Inhibitors of cyclin-dependent kinase 7 (CDK7)
원문보기
IPC분류정보
국가/구분
United States(US) Patent
등록
국제특허분류(IPC7판)
C07D-239/24
C07D-239/00
C07D-403/04
A61K-031/506
A61K-045/06
A61K-031/4439
A61K-031/635
C07D-401/04
C07D-417/04
C07D-471/04
C07D-513/04
G01N-033/50
출원번호
US-0436496
(2013-10-18)
등록번호
US-10112927
(2018-10-30)
국제출원번호
PCT/US2013/065708
(2013-10-18)
국제공개번호
WO2014/063068
(2014-04-24)
발명자
/ 주소
Gray, Nathanael
Zhang, Tinghu
Kwiatkowski, Nicholas Paul
출원인 / 주소
Dana-Farber Cancer Institute, Inc.
대리인 / 주소
Wolf, Greenfield & Sacks, P.C.
인용정보
피인용 횟수 :
0인용 특허 :
65
초록▼
The present invention provides novel compounds of Formula (I), and pharmaceutically acceptable salts, solvates, hydrates, polymorphs, co-crystals, tautomers, stereoisomers, isotopically labeled derivatives, prodrugs, and compositions thereof. Also provided are methods and kits involving the inventiv
The present invention provides novel compounds of Formula (I), and pharmaceutically acceptable salts, solvates, hydrates, polymorphs, co-crystals, tautomers, stereoisomers, isotopically labeled derivatives, prodrugs, and compositions thereof. Also provided are methods and kits involving the inventive compounds or compositions for treating or preventing proliferative diseases (e.g., cancers (e.g., leukemia, lymphoma, melanoma, multiple myeloma, breast cancer, Ewing's sarcoma, osteosarcoma, brain cancer, neuroblastoma, lung cancer), benign neoplasms, angiogenesis, inflammatory diseases, autoinflammatory diseases, and autoimmune diseases) in a subject. Treatment of a subject with a proliferative disease using a compound or composition of the invention may inhibit the aberrant activity of a kinase, such as cyclin-dependent kinase (CDK) (e.g., cyclin-dependent kinase 7 (CDK7)), and therefore, induce cellular apoptosis and/or inhibit transcription in the subject.
대표청구항▼
1. A compound of Formula (I): or a pharmaceutically acceptable salt thereof; wherein: Ring A is each instance of RA1 is independently selected from the group consisting of hydrogen and alkyl;each instance of RA2 is independently selected from the group consisting of hydrogen, halogen, alkyl, aryl,
1. A compound of Formula (I): or a pharmaceutically acceptable salt thereof; wherein: Ring A is each instance of RA1 is independently selected from the group consisting of hydrogen and alkyl;each instance of RA2 is independently selected from the group consisting of hydrogen, halogen, alkyl, aryl, and heteroaryl;Ring B is of the formula: RB1 is selected from the group consisting of hydrogen and alkyl,WB is CRB2, wherein RB2 is selected from the group consisting of hydrogen, cyano, halogen, optionally substituted alkyl, carbocyclyl, and ORB2a,wherein RB2a is selected from the group consisting of hydrogen and alkyl;or RB1 and RB2 are joined to form a carbocyclyl or aryl ring;X is NRX—, wherein RX is hydrogen or C1-6 alkyl;L2 is —NRL2aC(═O)— or —NRL2aS(═O)2—, wherein RL2a is hydrogen or C1-6 alkyl;each instance of RC is independently selected from the group consisting of hydrogen, halogen, and alkyl;n is 0, 1, 2, 3, or 4;each instance of RD is independently selected from the group consisting of hydrogen, halogen, alkyl, and —N(RD1)2,wherein each occurrence of RD1 is independently selected from the group consisting of hydrogen and alkyl;p is 0, 1, 2, 3, or 4;RE is RE and L2 are para or meta to each other;L3 is —NRL3a— or an optionally substituted C1-4 hydrocarbon chain, wherein RL3a is hydrogen;RE1 is selected from the group consisting of hydrogen and alkyl;RE2 is hydrogen or alkyl;RE3 is selected from the group consisting of hydrogen, alkyl, —CH2ORE3a, and —CH2N(RE3a)2,wherein each occurrence of RE3a is independently selected from the group consisting of hydrogen, alkyl, and alkynyl; andY is O; wherein “substituted” within each of RB2 and L3, refers independently to halogen, cyano, —NO2, —OH, —ORaa, —N(Rbb)2, —SH, —SRaa,—C(═O)Raa, —CO2H, —CHO, —CO2Raa, —OC(═O)Raa, —OCO2Raa, —C(═O)N(Rbb)2, —OC(═O)N(Rbb)2, —NRbbC(═O)Raa, —NRbbCO2Raa, —NRbbC(═O)N(Rbb)2, —C(═NRbb)Raa,—C(═NRbb)N(Rbb)2,—NRbbC(═NRbb)N(Rbb)2;each of Raa is independently alkyl; andeach of Rbb is independently hydrogen or alkyl. 2. The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein Ring A is: 3. The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein Ring A is: 4. The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein Ring A is: 5. The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein RB1 is hydrogen or methyl. 6. The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein L2 is —NH—C(O)—, —N(CH3)—C(O)—, or —NH—S(O)2—. 