Claims for Patent: 8,828,401

Summary for Patent: 8,828,401

Title:	Cytotoxic peptides and antibody drug conjugates thereof
Abstract:	The present invention is directed to cytotoxic pentapeptides, to antibody drug conjugates thereof, and to methods for using the same to treat cancer.
Inventor(s):	Doroski; Matthew David (Mystic, CT), Maderna; Andreas (Stony Point, NY), O\'Donnell; Christopher John (Mystic, CT), Subramanyam; Chakrapani (South Glastonburty, CT), Vetelino; Beth (North Stonington, CT), Dushin; Russell George (Old Lyme, CT), Strop; Pavel (San Mateo, CA), Graziani; Edmund Idris (Chestnut Ridge, NY)
Assignee:	Pfizer Inc. (New York, NY)
Application Number:	13/670,612
Patent Claims:	1. A compound of formula I: ##STR00202## or a pharmaceutically acceptable salt or solvate thereof, wherein, independently for each occurrence, W is ##STR00203## R.sup.1 is hydrogen, C.sub.1-C.sub.8 alkyl or C.sub.1-C.sub.8 haloalkyl; R.sup.2 is hydrogen, C.sub.1-C.sub.8 alkyl or C.sub.1-C.sub.8 haloalkyl; R.sup.3A and R.sup.3B are either of the following: (i) R.sup.3A is hydrogen, C.sub.1-C.sub.8 alkyl, C.sub.1-C.sub.8 haloalkyl, C.sub.3-C.sub.8 carbocyclyl, C.sub.1-C.sub.10 heterocyclyl, aryl, heteroaralkyl, halogen or aralkyl; and R.sup.3B is C.sub.1-C.sub.8 alkyl, C.sub.1-C.sub.8 haloalkyl, C.sub.3-C.sub.8 carbocyclyl, C.sub.1-C.sub.10 heterocyclyl, aryl, heteroaralkyl, aralkyl or halogen; or (ii) R.sup.3A and R.sup.3B taken together are C.sub.2-C.sub.8 alkylene or C.sub.1-C.sub.8 heteroalkylene; R.sup.4A and R.sup.4B are either of the following: (i) R.sup.4A is hydrogen, C.sub.1-C.sub.8 alkyl, C.sub.1-C.sub.8 haloalkyl, C.sub.3-C.sub.8 carbocyclyl, C.sub.1-C.sub.10 heterocyclyl, aryl, heteroaralkyl or aralkyl; and R.sup.4B is hydrogen, C.sub.1-C.sub.8 alkyl, C.sub.1-C.sub.8 haloalkyl, C.sub.3-C.sub.8 carbocyclyl, C.sub.1-C.sub.10 heterocyclyl, aryl, heteroaralkyl or aralkyl; or (ii) R.sup.4A and R.sup.4B taken together are C.sub.2-C.sub.8 alkylene or C.sub.1-C.sub.8 heteroalkylene; R.sup.5 is ##STR00204## C.sub.1-C.sub.10 heterocyclyl, C.sub.3-C.sub.8 carbocycly and C.sub.6-C.sub.14 aryl optionally substituted with 1, 2, 3, 4 or 5 groups independently selected from the group consisting of --C.sub.1-C.sub.8 alkyl, --C.sub.1-C.sub.8 alkyl-N(R').sub.2, --C.sub.1-C.sub.8 alkyl-C(O)R', --C.sub.1-C.sub.8 alkyl-C(O)OR'--O--(C.sub.1-C.sub.8 alkyl), --C(O)R', --OC(O)R', --C(O)OR', --C(O)N(R').sub.2, --NHC(O)R', --S(O).sub.2R', --S(O)R', --OH, halogen, --N.sub.3, --N(R').sub.2, --CN, --NHC(.dbd.NH)NH.sub.2, --NHCONH.sub.2, --S(.dbd.O).sub.2R' and --SR', wherein each R' is independently selected from the group consisting of hydrogen, C.sub.1-C.sub.8 alkyl and unsubstituted aryl, or two R' can, together with the nitrogen to which they are attached, form a C.sub.1-C.sub.10 heterocyclyl; or R.sup.5 is ##STR00205## optionally substituted with 1, 2, 3, 4 or 5 groups independently selected from the group consisting of C.sub.1-C.sub.8 alkyl, --C.sub.1-C.sub.8 alkyl-N(R').sub.2, --C.sub.1-C.sub.8 alkyl-C(O)R', --C.sub.1-C.sub.8 alkyl-C(O)OR', --O--(C.sub.1-C.sub.8 alkyl), --C(O)R', --OC(O)R', --C(O)OR', --C(O)N(R').sub.2, --NHC(O)R', --S(O).sub.2R', --S(O)R', --OH, halogen, --N.sub.3, --N(R').sub.2, --CN, --NHC(.dbd.NH)NH.sub.2, --NHCONH.sub.2, --S(.dbd.O).sub.2R', --SR' and arylene-R', wherein each R' is independently selected from the group consisting of hydrogen, C.sub.1-C.sub.8 alkyl, C.sub.1-C.sub.8heterocyclyl, C.sub.1-C.sub.10alkylene-C.sub.3-C.sub.8heterocyclyl and aryl, or two R' can, together with the nitrogen to which they are attached, form a C.sub.1-C.sub.10 heterocyclyl; R.sup.6 is hydrogen, --C.sub.1-C.sub.8 alkyl, --C.sub.2-C.sub.8 alkenyl, --C.sub.2-C.sub.8 alkynyl or --C.sub.1-C.sub.8 haloalkyl; R.sup.12 is hydrogen, C.sub.1-C.sub.4 alkyl, C.sub.1-C.sub.10 heterocyclyl or C.sub.6-C.sub.14 aryl; R.sup.13 is C.sub.1-C.sub.10 heterocyclyl; and X is O or S; provided that when R.sup.3A is hydrogen X is S. 2. A compound of formula IIa: ##STR00206## or a pharmaceutically acceptable salt or solvate thereof, wherein, independently for each occurrence, W is ##STR00207## R.sup.1 is ##STR00208## Y is --C.sub.2-C.sub.20 alkylene-, --C.sub.2-C.sub.20 heteroalkylene-; --C.sub.3-C.sub.8 carbocyclo-, -arylene-, --C.sub.3-C.sub.8heterocyclo-, --C.sub.1-C.sub.10 alkylene-arylene-, -arylene-C.sub.1-C.sub.10alkylene-, --C.sub.1-C.sub.10alkylene-(C.sub.3-C.sub.8-carbocyclo)-, --(C.sub.3-C.sub.8-carbocyclo)-C.sub.1-C.sub.10alkylene-, --C.sub.1-C.sub.10alkylene-(C.sub.3-C.sub.8heterocyclo)- or --C.sub.3-C.sub.8 heterocyclo)-C.sub.1-C.sub.10alkylene-; Z is ##STR00209## G is halogen, --OH, --SH or --S--C.sub.1-C.sub.6 alkyl; R.sup.2 is hydrogen, C.sub.1-C.sub.8 alkyl or C.sub.1-C.sub.8 haloalkyl; R.sup.3A and R.sup.3B are either of the following: (i) R.sup.3A is hydrogen, C.sub.1-C.sub.8 alkyl, C.sub.1-C.sub.8 haloalkyl, C.sub.3-C.sub.8 carbocyclyl, C.sub.1-C.sub.10 heterocyclyl, aryl, heteroaralkyl, aralkyl or halogen; and R.sup.3B is C.sub.1-C.sub.8 alkyl, C.sub.1-C.sub.8 haloalkyl, C.sub.3-C.sub.8 carbocyclyl, C.sub.1-C.sub.10 heterocyclyl, aryl, heteroaralkyl or aralkyl or halogen; or (ii) R.sup.3A and R.sup.3B taken together are C.sub.2-C.sub.8 alkylene or C.sub.1-C.sub.8 heteroalkylene; R.sup.4A and R.sup.4B are either of the following: (i) R.sup.4A is hydrogen, C.sub.1-C.sub.8 alkyl, C.sub.1-C.sub.8 haloalkyl, C.sub.3-C.sub.8 carbocyclyl, C.sub.1-C.sub.10 heterocyclyl, aryl, heteroaralkyl or aralkyl; and R.sup.4B is hydrogen, C.sub.1-C.sub.8 alkyl, C.sub.1-C.sub.8 haloalkyl, C.sub.3-C.sub.8 carbocyclyl, C.sub.1-C.sub.10 heterocyclyl, aryl, heteroaralkyl or aralkyl; or (ii) R.sup.4A and R.sup.4B taken together are C.sub.2-C.sub.8 alkylene or C.sub.1-C.sub.8 heteroalkylene; R.sup.5 is ##STR00210## C.sub.1-C.sub.10 heterocyclyl, C.sub.3-C.sub.8 carbocycly and C.sub.6-C.sub.14 aryl optionally substituted with 1, 2, 3, 4 or 5 groups independently selected from the group consisting of --C.sub.1-C.sub.8 alkyl, --C.sub.1-C.sub.8 alkyl-N(R').sub.2, --C.sub.1-C.sub.8 alkyl-C(O)R', --C.sub.1-C.sub.8 alkyl-C(O)OR'--O--(C.sub.1-C.sub.8 alkyl), --C(O)R', --OC(O)R', --C(O)OR', --C(O)N(R').sub.2, --NHC(O)R', --S(O).sub.2R', --S(O)R', --OH, halogen, --N.sub.3, --N(R').sub.2, --CN, --NHC(.dbd.NH)NH.sub.2, --NHCONH.sub.2, --S(.dbd.O).sub.2R' and --SR', wherein each R' is independently selected from the group consisting of hydrogen, C.sub.1-C.sub.8 alkyl and unsubstituted aryl, or two R' can, together with the nitrogen to which they are attached, form a C.sub.1-C.sub.10 heterocyclyl; or R.sup.5 is ##STR00211## optionally substituted with 1, 2, 3, 4 or 5 groups independently selected from the group consisting of C.sub.1-C.sub.8 alkyl, --C.sub.1-C.sub.8 alkyl-N(R').sub.2, --C.sub.1-C.sub.8 alkyl-C(O)R', --C.sub.1-C.sub.8 alkyl-C(O)OR', --O--(C.sub.1-C.sub.8 alkyl), --O(O)R', --OC(O)R', --C(O)OR', --C(O)N(R').sub.2, --NHC(O)R', --S(O).sub.2R', --S(O)R', --OH, halogen, --N.sub.3, --N(R').sub.2, --CN, --NHC(.dbd.NH)NH.sub.2, --NHCONH.sub.2, --S(.dbd.O).sub.2R', --SR' and arylene-R', wherein each R' is independently selected from the group consisting of hydrogen, C.sub.1-C.sub.8 alkyl, C.sub.1-C.sub.8heterocyclyl, C.sub.1-C.sub.10alkylene-C.sub.3-C.sub.8heterocyclyl and aryl, or two R' can, together with the nitrogen to which they are attached, form a C.sub.1-C.sub.10 heterocyclyl; R.sup.6 is hydrogen, --C.sub.1-C.sub.8 alkyl, --C.sub.2-C.sub.8 alkenyl, --C.sub.2-C.sub.8 alkynyl or --C.sub.1-C.sub.8 haloalkyl; R.sup.12 is hydrogen, C.sub.1-C.sub.4 alkyl, C.sub.1-C.sub.10 heterocyclyl or C.sub.6-C.sub.14 aryl; R.sup.13 is C.sub.1-C.sub.10 heterocyclyl; and R.sup.7 is independently selected for each occurrence from the group consisting of F, Cl, I, Br, NO.sub.2, CN and CF.sub.3; R.sup.10 is hydrogen, --C.sub.1-C.sub.10alkyl, --C.sub.3-C.sub.8-carbocyclyl, -aryl, --C.sub.1-C.sub.10heteroalkyl, --C.sub.3-C.sub.8heterocyclo, --C.sub.1-C.sub.10alkylene-aryl, -arylene--C.sub.1-C.sub.10alkyl, --C.sub.1-C.sub.10alkylene-(C.sub.3-C.sub.8-carbocyclo), --(C.sub.3-C.sub.8 carbocyclo)-C.sub.1-C.sub.10alkyl, --C.sub.1-C.sub.10alkylene-(C.sub.3-C.sub.8heterocyclo), and --(C.sub.3-C.sub.8 heterocyclo)-C.sub.1-C.sub.10alkyl, where aryl on R.sub.10 comprising aryl is optionally substituted with [R.sub.7].sub.h; h is 1, 2, 3, 4 or 5; and X is O or S; provided that when R.sup.3A is hydrogen X is S. 3. A compound of formula IIIa: ##STR00212## or a pharmaceutically acceptable salt or solvate thereof, wherein, independently for each occurrence, W is ##STR00213## R.sup.1 is hydrogen, C.sub.1-C.sub.8 alkyl or C.sub.1-C.sub.8 haloalkyl; R.sup.2 is hydrogen, C.sub.1-C.sub.8 alkyl or C.sub.1-C.sub.8 haloalkyl; R.sup.3A and R.sup.3B are either of the following: (i) R.sup.3A is hydrogen, C.sub.1-C.sub.8 alkyl, C.sub.1-C.sub.8 haloalkyl, C.sub.3-C.sub.8 carbocyclyl, C.sub.1-C.sub.10 heterocyclyl, aryl, heteroaralkyl, aralkyl or halogen; and R.sup.3B is C.sub.1-C.sub.8 