Silanol based therapeutic payloads

Abstract

Described herein in part are silanol based therapeutic payloads comprising a silanol terminus, a divalent spacer moiety, and a drug moiety capable of effecting a target cell or tissue.

What is claimed is: 
     
         1 . A silanol based payload represented by the formula 
       
         
           
           
               
               
           
         
         wherein:
 D is a drug moiety capable of effecting a target cell or tissue; 
 Y is a divalent spacer moiety selected from the group consisting of a bond and C 1-20 alkylene, wherein one, two, three or four methylene units of C 1-20 alkylene are optionally and independently replaced by C 3-8 cycloalkylene, C 2-10 alkenylene, C 2-10 alkynylene, aryl, spirocyclic, heteroaryl, —NR 1Y —, —N(R 1Y )C(O)—, —C(O)N(R 1Y )—, —O—, —C(O)—, —OC(O)—, —C(O)O—, —S—, —SO—, —SO 2 —, —C(═S)—, —C(═NR 1Y )—, —NR 1Y —C 1-15 alkyl-NR 1Y —C(O)—; —(CH 2 —CH 2 —O) s —, —(O—CH 2 —CH 2 ) s —, —NR 1Y —(CH 2 —CH 2 —O) s —C 1-6 alkyl-NR 1Y —C(O)—; —(O—CH 2 —CH 2 ) s —NR 1Y —C(O)—; —S—C 0-6 alkyl-; —NR 1Y —C 1-6 alkyl-; —N(C 1-3 alkyl)-C 1-6 alkyl-NH—C(O)—; —NH—C 1-6 alkyl-N(C 1-3 alkyl)-C(O)—; —SO 2 —NR 1Y —C 0-6 alkyl-; —N(R 1Y )SO 2 —C 0-6 alkyl-; —SO 2 -heterocyclyl-C 0-6 alkyl-; -heterocyclyl-C(O)—; -heterocyclyl-C 0-6 alkyl-NR 1Y —C(O)—; —NR 1Y —C 0-6 alkylene-heterocyclyl-C(O)—; —O—C 1-6 alkylene-C(O)—; —O—C 1-15 alkylene-NR 1Y —C(O)—; and —O—C 1-15 alkylene-C(O)—NR 1Y —; —O—C 1-6  alkylene-; wherein Y is optionally substituted; 
 wherein, independently for each occurrence, R 1Y  is selected from the group consisting of H, C 1-6 alkyl, cycloalkyl, haloalkyl, halocycloalkyl, heteroalkyl, heterocycloalkyl, heterohaloalkyl, heterohalocycloalkyl, aryl, biaryl, heteroaryl, heterobiaryl, mono or bicyclic heterocyclic, wherein the cycloalkyl, haloalkyl, halocycloalkyl, heteroalkyl, heterocycloalkyl, heterohaloalkyl, heterohalocycloalkyl, aryl, biaryl, heteroaryl, heterobiaryl, mono or bicyclic heterocyclic are optionally substituted with one or more substituents selected from —COH, carbonyl, oxime, hydrazide, hydrazone, urea, thiourea, amidine, guanidine, sulfonamide, acylsulfonamide, and sulfonyl amide; 
 s is an integer from 1 to 15; and 
 R 1  and R 2  are each methyl. 
 
       
     
     
         2 . The silanol based payload of  claim 1 , wherein D is a topoisomerase I inhibitor. 
     
     
         3 . The silanol based payload of  claim 1 , wherein D is exatecan. 
     
     
         4 . The silanol based payload of  claim 1 , wherein D is camptothecin. 
     
     
         5 . The silanol based payload of  claim 1 , wherein D is camptothecin analog. 
     
     
         6 . The silanol based payload of  claim 1 , wherein D is SN-38. 
     
     
         7 . The silanol based payload of  claim 1 , wherein the payload is selected from the group consisting of: