Affinity illudofulvene conjugates

A compound comprising an illudofulvene moiety and a linker, where the illudofulvene moiety is selected from the group consisting of:

• analog 333 ((2′S,3′R,6′R)-6′-hydroxy-2′,4′,6′-trimethyl-3′-(((4-nitrophenoxy)carbonyl)oxy)-7′-oxo-2′,3′,6′,7′-tetrahydrospiro[cyclopropane-1,5′-inden]-2′-yl)methyl acetate;
• analog 334 ((2′S,3′R,6′R)-3′-(((2-((tert-butoxycarbonyl)(methyl)amino)ethyl)(methyl)carbamoyl)oxy)-6′-hydroxy-2′,4′,6′-trimethyl-7′-oxo-2′,3′,6′,7′-tetrahydrospiro[cyclopropane-1,5′-inden]-2′-yl)methyl acetate;
• analog 335 tert-butyl ((2′S,3′R,6′R)-6′-hydroxy-2′-(hydroxymethyl)-2′,4′,6′-trimethyl-7′-oxo-2′,3′,6′,7′-tetrahydrospiro[cyclopropane-1,5′-inden]-3′-yl) ethane-1,2-diylbis(methylcarbamate);
• analog 339 ((2′S,3′R,6′R)-3′,6′-dihydroxy-2′,4′,6′-trimethyl-7′-oxo-2′,3′,6′,7′-tetrahydrospiro[cyclopropane-1,5′-inden]-2′-yl)methyl 4-methylbenzenesulfonate;
• analog 345 (2′S,3′R,6′R)-2′-(acetoxymethyl)-6′-hydroxy-2′,4′,6′-trimethyl-7′-oxo-2′,3′,6′,7′-tetrahydrospiro[cyclopropane-1,5′-inden]-3′-yl 4-(N-(2-(2-(2-(2-aminoacetamido)acetamido)acetamido)ethyl)-N-methylsulfamoyl)benzoate;
• analog 346 ((2′S,3′R,6′R)-3′,6′-dihydroxy-2′,4′,6′-trimethyl-7′-oxo-2′,3′,6′,7′-tetrahydrospiro[cyclopropane-1,5′-inden]-2′-yl)methyl 4-(N-(2-(2-(2-(2-aminoacetamido)acetamido)acetamido)ethyl)-N-methylsulfamoyl)benzoate;
• analog 351 (3'S,6′R)-6′-hydroxy-2′,2′,4′,6′-tetramethyl-7′-oxo-2′,3′,6′,7′-tetrahydrospiro[cyclopropane-1,5′-inden]-3′-yl 4-(N-(2-(2-(2-(2-aminoacetamido)acetamido)acetamido)ethyl)-N-methylsulfamoyl)benzoate;
• analog 353 ((6′R)-3′-(((2-((((4-((S)-2-((S)-2-(6-(2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)hexanamido)-3-methylbutanamido)-5-ureidopentanamido)benzyl)oxy)carbonyl)(methyl)amino)ethyl)(methyl)carbamoyl)oxy)-6′-hydroxy-2′,4′,6′-trimethyl-7′-oxo-2′,3′,6′,7′-tetrahydrospiro[cyclopropane-1,5′-inden]-2′-yl)methyl acetate;
• analog 356 ((2′S,3'S,6′R)-3′-(((1-(9H-fluoren-9-yl)-13-methyl-3,6,9,12-tetraoxo-2-oxa-4,7,10,13-tetraazapentadecan-15-yl)(methyl)carbamoyl)oxy)-6′-hydroxy-2′,4′,6′-trimethyl-7′-oxo-2′,3′,6′,7′-tetrahydrospiro[cyclopropane-1,5′-inden]-2′-yl)methyl acetate;
• analog 357 ((2′S,3'S,6′R)-3′-(((2-(2-(2-(2-aminoacetamido)acetamido)-N-methylacetamido)ethyl)(methyl)carbamoyl)oxy)-6′-hydroxy-2′,4′,6′-trimethyl-7′-oxo-2′,3′,6′,7′-tetrahydrospiro[cyclopropane-1,5′-inden]-2′-yl)methyl acetate;