alkyl, C.sub.1-C.sub.8 haloalkyl, C.sub.3-C.sub.8 carbocyclyl, C.sub.1-C.sub.10 heterocyclyl, aryl, heteroaralkyl, halogen or aralkyl; or (ii) R.sup.3A and R.sup.3B taken together are C.sub.2-C.sub.8 alkylene or C.sub.1-C.sub.8 heteroalkylene; R.sup.4A and R.sup.4B are either of the following: (i) R.sup.4A is hydrogen, C.sub.1-C.sub.8 alkyl, C.sub.1-C.sub.8 haloalkyl, C.sub.3-C.sub.8 carbocyclyl, C.sub.1-C.sub.10 heterocyclyl, aryl, heteroaralkyl or aralkyl; and R.sup.4B is hydrogen, C.sub.1-C.sub.8 alkyl, C.sub.1-C.sub.8 haloalkyl, C.sub.3-C.sub.8 carbocyclyl, C.sub.1-C.sub.10 heterocyclyl, aryl, heteroaralkyl or aralkyl; or (ii) R.sup.4A and R.sup.4B taken together are C.sub.2-C.sub.8 alkylene or C.sub.1-C.sub.8 heteroalkylene; R.sup.5 is ##STR00214## ##STR00215## optionally substituted with 1, 2, 3, 4 or 5 groups independently selected from the group consisting of C.sub.1-C.sub.8 alkyl, --O--(C.sub.1-C.sub.8 alkyl), --C(O)R', --OC(O)R', --C(O)OR', --C(O)NH.sub.2, --C(O)NHR', --C(O)N(R).sub.2, --NHC(O)R', --S(O).sub.2R', --S(O)R', --OH, halogen, --N.sub.3, --NH.sub.2, --NH(R'), --N(R').sub.2, --CN, --NHC(.dbd.NH)NH.sub.2, --NHCONH.sub.2, --S(.dbd.O).sub.2R' and --SR', wherein each R' is independently selected from the group consisting of hydrogen, C.sub.1-C.sub.8 alkyl and unsubstituted aryl; R.sup.11is ##STR00216## Y is --C.sub.2-C.sub.20 alkylene-, --C.sub.2-C.sub.20 heteroalkylene-, C.sub.3-C.sub.8 carbocyclo-, -arylene-, --C.sub.3-C.sub.8 heterocyclo-, --C.sub.1-C.sub.10alkylene-arylene-, -arylene-C.sub.1-C.sub.10alkylene-, --C.sub.1-C.sub.1alkylene-(C.sub.3-C.sub.10-carbocyclo)-, --(C.sub.3-C.sub.8-carbocyclo)-C.sub.1-C.sub.10alkylene-, --C.sub.1-C.sub.10alkylene-(C.sub.3-C.sub.10heterocyclo)-, or -(C.sub.3-C.sub.8 heterocyclo)-C.sub.1-C.sub.10alkylene-; Z is ##STR00217## R.sup.7 is independently selected for each occurrence from the group consisting of F, Cl, I, Br, NO.sub.2, CN and CF.sub.3; R.sup.10 is hydrogen, --C.sub.1-C.sub.10alkyl, --C.sub.3-C.sub.8-carbocycle, aryl, --C.sub.1-C.sub.10 heteroalkyl, --C.sub.3-C.sub.8heterocyclo, --C.sub.1-C.sub.10alkylene-aryl, -arylene-C.sub.1-C.sub.10alkyl, --C.sub.1-C.sub.10alkylene-(C.sub.3-C.sub.10-carbocyclo), --(C.sub.3-C.sub.10 carbocyclo)-C.sub.1-C.sub.10alkyl, --C.sub.1-C.sub.10alkylene-(C.sub.3-C.sub.10heterocyclo), and -(C.sub.3-C.sub.10 heterocyclo)-C.sub.1-C.sub.10alkyl, where aryl on R.sub.10 comprising aryl is optionally substituted with [R.sub.7].sub.h; X is O or S R.sup.6 is hydrogen, C.sub.1-C.sub.8 alkyl or C.sub.1-C.sub.8 haloalkyl; and h is 1, 2, 3, 4 or 5. 4. A compound of formula IIb: ##STR00218## or a pharmaceutically acceptable salt or solvate thereof, wherein, independently for each occurrence, W is ##STR00219## R.sup.1 is ##STR00220## Y is --C.sub.2-C.sub.20 alkylene-, --C.sub.2-C.sub.20 heteroalkylene-, --C.sub.3-C.sub.8 carbocyclo-, -arylene-, --C.sub.3-C.sub.8heterocyclo-, --C.sub.1-C.sub.10 alkylene-arylene-, -arylene-C.sub.1-C.sub.10alkylene-, --C.sub.1-C.sub.10alkylene-(C.sub.3-C.sub.8-carbocyclo)-, --(C.sub.3-C.sub.8-carbocyclo)-C.sub.1-C.sub.10alkylene-, --C.sub.1-C.sub.10alkylene-(C.sub.3-C.sub.8heterocyclo)-, or --(C.sub.3-C.sub.8 heterocyclo)-C.sub.1-C.sub.10alkylene-; Z is ##STR00221## L is an antibody; R.sup.2 is hydrogen, C.sub.1-C.sub.8 alkyl or C.sub.1-C.sub.8 haloalkyl; R.sup.3A and R.sup.3B are either of the following: (i) R.sup.3A is hydrogen, C.sub.1-C.sub.8 alkyl, C.sub.1-C.sub.8 haloalkyl, C.sub.3-C.sub.8 carbocyclyl, C.sub.1-C.sub.10 heterocyclyl, aryl, heteroaralkyl, aralkyl or halogen; and R.sup.3B is C.sub.1-C.sub.8 alkyl, C.sub.1-C.sub.8 haloalkyl, C.sub.3-C.sub.8 carbocyclyl, C.sub.1-C.sub.10 heterocyclyl, aryl, heteroaralkyl, halogen or aralkyl; or (ii) R.sup.3A and R.sup.3B taken together are C.sub.2-C.sub.8 alkylene or C.sub.1-C.sub.8 heteroalkylene; R.sup.4A and R.sup.4B are either of the following: (i) R.sup.4A is hydrogen, C.sub.1-C.sub.8 alkyl, C.sub.1-C.sub.8 haloalkyl, C.sub.3-C.sub.8 carbocyclyl, C.sub.1-C.sub.10 heterocyclyl, aryl, heteroaralkyl or aralkyl; and R.sup.4B is hydrogen, C.sub.1-C.sub.8 alkyl, C.sub.1-C.sub.8 haloalkyl, C.sub.3-C.sub.8 carbocyclyl, C.sub.1-O.sub.10 heterocyclyl, aryl, heteroaralkyl or aralkyl; or (ii) R.sup.4A and R.sup.4B taken together are C.sub.2-C.sub.8 alkylene or C.sub.1-C.sub.8 heteroalkylene; R.sup.5 is ##STR00222## C.sub.1-C.sub.10 heterocyclyl, C.sub.3-C.sub.8 carbocycly and C.sub.6-C.sub.14 aryl optionally substituted with 1, 2, 3, 4 or 