Polyoxazolines with inert terminating groups, polyoxazolines prepared from protected initiating groups and related compounds
원문보기
IPC분류정보
국가/구분
United States(US) Patent
등록
국제특허분류(IPC7판)
A61K-009/14
C08G-073/02
A61K-009/127
C08L-079/02
출원번호
US-0003306
(2009-07-10)
등록번호
US-8883211
(2014-11-11)
국제출원번호
PCT/US2009/050286
(2009-07-10)
§371/§102 date
20110109
(20110109)
국제공개번호
WO2010/006282
(2010-01-14)
발명자
/ 주소
Bentley, Michael David
Harris, J. Milton
Reif, Michael
Jordon, Rainer
Yoon, Kunsang
출원인 / 주소
Serina Therapeutics, Inc.
대리인 / 주소
Peterson, Thomas G.
인용정보
피인용 횟수 :
0인용 특허 :
32
초록▼
The present disclosure provides novel functional polyoxazoline derivatives prepared by terminating polyoxazoline polymerization with inert chemical groups. In addition, the present disclosure demonstrates the synthesis of novel electrophilic initiators with protected functional groups capable of ini
The present disclosure provides novel functional polyoxazoline derivatives prepared by terminating polyoxazoline polymerization with inert chemical groups. In addition, the present disclosure demonstrates the synthesis of novel electrophilic initiators with protected functional groups capable of initiating oxazoline polymerization and capable of surviving the conditions of polymerization. These initiators are used to synthesize the above inert-terminal polyoxazoline derivatives as well as other polyoxazolines with active terminal groups. Furthermore, the present disclosure provides for polyoxazoline-lipid conjugates and liposomal compositions prepared using such polyoxazoline-lipid conjugates. Methods of using the foregoing to prepare conjugates with target molecules are also disclosed.
대표청구항▼
1. A heterofunctional polyoxazoline of the following general structure: E-R3-{POZI—POZII}a—S—R*wherein:E is —OH, —CO2H or a group containing an active —OH group or an active —CO2H group;POZI is a polyoxazoline polymer of the structure [N(CO—R′—Z)CH2CH2]m POZII is a polyoxazoline polymer of the struc
1. A heterofunctional polyoxazoline of the following general structure: E-R3-{POZI—POZII}a—S—R*wherein:E is —OH, —CO2H or a group containing an active —OH group or an active —CO2H group;POZI is a polyoxazoline polymer of the structure [N(CO—R′—Z)CH2CH2]m POZII is a polyoxazoline polymer of the structure [N(COR2)CH2CH2]n R′ is an optional linking groupR3 is a linking group;Z is an active functional group or a group capable of being converted to an active functional group, the active functional group capable of forming a linkage with a binding partner on a target molecule;R2 is independently selected for each repeating unit of the polyoxazoline polymer from an unsubstituted or substituted alkyl, alkenyl, aralkyl or heterocycylalkyl group;R* is —(CH2)q—C6H5 and q is an integer from 1-25;n is an integer from 0-1000, provided that when n=0, then m is >1;m is an integer 1-1000; anda is ran, which indicates a random copolymer, or block, which indicates a block copolymer. 2. The heterofunctional polyoxazoline derivative of claim 1, wherein Z is an alkyne, an oxyamine, an aldehyde, a ketone, an acetal, a ketal, an ester, a carboxylic acid, an activated carboxylic acid, an active carbonate, a chloroformate, an alcohol, an azide, a hydrazide, an amine, a protected amine, a thiol, a vinyl sulfone, a maleimide or an orthopyridyl disulfide. 3. The heterofunctional polyoxazoline derivative of claim 1, wherein R3 is —(CH2)p— where p is an integer from 1-25. 4. The heterofunctional polyoxazoline derivative of claim 1, wherein R′ is —(CH2)o— where o is an integer from 1-25. 5. The heterofunctional polyoxazoline derivative of claim 1, wherein R2 is a C1-C12 alkyl or aralkyl group. 6. The heterofunctional polyoxazoline derivative of claim 1, wherein R2 is methyl, ethyl, isopropyl or n-propyl. 7. The heterofunctional polyoxazoline derivative of claim 1, wherein at least one active functional group is protected. 8. The heterofunctional polyoxazoline derivative of claim 1, wherein at least one of POZI and POZII has a polydispersity value of less than or equal to 1.2. 9. The heterofunctional polyoxazoline derivative of claim 1, wherein each of the POZI and POZII has a polydispersity value of less than or equal to 1.2. 10. The heterofunctional polyoxazoline derivative of claim 1, having the structure: HO—(CH2)p-{POZI—POZII}a—S—R*, wherein p is an integer selected from 1-25. 11. The heterofunctional polyoxazoline derivative of claim 1, having the structure: HO2C—(CH2)p-{POZI—POZII}a—S—R*, wherein p is an integer selected from 1-25. 12. A target molecule-POZ conjugate of the general formula: Aa-B-TMt wherein A is a POZ derivative of any one of claims 1-6 and 7-11, minus any leaving groups eliminated during the reaction of the active functional group on the POZ derivative with a binding partner on a target molecule;TM is the target molecule containing the binding partner;B is a linkage formed between the active functional group and the binding partner;a is an integer ranging from 1 up to the number of active functional groups on TM; andt is an integer ranging from 1 up to the number of active functional groups on A. 13. The target molecule-POZ conjugate of claim 12, wherein A is a POZ derivative of claim 2. 14. The target molecule-POZ conjugate of claim 12, wherein A is a POZ derivative of claim 10. 15. The target molecule-POZ conjugate of claim 12, wherein A is a POZ derivative of claim 11. 16. The target molecule-POZ conjugate of any one of claim 12, 14 or 15, wherein the target molecule is an organic small molecule, an oligonucleotide, a polypeptide, an antibody, an antibody fragment, a protein, a carbohydrate a lipid or a combination thereof. 17. The target molecule-POZ conjugate of claim 16, wherein the lipid is a phospholipid. 18. The target molecule-POZ conjugate of any one of claim 12, 14 or 15, wherein the target molecule is a targeting agent, a diagnostic agent or a therapeutic agent or a combination thereof.
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