Radiolabeled cationic steroid antimicrobials and diagnostic methods
원문보기
IPC분류정보
국가/구분
United States(US) Patent
등록
국제특허분류(IPC7판)
G01N-033/534
C07J-043/00
A61K-051/04
C07J-041/00
G01N-033/569
출원번호
US-0830356
(2015-08-19)
등록번호
US-10227376
(2019-03-12)
발명자
/ 주소
Savage, Paul B.
출원인 / 주소
BRIGHAM YOUNG UNIVERSITY
대리인 / 주소
Workman Nydegger
인용정보
피인용 횟수 :
0인용 특허 :
54
초록▼
The disclosure provides compounds, methods, and kits for diagnosis, detection, screening, and imaging of a disease condition (e.g., infection, cancer, tumor, neoplasia), in vitro, ex vivo, and/or in vivo. Certain embodiments include administering a cationic steroid antimicrobial (a “CSA” or “ceragen
The disclosure provides compounds, methods, and kits for diagnosis, detection, screening, and imaging of a disease condition (e.g., infection, cancer, tumor, neoplasia), in vitro, ex vivo, and/or in vivo. Certain embodiments include administering a cationic steroid antimicrobial (a “CSA” or “ceragenin”), the CSA including a steroidal backbone and a heterocyclic ring separated from the steroidal backbone by at least 4 atoms (and up to 24 atoms or more), to a subject having or at risk of having a disease condition in an amount effective to diagnose, detect, screen for or image the disease condition in the subject.
대표청구항▼
1. A cationic steroidal antimicrobial (CSA) compound of Formula III, or salt thereof: wherein, R3, R7, and R12 are independently selected from the group consisting of hydrogen, unsubstituted (C1-C6) alkyl, unsubstituted (C1-C6) hydroxyalkyl, unsubstituted (C1-C16) alkyloxy-(C1-C5) alkyl, unsubstitu
1. A cationic steroidal antimicrobial (CSA) compound of Formula III, or salt thereof: wherein, R3, R7, and R12 are independently selected from the group consisting of hydrogen, unsubstituted (C1-C6) alkyl, unsubstituted (C1-C6) hydroxyalkyl, unsubstituted (C1-C16) alkyloxy-(C1-C5) alkyl, unsubstituted (C1-C16) alkylcarboxy-(C1-C5) alkyl, unsubstituted (C1-C16) alkylamino-(C1-C5)alkyl, unsubstituted (C1-C16) alkylamino-(C1-C5) alkylamino, unsubstituted (C1-C16) alkylamino-(C1-C16) alkylamino-(C1-C5) alkylamino, unsubstituted (C1-C16) aminoalkyl, unsubstituted arylamino-(C1-C5) alkyl, unsubstituted (C1-C5) aminoalkyloxy, unsubstituted (C1-C16) aminoalkyloxy-(C1-C5) alkyl, unsubstituted (C1-C5) aminoalkylcarboxy, unsubstituted (C1-C5) aminoalkylaminocarbonyl, unsubstituted (C1-C5) aminoalkylcarboxamido, unsubstituted di(C1-C5 alkyl)amino-(C1-C5) alkyl, unsubstituted (C1-C5) guanidinoalkyloxy, unsubstituted (C1-C16) quaternary ammonium alkylcarboxy, and unsubstituted (C1-C16) guanidinoalkylcarboxy, wherein 0 or 1 of R3, R7, and R12 is hydrogen; andR18 is wherein, R20 is an alkyl, alkenyl, alkynyl, or aryl connected to R22 by a urea;R21 is selected from the group consisting of hydrogen, C1-C24 alkyl, C2-C24 alkenyl, C2-C24 alkynyl, C7-C13 aralkyl, C1-C6 alkyl-(5 to 10 membered heteroaryl), C3-C10 carbocyclyl, C4-C10 (carbocyclyl)alkyl, and amido; andR22 is a heterocyclic ring chelator having at least 2 heteroatoms and being attached to the urea by a linkage selected from the group consisting of alkyl, -[alkoxy]n, -[alkoxy]n-alkyl, alkylcarboxamido-alkyl, alkylcarboxamido-[alkoxy]n, alkylcarboxamido-[alkoxy]n-alkyl, alkylcarboxyalkyl, alkylaminoalkyl, aryl, arylaminoalkyl, alkenyl, and alkynyl, where n is 1 to 10,wherein each of R20, R21, and R22 may be optionally substituted, andwherein the heterocyclic ring chelator is spaced apart from the steroidal backbone by a linkage having at least 10 atoms. 2. The CSA compound of claim 1, wherein the heterocyclic ring chelator is selected from the group consisting of: 1,4,7-triazacyclononane-N,N′,N″-triacetic acid (NOTA), 1,4,7-triazacyclodecane-N,N′,N″-triacetic acid (DETA), 1,4,8-triazacycloundecane-N,N′,N″-triacetic acid (UNTA), 1,5,9-triazacyclododecane-N,N′,N″-triacetic acid (DOTRA), 9,10-benzylidene-1,4,7-triazacyclotridecane-N,N′,N″-triacetic acid (BUNTA), and 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetracetic acid (DOTA). 