5 groups independently selected from the group consisting of --C.sub.1-C.sub.8 alkyl, --C.sub.1-C.sub.8 alkyl-N(R').sub.2, --C.sub.1-C.sub.8 alkyl-C(O)R', --C.sub.1-C.sub.8 alkyl-C(O)OR'--O--(C.sub.1-C.sub.8 alkyl), --C(O)R', --OC(O)R', --C(O)OR', --C(O)N(R').sub.2, --NHC(O)R', --S(O).sub.2R', --S(O)R', --OH, halogen, --N.sub.3, --N(R').sub.2, --CN, --NHC(.dbd.NH)NH.sub.2, --NHCONH.sub.2, --S(.dbd.O).sub.2R' and --SR', wherein each R' is independently selected from the group consisting of hydrogen, C.sub.1-C.sub.8 alkyl and unsubstituted aryl, or two R' can, together with the nitrogen to which they are attached, form a C.sub.1-C.sub.10 heterocyclyl; or R.sup.5 is ##STR00223## optionally substituted with 1, 2, 3, 4 or 5 groups independently selected from the group consisting of C.sub.1-C.sub.8 alkyl, --C.sub.1-C.sub.8 alkyl-N(R').sub.2, --C.sub.1-C.sub.8 alkyl-C(O)R', --C.sub.1-C.sub.8 alkyl-C(O)OR', --O--(C.sub.1-C.sub.8 alkyl), --C(O)R', --OC(O)R', --C(O)OR', --C(O)N(R).sub.2, --NHC(O)R', --S(O).sub.2R', --S(O)R', --OH, halogen, --N.sub.3, --N(R').sub.2, --CN, --NHC(.dbd.NH)NH.sub.2, --NHCONH.sub.2, --S(.dbd.O).sub.2R', --SR' and arylene-R', wherein each R' is independently selected from the group consisting of hydrogen, C.sub.1-C.sub.8 alkyl, C.sub.1-C.sub.8heterocyclyl, C.sub.1-C.sub.10 alkylene--C.sub.3-C.sub.8heterocyclyl and aryl, or two R' can, together with the nitrogen to which they are attached, form a C.sub.1-C.sub.10 heterocyclyl; R.sup.6 is hydrogen, --C.sub.1-C.sub.8 alkyl, --C.sub.2-C.sub.8 alkenyl, --C.sub.2-C.sub.8 alkynyl or --C.sub.1-C.sub.8 haloalkyl; R.sup.12 is hydrogen, C.sub.1-C.sub.4 alkyl, C.sub.1-C.sub.10 heterocyclyl or C.sub.6-C.sub.14 aryl; R.sup.13 is C.sub.1-C.sub.10 heterocyclyl; and X is O or S; provided that when R.sup.3A is hydrogen X is S. 5. A compound of formula IIIb: ##STR00224## or a pharmaceutically acceptable salt or solvate thereof, wherein, independently for each occurrence, W is R.sup.1 is hydrogen, C.sub.1-C.sub.8 alkyl or C.sub.1-C.sub.8 haloalkyl; ##STR00225## R.sup.2 is hydrogen, C.sub.1-C.sub.8 alkyl or C.sub.1-C.sub.8 haloalkyl; R.sup.3A and R.sup.3B are either of the following: (i) R.sup.3A is hydrogen, C.sub.1-C.sub.8 alkyl, C.sub.1-C.sub.8 haloalkyl, C.sub.3-C.sub.8 carbocyclyl, C.sub.1-C.sub.10 heterocyclyl, aryl, heteroaralkyl, aralkyl or halogen; and R.sup.3B is C.sub.1-C.sub.8 alkyl, C.sub.1-C.sub.8 haloalkyl, C.sub.3-C.sub.8 carbocyclyl, C.sub.1-C.sub.10 heterocyclyl, aryl, heteroaralkyl, halogen or aralkyl; or (ii) R.sup.3A and R.sup.3B taken together are C.sub.2-C.sub.8 alkylene or C.sub.1-C.sub.8 heteroalkylene; R.sup.4A and R.sup.4B are either of the following: (i) R.sup.4A is hydrogen, C.sub.1-C.sub.8 alkyl, C.sub.1-C.sub.8 haloalkyl, C.sub.3-C.sub.8 carbocyclyl, C.sub.1-C.sub.10 heterocyclyl, aryl, heteroaralkyl or aralkyl; and R.sup.4B is hydrogen, C.sub.1-C.sub.8 alkyl, C.sub.1-C.sub.8 haloalkyl, C.sub.3-C.sub.8 carbocyclyl, C.sub.1-C.sub.10 heterocyclyl, aryl, heteroaralkyl or aralkyl; or (ii) R.sup.4A and R.sup.4B taken together are C.sub.2-C.sub.8 alkylene or C.sub.1-C.sub.8 heteroalkylene; R.sup.5 is ##STR00226## ##STR00227## optionally substituted with 1, 2, 3, 4 or 5 groups independently selected from the group consisting of C.sub.1-C.sub.8 alkyl, --O--(C.sub.1-C.sub.8 alkyl), --C(O)R', --OC(O)R', --C(O)OR', --C(O)NH.sub.2, --C(O)NHR', --C(O)N(R).sub.2, --NHC(O)R', --S(O).sub.2R', --S(O)R', --OH, halogen, --N.sub.3, --NH.sub.2, --NH(R'), --N(R').sub.2, --CN, --NHC(.dbd.NH)NH.sub.2, --NHCONH.sub.2, --S(.dbd.O).sub.2R' and --SR', wherein each R' is independently selected from the group consisting of hydrogen, C.sub.1-C.sub.8 alkyl and unsubstituted aryl; R.sup.11 is ##STR00228## Y is --C.sub.2-C.sub.20 alkylene-, --C.sub.2-C.sub.20 heteroalkylene-, --C.sub.3-C.sub.8 carbocyclo-, -arylene-, --C.sub.3-C.sub.8heterocyclo-, --C.sub.1-C.sub.10 alkylene-arylene-, -arylene-C.sub.1-C.sub.10alkylene-, --C.sub.1-C.sub.10alkylene-(C.sub.3-C.sub.8-carbocyclo)-, --(C.sub.3-C.sub.8-carbocyclo)-C.sub.1-C.sub.10alkylene-, --C.sub.1-C.sub.10alkylene-(C.sub.3-C.sub.8heterocyclo)-, or --(C.sub.3-C.sub.8 heterocyclo)-C.sub.1-C.sub.10alkylene-; Z is ##STR00229## L is an antibody; X is O or S. 6. A compound of formula IIc: ##STR00230## or a pharmaceutically acceptable salt or solvate thereof, wherein, independently for each occurrence, R.sup.1' is ##STR00231## Y is --C.sub.2-C.sub.20 alkylene-, --C.sub.2-C.sub.20 heteroalkylene-, --C.sub.3-C.sub.8 