

O)NHC_1-6alkyl(R₁₃), —

NH—

C(═

O)C_1-6alkylC(═

O)(R₁₃), —

CH₂O—

C(═

O)C_1-8alkylC(═

O)(R₁₃), —

NH—

C(═

O)NHC_1-8alkylC(═

O)(R₁₃), —

CH₂O—

C(═

O)NHC_1-8alkylC(═

O)(R₁₃), —

CH₂NH—

C(═

O)NHC_1-8alkylC(═

O)(R₁₃), —

OCH₂CH₂O(CH₂CH₂O)_rCH₂CH₂(R₁₃), —

NHCH₂CH₂O(CH₂CH₂O)_rCH₂CH₂(R₁₃), —

SCH₂CH₂O(CH₂CH₂O)_rCH₂CH₂(R₁₃), —

OCH₂CH₂O(CH₂CH₂O)_rCH₂C(═

O)(R₁₃), —

NHCH₂CH₂O(CH₂CH₂O)_rCH₂C(═

O)(R₁₃), —

OC(═

O)NHCH₂CH₂O(CH₂CH₂O)_rCH₂CH₂(R₁₃), —

NH(C═

O)CH₂O(CH₂CH₂O)_rCH₂CH₂(R₁₃), —

NHC(═

O)OCH₂CH₂O(CH₂CH₂O)_rCH₂CH₂(R₁₃), —

NHC(═

O)NHCH₂CH₂O(CH₂CH₂O)_rCH₂CH₂(R₁₃), —

SO₂CH₂CH₂O(CH₂CH₂O)_rCH₂CH₂(R₁₃), —

SO₂NHCH₂CH₂O(CH₂CH₂O)_rCH₂CH₂(R₁₃), —

CH₂OCH₂CH₂O(CH₂CH₂O)_rCH₂CH₂(R₁₃), —

CH₂NHCH₂CH₂O(CH₂CH₂O)_rCH₂CH₂(R₁₃), —

CH₂SCH₂CH₂O(CH₂CH₂O)_rCH₂CH₂(R₁₃), —

CH₂OCH₂CH₂O(CH₂CH₂O)_rCH₂C(═

O)(R₁₃), —

OC(═

O)NHCH₂CH₂O(CH₂CH₂O)_rCH₂C(═

O)(R₁₃), —

NH(C═

O)CH₂O(CH₂CH₂O)_rCH₂C(═

O)(R₁₃), —

NHC(═

O)OCH₂CH₂O(CH₂CH₂O)_rCH₂C(═

O)(R₁₃), —

NHC(═

O)NHCH₂CH₂O(CH₂CH₂O)_rCH₂C(═

O)(R₁₃), —

CH₂OC(═

O)CH₂O(CH₂CH₂O)_rCH₂C(═

O)(R₁₃), —

CH₂NH(C═

O)CH₂O(CH₂CH₂O)_rCH₂C(═

O)(R₁₃), —

CH₂NHC(═

O)OCH₂CH₂O(CH₂CH₂O)_rCH₂C(═

O)(R₁₃), and —

CH₂NHC(═

O)NHCH₂CH₂O(CH₂CH₂O)_rCH₂C(═

O)(R₁₃);

wherein when R₁₁ or R₁₂ terminates with a —

C(═

O)—

, R₁₃ is selected from the group consisting of

and when R₁₁ or R₁₂ does not terminate with a —

C(═

O)—

, R₁₃ is selected from the group consisting of

81. The liposome of claim 79 wherein R₁₂ is selected from the group consisting of —

CH₂O—

C_1-6alkyl(R₁₃), —

CH₂NH—

C_1-6akyl(R₁₃), —

CH₂S—

C_1-6alkyl(R₁₃), —

NH—

C(═

O)C_1-8alkyl(R₁₃), —

CH₂NH—

C(═

O)C_1-6alkyl(R₁₃), —

NH—

C(═

O)NHC_1-6alkyl(R₁₃), —

NH—

C(═

O)C_1-6alkylC(═

O)(R₁₃), —

OCH₂CH₂O(CH₂CH₂O)_rCH₂CH₂(R₁₃), —

NHCH₂CH₂O(CH₂CH₂O)_rCH₂CH₂(R₁₃), —

OCH₂CH₂O(CH₂CH₂O)_rCH₂C(═

O)(R₁₃), —

NH(C═

O)CH₂O(CH₂CH₂O)_rCH₂CH₂(R₁₃), —

CH₂OCH₂CH₂O(CH₂CH₂O)_rCH₂CH₂(R₁₃), —

CH₂NHCH₂CH₂O(CH₂CH₂O)_rCH₂CH₂(R₁₃), —

CH₂SCH₂CH₂O(CH₂CH₂O)_rCH₂CH₂(R₁₃), —

NH(C═

O)CH₂O(CH₂CH₂O)_rCH₂C(═

O)(R₁₃), and —

CH₂NH(C═

O)CH₂O(CH₂CH₂O)_rCH₂C(═

O)(R₁₃).

wherein when R₁₁ or R₁₂ terminates with a —

C(═

O)—

, R₁₃ is selected from the group consisting of

and when R₁₁ or R₁₂ does not terminate with a —

C(═

O)—

, R₁₃ is selected from the group consisting of

82. The liposome of claim 79 wherein said —

O—

(CH₂CH₂O—

)_p—

or

83. The liposome of claim 79 wherein wherein Q and Q¹ of substituents R₁₂ and R₁₃ are the same within a given compound and are selected from the group consisting of the C₁₅ saturated chain of palmitoic acid, the C₁₇ saturated chain of stearoic acid, and the C₁₇ mono-unsaturated chain of oleoic acid.

84. The liposome of claim 79 wherein

W is preferably is selected from the group consisting of —

C_0-4alkyl(R₁), —

C_1-4alkyl(R_1a), —

C_0-4alkyl-aryl(R₁,R₈), —

C_0-4alkyl-heterocyclyl(R₁,R₈), —

C_0-4alkoxy(R₁), —

C_0-4alkoxy-aryl(R₁,R₈), and —

C_0-4alkoxy-heterocyclyl(R₁,R₈);

R₁ is —

N(R₄)(R₆), -heterocyclyl(R₈) or -heteroaryl(R₈);

R_1a is —

C(R₄)(═

N—

R₄), —

C(═

N—

R₄)—

N(R₄)₂, —

C(═

N—

R₄)—

N(R₄)(R₆), —

C(═

N—

R₄)—

N(R₄)—

C(═

O)—

R₄, —

C(═

N—

R₄)—

N(R₄)—

C(═

O)—

N(R₄)₂, —

C(═

N—

R₄)—

N(R₄)—

CO₂—

R₄, —

C(═

N—

R₄)—

N(R₄)—

SO₂—

C_1-4alkyl(R₇) or —

C(═

N—

R₄)—

N(R₄)—

SO₂—

N(R₄)₂;

R₄ is hydrogen or —

C_1-4alkyl(R₇);