• analog 359 ((2′S,3'S,6′R)-6′-hydroxy-2′,4′,6′-trimethyl-3′-((methyl(2,2,14-trimethyl-4,7,10,13-tetraoxo-3-oxa-5,8,11,14-tetraazahexadecan-16-yl)carbamoyl)oxy)-7′-oxo-2′,3′,6′,7′-tetrahydrospiro[cyclopropane-1,5′-inden]-2′-yl)methyl acetate;
• analog 361 ((2′S,3′R,6′R)-3′-((((2,5-dioxopyrrolidin-1-yl)oxy)carbonyl)oxy)-6′-hydroxy-2′,4′,6′-trimethyl-7′-oxo-2′,3′,6′,7′-tetrahydrospiro[cyclopropane-1,5′-inden]-2′-yl)methyl acetate;
• analog 362 ((2′S,3′R,6′R)-3′,6′-dihydroxy-2′,4′,6′-trimethyl-7′-oxo-2′,3′,6′,7′-tetrahydrospiro[cyclopropane-1,5′-inden]-2′-yl)methyl methanesulfonate;
• analog 363 (2′S,3′R,6′R)-2′-(aminomethyl)-3′,6′-dihydroxy-2′,4′,6′-trimethyl-2′,3′-dihydrospiro[cyclopropane-1,5′-inden]-7′(6′H)-one;
• analog 370 (2′S,3′R,6′R)-2′-(((tert-butyldimethylsilyl)oxy)methyl)-6′-hydroxy-2′,4′,6′-trimethyl-7′-oxo-2′,3′,6′,7′-tetrahydrospiro[cyclopropane-1,5′-inden]-3′-yl acetate;
• analog 371 (2′S,3′R,6′R)-6′-hydroxy-2′-(hydroxymethyl)-2′,4′,6′-trimethyl-7′-oxo-2′,3′,6′,7′-tetrahydrospiro[cyclopropane-1,5′-inden]-3′-yl acetate;
• analog 372 (2′R,3′R,6′R)-2′-formyl-6′-hydroxy-2′,4′,6′-trimethyl-7′-oxo-2′,3′,6′,7′-tetrahydrospiro[cyclopropane-1,5′-inden]-3′-yl acetate;
• analog 373 (2′S,3′R,6′R)-2′-(((((9H-fluoren-9-yl)methoxy)carbonyl)amino)methyl)-6′-hydroxy-2′,4′,6′-trimethyl-7′-oxo-2′,3′,6′,7′-tetrahydrospiro[cyclopropane-1,5′-inden]-3′-yl acetate;
• analog 374 (2′S,3′R,6′R)-2′-(aminomethyl)-6′-hydroxy-2′,4′,6′-trimethyl-7′-oxo-2′,3′,6′,7′-tetrahydrospiro[cyclopropane-1,5′-inden]-3′-yl acetate;
• analog 377 ((2′S,3′R,6′R)-6′-hydroxy-2′,4′,6′-trimethyl-7′-oxo-3′-((tributylsilyl)oxy)-2′,3′,6′,7′-tetrahydrospiro[cyclopropane-1,5′-inden]-2′-yl)methyl acetate;
• analog 378 (2′S,3′R,6′R)-2′-(((tert-butoxycarbonyl)amino)methyl)-6′-hydroxy-2′,4′,6′-trimethyl-7′-oxo-2′,3′,6′,7′-tetrahydrospiro[cyclopropane-1,5′-inden]-3′-yl acetate;
• analog 379 ((2′S,3′R,6′R)-3′-(((2-((((4-((14S,17S)-1-(9H-fluoren-9-yl)-14-isopropyl-3,6,9,12,15-pentaoxo-17-(3-ureidopropyl)-2-oxa-4,7,10,13,16-pentaazaoctadecan-18-amido)benzyl)oxy)carbonyl)(methyl)amino)ethyl)(methyl)carbamoyl)oxy)-6′-hydroxy-2′,4′,6′-trimethyl-7′-oxo-2′,3′,6′,7′-tetrahydrospiro[cyclopropane-1,5′-inden]-2′-yl)methyl acetate;
• analog 380 ((2′S,3′R,6′R)-3′-(((2-((((4-((2S,5S)-14-amino-5-isopropyl-4,7,10,13-tetraoxo-2-(3-ureidopropyl)-3,6,9,12-tetraazatetradecanamido)benzyl)oxy)carbonyl)(methyl)amino)ethyl)(methyl)carbamoyl)oxy)-6′-hydroxy-2′,4′,6′-trimethyl-7′-oxo-2′,3′,6′,7′-tetrahydrospiro[cyclopropane-1,5′-inden]-2′-yl)methyl acetate;