3. The CSA compound of claim 1, wherein the heterocyclic ring chelator is spaced apart from the steroidal backbone by a linkage having at least 12 atoms. 4. The CSA compound of claim 1, wherein the heterocyclic ring chelator is spaced apart from the steroidal backbone by a linkage having at least 16 atoms. 5. The CSA compound of claim 1, wherein the heterocyclic ring chelator is spaced apart from the steroidal backbone by a linkage having at least 20 atoms. 6. The CSA compound of claim 1, wherein the heterocyclic ring chelator is spaced apart from the steroidal backbone by a linkage having at least 24 atoms. 7. The CSA compound of claim 1, wherein the heterocyclic ring chelator is a 5 to 13 member ring. 8. The CSA compound of claim 1, wherein the heterocyclic ring chelator is an 8 to 12 member ring. 9. The CSA compound of claim 1, wherein the heterocyclic ring chelator is a 9-10 member ring. 10. The CSA compound of claim 1, wherein R3, R7, and R12 are independently selected from the group consisting of aminoalkyloxy; aminoalkylcarboxy; alkylaminoalkyl; alkoxycarbonylalkyl; alkylcarbonylalkyl; di(alkyl)aminoalkyl; alkylcarboxyalkyl; and hydroxyalkyl. 11. The CSA compound of claim 1, wherein R3, R7, and R12 are independently selected from the group consisting of aminoalkyloxy and aminoalkylcarboxy. 12. The CSA compound of claim 1, wherein R3, R7, and R12 are the same. 13. The CSA compound of claim 1, wherein R3, R7, and R12 are independently selected from the group consisting of amino-C3-alkyloxy; amino-C3-alkyl-carboxy; C8-alkylamino-C5-alkyl; C8-alkoxy-carbonyl-C4-alkyl; C8-alkyl-carbonyl-C4-alkyl; di-(C5-alkyl)amino-C5-alkyl; C13-alkylamino-C5-alkyl; C6-alkoxy-carbonyl-C4-alkyl; C6-alkyl-carboxy-C4-alkyl; and C16-alkylamino-C5-alkyl. 14. The CSA compound of claim 1, wherein the CSA compound is 15. The CSA compound of claim 1, further comprising a detectable label that is 64Cu. 16. The CSA compound of claim 1, further comprising a detectable label that is a metal crystal or metal oxide crystal. 17. The CSA compound of claim 1, further comprising a detectable label that is selected from the group consisting of: gold, silver, copper, boron, manganese, gadolinium, iron, chromium, barium, europium, erbium, praseodymium, indium, and technetium. 18. The CSA compound of claim 1, further comprising a detectable label that is a metal oxide selected from the group consisting of: Gd(III), Mn(II), Mn(III), Cr(II), Cr(III), Cu(II), Fe(III), Pr(III), Nd(III) Sm(III), Tb(III), Yb(III) Dy(III), Ho(III), Eu(II), Eu(III), or Er(III). 19. A cationic steroidal antimicrobial (CSA) compound of Formula III, or salt thereof: wherein, R3, R7, and R12 are independently selected from the group consisting of hydrogen, unsubstituted (C1-C6) alkyl, unsubstituted (C1-C6) hydroxyalkyl, unsubstituted (C1-C16) alkyloxy-(C1-C5) alkyl, unsubstituted (C1-C16) alkylcarboxy-(C1-C5) alkyl, unsubstituted (C1-C16) alkylamino-(C1-C5)alkyl, unsubstituted (C1-C16) alkylamino-(C1-C5) alkylamino, unsubstituted (C1-C16) alkylamino-(C1-C16) alkylamino-(C1-C5) alkylamino, unsubstituted (C1-C16) aminoalkyl, unsubstituted arylamino-(C1-C5) alkyl, unsubstituted (C1-C5) aminoalkyloxy, unsubstituted (C1-C16) aminoalkyloxy-(C1-C5) alkyl, unsubstituted (C1-C5) aminoalkylcarboxy, unsubstituted (C1-C5) aminoalkylaminocarbonyl, unsubstituted (C1-C5) aminoalkylcarboxamido, unsubstituted di(C1-C5 alkyl)amino-(C1-C5) alkyl, unsubstituted (C1-C5) guanidinoalkyloxy, unsubstituted (C1-C16) quaternary ammonium alkylcarboxy, and unsubstituted (C1-C16) guanidinoalkylcarboxy, wherein 0 or 1 of R3, R7, and