R₅ is —

C(═

O)—

R₄, —

C(═

O)—

N(R₄)₂, —

C(═

O)-cycloalkyl(R₈), —

C(═

O)-heterocyclyl(R₈), —

C(═

O)-aryl(R₈), —

C(═

O)-heteroaryl(R₈), —

C(═

O)—

N(R₄)-cycloalkyl(R₈), —

C(═

O)—

N(R₄)-aryl(R₈), —

CO₂—

R₄, —

CO₂-cycloalkyl(R₈), —

CO₂-aryl(R₈), —

C(R₄)(═

N—

R₄), —

C(═

N—

R₄)—

N(R₄)₂, —

C(═

N—

R₄)—

N(R₄)(R₆), —

C(═

N—

R₄)—

N(R₄)—

C(═

O)—

R₄, —

C(═

N—

R₄)—

N(R₄)—

C(═

O)—

N(R₄)₂, —

C(═

N—

R₄)—

N(R₄)—

CO₂—

R₄, —

C(═

N—

R₄)—

N(R₄)—

SO₂—

C_1-4alkyl(R₇), —

C(═

N—

R₄)—

N(R₄)—

SO₂—

N(R₄)₂, —

N(R₄)—

C(R₄)(═

N—

R₄), —

N(R₄)—

C(═

N—

R₄)—

N(R₄)₂, —

N(R₄)—

C(═

N—

R₄)—

N(R₄)(R₆), —

N(R₄)—

C(═

N—

R₄)—

N(R₄)—

C(═

O)—

R₄, —

N(R₄)—

C(═

N—

R₄)—

N(R₄)—

C(═

O)—

N(R₄)₂, —

N(R₄)—

C(═

N—

R₄)—

N(R₄)—

CO₂—

R₄, —

N(R₄)—

C(═

N—

R₄)—

N(R₄)—

SO₂—

C_1-4alkyl(R₇), —

N(R₄)—

C(═

N—

R₄)—

N(R₄)—

SO₂—

N(R₄)₂, —

SO₂—

C_1-4alkyl(R₇), —

SO₂—

N(R₄)₂, —

SO₂-cycloalkyl(R₈) or —

SO₂-aryl(R₈);

R₆ is -heterocyclyl(R₈) or -heteroaryl(R₈);

R₇ is one to two substituents independently selected from hydrogen, —

C_1-4alkoxy(R₉), —

NH₂, —

NH—

C_1-4alkyl(R₉), —

N(C_1-4alkyl(R₉))₂, —

C(═

O)H, —

C(═

O)—

C_1-4alkyl(R₉), —

C(═

O)—

NH₂, —

C(═

O)—

NH—

C_1-4alkyl(R₉), —

C(═

O)—

N(C_1-4alkyl(R₉))₂, —

C(═

O)—

NH-aryl(R₁₀), —

C(═

O)-cycloalkyl(R₁₀), —

C(═

O)-heterocyclyl(R₁₀), —

C(═

O)-aryl(R₁₀), —

C(═

O)-heteroaryl(R₁₀), —

CO₂H, —

CO₂—

C_1-4alkyl(R₉), —

CO₂-aryl(R₁₀), —

C(═

NH)—

NH₂, —

SH, —

S—

C_1-4alkyl(R₉), —

S—

C_1-4alkyl—

S—

C_1-4alkyl(R₉), —

S—

C_1-4alkyl—

C_1-4alkoxy(R₉), —

S—

C_1-4alkyl—

NH—

C_1-4alkyl(R₉), —

SO₂—

C_1-4alkyl(R₉), —

SO₂—

NH₂, —

SO₂—

NH—

C_1-4alkyl(R₉), —

SO₂—

N(C_1-4alkyl(R₉))₂, —

SO₂-aryl(R₁₀), cyano, (halo)_1-3, hydroxy, nitro, oxo, -cycloalkyl(R₁₀), -heterocyclyl(R₁₀), -aryl(R₁₀) or -heteroaryl(R₁₀);

R₈ is one to four substituents independently selected from hydrogen, —

C_1-4alkyl(R₉), —

C(═

O)H, —

C(═

O)—

NH₂, —

C(═

O)—

NH—

C_1-4alkyl(R₉), —

C(═

O)—

N(C_1-4alkyl(R₉))₂, —

CO₂H, —

CO₂—

C_1-4alkyl(R₉) or —

SO₂—

NH₂ when attached to a nitrogen atom; and

, wherein R₈ is one to four substituents independently selected from hydrogen, —

C_1-4alkyl(R₉), —

C_1-4alkoxy(R₉), —

O-aryl(R₁₀), —

C(═

O)H, —

C(═

O)—

NH₂, —

C(═

O)—

NH—

C_1-4alkyl(R₉), —

C(═

O)—

N(C_1-4alkyl(R₉))₂, —

CO₂H, —

CO₂—

C_1-4alkyl(R₉), —

SO₂—

NH₂, —

NH₂, —

NH—

C_1-4alkyl(R₉), —

N(C_1-4alkyl(R₉))₂, cyano, halo, hydroxy, nitro or oxo when attached to a carbon atom;