• analog 381 (2′S,3′R,6′R)-6′-hydroxy-2′-(hydroxymethyl)-2′,4′,6′-trimethyl-3′-((tributylsilyl)oxy)-2′,3′-dihydrospiro[cyclopropane-1,5′-inden]-7′(6′H)-one;
• analog 382 (2′R,3′R,6′R)-6′-hydroxy-2′,4′,6′-trimethyl-7′-oxo-3′-((tributylsilyl)oxy)-2′,3′,6′,7′-tetrahydrospiro[cyclopropane-1,5′-indene]-2′-carbaldehyde;
• analog 384 tert-butyl (((2′S,3′R,6′R)-6′-hydroxy-2′,4′,6′-trimethyl-7′-oxo-3′-((tributylsilyl)oxy)-2′,3′,6′,7′-tetrahydrospiro[cyclopropane-1,5′-inden]-2′-yl)methyl)carbamate;
• analog 389 tert-butyl (((2′S,3′R,6′R)-3′,6′-dihydroxy-2′,4′,6′-trimethyl-7′-oxo-2′,3′,6′,7′-tetrahydrospiro[cyclopropane-1,5′-inden]-2′-yl)methyl)carbamate;
• analog 392 ((2′S,3'S,6′R)-3′-(((2-(2-(2-(2-azidoacetamido)acetamido)-N-methylacetamido)ethyl)(methyl)carbamoyl)oxy)-6′-hydroxy-2′,4′,6′-trimethyl-7′-oxo-2′,3′,6′,7′-tetrahydrospiro[cyclopropane-1,5′-inden]-2′-yl)methyl acetate;
• analog 393 ((2′S,3′R,6′R)-3′-(((2-(2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)ethyl)carbamoyl)oxy)-6′-hydroxy-2′,4′,6′-trimethyl-7′-oxo-2′,3′,6′,7′-tetrahydrospiro[cyclopropane-1,5′-inden]-2′-yl)methyl acetate;
• analog 397 tert-butyl (((2′S,3′R,6′R)-3′,6′-dihydroxy-2′,4′,6′-trimethyl-7′-oxo-2′,3′,6′,7′-tetrahydrospiro[cyclopropane-1,5′-inden]-2′-yl)methyl)(hydroxy)carbamate;
• analog 398 (2′S,3′R,6′R)-3′,6′-dihydroxy-2′-((hydroxyamino)methyl)-2′,4′,6′-trimethyl-2′,3′-dihydrospiro[cyclopropane-1,5′-inden]-7′(6′H)-one;
• analog 399 ((2′S,3′R,6′R)-3′,6′-dihydroxy-2′,4′,6′-trimethyl-7′-oxo-2′,3′,6′,7′-tetrahydrospiro[cyclopropane-1,5′-inden]-2′-yl)methyl sulfamate;
• analog 401 ((6′R)-3′-(((2-((((4-((S)-2-((S)-2-((((9H-fluoren-9-yl)methoxy)carbonyl)amino)-3-methylbutanamido)-5-ureidopentanamido)benzyl)oxy)carbonyl)(methyl)amino)ethyl)(methyl)carbamoyl)oxy)-6′-hydroxy-2′,4′,6′-trimethyl-7′-oxo-2′,3′,6′,7′-tetrahydrospiro[cyclopropane-1,5′-inden]-2′-yl)methyl acetate;
• analog 403 ((2′S,6′R)-6′-hydroxy-2′,6′-dimethyl-4′-methylene-7′-oxo-2′,4′,6′,7′-tetrahydrospiro[cyclopropane-1,5′-inden]-2′-yl)methyl methanesulfonate;
• analog 404 ((6′R)-3′-(((2-((((4-((S)-2-((S)-2-amino-3-methylbutanamido)-5-ureidopentanamido)benzyl)oxy)carbonyl)(methyl)amino)ethyl)(methyl)carbamoyl)oxy)-6′-hydroxy-2′,4′,6′-trimethyl-7′-oxo-2′,3′,6′,7′-tetrahydrospiro[cyclopropane-1,5′-inden]-2′-yl)methyl acetate;
• analog 405 ((2′S,3'S,6′R)-6′-hydroxy-3′-(((2-((((4-((2S,5S)-5-isopropyl-25-(6-methyl-4-vinylpyridin-2-yl)-4,7,23-trioxo-2-(3-ureidopropyl)-10,13,16,19-tetraoxa-3,6,22-triazapentacosanamido)benzyl)oxy)carbonyl)(methyl)amino)ethyl)(methyl)carbamoyl)oxy)-2′,4′,6′-trimethyl-7′-oxo-2′,3′,6′,7′-tetrahydrospiro[cyclopropane-1,5′-inden]-2′-yl)methyl acetate;
