IPC분류정보
국가/구분 |
United States(US) Patent
등록
|
국제특허분류(IPC7판) |
|
출원번호 |
US-0263328
(2010-04-07)
|
등록번호 |
US-8546564
(2013-10-01)
|
국제출원번호 |
PCT/US2010/030272
(2010-04-07)
|
§371/§102 date |
20111223
(20111223)
|
국제공개번호 |
WO2010/118155
(2010-10-14)
|
발명자
/ 주소 |
- Castro, Alfredo C.
- Grogan, Michael J.
- Snyder, Daniel A.
|
출원인 / 주소 |
- Infinity Pharmaceuticals, Inc.
|
대리인 / 주소 |
|
인용정보 |
피인용 횟수 :
0 인용 특허 :
88 |
초록
▼
Provided herein are compounds of formula (I) or pharmaceutically acceptable salts, solvates or prodrugs thereof, or mixtures thereof, wherein Z1, Z2, X1, X2, X3, R1, R2 R3, m and n are defined herein. Also provided are pharmaceutically acceptable compositions that include a compound of formula I and
Provided herein are compounds of formula (I) or pharmaceutically acceptable salts, solvates or prodrugs thereof, or mixtures thereof, wherein Z1, Z2, X1, X2, X3, R1, R2 R3, m and n are defined herein. Also provided are pharmaceutically acceptable compositions that include a compound of formula I and a pharmaceutically acceptable excipient. Also provided are methods for treating FAAH-mediated disorders comprising administering to a subject in need thereof a therapeutically effective amount of a compound or composition of the present invention.
대표청구항
▼
1. A compound of formula I: or a pharmaceutically acceptable salt, solvate or prodrug thereof, or mixture thereof,wherein: is selected from a single bond and a double bond;when is a single bond, X1 is selected from CR4R5 and NR6, and X2 is selected from CR7R8 and NR9;when is a double bond, X1 is s
1. A compound of formula I: or a pharmaceutically acceptable salt, solvate or prodrug thereof, or mixture thereof,wherein: is selected from a single bond and a double bond;when is a single bond, X1 is selected from CR4R5 and NR6, and X2 is selected from CR7R8 and NR9;when is a double bond, X1 is selected from CR4 and N, and X2 is selected from CR7 and N;X3 is NR12;provided that at least one of X1, X2 and X3 is selected from N, NR6, NR9, and N12;m is 0 or 1;Z1 is —OR13;Z2 is —OR14;n is 0;R1 and R2, taken together with the carbon to which they are bound, form a carbonyl group;R3, at each occurrence, independently is selected from halogen, C1-6 alkyl C2-6 alkenyl, C2-6 alkynyl, C1-6 perhaloalkyl, —OH, C1-6 alkoxy and —CN;R4, R5, R7, and R8 each independently is selected from H, halogen, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 perhaloalkyl, —CN, —OR16, NR17R18; —C(O)R19, C3-10 carbocyclyl, C6-10 aryl, C7-12 aralkyl, 3-10 membered heterocyclyl, and 5-10 membered heteroaryl;R6, R9, and R12 each independently is selected from C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, —C(O)R20, S(O)2R22, C3-10 carbocyclyl, C6-10 aryl, 3-10 membered heterocyclyl, 5-10 membered heteroaryl, and —(CR27R28)p—R23;R13 and R14, at each occurrence, each independently is selected from H, C1-6 alkyl, C2-6 alkenyl, and C2-6 alkynyl;R16, at each occurrence, independently is selected from H, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 carbocyclyl, C6-10 aryl, C7-12 aralkyl, 3-10 membered heterocyclyl, and 5-10 membered heteroaryl;R17 and R18, at each occurrence, each independently is selected from H, C1-6 alkyl, C7-6 alkenyl, C2-6 alkynyl, —C(O)R24, —C(O)OR25, C3-10 carbocyclyl, C6-10 aryl, C7-12 aralkyl, 3-10 membered heterocyclyl, and 5-10 membered heteroaryl;R19 and R20, at each occurrence, each independently is selected from C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 carbocyclyl, C6-10 aryl, C7-12 aralkyl, 3-10 membered heterocyclyl, and 5-10 membered heteroaryl;R22 is selected from C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 carbocyclyl, C6-10 aryl, 3-10 membered heterocyclyl, 5-10 membered heteroaryl, and —(CR29R30)q—R26;R23, at each occurrence, independently is selected from C3-10 carbocyclyl, C6-10 aryl, 3-10 membered heterocyclyl, and 5-10 membered heteroaryl;R24 and R25, at each occurrence, each independently is selected from C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 carbocyclyl, C6-10 aryl, C7-12 aralkyl, 3-10 membered heterocyclyl, and 5-10 membered heteroaryl;R26, at each occurrence, independently is selected from C3-10 carbocyclyl, C6-10 aryl, 3-10 membered heterocyclyl, and 5-10 membered heteroaryl;R27, R28, R29 and R30, at each occurrence, each independently is selected from H and C1-6 alkyl; andp, and q, at each occurrence, each independently is selected from 1, 2, 3, 4, 5 and 6. 