carbocyclo-, -arylene-, --C.sub.3-C.sub.8heterocyclo-, --C.sub.1-C.sub.10 alkylene-arylene-, -arylene-C.sub.1-C.sub.10alkylene-, --C.sub.1-C.sub.10alkylene-(C.sub.3-C.sub.8-carbocyclo)-, --(C.sub.3-C.sub.8-carbocyclo)-C.sub.1-C.sub.10alkylene-, --C.sub.1-C.sub.10alkylene-(C.sub.3-C.sub.8heterocyclo)-, or --(C.sub.3-C.sub.8 heterocyclo)-C.sub.1-C.sub.10alkylene-; Z' is ##STR00232## L is an antibody; D is --C(R.sup.4A')(R.sup.4B')-- or is absent; R.sup.2' is hydrogen, C.sub.1-C.sub.8 alkyl, C.sub.1-C.sub.8 haloalkyl, or is absent if is present; R.sup.3A' and R.sup.3B' are either of the following: (i) R.sup.3A' is hydrogen, C.sub.1-C.sub.8 alkyl, C.sub.1-C.sub.8 haloalkyl, C.sub.3-C.sub.8 carbocyclyl, C.sub.1-C.sub.10 heterocyclyl, aryl, heteroaralkyl, aralkyl or halogen; and R.sup.3B' is C.sub.1-C.sub.8 alkyl, C.sub.1-C.sub.8 haloalkyl, C.sub.3-C.sub.8 carbocyclyl, C.sub.1-C.sub.10 heterocyclyl, aryl, heteroaralkyl, halogen or aralkyl, or R.sup.3B' is C.sub.2-C.sub.4 alkylene and forms 5-7 member ring as indicated by ; or (ii) R.sup.3A' and R.sup.3B' taken together are C.sub.2-C.sub.8 alkylene or C.sub.1-C.sub.8 heteroalkylene; R.sup.4A' and R.sup.4B' are either of the following: (i) R.sup.4A' is hydrogen, C.sub.1-C.sub.8 alkyl, C.sub.1-C.sub.8 haloalkyl, C.sub.3-C.sub.8 carbocyclyl, C.sub.1-C.sub.10 heterocyclyl, aryl, heteroaralkyl or aralkyl; and R.sup.4B' is hydrogen, C.sub.1-C.sub.8 alkyl, C.sub.1-C.sub.8 haloalkyl, C.sub.3-C.sub.8 carbocyclyl, C.sub.1-C.sub.10 heterocyclyl, aryl, heteroaralkyl or aralkyl; or (ii) R.sup.4A' and R.sup.4B' taken together are C.sub.2-C.sub.8 alkylene or C.sub.1-C.sub.8 heteroalkylene; R.sup.5 is ##STR00233## C.sub.1-C.sub.10 heterocyclyl, C.sub.3-C.sub.8 carbocycly and C.sub.6-C.sub.14 aryl optionally substituted with 1, 2, 3, 4 or 5 groups independently selected from the group consisting of --C.sub.1-C.sub.8 alkyl, --C.sub.1-C.sub.8 alkyl-N(R').sub.2, --C.sub.1-C.sub.8 alkyl-C(O)R', --C.sub.1-C.sub.8 alkyl-C(O)OR'--O--(C.sub.1-C.sub.8 alkyl), --C(O)R', --OC(O)R', --C(O)OR', --C(O)N(R').sub.2, --NHC(O)R', --S(O).sub.2R', --S(O)R', --OH, halogen, --N.sub.3, --N(R').sub.2, --CN, --NHC(.dbd.NH)NH.sub.2, --NHCONH.sub.2, --S(.dbd.O).sub.2R' and --SR', wherein each R' is independently selected from the group consisting of hydrogen, C.sub.1-C.sub.8 alkyl and unsubstituted aryl, or two R' can, together with the nitrogen to which they are attached, form a C.sub.1-C.sub.10 heterocyclyl; or R.sup.5 is ##STR00234## optionally substituted with 1, 2, 3, 4 or 5 groups independently selected from the group consisting of C.sub.1-C.sub.8 alkyl, --C.sub.1-C.sub.8 alkyl-N(R').sub.2, --C.sub.1-C.sub.8 alkyl-C(O)R', --C.sub.1-C.sub.8 alkyl-C(O)OR', --O--(C.sub.1-C.sub.8 alkyl), --C(O)R', --OC(O)R', --C(O)OR', --C(O)N(R').sub.2, --NHC(O)R', --S(O).sub.2R', --S(O)R', --OH, halogen, --N.sub.3, --N(R').sub.2, --CN, --NHC(.dbd.NH)NH.sub.2, --NHCONH.sub.2, --S(.dbd.O).sub.2R', --SR' and arylene-R', wherein each R' is independently selected from the group consisting of hydrogen, C.sub.1-C.sub.8 alkyl, C.sub.1-C.sub.8heterocyclyl, C.sub.1-C.sub.10 alkylene-C.sub.3-C.sub.8heterocyclyl and aryl, or two R' can, together with the nitrogen to which they are attached, form a C.sub.1-C.sub.10 heterocyclyl; R.sup.6 is hydrogen, --C.sub.1-C.sub.8 alkyl, --C.sub.2-C.sub.8 alkenyl, --C.sub.2-C.sub.8 alkynyl or --C.sub.1-C.sub.8 haloalkyl; R.sup.12 is hydrogen, C.sub.1-C.sub.4 alkyl, C.sub.1-C.sub.10 heterocyclyl or C.sub.6-C.sub.14 aryl; R.sup.13 is C.sub.1-C.sub.10 heterocyclyl; and X is O or S; provided that when R.sup.3A is hydrogen X is S. 7. A compound of formula IIIc: ##STR00235## or a pharmaceutically acceptable salt or solvate thereof, wherein, independently for each occurrence, ##STR00236## W is R.sup.1 is hydrogen, C.sub.1-C.sub.8 alkyl or C.sub.1-C.sub.8 haloalkyl; R.sup.2 is hydrogen, C.sub.1-C.sub.8 alkyl or C.sub.1-C.sub.8 haloalkyl; R.sup.3A and R.sup.3B are either of the following: (i) R.sup.3A is hydrogen, C.sub.1-C.sub.8 alkyl, C.sub.1-C.sub.8 haloalkyl, C.sub.3-C.sub.8 carbocyclyl, C.sub.1-C.sub.10 heterocyclyl, aryl, heteroaralkyl, aralkyl or halogen; and R.sup.3B is C.sub.1-C.sub.8 alkyl, C.sub.1-C.sub.8 haloalkyl, C.sub.3-C.sub.8 carbocyclyl, C.sub.1-C.sub.10 heterocyclyl, aryl, heteroaralkyl, halogen or aralkyl; or (ii) R.sup.3A and R.sup.3B taken together are C.sub.2-C.sub.8 alkylene or C.sub.1-C.sub.8 heteroalkylene; R.sup.4A and R.sup.4B are either of the following: (i) R.sup.4A is hydrogen, C.sub.1-C.sub.8 alkyl, C.sub.1-C.sub.8 haloalkyl, C.sub.3-C.sub.8 carbocyclyl, C.sub.1-C.sub.10 heterocyclyl, aryl, heteroaralkyl or aralkyl; and R.sup.4B is hydrogen, C.sub.1-C.sub.8 alkyl, C.sub.1-C.sub.8 haloalkyl, C.sub.3-C.sub.8 carbocyclyl, C.sub.1-C.sub.10 heterocyclyl, aryl, heteroaralkyl or aralkyl; or (ii) R.sup.4A and R.sup.4B taken together are C.sub.2-C.sub.8 alkylene or C.sub.1-C.sub.8 heteroalkylene; R.sup.5 is ##STR00237## ##STR00238## optionally substituted with 1, 2, 3, 4 or 5 groups independently selected from the group consisting of C.sub.1-C.sub.8 alkyl, --O--(C.sub.1-C.sub.8 alkyl), --C(O)R', --OC(O)R', --C(O)OR', --C(O)NH.sub.2, --C(O)NHR', --C(O)N(R).sub.2, --NHC(O)R', --S(O).sub.2R', --S(O)R', --OH, halogen, --N.sub.3, --NH.sub.2, --NH(R'), --N(R').sub.2, --CN, --NHC(.dbd.NH)NH.sub.2, --NHCONH.sub.2, --S(.dbd.O).sub.2R' and --SR', wherein each R' is independently selected from the group consisting of hydrogen, C.sub.1-C.sub.8 alkyl and unsubstituted aryl; ##STR00239## Y is is --C.sub.2-C.sub.20 alkylene-, --C.sub.2-C.sub.20 heteroalkylene-, --C.sub.3-C.sub.8 carbocyclo-, -arylene-, --C.sub.3-C.sub.8heterocyclo-, --C.sub.1-C.sub.10 alkylene-arylene-, -arylene-C.sub.1-C.sub.10alkylene-, --C.sub.1-C.sub.10alkylene-(C.sub.3-C.sub.8-carbocyclo)-, --(C.sub.3-C.sub.8-carbocyclo)-C.sub.1-C.sub.10alkylene-, --C.sub.1-C.sub.10alkylene-(C.sub.3-C.sub.8heterocyclo)-, or --(C.sub.3-C.sub.8 heterocyclo)-C.sub.1-C.sub.10alkylene-; Z' is ##STR00240## L is an antibody; X is O or S. 8. A compound of formula IId: ##STR00241## or a pharmaceutically acceptable salt or solvate thereof, wherein, independently for each occurrence, L is an antibody; [linker] is a divalent linker; D is --C(R.sup.4A')(R.sup.4B')-- or is absent; R.sup.2' is hydrogen, C.sub.1-C.sub.8 alkyl, C.sub.1-C.sub.8 haloalkyl, or is absent if , is present; R.sup.3A' and R.sup.B' are either of the following: (i) R.sup.3A' is hydrogen, C.sub.1-C.sub.8 alkyl, C.sub.1-C.sub.8 haloalkyl, C.sub.3-C.sub.8 carbocyclyl, C.sub.1-C.sub.10 heterocyclyl, aryl, heteroaralkyl, aralkyl or halogen; and R.sup.3B' is C.sub.1-C.sub.8 alkyl, C.sub.1-C.sub.8 haloalkyl, C.sub.3-C.sub.8 carbocyclyl, C.sub.1-C.sub.10 heterocyclyl, aryl, heteroaralkyl, halogen or aralkyl, or R.sup.3B' is C.sub.2-C.sub.4 alkylene and forms 5-7 member ring as indicated by ; or (ii) R.sup.3A' and R.sup.3B' taken together are C.sub.2-C.sub.8 alkylene or C.sub.1-C.sub.8 heteroalkylene; R.sup.4A' and R.sup.4B' are either of the following: (i) R.sup.4A' is hydrogen, C.sub.1-C.sub.8 alkyl, C.sub.1-C.sub.8 haloalkyl, C.sub.3-C.sub.8 carbocyclyl, C.sub.1-C.sub.10 heterocyclyl, aryl, heteroaralkyl or aralkyl; and R.sup.4B' is hydrogen, C.sub.1-C.sub.8 alkyl, C.sub.1-C.sub.8 haloalkyl, C.sub.3-C.sub.8 carbocyclyl, C.sub.1-C.sub.10 heterocyclyl, aryl, heteroaralkyl or aralkyl; or (ii) R.sup.4A' and R.sup.4B' taken together are C.sub.2-C.sub.8 alkylene or C.sub.1-C.sub.8 heteroalkylene; R.sup.5 is ##STR00242## C.sub.1-C.sub.10 heterocyclyl, C.sub.3-C.sub.8 carbocycly and C.sub.6-C.sub.14 aryl optionally substituted with 1, 2, 3, 4 or 5 groups independently selected from the group consisting of --C.sub.1-C.sub.8 alkyl, --C.sub.1-C.sub.8 alkyl-N(R').sub.2, --C.sub.1-C.sub.8 alkyl-C(O)R', --C.sub.1-C.sub.8 alkyl-C(O)OR'--O--(C.sub.1-C.sub.8 alkyl), --C(O)R', --OC(O)R', --C(O)OR', --C(O)N(R').sub.2, --NHC(O)R', --S(O).sub.2R', --S(O)R', --OH, halogen, --N.sub.3, --N(R').sub.2, --CN, --NHC(.dbd.NH)NH.sub.2, --NHCONH.sub.2, --S(.dbd.O).sub.2R' and --SR', wherein each R' is independently selected from the group consisting of hydrogen, C.sub.1-C.sub.8 alkyl and unsubstituted aryl, or two R' can, together with the nitrogen to which they are attached, form a C.sub.1-C.sub.10 heterocyclyl; or R.sup.5 is ##STR00243## optionally substituted with 1, 2, 3, 4 or 5 groups independently selected from the group consisting of C.sub.1-C.sub.8 alkyl, --C.sub.1-C.sub.8 alkyl-N(R').sub.2, --C.sub.1-C.sub.8 alkyl-C(O)R', --C.sub.1-C.sub.8 alkyl-C(O)OR', --O--(C.sub.1-C.sub.8 alkyl), --C(O)R', --OC(O)R', --C(O)OR', --C(O)N(R').sub.2, --NHC(O)R', --S(O).sub.2R', --S(O)R', --OH, halogen, --N.sub.3, --N(R').sub.2, --CN, --NHC(.dbd.NH)NH.sub.2, --NHCONH.sub.2, --S(.dbd.O).sub.2R', --SR' and arylene-R', wherein each R' is independently selected from the group consisting of hydrogen, C.sub.1-C.sub.8 alkyl, C.sub.1-C.sub.8heterocyclyl, C.sub.1-C.sub.10alkylene-C.sub.3-C.sub.8heterocyclyl