• analog 407 ((2′S,3′R,6′R)-3′,6′-dihydroxy-2′,4′,6′-trimethyl-7′-oxo-2′,3′,6′,7′-tetrahydrospiro[cyclopropane-1,5′-inden]-2′-yl)methyl trifluoromethanesulfonate;
• analog 408 4-((2S,5S)-14-amino-5-isopropyl-4,7,10,13-tetraoxo-2-(3-ureidopropyl)-3,6,9,12-tetraazatetradecanamido)benzyl ((2′S,3′R,6′R)-6′-hydroxy-2′-(hydroxymethyl)-2′,4′,6′-trimethyl-7′-oxo-2′,3′,6′,7′-tetrahydrospiro[cyclopropane-1,5′-inden]-3′-yl) ethane-1,2-diylbis(methylcarbamate);
• analog 409 4-((S)-2-((S)-2-amino-3-methylbutanamido)-5-ureidopentanamido)benzyl ((6′R)-6′-hydroxy-2′-(hydroxymethyl)-2′,4′,6′-trimethyl-7′-oxo-2′,3′,6′,7′-tetrahydrospiro[cyclopropane-1,5′-inden]-3′-yl) ethane-1,2-diylbis(methylcarbamate);
• and
• analog 410 4-((S)-2-((S)-2-(6-(2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)hexanamido)-3-methylbutanamido)-5-ureidopentanamido)benzyl ((6′R)-6′-hydroxy-2′-(hydroxymethyl)-2′,4′,6′-trimethyl-7′-oxo-2′,3′,6′,7′-tetrahydrospiro[cyclopropane-1,5′-inden]-3′-yl) ethane-1,2-diylbis(methylcarbamate).

A compound comprising an illudofulvene moiety, a linker and an affinity moiety, where the illudofulvene moiety is selected from the group consisting of:

• analog 333 ((2′S,3′R,6′R)-6′-hydroxy-2′,4′,6′-trimethyl-3′-(((4-nitrophenoxy)carbonyl)oxy)-7′-oxo-2′,3′,6′,7′-tetrahydrospiro[cyclopropane-1,5′-inden]-2′-yl)methyl acetate;
• analog 334 ((2′S,3′R,6′R)-3′-(((2-((tert-butoxycarbonyl)(methyl)amino)ethyl)(methyl)carbamoyl)oxy)-6′-hydroxy-2′,4′,6′-trimethyl-7′-oxo-2′,3′,6′,7′-tetrahydrospiro[cyclopropane-1,5′-inden]-2′-yl)methyl acetate;
• analog 335 tert-butyl ((2′S,3′R,6′R)-6′-hydroxy-2′-(hydroxymethyl)-2′,4′,6′-trimethyl-7′-oxo-2′,3′,6′,7′-tetrahydrospiro[cyclopropane-1,5′-inden]-3′-yl) ethane-1,2-diylbis(methylcarbamate);
• analog 339 ((2′S,3′R,6′R)-3′,6′-dihydroxy-2′,4′,6′-trimethyl-7′-oxo-2′,3′,6′,7′-tetrahydrospiro[cyclopropane-1,5′-inden]-2′-yl)methyl 4-methylbenzenesulfonate;
• analog 345 (2′S,3′R,6′R)-2′-(acetoxymethyl)-6′-hydroxy-2′,4′,6′-trimethyl-7′-oxo-2′,3′,6′,7′-tetrahydrospiro[cyclopropane-1,5′-inden]-3′-yl 4-(N-(2-(2-(2-(2-aminoacetamido)acetamido)acetamido)ethyl)-N-methylsulfamoyl)benzoate;
• analog 346 ((2′S,3′R,6′R)-3′,6′-dihydroxy-2′,4′,6′-trimethyl-7′-oxo-2′,3′,6′,7′-tetrahydrospiro[cyclopropane-1,5′-inden]-2′-yl)methyl 4-(N-(2-(2-(2-(2-aminoacetamido)acetamido)acetamido)ethyl)-N-methylsulfamoyl)benzoate;
