IPC분류정보
국가/구분 |
United States(US) Patent
등록
|
국제특허분류(IPC7판) |
|
출원번호 |
US-0000010
(2009-06-16)
|
등록번호 |
US-9943614
(2018-04-17)
|
국제출원번호 |
PCT/US2009/047485
(2009-06-16)
|
§371/§102 date |
20101217
(20101217)
|
국제공개번호 |
WO2010/036427
(2010-04-01)
|
발명자
/ 주소 |
|
출원인 / 주소 |
|
대리인 / 주소 |
|
인용정보 |
피인용 횟수 :
0 인용 특허 :
41 |
초록
▼
The invention relates to diagnostic, detection, screening and imaging methods. In various embodiments, methods of diagnosis, detection, screening and imaging include administering a cationic steroid antimicrobial or CSA to a subject having or at risk of having an infection or a hyperproliferative di
The invention relates to diagnostic, detection, screening and imaging methods. In various embodiments, methods of diagnosis, detection, screening and imaging include administering a cationic steroid antimicrobial or CSA to a subject having or at risk of having an infection or a hyperproliferative disorder (e.g., a tumor, cancer or neoplasia) in an amount effective to diagnose or detect the infection or the hyperproliferative disorder (e.g., a tumor, cancer or neoplasia) in the subject. In a particular aspect, a detectable CSA, namely CSA-13 labeled with 99mTc is used to detect the presence of an infection.
대표청구항
▼
1. A method of detecting a tumor, cancer or neoplasia, or diagnosing a subject having or at risk of having a tumor, cancer or neoplasia, comprising: administering a detectably labeled cationic steroid antimicrobial (CSA) of formula V, or a pharmaceutically acceptable salt thereof, to the subject und
1. A method of detecting a tumor, cancer or neoplasia, or diagnosing a subject having or at risk of having a tumor, cancer or neoplasia, comprising: administering a detectably labeled cationic steroid antimicrobial (CSA) of formula V, or a pharmaceutically acceptable salt thereof, to the subject under conditions whereby the labeled CSA binds to cell membranes in cells of a tumor, cancer or neoplasia: where: each of fused rings A, B, C, and D is independently saturated, or is fully or partially unsaturated, provided that at least two of A, B, C, and D are saturated, wherein rings A, B, C, and D form a ring system;each of m, n, p, and q is independently 0 or 1; andeach of R1 through R4, R6, R7, R11, R12, R15, R16, R17, and R18 is independently selected from the group consisting of hydrogen, hydroxyl, substituted or unsubstituted (C1-C10) alkyl, (C1-C10) hydroxyalkyl, (C1-C10) alkyloxy-(C1-C10) alkyl, (C1-C10) alkylcarboxy-(C1-C10) alkyl, (C1-C10) alkylamino-(C1-C10) alkyl, (C1-C10) alkylamino-(C1-C10) alkylamino, (C1-C10) alkylamino-(C1-C10) alkylamino-(C1-C10) alkylamino, substituted or unsubstituted (C1-C10) aminoalkyl, substituted or unsubstituted aryl, substituted or unsubstituted arylamino-(C1-C10) alkyl, (C1-C10) haloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, oxo, linking group attached to a second steroid, substituted or unsubstituted (C1-C10) aminoalkyloxy, substituted or unsubstituted (C1-C10) aminoalkyloxy-(C1-C10) alkyl, substituted or unsubstituted (C1-C10) aminoalkylcarboxy, substituted or unsubstituted (C1-C10) aminoalkylaminocarbonyl, substituted or unsubstituted (C1-C10) aminoalkylcarboxamido, H2N—HC(Q5)-C(O)—O—, H2N—HC(Q5)-C(O)—N(H)—, (C1-C10) azidoalkyloxy, (C1-C10) cyanoalkyloxy, P.G.