R₉ is hydrogen, —

C_1-4alkoxy, —

NH₂, —

NH—

C_1-4alkyl, —

N(C_1-4alkyl)₂, —

C(═

O)H, —

C(═

O)—

NH₂, —

C(═

O)—

NH—

C_1-4alkyl, —

C(═

O)—

N(C_1-4alkyl)₂, —

CO₂H, —

CO₂—

C_1-4alkyl, —

SO₂—

C_1-4alkyl, —

SO₂—

NH₂, —

SO₂—

NH—

C_1-4alkyl, —

SO₂—

N(C_1-4alkyl)₂, cyano, (halo)_1-3, hydroxy, nitro or oxo;

R₁₀ is one to four substituents independently selected from hydrogen, —

C_1-4alkyl, —

C(═

O)H, —

C(═

O)—

C_1-4alkyl, —

C(═

O)—

NH₂, —

C(═

O)—

NH—

C_1-4alkyl, —

C(═

O)—

N(C_1-4alkyl)₂, —

CO₂H, —

CO₂—

C_1-4alkyl, —

SO₂—

C_1-4alkyl, —

SO₂—

NH₂, —

SO₂—

NH—

C_1-4alkyl or —

SO₂—

N(C_1-4alkyl)₂ when attached to a nitrogen atom; and

, wherein R₁₀ is one to four substituents independently selected from hydrogen, —

C_1-4alkyl, —

C_1-4alkoxy, —

C(═

O)H, —

C(═

O)—

C_1-4alkyl, —

C(═

O)—

NH₂, —

C(═

O)—

NH—

C_1-4alkyl, —

C(═

O)—

N(C_1-4alkyl)₂, —

CO₂H, —

CO₂—

C_1-4alkyl, —

SO₂—

C_1-4alkyl, —

SO₂—

NH₂, —

SO₂—

NH—

C_1-4alkyl, —

SO₂—

N(C_1-4alkyl)₂, —

NH₂, —

NH—

C_1-4alkyl, —

N(C_1-4alkyl)₂, cyano, halo, hydroxy, nitro or oxo when attached to a carbon atom;

R_2a is -cycloalkyl(R₈)(R₁₁), -heterocyclyl(R₈)(R₁₂), -aryl(R₈)(R₁₂) or -heteroaryl(R₈)(R₁₂);

q is 1, 2 or 3.

R₁₁ is selected from the group consisting of —

C_1-8alkyl(R₁₃), —

O—

C_1-8alkyl(R₁₃), —

NH—

C_1-8alkyl(R₁₃), —

S—

C_1-8alkyl(R₁₃), —

C(═

O)C_1-8alkyl(R₁₃), —

O—

C(═

O)C_1-8alkyl(R₁₃), —

NH—

C(═

O)C_1-8alkyl(R₁₃), —

C(═

O)OC_1-8alkyl(R₁₃), —

C(═

O)NHC_1-8alkyl(R₁₃), —

O—

C(═

O)OC_1-8alkyl(R₁₃), —

O—

C(═

O)NHC_1-8alkyl(R₁₃), —

O—

C(═

O)C_1-8alkylC(═

O)(R₁₃), —

NH—

C(═

O)C_1-8alkylC(═

O)(R₁₃), —

C(═

O)OC_1-8alkylC(═

O)(R₁₃), —

O—

C(═

O)OC_1-8alkylC(═

O)(R₁₃), —

NH—

C(═

O)OC_1-8alkylC(═

O)(R₁₃), —

C(═

O)NHC_1-8alkylC(═

O)(R₁₃), —

O—

C(═

O)NHC_1-8alkylC(═

O)(R₁₃), —

NH—

C(═

O)NHC_1-8alkylC(═

O)(R₁₃), —

SCH₂CH₂O(CH₂CH₂O)_rCH₂CH₂(R₁₃), —

NHCH₂CH₂O(CH₂CH₂O)_rCH₂C(═

O)(R₁₃), —

SO₂NHCH₂CH₂O(CH₂CH₂O)_rCH₂CH₂(R₁₃), —

C(═

O)CH₂O(CH₂CH₂O)_rCH₂C(═

O)(R₁₃), —

OC(═

O)OCH₂CH₂O(CH₂CH₂O)_rCH₂C(═

O)(R₁₃), —

OC(═

O)NHCH₂CH₂O(CH₂CH₂O)_rCH₂C(═

O)(R₁₃), —

NHC(═

O)NHCH₂CH₂O(CH₂CH₂O)_rCH₂C(═

O)(R₁₃), and —

SO₂NHCH₂CH₂O(CH₂CH₂O)_rCH₂C(═

O)(R₁₃);