R12 is hydrogen; andR18 has the following structure: wherein, R20 is an alkyl, alkenyl, alkynyl, or aryl connected to R22 by a urea;R21 is selected from the group consisting of hydrogen, C1-C24 alkyl, C2-C24 alkenyl, C2-C24 alkynyl, C7-C13 aralkyl, C1-C6 alkyl-(5 to 10 membered heteroaryl), C3-C10 carbocyclyl, C4-C10 (carbocyclyl)alkyl, and amido; andR22 is a 5 to 13 member, 8 to 12 member, or 9 to 10 member heterocyclic ring attached to the urea by a linkage selected from the group consisting of alkyl, -[alkoxy]n, -[alkoxy]n-alkyl, alkylcarboxamido-alkyl, alkylcarboxamido-[alkoxy]n, alkylcarboxamido-[alkoxy]n-alkyl, alkylcarboxyalkyl, alkylaminoalkyl, aryl, arylaminoalkyl, alkenyl, and alkynyl, where n is 1 to 10,wherein the heterocyclic ring is selected from triazamacrocyclic ring and tetraazamacrocyclic ring,wherein each of R20, R21, and R22 may be optionally substituted, andwherein the heterocyclic ring is spaced apart from the steroidal backbone by a linkage having at least 14 atoms,the CSA compound further comprising a detectable label, the detectable label comprising a metal or metal compound bound or complexed to the heterocyclic ring. 20. A cationic steroidal antimicrobial (CSA) compound selected from the group consisting of: 21. The CSA compound of claim 1, wherein the heterocyclic ring chelator is spaced apart from the urea by 1 to 6 ether moieties. 22. The CSA compound of claim 1, wherein the heterocyclic ring chelator is spaced apart from the urea by 3 ether moieties. 23. The CSA compound of claim 1, wherein the heterocyclic ring chelator is spaced apart from the urea by 4 ether moieties. 24. The CSA compound of claim 19, wherein the heterocyclic ring is spaced apart from the urea by 1 to 6 ether moieties. 25. The CSA compound of claim 19, wherein the heterocyclic ring is spaced apart from the urea by 3 ether moieties. 26. The CSA compound of claim 19, wherein the heterocyclic ring is spaced apart from the urea by 4 ether moieties.
연구과제 타임라인
LOADING...
LOADING...
LOADING...
LOADING...
LOADING...
이 특허에 인용된 특허 (54)
Hansen Richard E. (Roswell GA) Rippl Carl G. (Woodstock GA) Midkiff David G. (Alpharetta GA) Neuwirth Joseph G. (Cumming GA), Antimicrobial absorbent food pad.
Darouiche Rabih O. (Houston TX) Raad Issam (Houston TX), Antimicrobial impregnated catheters and other medical implants and method for impregnating catheters and other medical i.
De Haen, Christoph; Beltrami, Andrea; Cappelletti, Enrico; Lattuada, Luciano; Virtuani, Mario, Bile acids conjugates with metal ion chelates and the use thereof.
Hibbs, Michael; Altman, Susan J.; Jones, Howland D. T.; Savage, Paul B., Biofouling-resistant ceragenin-modified materials and structures for water treatment.
Dunn Michael J. ; Bergren Michael S. ; Hardee Gregory E. ; Shephard Kenneth Paul ; Chao Robert S. ; Havens Jeffrey L., Crystalline ceftiofur free acid.
Laurencin Cato T. (Somerville MA) Lucas Paul A. (Macon GA) Syftestad Glenn T. (Sacramento CA) Domb Abraham (Baltimore MD) Glowacki Julianne (Jamaica Plan MA) Langer Robert S. (Newton MA), Delivery system for controlled release of bioactive factors.
Di Domenico Edward D. (Anoka MN) Hobot Christopher M. (Tonka Bay MN) Stokes Kenneth B. (Minneapolis MN) Coury Arthur J. (St. Paul MN) Doan Phong D. (Shoreview MN) Sandstrom Richard D. (Scandia MN), Medical electrical lead with polymeric monolithic controlled release device and method of manufacture.
Eisen Drore (6720 E. Beechlands Dr. Cincinnati OH 65237), Method of treatment using mouthwashes containing steroids and antifungal agents and compositions of matter.
Garlich Joseph R. (Lake Jackson TX) Masterson Tipton T. (Lake Jackson TX) Simon Jaime (Angleton TX) Hegde Vidyadhar B. (Indianapolis IN), Oral compositions for suppressing mouth odors.
※ AI-Helper는 부적절한 답변을 할 수 있습니다.