7. The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein RE is of Formula (ii-1): wherein Y is O;L3 is —NH— or RE1 and RE2 are each hydrogen; andRE3 is selected from hydrogen, —CH2N(CH3)C≡CH, —CH2N(CH3)2, and —CH2OH. 8. The compound of claim 1, wherein the compound is of Formula (I-3): or a pharmaceutically acceptable salt thereof. 9. The compound of claim 1, wherein the compound is of Formula (I-5): or a pharmaceutically acceptable salt thereof. 10. The compound of claim 1, wherein the compound is of Formula (I-7): or a pharmaceutically acceptable salt thereof. 11. The compound of claim 1, wherein the compound is selected from the group consisting of: and pharmaceutically acceptable salts thereof. 12. A pharmaceutical composition comprising a compound of claim 1, or a pharmaceutically acceptable salt thereof, and optionally a pharmaceutically acceptable excipient. 13. The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein RB2 is selected from hydrogen, methyl, ethyl, chloro, CF3, cyclopropyl, —OCH3, cyano, and isopropyl. 14. The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein Ring A is 15. The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein L2 is —NRL2aC(═O)—. 16. The compound of claim 1, wherein the compound is of the formula: or a pharmaceutically acceptable salt thereof. 17. The compound of claim 1, wherein the compound is of the formula: or a pharmaceutically acceptable salt thereof. 18. The compound of claim 1, wherein the compound is of the formula: or a pharmaceutically acceptable salt thereof. 19. The compound of claim 1, wherein the compound is of the formula: or a pharmaceutically acceptable salt thereof. 20. The compound of claim 1, wherein the compound is of the formula: or a pharmaceutically acceptable salt thereof.
Buchanan,John L.; Chaffee,Stuart; Harmange,Jean Christophe; Novak,Perry M.; Zhu,Xiaotian, Amino-substituted pyrimidinyl derivatives and methods of use.
Hubbard Vance M. (Bedford) Brunson Welton K. (Bedford) Saied V. C. (Wichita Falls TX), Apparatus and method for raising a skin wheal and anesthetizing skin.
Hochlowski Jill E. (Green Oaks IL) Jackson Marianna (Waukegan IL) Kadam Sunil K. (Kenosha WI) Karwowski James P. (Mundelein IL) McAlpine James B. (Libertyville IL), Dorrigocin antitumor agents.
Bolton Gary L. (Ann Arbor MI) Hodges John C. (Ann Arbor MI) Wilson Michael W. (Ann Arbor MI), Histidine and homohistidine derivatives as inhibitors of protein farnesyltransferase.
Monaghan Richard L. (Somerset NJ) Alberts Alfred W. (Short Hills NJ) Hoffman Carl H. (Scotch Plains NJ) Albers-Schonberg George (Princeton NJ), Hypocholesteremic fermentation products and process of preparation.
Lilley Stephen J. (Sawston GBX) Taylor Hugh F. (Sawston GBX) Theobald David R. (Huntingdon GBX) Carlson Craig J. (Andover MA) Rosen David I. (Arlington MA) Johnson Thomas R. (Milford NH), Medical injection system and method, gas spring thereof and launching device using gas spring.
Roth Jack A. ; Fujiwara Toshiyoshi,JPX ; Grimm Elizabeth A. ; Mukhopadhyay Tapas ; Zhang Wei-Wei ; Owen-Schaub Laurie B., Methods and compositions comprising DNA damaging agents and p53.
McKinnon ; Jr. Charles N. (Laguna Niguel CA) Peterson Steven F. (West Linn OR) Smith Paul E. (Tualatin OR) Nakagawa Takaaki (Tigard OR) Bartholomew Victor L. (Tigard OR), Needleless hypodermic injection device.
Peterson Steven F. (West Linn OR) McKinnon ; Jr. Charles N. (Laguna Niguel CA) Smith Paul E. (Tualatin OR) Nakagawa Takaaki (Tigard OR) Bartholomew Victor L. (Tigard OR), Needleless hypodermic injection methods and device.
Marsters ; Jr. James C. (Oakland CA) Brown Michael S. (Dallas TX) Crowley Craig W. (Portola Valley CA) Goldstein Joseph L. (Dallas TX) James Guy L. (Dallas TX) McDowell Robert S. (San Francisco CA) O, Ras farnesyl transferase inhibitors.
Cohen, Philip; Clark, Kristopher; Choi, Hwan Geun; Gray, Nathanael, SIK inhibitor for use in a method of treating an inflammatory and/or immune disorder.
Harmange, Jean-Christophe; Buchanan, John L.; Chaffee, Stuart; Novak, Perry M.; Van Der Plas, Simon; Zhu, Xiaotian, Substituted pyrimidinyl derivatives and methods of use.
Bishop W. Robert (Pompton Plains NJ) Doll Ronald J. (Maplewood NJ) Mallams Alan K. (Long Valley NJ) Njoroge F. George (Union NJ) Petrin Joanne M. (Cedar Grove NJ) Piwinski John J. (Clinton Township N, Tricyclic sulfonamide compounds useful for inhibition of G-protein function and for treatment of proliferative diseases.
※ AI-Helper는 부적절한 답변을 할 수 있습니다.