R₁₂ is selected from the group consisting of —

C_1-6alkyl(R₁₃), —

O—

C_1-6alkyl(R₁₃), —

NH—

C_1-4alkyl(R₁₃), —

S_1-6alkyl(R₁₃), —

CH₂O—

C_1-6alkyl(R₁₃), —

CH₂NH—

C_1-6alkyl(R₁₃), —

CH₂S—

C_1-6alkyl(R₁₃), —

C(═

O)C_1-6alkyl(R₁₃), —

O—

C(═

O)C_1-6alkyl(R₁₃), —

NH—

C(═

O)C_1-8alkyl(R₁₃), —

CH₂O—

C(═

O)C_1-8alkyl(R₁₃), —

CH₂NH—

C(═

O)C_1-6alkyl(R₁₃), —

C(═

O)OC_1-6alkyl(R₁₃), —

C(═

O)NHC_1-6alkyl(R₁₃), —

O—

C(═

O)OC_1-6alkyl(R₁₃), —

O—

C(═

O)NHC_1-6alkyl(R₁₃), —

NH—

C(═

O)OC_1-6alkyl(R₁₃), —

NH—

C(═

O)NHC_1-6alkyl(R₁₃), —

NH—

C(═

O)C_1-6alkylC(═

O)(R₁₃), —

CH₂O—

C(═

O)C_1-8alkylC(═

O)(R₁₃), —

NH—

C(═

O)NHC_1-8alkylC(═

O)(R₁₃), —

CH₂O—

C(═

O)NHC_1-8alkylC(═

O)(R₁₃), —

CH₂NH—

C(═

O)NHC_1-8alkylC(═

O)(R₁₃), —

OCH₂CH₂O(CH₂CH₂O)_rCH₂CH₂(R₁₃), —

NHCH₂CH₂O(CH₂CH₂O)_rCH₂CH₂(R₁₃), —

SCH₂CH₂O(CH₂CH₂O)_rCH₂CH₂(R₁₃), —

OCH₂CH₂O(CH₂CH₂O)_rCH₂C(═

O)(R₁₃), —

NHCH₂CH₂O(CH₂CH₂O)_rCH₂C(═

O)(R₁₃), —

OC(═

O)NHCH₂CH₂O(CH₂CH₂O)_rCH₂CH₂(R₁₃), —

NH(C═

O)CH₂O(CH₂CH₂O)_rCH₂CH₂(R₁₃), —

NHC(═

O)OCH₂CH₂O(CH₂CH₂O)_rCH₂CH₂(R₁₃), —

NHC(═

O)NHCH₂CH₂O(CH₂CH₂O)_rCH₂CH₂(R₁₃), —

SO₂CH₂CH₂O(CH₂CH₂O)_rCH₂CH₂(R₁₃), —

SO₂NHCH₂CH₂O(CH₂CH₂O)_rCH₂CH₂(R₁₃), —

CH₂OCH₂CH₂O(CH₂CH₂O)_rCH₂CH₂(R₁₃), —

CH₂NHCH₂CH₂O(CH₂CH₂O)_rCH₂CH₂(R₁₃), —

CH₂SCH₂CH₂O(CH₂CH₂O)_rCH₂CH₂(R₁₃), —

CH₂OCH₂CH₂O(CH₂CH₂O)_rCH₂C(═

O)(R₁₃), —

OC(═

O)NHCH₂CH₂O(CH₂CH₂O)_rCH₂C(═

O)(R₁₃), —

NH(C═

O)CH₂O(CH₂CH₂O)_rCH₂C(═

O)(R₁₃), —

NHC(═

O)OCH₂CH₂O(CH₂CH₂O)_rCH₂C(═

O)(R₁₃), —

NHC(═

O)NHCH₂CH₂O(CH₂CH₂O)_rCH₂C(═

O)(R₁₃), —

CH₂OC(═

O)CH₂O(CH₂CH₂O)_rCH₂C(═

O)(R₁₃), —

CH₂NH(C═

O)CH₂O(CH₂CH₂O)_rCH₂C(═

O)(R₁₃), —

CH₂NHC(═

O)OCH₂CH₂O(CH₂CH₂O)_rCH₂C(═

O)(R₁₃), and —

CH₂NHC(═

O)NHCH₂CH₂O(CH₂CH₂O)_rCH₂C(═

O)(R₁₃);

wherein when R₁₁ or R₁₂ terminates with a —

C(═

O)—

, R₁₃ is selected from the group consisting of

and when R₁₁ or R₁₂ does not terminate with a —

C(═