2. The compound of claim 1, wherein m is 1 and X3 is NR12. 3. The compound of claim 2, wherein is a double bond. 4. The compound of claim 3, wherein X1 is CR4. 5. The compound of claim 4, wherein X2 is CR7. 6. The compound of claim 5, wherein R7 is selected from H, C1-6 alkyl and C7-10 aralkyl. 7. The compound of claim 4, wherein X2 is N. 8. The compound of claim 4, wherein R4 is selected from H, C1-6 alkyl and C7-10 aralkyl. 9. The compound of claim 3, wherein X1 is N. 10. The compound of claim 9, wherein X2 is CR7. 11. The compound of claim 10, wherein R7 is selected from H, C1-6 alkyl and C7-10 aralkyl. 12. The compound of claim 2, wherein is a single bond. 13. The compound of claim 12, wherein X1 is CR4R5. 14. The compound of claim 12, wherein X2 is CR7R8. 15. The compound of claim 14, wherein R7 is H and R8 is H. 16. The compound of claim 13, wherein R4 is H and R5 is H. 17. The compound of claim 2, wherein R12 is selected from C1-6 alkyl and —(CR27R28)p—R23. 18. The compound of claim 1, wherein m is 0. 19. The compound of claim 18, wherein is a single bond. 20. The compound of claim 9 wherein X2 is NR9. 21. The compound of claim 20, wherein R9 is selected from C1-6 alkyl and —(CR27R28)p—R23. 22. The compound of claim 19, wherein X1 is CR4R5. 23. The compound of claim 22, wherein R4 is H and R5 is H. 24. The compound of claim 1, wherein the compound is of the formula Ia: or a pharmaceutically acceptable salt, solvate or prodrug thereof, or mixture thereof. 25. The compound of claim 1, wherein the compound is of the formula Ib: or a pharmaceutically acceptable salt, solvate or prodrug thereof, or mixture thereof. 26. The compound of claim 1, wherein the compound is of the formula V: or a pharmaceutically acceptable salt, solvate or prodrug thereof, or mixture thereof. 27. The compound of claim 26, wherein the compound is of the formulae Va or Vb: or a pharmaceutically acceptable salt, solvate or prodrug thereof, or mixture thereof. 28. The compound of claim 1, wherein the compound is of the formula IX: or a pharmaceutically acceptable salt, solvate or prodrug thereof, or mixture thereof. 29. The compound of claim 28, wherein the compound is of the formulae IXa or IXb: or a pharmaceutically acceptable salt, solvate or prodrug thereof, or mixture thereof. 30. The compound of claim 1, wherein the compound is of the formula XI: or a pharmaceutically acceptable salt, solvate or prodrug thereof, or mixture thereof. 31. The compound of claim 30, wherein the compound is of the formulae XIa or XIb: or a pharmaceutically acceptable salt, solvate or prodrug thereof, or mixture thereof. 32. The compound of claim 1, wherein the compound is of the formula VII: or a pharmaceutically acceptable salt, solvate or prodrug thereof, or mixture thereof. 33. The compound of claim 32, wherein the compound is of the formulae VIIa or VIIb: or a pharmaceutically acceptable salt, solvate or prodrug thereof, or mixture thereof. 34. The compound of claim 1, wherein R12 is selected from C1-6 alkyl and —(CH2)p—R23. 35. The compound of claim 34, wherein R23 is phenyl. 36. The compound of claim 1, wherein the compound is of the formula XV: or a pharmaceutically acceptable salt, solvate or prodrug thereof, or mixture thereof. 37. The compound of claim 36, wherein the compound is of the formulae XVa or XVb: or a pharmaceutically acceptable salt, solvate or prodrug thereof, or mixture thereof. 38. The compound of claim 36, wherein R9 is selected from C1-6 alkyl and —(CH2)p—R23. 39. The compound of claim 38, wherein R23 is phenyl. 40. The compound of claim 1, wherein R13 is H and R14 is H. 41. The compound of claim 1, wherein the compound is selected from: or a pharmaceutically acceptable salt, solvate or prodrug thereof, or mixture thereof. 42. A pharmaceutical composition comprising a compound of claim 1 or a pharmaceutically acceptable salt, solvate or prodrug thereof, or mixture thereof, and a pharmaceutically acceptable excipient.
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