—HN—HC(Q5)-C(O)—O—, (C1-C10) guanidinoalkyl oxy, (C1-C10) quaternary ammonium alkylcarboxy, and (C1-C10) guanidinoalkyl carboxy, where Q5 is a side chain of an amino acid, and P.G. is an amino protecting group, andeach of R5, R8, R9, R10, R13, and R14 is independently: deleted when one of fused rings A, B, C, or D is unsaturated so as to complete the valency of the carbon atom at that site, or selected from the group consisting of hydrogen, hydroxyl, substituted or unsubstituted (C1-C10) alkyl, (C1-C10) hydroxyalkyl, (C1-C10) alkyloxy-(C1-C10) alkyl, substituted or unsubstituted (C1-C10) aminoalkyl, substituted or unsubstituted aryl, C1-C10) haloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, oxo, linking group attached to a second steroid, substituted or unsubstituted (C1-C10) aminoalkyloxy, substituted or unsubstituted (C1-C10) aminoalkylcarboxy, substituted or unsubstituted (C1-C10) aminoalkylaminocarbonyl, H2N—HC(Q5)-C(O)—O—, H2N—HC(Q5)-C(O)—N(H)—, (C1-C10) azidoalkyloxy, (C1-C10) cyanoalkyloxy, P.G.—HN—HC(Q5)-C(O)—O—, (C1-C10) guanidinoalkyloxy, and (C1-C10) guanidinoalkylcarboxy, where Q5 is a side chain of any amino acid, P.G. is an amino protecting group,provided that at least three of R6, R7, R11, R12, R15, R16, R17, and R18 are disposed on the same face of the ring system and are independently selected from the group consisting of substituted or unsubstituted (C1-C10) aminoalkyloxy, (C1-C10) alkylcarboxy-(C1-C10) alkyl, (C1-C10) alkylamino-(C1-C10) alkylamino, (C1-C10) alkylamino-(C1-C10) alkylamino-(C1-C10) alkylamino, substituted or unsubstituted (C1-C10) aminoalkylcarboxy, substituted or unsubstituted arylamino-(C1-C10) alkyl, substituted or unsubstituted (C1-C10) aminoalkyloxy-(C1-C10) alkyl, substituted or unsubstituted (C1-C10) aminoalkylaminocarbonyl, (C1-C10) quaternary ammonium alkylcarboxy, H2NHC(Q5)-C(O)—O—, H2N—HC(Q5)-C(O)—N(H)—, (C1-C10) azidoalkyloxy, (C1-C10) cyanoalkyloxy, P.G.—HN—HC(Q5)-C(O)—O—, (C1-C10) guanidinoalkyloxy, and (C1-C10) guanidinoalkylcarboxy, andwherein the detectably labeled CSA includes at least one radioisotope label selected from the group consisting of (i) a radioisotope of carbon, hydrogen, nitrogen, oxygen, or sulfur included in the structure of the CSA and (ii) a radioisotope of a metal or metal oxide covalently linked or conjugated to a basic site of the CSA selected from oxygen, sulfur, or nitrogen; anddetecting the presence, absence, or distribution of the detectably labeled CSA in a whole body, a particular region, a general area, a specific organ, a specific tissue, or a local portion of a region, organ, or tissue of the subject to ascertain the presence or absence of, a tumor, cancer or neoplasia, thereby detecting the tumor, cancer or neoplasia, or diagnosing the subject as having or not having a tumor, cancer or neoplasia. 2. A method of imaging a tumor, cancer or neoplasia in a subject having or at risk of having a tumor, cancer or neoplasia, comprising: administering a detectably labeled cationic steroid antimicrobial (CSA) of formula V, or a pharmaceutically acceptable salt thereof, to the subject under conditions whereby the labeled CSA binds to cell membranes in cells of a tumor, cancer or neoplasia: where: each of fused rings A, B, C, and D is independently saturated, or is fully or partially unsaturated, provided that at least two of A, B, C, and D are saturated, wherein