O)—

, R₁₃ is selected from the group consisting of

said —

O—

(CH₂CH₂O—

)_p—

or

 

of R₁₂ and R₁₃ is a polyethylene glycol (PEG) polymer ranging in molecular weight from 750 to 5000 daltons;

r is an integer from 0 to 8;

Q and Q₁ of substituents R₁₂ and R₁₃ are the same within a given compound and are selected from the group consisting of

the C₁₁ saturated chain of lauric acid,

the C₁₅ saturated chain of palmitoic acid,

the C₁₇ saturated chain of stearoic acid,

the C₁₇ mono-unsaturated chain of oleoic acid, and

the C₁₇ di-unsaturated chain of linoleic acid;

Z is selected from the group consisting of hydroxy, —

NH₂, —

NH—

C_1-8alkyl, —

N(C_1-8alkyl)₂, —

O—

C_1-8alkyl, —

O—

C_1-8alkyl—

OH, —

O—

C_1-8alkyl_1-4alkoxy, —

O—

C_1-8alkylcarbonylC_1-4alkyl, —

O—

C_1-8alkyl—

CO₂H, —

O—

C_1-8alkyl—

C(O)O—

C_1-6alkyl, —

O—

C_1-8alkyl—

O—

C(O)C_1-8alkyl, —

O—

C_1-8alkyl—

NH₂, —

O—

C_1-8alkyl—

NH—

C_1-8alkyl, —

O—

C_1-8alkyl—

N(C_1-8alkyl)₂, —

O—

C_1-8alkylamide—

O—

C_1-8alkyl—

C(O)—

NH—

C_1-8alkyl, —

O—

C_1-8alkyl—

C(O)—

N(C_1-8alkyl)₂ and —

NHC(O)C_1-8alkyl.

85. The liposome of claim 79 wherein

W is preferably —

C_0-4alkyl(R₁) or —

C_0-4alkyl—

phenyl(R₁,R₈);

R₁ is —

N(R₄)(R₆), -tetrahydropyrimidinyl(R₈) or -tetrahydro-1,8-naphthyridinyl(R₈);

R_1a is —

C(R₄)(═

N—

R₄), —

C(═

N—

R₄)—

N(R₄)₂, —

C(═

N—

R₄)—

N(R₄)(R₆), —

C(═

N—

R₄)—

N(R₄)—

C(═

O)—

R₄, —

C(═

N—

R₄)—

N(R₄)—

C(═

O)—

N(R₄)₂, —

C(═

N—

R₄)—

N(R₄)—

CO₂—

R₄, —

C(═

N—

R₄)—

N(R₄)—

SO₂—

C_1-4alkyl(R₇) or —

C(═

N—

R₄)—

N(R₄)—

SO₂—

N(R₄)₂;

R₄ is hydrogen;

R₅ is —

C(═

O)—

R₄, —

C(═

O)—

N(R₄)₂, —

CO₂—

R₄, —

C(R₄)(═

N—

R₄), —

C(═

N—

R₄)—

N(R₄)₂, —

C(═

N—

R₄)—

N(R₄)(R₆), —

N(R₄)—

C(R₄)(═

N—

R₄), —

N(R₄)—

C(═

N—

R₄)—

N(R₄)₂, —

N(R₄)—

C(═

N—

R₄)—

N(R₄)(R₆), —

SO₂—

C_1-4alkyl(R₇) or —

SO₂—

N(R₄)₂;