• analog 351 (3'S,6′R)-6′-hydroxy-2′,2′,4′,6′-tetramethyl-7′-oxo-2′,3′,6′,7′-tetrahydrospiro[cyclopropane-1,5′-inden]-3′-yl 4-(N-(2-(2-(2-(2-aminoacetamido)acetamido)acetamido)ethyl)-N-methylsulfamoyl)benzoate;
• analog 353 ((6′R)-3′-(((2-((((4-((S)-2-((S)-2-(6-(2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)hexanamido)-3-methylbutanamido)-5-ureidopentanamido)benzyl)oxy)carbonyl)(methyl)amino)ethyl)(methyl)carbamoyl)oxy)-6′-hydroxy-2′,4′,6′-trimethyl-7′-oxo-2′,3′,6′,7′-tetrahydrospiro[cyclopropane-1,5′-inden]-2′-yl)methyl acetate;
• analog 356 ((2′S,3'S,6′R)-3′-(((1-(9H-fluoren-9-yl)-13-methyl-3,6,9,12-tetraoxo-2-oxa-4,7,10,13-tetraazapentadecan-15-yl)(methyl)carbamoyl)oxy)-6′-hydroxy-2′,4′,6′-trimethyl-7′-oxo-2′,3′,6′,7′-tetrahydrospiro[cyclopropane-1,5′-inden]-2′-yl)methyl acetate;
• analog 357 ((2′S,3'S,6′R)-3′-(((2-(2-(2-(2-aminoacetamido)acetamido)-N-methylacetamido)ethyl)(methyl)carbamoyl)oxy)-6′-hydroxy-2′,4′,6′-trimethyl-7′-oxo-2′,3′,6′,7′-tetrahydrospiro[cyclopropane-1,5′-inden]-2′-yl)methyl acetate;
• analog 359 ((2′S,3'S,6′R)-6′-hydroxy-2′,4′,6′-trimethyl-3′-((methyl(2,2,14-trimethyl-4,7,10,13-tetraoxo-3-oxa-5,8,11,14-tetraazahexadecan-16-yl)carbamoyl)oxy)-7′-oxo-2′,3′,6′,7′-tetrahydrospiro[cyclopropane-1,5′-inden]-2′-yl)methyl acetate;
• analog 361 ((2′S,3′R,6′R)-3′-((((2,5-dioxopyrrolidin-1-yl)oxy)carbonyl)oxy)-6′-hydroxy-2′,4′,6′-trimethyl-7′-oxo-2′,3′,6′,7′-tetrahydrospiro[cyclopropane-1,5′-inden]-2′-yl)methyl acetate;
• analog 362 ((2′S,3′R,6′R)-3′,6′-dihydroxy-2′,4′,6′-trimethyl-7′-oxo-2′,3′,6′,7′-tetrahydrospiro[cyclopropane-1,5′-inden]-2′-yl)methyl methanesulfonate;
• analog 363 (2′S,3′R,6′R)-2′-(aminomethyl)-3′,6′-dihydroxy-2′,4′,6′-trimethyl-2′,3′-dihydrospiro[cyclopropane-1,5′-inden]-7′(6′H)-one;
• analog 370 (2′S,3′R,6′R)-2′-(((tert-butyldimethylsilyl)oxy)methyl)-6′-hydroxy-2′,4′,6′-trimethyl-7′-oxo-2′,3′,6′,7′-tetrahydrospiro[cyclopropane-1,5′-inden]-3′-yl acetate;
• analog 371 (2′S,3′R,6′R)-6′-hydroxy-2′-(hydroxymethyl)-2′,4′,6′-trimethyl-7′-oxo-2′,3′,6′,7′-tetrahydrospiro[cyclopropane-1,5′-inden]-3′-yl acetate;
• analog 372 (2′R,3′R,6′R)-2′-formyl-6′-hydroxy-2′,4′,6′-trimethyl-7′-oxo-2′,3′,6′,7′-tetrahydrospiro[cyclopropane-1,5′-inden]-3′-yl acetate;
• analog 373 (2′S,3′R,6′R)-2′-(((((9H-fluoren-9-yl)methoxy)carbonyl)amino)methyl)-6′-hydroxy-2′,4′,6′-trimethyl-7′-oxo-2′,3′,6′,7′-tetrahydrospiro[cyclopropane-1,5′-inden]-3′-yl acetate;
