Non-peptide macrocyclic histone deacetylase (hdac) inhibitors and methods of making and using thereof 机翻标题: 暂无翻译,请尝试点击翻译按钮。

公开号/公开日
WO2009006403 A2 2009-01-08 [WO200906403]WO2009006403 A3 2010-01-07 [WO200906403] / 2009-01-082010-01-07
申请号/申请日
2008WO-US68787 / 2008-06-30
发明人
OYELERE ADEGBOYEGA;
申请人
GEORGIA TECH RESEARCH;
主分类号
IPC分类号
A01N-043/02A61K-031/335A61K-031/35
摘要
(WO200906403) Compounds of Formula (I) or (II), and methods of making and using thereof, are described herein. wherein M represents a macrolide subunit, n is a C1-6 group, optionally containing one or more heteroatoms, wherein the carbon atoms and/or heteroatoms are in a linear and/or cyclic arrangement, D is an alkyl or aryl group, A is a linking group connected to D, B is an alkyl, wherein M represents a macrolide subunit, R1, R2 and R4 are independently are selected from hydrogen, a C 1-6 alkyl group, a C2-6 alkenyl group, a C2-6 alkynyl group, a C1-6 alkanoate group, a C2-6 carbamate group, a C2-6 carbonate group, a C2-6 carbamate group, or a C2-6 thiocarbamate group, R3 is hydrogen or -OR5, R5 is selected from a group consisting of Hydrogen, a C1-6 alkyl hgroup, a C2-6 alkenyl group, a C2-6 alkynyl group, C1-6 alkanoate group, C2-6 carbamate group, C2-6 carbonate group, C2-6 carbamate group, or C2-6 thiocarbamate group.
机翻摘要
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地址
代理人
代理机构
;
优先权号
2007US-60947036 2007-06-29
主权利要求
(WO200906403) I claim: 1. A compound of Formula I or II : wherein M represents a macrolide subunit, n is a C i-6group, optionally containing one or more heteroatoms, wherein the carbon atoms and/or heteroatoms are in a linear and/or cyclic arrangement, D is an alkyl or aryl group, A is a linking group connected to D, B is an alkyl, alkylaryl or alkylheteroaryl spacer group, ZBG is a Zinc Binding Group, R], Kz and R4are independently selected from the group consisting of hydrogen, a Cl -6 alkyl group, a C2-6alkenyl group, a Oι-dalkynyi group, a C 1-6alkanoate group, a C2-6carbamate group, a C2^ carbonate group, a C2-6carbamate group, or a C2.6thiocarbamate group, R3is hydrogen or -ORs, Rs is selected from the group consisting of hydrogen, a C\.(, alkyl hgroup, a C2-6alkenyl group, a C2-6alkynyi group, a C1-e alkanoate group, a C2-6carbamate group, a C2-6carbonate group, a C2-6carbamate group, or a C2-6thiocarbamate group. 2. The compound of claim 1 , wherein the macrolide subunit is a multi- member lactonic ring structure. 3. The compound of claim 2, wherein the multi-member lactonic ring structure is selected from the group consisting of the compounds in Table 1. 4. The compound of claim 2, wherein the multi-member lactonic ring structure is selected from the group consisting of the compounds in Table 2. 5. The compound of any one of claims 1 to 4, wherein Rj-R-3 is hydrogen. 6. The compound of any one of claims 1-5, wherein n is 1, 2, or 3. 7. The compound of any one of claims 1-6, wherein D is a phenyl, biphenyl, or naphthyl group. 8. The compound of any one of claims 1 -7, wherein A is an amide or 1,2,3-triazolyl group. 9. The compound of any one of claims 1 -8, wherein B is an alkyl group having from 4-6 carbon atoms. 10. The compound of any one of claims 1 -9, wherein the zinc binding group is selected from the group consisting of hydroxamate and N-formyl hydroxylamine. 11. The compound of any one of claims 1-10 selected from the group consisting of the compounds in Table 3. 12. The compound of claim 11 , wherein the compound is azithromycin- arylalkyltriazolyl hydroxamate or clarithromycin-arylalkyltriazolyl hydroxamate. 13. The compound of claim 11 , wherein the compound is desclasmoseazithromycin-arylalkyltriazolyl hydroxamate or desclasinoseclarithromycin-ary lalkyltriazolyl hydroxamate . 14. A pharmaceutical composition comprising an effective amount of the compound of any one of claims 1-13 in combination with a pharmaceutically acceptable diluent, excipient, or carrier. 15. The composition of claim 14, wherein the composition is administered enterally, 16. The composition of claim 14, wherein the composition is administered parenterally. 17. The composition of claim 14 , wherein the composition is formulated for immediate release, modified release, and combinations thereof. 18. The composition of claim 17, wherein the formulation is selected from the group consisting of delayed release, extended release, pulsatile release, and combinations thereof. 19. A method of treating a disease or disorder in a human or animal comprising administering an effective amount of a compound of any one of claims 1-13. 20. The method of claim 19 wherein the disease or disorder to be treated is selected from the group consisting of cancer, inflammation, infections, and cognitive disorders. 21. The method of claim 20, wherein the disease or disorder to be treated is cancer, 22. The method of claim 21 , wherein the cancer is selected from the group consisting of lung cancer, myeloma, leukemia, lymphoma, breast cancer, prostate cancer, pancreatic cancer, cervical cancer, ovarian cancer, and liver cancer. 23. The method of claim 19 wherein the compound is administered enterally. 24. The method of claim 23, wherein the compound is formulated in a solid oral dosage form selected from the group consisting of tablets, capsules, dragees, and caplets. 25. The method of claim 23, wherein the compound is formulated in a liquid oral dosage form selected from the group consisting of solutions, suspensions, and syrups. 26. The method of claim 19, wherein the compound is administered parenterally.
法律状态
(WO200906403) LEGAL DETAILS FOR WO2009006403  Actual or expected expiration date=2010-12-29    Legal state=DEAD    Status=LAPSED     Event publication date=2008-06-30  Event code=WO/APP  Event indicator=Pos  Event type=Examination events  Application details  Application country=WO WOUS2008068787  Application date=2008-06-30  Standardized application number=2008WO-US68787     Event publication date=2009-01-08  Event code=WO/A2  Event type=Examination events  International application published with declaration under Article 17 (2) (a)  Publication country=WO  Publication number=WO2009006403  Publication stage Code=A2  Publication date=2009-01-08  Standardized publication number=WO200906403     Event publication date=2010-01-07  Event code=WO/A3  Event indicator=Pos  Event type=Examination events  Later publication of ISR with revised front page  Publication country=WO  Publication number=WO2009006403  Publication stage Code=A3  Publication date=2010-01-07  Standardized publication number=WO200906403     Event publication date=2010-12-29  Event code=WO/EETL  Event type=Event indicating Not In Force  PCT Application validity period expired. LEGAL DETAILS FOR DESIGNATED STATE DE  Actual or expected expiration date=2009-12-30    Legal state=DEAD    Status=LAPSED   Corresponding cc:  Designated or member state=DE     Event publication date=2009-12-30  Event code=WO/NENP  Event type=Event indicating Not In Force  Non-entry into the national phase in: Corresponding cc:  Designated or member state=DE
专利类型码
A2A3
国别省市代码
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