rings A, B, C, and D form a ring system;each of m, n, p, and q is independently 0 or 1; andeach of R1 through R4, R6, R7, R11, R12, R15, R16, R17, and R18 is independently selected from the group consisting of hydrogen, hydroxyl, substituted or unsubstituted (C1-C10) alkyl, (C1-C10) hydroxyalkyl, (C1-C10) alkyloxy-(C1-C10) alkyl, (C1-C10) alkylcarboxy-(C1-C10) alkyl, (C1-C10) alkylamino-(C1-C10) alkyl, (C1-C10) alkylamino-(C1-C10) alkylamino, (C1-C10) alkylamino-(C1-C10) alkylamino-(C1-C10) alkylamino, substituted or unsubstituted (C1-C10) aminoalkyl, substituted or unsubstituted aryl, substituted or unsubstituted arylamino-(C1-C10) alkyl, (C1-C10) haloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, oxo, linking group attached to a second steroid, substituted or unsubstituted (C1-C10) aminoalkyloxy, substituted or unsubstituted (C1-C10) aminoalkyloxy-(C1-C10) alkyl, substituted or unsubstituted (C1-C10) aminoalkylcarboxy, substituted or unsubstituted (C1-C10) aminoalkylaminocarbonyl, substituted or unsubstituted (C1-C10) aminoalkylcarboxamido, H2N—HC(Q5)-C(O)—O—, H2N—HC(Q5)-C(O)—N(H)—, (C1-C10) azidoalkyloxy, (C1-C10) cyanoalkyloxy, P.G.—HN—HC(Q5)-C(O)—O—, (C1-C10) guanidinoalkyl oxy, (C1-C10) quaternary ammonium alkylcarboxy, and (C1-C10) guanidinoalkyl carboxy, where Q5 is a side chain of an amino acid, and P.G. is an amino protecting group, andeach of R5, R8, R9, R10, R13, and R14 is independently: deleted when one of fused rings A, B, C, or D is unsaturated so as to complete the valency of the carbon atom at that site, or selected from the group consisting of hydrogen, hydroxyl, substituted or unsubstituted (C1-C10) alkyl, (C1-C10) hydroxyalkyl, (C1-C10) alkyloxy-(C1-C10) alkyl, substituted or unsubstituted (C1-C10) aminoalkyl, substituted or unsubstituted aryl, C1-C10 haloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, oxo, linking group attached to a second steroid, substituted or unsubstituted (C1-C10) aminoalkyloxy, substituted or unsubstituted (C1-C10) aminoalkylcarboxy, substituted or unsubstituted (C1-C10) aminoalkylaminocarbonyl, H2N—HC(Q5)-C(O)—O—, H2N—HC(Q5)-C(O)—N(H)—, (C1-C10) azidoalkyloxy, (C1-C10) cyanoalkyloxy, P.G.—HN—HC(Q5)-C(O)—O—, (C1-C10) guanidinoalkyloxy, and (C1-C10) guanidinoalkylcarboxy, where Q5 is a side chain of any amino acid, P.G. is an amino protecting group,provided that at least three of R6, R7, R11, R12, R15, R16, R17, and R18 are disposed on the same face of the ring system and are independently selected from the group consisting of substituted or unsubstituted (C1-C10) aminoalkyloxy, (C1-C10) alkylcarboxy-(C1-C10) alkyl, (C1-C10) alkylamino-(C1-C10) alkylamino, (C1-C10) alkylamino-(C1-C10) alkylamino-(C1-C10) alkylamino, substituted or unsubstituted (C1-C10) aminoalkylcarboxy, substituted or unsubstituted aryl amino-(C1-C10) alkyl, substituted or unsubstituted (C1-C10) aminoalkyloxy-(C1-C10) alkyl, substituted or unsubstituted (C1-C10) aminoalkylaminocarbonyl, (C1-C10) quaternary ammonium alkylcarboxy, H2NHC(Q5)-C(O)—O—, H2N—HC(Q5)-C(O)—N(H)—, (C1-C10) azidoalkyloxy, (C1-C10) cyanoalkyloxy, P.G.