• analog 374 (2′S,3′R,6′R)-2′-(aminomethyl)-6′-hydroxy-2′,4′,6′-trimethyl-7′-oxo-2′,3′,6′,7′-tetrahydrospiro[cyclopropane-1,5′-inden]-3′-yl acetate;
• analog 377 ((2′S,3′R,6′R)-6′-hydroxy-2′,4′,6′-trimethyl-7′-oxo-3′-((tributylsilyl)oxy)-2′,3′,6′,7′-tetrahydrospiro[cyclopropane-1,5′-inden]-2′-yl)methyl acetate;
• analog 378 (2′S,3′R,6′R)-2′-(((tert-butoxycarbonyl)amino)methyl)-6′-hydroxy-2′,4′,6′-trimethyl-7′-oxo-2′,3′,6′,7′-tetrahydrospiro[cyclopropane-1,5′-inden]-3′-yl acetate;
• analog 379 ((2′S,3′R,6′R)-3′-(((2-((((4-((14S,17S)-1-(9H-fluoren-9-yl)-14-isopropyl-3,6,9,12,15-pentaoxo-17-(3-ureidopropyl)-2-oxa-4,7,10,13,16-pentaazaoctadecan-18-amido)benzyl)oxy)carbonyl)(methyl)amino)ethyl)(methyl)carbamoyl)oxy)-6′-hydroxy-2′,4′,6′-trimethyl-7′-oxo-2′,3′,6′,7′-tetrahydrospiro[cyclopropane-1,5′-inden]-2′-yl)methyl acetate;
• analog 380 ((2′S,3′R,6′R)-3′-(((2-((((4-((2S,5S)-14-amino-5-isopropyl-4,7,10,13-tetraoxo-2-(3-ureidopropyl)-3,6,9,12-tetraazatetradecanamido)benzyl)oxy)carbonyl)(methyl)amino)ethyl)(methyl)carbamoyl)oxy)-6′-hydroxy-2′,4′,6′-trimethyl-7′-oxo-2′,3′,6′,7′-tetrahydrospiro[cyclopropane-1,5′-inden]-2′-yl)methyl acetate;
• analog 381 (2′S,3′R,6′R)-6′-hydroxy-2′-(hydroxymethyl)-2′,4′,6′-trimethyl-3′-((tributylsilyl)oxy)-2′,3′-dihydrospiro[cyclopropane-1,5′-inden]-7′(6′H)-one;
• analog 382 (2′R,3′R,6′R)-6′-hydroxy-2′,4′,6′-trimethyl-7′-oxo-3′-((tributylsilyl)oxy)-2′,3′,6′,7′-tetrahydrospiro[cyclopropane-1,5′-indene]-2′-carbaldehyde;
• analog 384 tert-butyl (((2′S,3′R,6′R)-6′-hydroxy-2′,4′,6′-trimethyl-7′-oxo-3′-((tributylsilyl)oxy)-2′,3′,6′,7′-tetrahydrospiro[cyclopropane-1,5′-inden]-2′-yl)methyl)carbamate;
• analog 389 tert-butyl (((2′S,3′R,6′R)-3′,6′-dihydroxy-2′,4′,6′-trimethyl-7′-oxo-2′,3′,6′,7′-tetrahydrospiro[cyclopropane-1,5′-inden]-2′-yl)methyl)carbamate;
• analog 392 ((2′S,3'S,6′R)-3′-(((2-(2-(2-(2-azidoacetamido)acetamido)-N-methylacetamido)ethyl)(methyl)carbamoyl)oxy)-6′-hydroxy-2′,4′,6′-trimethyl-7′-oxo-2′,3′,6′,7′-tetrahydrospiro[cyclopropane-1,5′-inden]-2′-yl)methyl acetate;
• analog 393 ((2′S,3′R,6′R)-3′-(((2-(2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)ethyl)carbamoyl)oxy)-6′-hydroxy-2′,4′,6′-trimethyl-7′-oxo-2′,3′,6′,7′-tetrahydrospiro[cyclopropane-1,5′-inden]-2′-yl)methyl acetate;
• analog 397 tert-butyl (((2′S,3′R,6′R)-3′,6′-dihydroxy-2′,4′,6′-trimethyl-7′-oxo-2′,3′,6′,7′-tetrahydrospiro[cyclopropane-1,5′-inden]-2′-yl)methyl)(hydroxy)carbamate;
• analog 398 (2′S,3′R,6′R)-3′,6′-dihydroxy-2′-((hydroxyamino)methyl)-2′,4′,6′-trimethyl-2′,3′-dihydrospiro[cyclopropane-1,5′-inden]-7′(6′H)-one;