R₆ is -dihydroimidazolyl(R₈), -tetrahydropyridinyl(R₈), -tetrahydropyrimidinyl(R₈) or -pyridinyl(R₈);

R₇ is hydrogen;

R₈ is one to four substituents independently selected from hydrogen or —

C_1-4alkyl(R₉) when attached to a nitrogen atom; and

, wherein R₈ is one to four substituents independently selected from hydrogen, —

C_1-4alkyl(R₉), —

C_1-4alkoxy(R₉)—

O-aryl(R₁₀) or hydroxy when attached to a carbon atom;

R₉ is hydrogen, —

C_1-4alkoxy, —

NH₂, —

NH—

C_1-4alkyl, —

N(C_1-4alkyl)₂, (halo)_1-3, or hydroxy;

R₁₀ is hydrogen;

R_2a is -tetrahydropyrimidinyl(R₈)(R₁₂), -1,3-benzodioxolyl(R₈)(R₁₂), -dihydrobenzofuranyl(R₈)(R₁₂), -tetrahydroquinolinyl(R₈)(R₁₂), -phenyl(R₈)(R₁₂), -naphthalenyl(R₈)(R₁₂), -pyridinyl(R₈)(R₁₂), -pyrimidinyl(R₈)(R₁₂) or -quinolinyl(R₈)(R₁₂);

q is 1 or 2;

R₁₂ is selected from the group consisting of —

CH₂—

O—

(CH₂)₄(R₁₃)—

, —

CH₂—

NH—

(CH₂)₄(R₁₃)—

, —

CH₂—

S—

(CH₂)₄(R₁₃)—

, —

CH₂—

O—

(CH₂)₆(R₁₃)—

, —

CH₂—

NH—

(CH₂)₆(R₁₃)—

, —

CH₂—

S—

(CH₂)₆(R₁₃)—

, —

NH—

C(═

O)—

(CH₂)₄(R₁₃)—

, —

NH—

C(═

O)—

(CH₂)₇(R₁₃)—

, —

NH—

C(═

O)NH—

(CH₂)₃(R₁₃)—

, —

NH—

C(═

O)NH—

(CH₂)₆(R₁₃)—

, —

CH₂NH—

C(═

O)NH—

(CH₂)₂(R₁₃)—

, —

CH₂NH—

C(═

O)NH—

((CH₂)₅(R₁₃)—

, —

NHC(═

O)—

(CH₂)₂—

C(═

O)(R₁₃)—

, —

NHC(═

O)—

(CH₂)₃—

C(═

O)(R₁₃)—

, —

NHC(═

O)—

(CH₂)₄—

C(═

O)(R₁₃)—

, —

OCH₂CH₂OCH₂CH₂(R₁₃)—

, —

NHCH₂CH₂OCH₂CH₂(R₁₃)—

, —

OCH₂CH₂OCH₂CH₂OCH₂CH₂(R₁₃)—

, —

NHCH₂CH₂OCH₂CH₂OCH₂CH₂(R₁₃)—

, —

OCH₂CH₂OCH₂C(═

O)(R₁₃)—

, —

OCH₂CH₂OCH₂CH₂OCH₂C(═

O)(R₁₃)—

, —

NHC(═

O)CH₂OCH₂CH₂(R₁₃)—

, —

NHC(═

O)CH₂OCH₂CH₂OCH₂CH₂(R₁₃)—

, —

CH₂OCH₂CH₂OCH₂CH₂(R₁₃)—

, —

CH₂NHCH₂CH₂OCH₂CH₂(R₁₃)—

, —

CH₂SCH₂CH₂OCH₂CH₂(R₁₃)—

, —

CH₂OCH₂CH₂OCH₂CH₂OCH₂CH₂(R₁₃)—

, —

CH₂NHCH₂CH₂OCH₂CH₂OCH₂CH₂(R₁₃)—

, —

CH₂SCH₂CH₂OCH₂CH₂OCH₂CH₂(R₁₃)—

, —

CH₂NHC(═

O)CH₂OCH₂C(═

O)(R₁₃)—

, and —

NHC(═

O)CH₂OCH₂C(═

O)(R₁₃)—

;