—HN—HC(Q5)-C(O)—O—, (C1-C10) guanidinoalkyloxy, and (C1-C10) guanidinoalkylcarboxy, andwherein the detectably labeled CSA includes at least one radioisotope label selected from the group consisting of (i) a radioisotope of carbon, hydrogen, nitrogen, oxygen, or sulfur included in the structure of the CSA and (ii) a radioisotope of a metal or metal oxide covalently linked or conjugated to a basic site of the CSA selected from oxygen, sulfur, or nitrogen; andimaging a whole body, a particular region, a general area, a specific organ, a specific tissue, or a local portion of a region, organ, or tissue of the subject to determine the presence, absence or distribution of the labeled CSA in the subject to ascertain the presence or absence of a tumor, cancer or neoplasia. 3. The method of claim 1 or 2, wherein the labeled CSA contains a plurality of cationic amine groups and the at least one radioisotope label is associated with one or more of the amine groups, and wherein the at least one radioisotope label is of one or more radioisotopes of: C, N, O, H, S, Cu, Fe, Ga, Ti, Sr, Y, Tc, In, Pm, Gd, Sm, Ho, Lu, Re, At, Bi or Ac. 4. The method of claim 1, wherein the radioisotope of a metal or metal oxide comprises a crystal. 5. The method of claim 1, wherein the radioisotope of a metal or metal oxide includes one or more of: gold, silver, copper, boron, manganese, gadolinium, iron, chromium, barium, europium, erbium, praseodynium, indium, or technetium. 6. The method of claim 1, wherein the radioisotope of a metal oxide comprises one or more 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). 7. The method of claim 1 or 2, wherein the method detects the presence or absence, type, kind, location, extent, severity, or progression of the tumor, cancer or neoplasia. 8. The method of claim 1 or 2, wherein the detecting or imaging is performed using positron-emission tomography (PET), gamma-scintigraphy, computed tomography (CT), Computed Axial Tomography (CAT), or single photon emission tomography (SPECT). 9. The method of claim 1 or 2, wherein R18 includes a substituted or unsubstituted (C1-C10) aminoalkyl and the following group bonded thereto: 10. The method of claim 9, wherein the CSA is CSA-110: 11. A method of detecting a tumor, cancer or neoplasia, or diagnosing a subject having or at risk of having a tumor, cancer or neoplasia, comprising: administering a detectably labeled cationic steroid antimicrobial (CSA) of Formula (I), or a pharmaceutically acceptable salt thereof, to the subject under conditions whereby the labeled CSA binds to cell membranes in cells of a tumor, cancer or neoplasia: wherein:fused rings A, B, C, and D are independently saturated or fully or partially unsaturated;each of R1 through R4, R6, R7, R11, R12, R15, R16, and R17 is independently selected from the group consisting of hydrogen, hydroxyl, a substituted or unsubstituted (C1-C10) alkyl, (C1-C10) hydroxyalkyl, (C1-C10) alkyloxy-(C1-C10) alkyl, (C1-C10) alkylcarboxy-(C1-C10) alkyl, (C1-C10) alkylamino-(C1-C10) alkyl, (C1-C10) alkylamino-(C1-C10) alkylamino, (C1-C10) alkylamino-(C1-C10) alkylamino-(C1-C10) alkylamino, a substituted or unsubstituted (C1-C10) aminoalkyl, a substituted or unsubstituted aryl, a substituted or unsubstituted arylamino-(C1-C10) alkyl, (C1-C10) haloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, oxo, a linking group attached to a second steroid, a substituted or unsubstituted (C1-C10) aminoalkyloxy, a substituted or unsubstituted (C1-C10) aminoalkyloxy-(C1-C10) alkyl, a substituted or unsubstituted (C1-C10) aminoalkylcarboxy, a substituted or unsubstituted (C1-C10) aminoalkylaminocarbonyl, a substituted or unsubstituted (C1-C10) aminoalkylcarboxamido, H2N—HC(Q5)-C(O)—O—, H2N—HC(Q5)-C(O)—N(H)—, (C1-C10) azidoalkyloxy, (C1-C10) cyanoalkyloxy, P.G. —HN—HC(Q5)-C(O)—O—, (C1-C10) guanidinoalkyl oxy, (C1-C10) quaternary ammonium alkylcarboxy, and (C1-C10) guanidinoalkyl carboxy, where Q5 is a side chain of an amino acid, P.G. is an amino protecting group, andR5, R8, R9, R10, R13, and R14 is each independently deleted when one of fused rings A, B, C, or D is unsaturated so as to complete the valency of the carbon atom at that site, or selected from the group consisting of hydrogen, hydroxyl, a substituted or unsubstituted (C1-C10) alkyl, (C1-C10) hydroxyalkyl, (C1-C10) alkyloxy-(C1-C10) alkyl, a substituted or unsubstituted (C1-C10) aminoalkyl, a substituted or unsubstituted aryl, C1-C10 haloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, oxo, a linking group attached to a second steroid, a substituted or unsubstituted (C1-C10) aminoalkyloxy, a substituted or unsubstituted (C1-C10) aminoalkylcarboxy, a substituted or unsubstituted (C1-C10) aminoalkylaminocarbonyl, H2N—HC(Q5)-C(O)—O—, H2N—HC(Q5)-C(O)—N(H)—, (C1-C10) azidoalkyloxy, (C1-C10) cyanoalkyloxy, P.G.—HN—HC(Q5)-C(O)—O—, (C1-C10) guanidinoalkyloxy, and (C1-C10) guanidinoalkyl carboxy, where Q5 is a side chain of an amino acid, P.G. is an amino protecting group,provided that at least two of R1 through R4, R6, R7, R11, R12, R15, R16, and R17 are independently selected from the group consisting of a substituted or unsubstituted (C1-C10) aminoalkyloxy, (C1-C10) alkylcarboxy-(C1-C10) alkyl, (C1-C10) alkylamino-(C1-C10) alkylamino, (C1-C10) alkylamino-(C1-C10) alkylamino-(C1-C10) alkylamino, a substituted or unsubstituted (C1-C10) aminoalkylcarboxy, a substituted or unsubstituted arylamino-(C1-C10) alkyl, a substituted or unsubstituted (C1-C10) aminoalkyloxy-(C1-C10) alkyl, a substituted or unsubstituted (C1-C10) aminoalkylaminocarbonyl, (C1-C10) quaternary ammonium alkylcarboxy, H2N—HC(Q5)-C(O)—O—, H2N—HC(Q5)-C(O)—N(H)—, (C1-C10) azidoalkyloxy, (C1-C10) cyanoalkyloxy, P.G. —HN—HC(Q5)-C(O)—O—, (C1-C10) guanidinoalkyloxy, and (C1-C10) guanidinoalkylcarboxy, andprovided that R17 includes a substituted or unsubstituted (C1-C10) aminoalkyl and the following group bonded thereto: and wherein the detectably labeled CSA includes at least one radioisotope label selected from the group consisting of (i) a radioisotope of carbon, hydrogen, nitrogen, oxygen, or sulfur included in the structure of the CSA and (ii) a radioisotope of a metal or metal oxide covalently linked or conjugated to a basic site of the CSA selected from oxygen, sulfur, or nitrogen; anddetecting the presence, absence, or distribution of the detectably labeled CSA in a whole body, a particular region, a general area, a specific organ, a specific tissue, or a local portion of a region, organ, or tissue of the subject to ascertain the presence or absence of a tumor, cancer or neoplasia, thereby detecting the tumor, cancer or neoplasia, or diagnosing the subject as having or not having a tumor, cancer or neoplasia. 12. The method of claim 11, wherein R17 includes an amide group at the C24 position. 13. The method of claim 11, wherein the CSA is CSA-110:
※ AI-Helper는 부적절한 답변을 할 수 있습니다.