Cyclic peroxides as prodrugs for selective delivery of agents

Patent metadata

Field	Value
Publication number	US-10662215-B2
Application number	US-201916364577-A
Country	US
Kind code	B2
Filing date	Mar 26, 2019
Priority date	Feb 14, 2014
Publication date	May 26, 2020
Grant date	May 26, 2020

Abstract

Disclosed herein, inter alia, are prodrug compositions and methods of using the same for treatment and detection of disease. Specifically, disclosed herein is a compound of formula (I) having spiro-fused 1,2,4-trioxolane and piperidine rings, namely, 1,2,4-trioxa-8-azaspiro[4.5]decane. Also disclosed is a pharmaceutical composition containing the compound and a pharmaceutically acceptable carrier.

First claim

What is claimed is:

1. A compound having the formula:

wherein
L 1 -R 1 is —H;
L 2 , L 3 , L 4 , L 6 , L 7 , L 8 , and L 9 are each a bond;
R 2 , R 3 , R 4 , R 6 , R 7 , R 8 , and R 9 are each hydrogen;
L 10 is —CH 2 —;
L 5 is independently selected from a bond, —N(R 17 )—, —N(R 17 )C(O)O—, —O—, —S—, —OC(O)—, —OC(O)N(R 17 )—, —OC(O)O—, —OSO 2 —, —C(O)N(R 17 )—, —N(R 17 )C(O)—, —S(O) 2 N(R 17 )—, —N(R 17 )S(O) 2 —, substituted or unsubstituted alkylene, substituted or unsubstituted heteroalkylene, substituted or unsubstituted cycloalkylene, substituted or unsubstituted heterocycloalkylene, substituted or unsubstituted arylene, or substituted or unsubstituted heteroarylene;
R 17 is independently hydrogen, halogen, —CF 3 , —CN, —OH, —NH 2 , —COOH, —CONH 2 , —NO 2 , —SH, —SO 2 Cl, —SO 3 H, —SO 4 H, —SO 2 NH 2 , —NHNH 2 , —ONH 2 , —NHC═(O)NHNH 2 , —NHC═(O)NH 2 , —NHSO 2 H, —NHC═(O)H, —NHC(O)—OH, —NHOH, —OCF 3 , —OCHF 2 , substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl; and
R 5 is independently a monovalent form of GDC-0973, a monovalent form of selumetinib, a monovalent form of ARRY-162,

2. The compound of claim 1 , wherein L 5 is a bond.

3. The compound of claim 1 , wherein L 5 is —OC(O)—.

4. The compound of claim 1 , wherein R 5 is a monovalent form of GDC-0973.

5. The compound of claim 1 , wherein R 5 is a monovalent form of selumetinib.

6. The compound of claim 1 , wherein R 5 is a monovalent form of ARRY-162.

7. The compound of claim 1 , wherein R 5 is

8. The compound of claim 1 , wherein R 5 is

9. The compound of claim 1 , wherein the compound has the formula:

10. The compound of claim 1 , wherein the compound has the formula:

11. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound of claim 1 .

12. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound of claim 2 .

13. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound of claim 3 .

14. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound of claim 4 .

15. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound of claim 5 .

16. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound of claim 6 .

17. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound of claim 7 .

18. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound of claim 8 .

19. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound of claim 9 .

20. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound of claim 10 .

Assignees

• Univ California

Inventors

• Renslo Adam R
• Lauterwasser Erica M W
• Fontaine Shaun D
• Spangler Benjamin B
• Wells James A

Classifications

• A61K47/6889

  Conjugates wherein the antibody being the modifying agent and wherein the linker, binder or spacer confers particular properties to the conjugates, e.g. peptidic enzyme-labile linkers or acid-labile linkers, providing for an acid-labile immuno conjugate wherein the drug may be released from its antibody conjugated part in an acidic, e.g. tumoural or environment · CPC title

• C07D405/14

  containing three or more hetero rings · CPC title

• C07D487/04

  Ortho-condensed systems · CPC title

• C07D323/02

  Five-membered rings · CPC title

• A61K31/496

  Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin · CPC title