• analog 399 ((2′S,3′R,6′R)-3′,6′-dihydroxy-2′,4′,6′-trimethyl-7′-oxo-2′,3′,6′,7′-tetrahydrospiro[cyclopropane-1,5′-inden]-2′-yl)methyl sulfamate;
• analog 401 ((6′R)-3′-(((2-((((4-((S)-2-((S)-2-((((9H-fluoren-9-yl)methoxy)carbonyl)amino)-3-methylbutanamido)-5-ureidopentanamido)benzyl)oxy)carbonyl)(methyl)amino)ethyl)(methyl)carbamoyl)oxy)-6′-hydroxy-2′,4′,6′-trimethyl-7′-oxo-2′,3′,6′,7′-tetrahydrospiro[cyclopropane-1,5′-inden]-2′-yl)methyl acetate;
• analog 403 ((2′S,6′R)-6′-hydroxy-2′,6′-dimethyl-4′-methylene-7′-oxo-2′,4′,6′,7′-tetrahydrospiro[cyclopropane-1,5′-inden]-2′-yl)methyl methanesulfonate;
• analog 404 ((6′R)-3′-(((2-((((4-((S)-2-((S)-2-amino-3-methylbutanamido)-5-ureidopentanamido)benzyl)oxy)carbonyl)(methyl)amino)ethyl)(methyl)carbamoyl)oxy)-6′-hydroxy-2′,4′,6′-trimethyl-7′-oxo-2′,3′,6′,7′-tetrahydrospiro[cyclopropane-1,5′-inden]-2′-yl)methyl acetate;
• analog 405 ((2′S,3'S,6′R)-6′-hydroxy-3′-(((2-((((4-((2S,5S)-5-isopropyl-25-(6-methyl-4-vinylpyridin-2-yl)-4,7,23-trioxo-2-(3-ureidopropyl)-10,13,16,19-tetraoxa-3,6,22-triazapentacosanamido)benzyl)oxy)carbonyl)(methyl)amino)ethyl)(methyl)carbamoyl)oxy)-2′,4′,6′-trimethyl-7′-oxo-2′,3′,6′,7′-tetrahydrospiro[cyclopropane-1,5′-inden]-2′-yl)methyl acetate;
• analog 407 ((2′S,3′R,6′R)-3′,6′-dihydroxy-2′,4′,6′-trimethyl-7′-oxo-2′,3′,6′,7′-tetrahydrospiro[cyclopropane-1,5′-inden]-2′-yl)methyl trifluoromethanesulfonate;
• analog 408 4-((2S,5S)-14-amino-5-isopropyl-4,7,10,13-tetraoxo-2-(3-ureidopropyl)-3,6,9,12-tetraazatetradecanamido)benzyl ((2′S,3′R,6′R)-6′-hydroxy-2′-(hydroxymethyl)-2′,4′,6′-trimethyl-7′-oxo-2′,3′,6′,7′-tetrahydrospiro[cyclopropane-1,5′-inden]-3′-yl) ethane-1,2-diylbis(methylcarbamate);
• analog 409 4-((S)-2-((S)-2-amino-3-methylbutanamido)-5-ureidopentanamido)benzyl ((6′R)-6′-hydroxy-2′-(hydroxymethyl)-2′,4′,6′-trimethyl-7′-oxo-2′,3′,6′,7′-tetrahydrospiro[cyclopropane-1,5′-inden]-3′-yl) ethane-1,2-diylbis(methylcarbamate);
• and
• analog 410 4-((S)-2-((S)-2-(6-(2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)hexanamido)-3-methylbutanamido)-5-ureidopentanamido)benzyl ((6′R)-6′-hydroxy-2′-(hydroxymethyl)-2′,4′,6′-trimethyl-7′-oxo-2′,3′,6′,7′-tetrahydrospiro[cyclopropane-1,5′-inden]-3′-yl) ethane-1,2-diylbis(methylcarbamate),
• where the affinity moiety is selected from the group consisting of an antibody, an antibody fragment, a protein, a growth factor, a peptide, and a non-peptide moiety.