and aryl, or two R' can, together with the nitrogen to which they are attached, form a C.sub.1-C.sub.10 heterocyclyl; R.sup.6 is hydrogen, --C.sub.1-C.sub.8 alkyl, --C.sub.2-C.sub.8 alkenyl, --C.sub.2-C.sub.8 alkynyl or --C.sub.1-C.sub.8 haloalkyl; R.sup.12 is hydrogen, C.sub.1-C.sub.4 alkyl, C.sub.1-C.sub.10 heterocyclyl or C.sub.6-C.sub.14 aryl; R.sup.13 is C.sub.1-C.sub.10 heterocyclyl; and X is O or S; provided that when R.sup.3A is hydrogen X is S. 9. A compound of formula IIId: ##STR00244## or a pharmaceutically acceptable salt or solvate thereof, wherein, independently for each occurrence, W is ##STR00245## R.sup.1 is hydrogen, C.sub.1-C.sub.8 alkyl or C.sub.1-C.sub.8 haloalkyl; R.sup.2 is hydrogen, C.sub.1-C.sub.8 alkyl or C.sub.1-C.sub.8 haloalkyl; R.sup.3A and R.sup.3B are either of the following: (i) R.sup.3A is hydrogen, C.sub.1-C.sub.8 alkyl, C.sub.1-C.sub.8 haloalkyl, C.sub.3-C.sub.8 carbocyclyl, C.sub.1-C.sub.10 heterocyclyl, aryl, heteroaralkyl, aralkyl or halogen; and R.sup.3B is C.sub.1-C.sub.8 alkyl, C.sub.1-C.sub.8 haloalkyl, C.sub.3-C.sub.8 carbocyclyl, C.sub.1-C.sub.10 heterocyclyl, aryl, heteroaralkyl, halogen or aralkyl; or (ii) R.sup.3A and R.sup.3B taken together are C.sub.2-C.sub.8 alkylene or C.sub.1-C.sub.8 heteroalkylene; R.sup.4A and R.sup.4B are either of the following: (i) R.sup.4A is hydrogen, C.sub.1-C.sub.8 alkyl, C.sub.1-C.sub.8 haloalkyl, C.sub.3-C.sub.8 carbocyclyl, C.sub.1-C.sub.10 heterocyclyl, aryl, heteroaralkyl or aralkyl; and R.sup.4B is hydrogen, C.sub.1-C.sub.8 alkyl, C.sub.1-C.sub.8 haloalkyl, C.sub.3-C.sub.8 carbocyclyl, C.sub.1-C.sub.10 heterocyclyl, aryl, heteroaralkyl or aralkyl; or (ii) R.sup.4A and R.sup.4B taken together are C.sub.2-C.sub.8 alkylene or C.sub.1-C.sub.8 heteroalkylene; R.sup.5 is ##STR00246## ##STR00247## optionally substituted with 1, 2, 3, 4 or 5 groups independently selected from the group consisting of C.sub.1-C.sub.8 alkyl, --O--(C.sub.1-C.sub.8 alkyl), --C(O)R', --OC(O)R', --C(O)OR', --C(O)NH.sub.2, --C(O)NHR', --C(O)N(R).sub.2, --NHC(O)R', --S(O).sub.2R', --S(O)R', --OH, halogen, --N.sub.3, --NH.sub.2, --NH(R'), --N(R').sub.2, --CN, --NHC(.dbd.NH)NH.sub.2, --NHCONH.sub.2, --S(.dbd.O).sub.2R' and --SR', wherein each R' is independently selected from the group consisting of hydrogen, C.sub.1-C.sub.8 alkyl and unsubstituted aryl; [linker] is a divalent linker; L is an antibody; X is O or S. 10. The compound, salt or solvate of claim 1, wherein W is ##STR00248## 11. The compound, salt or solvate of claim 1, wherein R.sup.1 is hydrogen, C.sub.1-C.sub.8 alkyl or C.sub.1-C.sub.8 haloalkyl. 12. The compound, salt or solvate of claim 2, wherein R.sup.1 is ##STR00249## 13. The compound, salt or solvate of claim 4 wherein R.sup.1 is ##STR00250## 14. The compound, salt or solvate of claim 1, wherein R.sup.3A is hydrogen, C.sub.1-C.sub.8 alkyl, C.sub.1-C.sub.8 haloalkyl, C.sub.3-C.sub.8 carbocyclyl, C.sub.1-C.sub.10 heterocyclyl, aryl, heteroaralkyl or aralkyl; and R.sup.3B is C.sub.1-C.sub.8 alkyl, C.sub.1-C.sub.8 haloalkyl, C.sub.3-C.sub.8 carbocyclyl, C.sub.1-C.sub.10 heterocyclyl, aryl, heteroaralkyl, aralkyl or halogen. 15. The compound, salt or solvate of claim 1, wherein R.sup.3A and R.sup.3B taken together are C.sub.2-C.sub.8 alkylene or C.sub.1-C.sub.8 heteroalkylene. 16. The compound, salt or solvate of claim 1, wherein R.sup.4A is hydrogen, C.sub.1-C.sub.8 alkyl, C.sub.1-C.sub.8 haloalkyl, C.sub.3-C.sub.8 carbocyclyl, C.sub.1-C.sub.10 heterocyclyl, aryl, heteroaralkyl or aralkyl; and R.sup.4B is C.sub.1-C.sub.8 alkyl, C.sub.1-C.sub.8 haloalkyl, C.sub.3-C.sub.8 carbocyclyl, C.sub.1-C.sub.10 heterocyclyl, aryl, heteroaralkyl or aralkyl; or R.sup.4A and R.sup.4B taken together are C.sub.2-C.sub.8 alkylene or C.sub.1-C.sub.8 heteroalkylene. 17. The compound, salt or solvate of claim 6, wherein R.sup.3A' and R.sup.3B' are defined as either of the following: (i) R.sup.3A' is hydrogen, C.sub.1-C.sub.8 alkyl, C.sub.1-C.sub.8 haloalkyl, C.sub.3-C.sub.8 carbocyclyl, C.sub.1-C.sub.10 heterocyclyl, aryl, heteroaralkyl, aralkyl or halogen; and R.sup.3B' C.sub.1-C.sub.8 alkyl, C.sub.1-C.sub.8 haloalkyl, C.sub.3-C.sub.8 carbocyclyl, C.sub.1-C.sub.10 heterocyclyl, aryl, heteroaralkyl, halogen or aralkyl, or R.sup.3B' is C.sub.2-C.sub.4 alkylene and forms 5-7 member ring as indicated by ; or (ii) R.sup.3A' and R.sup.3B' taken together are C.sub.2-C.sub.8 alkylene or C.sub.1-C.sub.8 heteroalkylene. 