wherein when R₁₁ or R₁₂ terminates with a —

C(═

O)—

, R₁₃ is selected from the group consisting of

and when R₁₁ or R₁₂ does not terminate with a —

C(═

O)—

, R₁₃ is selected from the group consisting of

wherein said —

O—

(CH₂CH₂O—

)_p—

or

 

of R₁₂ and R₁₃ is a polyethylene glycol (PEG) polymer selected from 2000 (PEG

     2000), 3400 (PEG

     3400), or 5000 (PEG

     5000) Daltons;

r is an integer from 0 to 8;

Q and Q¹ of substituents R₁₂ and R₁₃ are the same within a given compound and is the C₁₇ saturated chain of stearoic acid;

Z is selected from the group consisting of hydroxy, —

NH₂, —

NH—

C_1-8alkyl, —

N(C_1-8alkyl)₂, —

O—

C_1-8alkyl, —

O—

C_1-8alkyl—

OH, —

O—

C_1-8alkylC_1-4alkoxy, —

O—

C_1-8alkylcarbonylC_1-4alkyl, —

O—

C_1-8alkyl—

CO₂H, —

O—

C_1-8alkyl—

C(O)O—

C_1-6alkyl, —

O—

C_1-8alkyl—

O—

C(O)C_1-8alkyl, —

O—

C_1-8alkyl—

NH₂, —

O—

C_1-8alkyl—

NH—

C_1-8alkyl, —

O—

C_1-8alkyl—

N(C_1-8alkyl)₂, —

O—

C_1-8alkylamide—

O—

C_1-8alkyl—

C(O)—

NH—

C_1-8alkyl, —

O—

C_1-8alkyl—

C(O)—

N(C_1-8alkyl)₂ and —

NHC(O)C_1-8alkyl.

86. The therapeutic liposome composition of claim 78 wherein the therapeutic agent is selected from the group consisting of steroids, immunosuppressants, antihistamines, non-steroidal anti-asthamtics, non-steroidal anti-inflammatory agents, cyclooxygenase-2 inhibitors, cytotoxic agents, gene therapy agents, radiotherapy agents, and imaging agents.

87. The therapeutic liposome composition of claim 78 wherein the therapeutic agent is a cytotoxic drug.

88. The therapeutic liposome composition of claim 87 wherein the cytotoxic drug is selected from the group consisting of anthracycline antibiotics, platinum compounds, topoisomerase 1 inhibitors, and vinca alkaloids.

89. The therapeutic liposome composition of claim 87 wherein the cytotoxic agent is selected from the group consisting of doxorubicin, daunorubicin, epirubicin, idarubicin, cisplatin, carboplatin, ormaplatin, oxaliplatin, zeniplatin, enloplatin, lobaplatin, spiroplatin, ((-)-(R)-2-aminomethylpyrrolidine (1,1-cyclobutane dicarboxylato)platinum), (SP-4-3(R)1,1-cyclobutane-dicarboxylato(2-)-(2-methyl-1,4-butanediamine-N,N′

)platinum), nedaplatin, (bis-acetato-ammine-dichloro-cyclohexylamine-platinum(IV), topotecan, irinotecan, (7-(4-methylpiperazino-methylene)-10,11-ethylenedioxy-20(S)-camptothecin), 7-(2-(N-isopropylamino)ethyl)-(20S)-camptothecin, 9-aminocamptothecin, 9-nitrocamptothecin, vincristine, vinblastine, vinleurosine, vinrodisine, vinorelbine, and vindesine.

90. The therapeutic liposome composition of claim 87 wherein the cytotoxic agent is selected from the group consisting of doxorubicin, daunorubicin, epirubicin, idarubicin, cisplatin, including salts.