18. The compound, salt or solvate of claim 6, wherein R.sup.4A' and R.sup.4B' are defined as either of the following: (i) R.sup.4A' is hydrogen, C.sub.1-C.sub.8 alkyl, C.sub.1-C.sub.8 haloalkyl, C.sub.3-C.sub.8 carbocyclyl, C.sub.1-C.sub.10 heterocyclyl, aryl, heteroaralkyl or aralkyl; and R.sup.4B' is hydrogen, C.sub.1-C.sub.8 alkyl, C.sub.1-C.sub.8 haloalkyl, C.sub.3-C.sub.8 carbocyclyl, C.sub.1-C.sub.10 heterocyclyl, aryl, heteroaralkyl or aralkyl; or (ii) R.sup.4A' and R.sup.4B' taken together are C.sub.2-C.sub.8 alkylene or C.sub.1-C.sub.8 heteroalkylene. 19. The compound, salt or solvate of claim 1, wherein R.sup.5 is ##STR00251## 20. The compound, salt or solvate of claim 2, wherein Y is --C.sub.2-C.sub.20 alkylene-, --C.sub.2-C.sub.20 heteroalkylene-, --C.sub.3-C.sub.8 carbocyclo-, -arylene-, --C.sub.3-C.sub.8heterocyclo-, --C.sub.1-C.sub.10 alkylene-arylene-, -arylene-C.sub.1-C.sub.10alkylene-, --C.sub.1-C.sub.10alkylene-(C.sub.3-C.sub.8-carbocyclo)-, --(C.sub.3-C.sub.8-carbocyclo)-C.sub.1-C.sub.10alkylene-, --C.sub.1-C.sub.10alkylene-(C.sub.3-C.sub.8heterocyclo)-, or --(C.sub.3-C.sub.8 heterocyclo)-C.sub.1-C.sub.10alkylene-. 21. The compound, salt or solvate of claim 5, wherein antibody is selected from trastuzumab, oregovomab, edrecolomab, cetuximab, a humanized monoclonal antibody to the vitronectin receptor (.alpha..sub.v.beta..sub.3); alemtuzumab; a humanized anti-HLA-DR antibody for the treatment of non-Hodgkin's lymphoma; 131I Lym-1; a murine anti-HLA-Dr10 antibody for the treatment of non-Hodgkin's lymphoma; a humanized anti-CD2 mAb for the treatment of Hodgkin's Disease or non-Hodgkin's lymphoma; labetuzumab; bevacizumab; ibritumomab tiuxetan; ofatumumab; panitumumab; rituximab; tositumomab; ipilimumab; gemtuzumab; an anti-IL13 antibody; and an anti-Notch antibody. 22. A compound, or a pharmaceutically acceptable salt or solvate thereof, selected from: ##STR00252## ##STR00253## ##STR00254## ##STR00255## ##STR00256## ##STR00257## ##STR00258## ##STR00259## ##STR00260## ##STR00261## ##STR00262## ##STR00263## ##STR00264## ##STR00265## ##STR00266## ##STR00267## ##STR00268## ##STR00269## ##STR00270## 23. A compound, or a pharmaceutically acceptable salt or solvate thereof, selected from: ##STR00271## ##STR00272## ##STR00273## ##STR00274## ##STR00275## ##STR00276## ##STR00277## ##STR00278## ##STR00279## ##STR00280## ##STR00281## ##STR00282## ##STR00283## ##STR00284## ##STR00285## ##STR00286## ##STR00287## 24. A payload-linker comprising a radical of a compound of claim 22 or 23. 25. An antibody drug conjugate comprising a radical of a compound of any of claims 1, 2, or 3. 26. A compound, or a pharmaceutically acceptable salt or solvate thereof, selected from: ##STR00288## ##STR00289## ##STR00290## ##STR00291## ##STR00292## ##STR00293## ##STR00294## ##STR00295## ##STR00296## ##STR00297## ##STR00298## ##STR00299## ##STR00300## ##STR00301## ##STR00302## ##STR00303## ##STR00304## ##STR00305## ##STR00306## ##STR00307## ##STR00308## ##STR00309## ##STR00310## ##STR00311## ##STR00312## ##STR00313## ##STR00314## ##STR00315## ##STR00316## ##STR00317## ##STR00318## ##STR00319## 27. An antibody-drug-conjugate comprising a radical of a compound of any one of claims 22, 23, 24, 25, or 26. 28. A pharmaceutical composition comprising a compound of claim 1, or a pharmaceutically acceptable salt or solvate thereof, and pharmaceutically acceptable excipient. 29. A method of treating cancer comprising administering to a patient in need thereof a therapeutically effective amount of a compound of claim 4. 30. The compound: ##STR00320## or a pharmaceutically acceptable salt or solvate thereof. 31. The compound: ##STR00321## or a pharmaceutically acceptable salt or solvate thereof. 32. The compound: ##STR00322## or a pharmaceutically acceptable salt or solvate thereof. 33. The compound: ##STR00323## or a pharmaceutically acceptable salt or solvate thereof. 34. The compound: ##STR00324## or a pharmaceutically acceptable salt or solvate thereof. 35. The compound: ##STR00325## or a pharmaceutically acceptable salt or solvate thereof. 36. The compound: ##STR00326## or a pharmaceutically acceptable salt or solvate thereof.

Details for Patent 8,828,401

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Genentech, Inc.	RITUXAN	rituximab	Injection	103705	11/26/1997		2031-11-17
Idec Pharmaceuticals Corp.	RITUXAN	rituximab	Injection	103737	02/19/2002		2031-11-17
Genentech, Inc.	HERCEPTIN	trastuzumab	For Injection	103792	09/25/1998		2031-11-17