JPWO2019212990A5 - - Google Patents

Download PDF

Info

Publication number
JPWO2019212990A5
JPWO2019212990A5 JP2020561074A JP2020561074A JPWO2019212990A5 JP WO2019212990 A5 JPWO2019212990 A5 JP WO2019212990A5 JP 2020561074 A JP2020561074 A JP 2020561074A JP 2020561074 A JP2020561074 A JP 2020561074A JP WO2019212990 A5 JPWO2019212990 A5 JP WO2019212990A5
Authority
JP
Japan
Prior art keywords
cancer
tautomer
stereoisomer
pharmaceutically acceptable
acceptable salt
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Granted
Application number
JP2020561074A
Other languages
Japanese (ja)
Other versions
JP2021523112A (en
JP7358387B2 (en
Publication date
Application filed filed Critical
Priority claimed from PCT/US2019/029737 external-priority patent/WO2019212990A1/en
Publication of JP2021523112A publication Critical patent/JP2021523112A/en
Publication of JPWO2019212990A5 publication Critical patent/JPWO2019212990A5/ja
Priority to JP2023164097A priority Critical patent/JP2023182654A/en
Application granted granted Critical
Publication of JP7358387B2 publication Critical patent/JP7358387B2/en
Active legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Claims (37)

式Ｉｃの化合物：
Figure 2019212990000001
 （式中：
Ｒ３２は、－Ｈ、＝Ｏ、－ＯＲ３、－Ｎ３または－Ｏ－Ｃ（＝Ｚ１）－Ｒ３２ａであり；
Ｒ２８は、－Ｈ、（Ｃ１～Ｃ６）アルキルまたは－Ｃ（＝Ｚ１）－Ｒ２８ａであり；
Ｒ４０は、－Ｈまたは－Ｃ（＝Ｚ１）－Ｒ４０ａであり；
ここで、Ｒ２８およびＲ４０がＨである場合、Ｒ３２は、＝Ｏではなく；
ここで、該化合物は、以下の構成:ａ）Ｒ32は、－Ｏ－Ｃ（＝Ｚ1）－Ｒ32aであり；ｂ） Ｒ28は、－Ｃ（＝Ｚ1）－Ｒ28aであり；ｃ）Ｒ40は、－Ｃ（＝Ｚ1）－Ｒ40aである、の１、２または３つを有し：
各Ｚ１は、独立して、ＯまたはＳであり；
Ｒ２８ａ、Ｒ３２ａおよびＲ４０ａは、独立して、－Ａ１－Ｌ１－Ａ２－Ｂ；－Ａ１－Ａ２－ Ｂ；－Ｌ２－Ａ１－Ｌ１－Ａ２－Ｌ３－Ｂであり；
Ａ１およびＡ２は、独立して、存在せず、または、独立して、
Figure 2019212990000002
 から選択され；
ここで、描かれているＡ１の左側の結合は、－Ｃ（＝Ｚ１）－またはＬ２に結合し；ここで、描かれているＡ２部分の右側の結合は、ＢまたはＬ３に結合し；
各Ｑは、独立して、アリーレン、シクロアルキレン、ヘテロアリーレンおよびヘテロシクリレンから選択される１から３個の環であり；
各Ｘは、独立して、存在せず、またはアリーレン、シクロアルキレン、ヘテロアリーレンおよびヘテロシクリレンから選択される１から２個の環であり；
各Ｘ１は、独立して、ヘテロアリーレンまたはヘテロシクリレン環であり；
各Ｗは、独立して、存在せず、またはアリーレン、シクロアルキレン、ヘテロアリーレンおよびヘテロシクリレンから選択される１から２個の環であり；
各Ｗ１は、独立して、ヘテロアリーレンまたはヘテロシクリレン環であり；
各Ｇは、独立して、存在せず、またはアリーレン、シクロアルキレン、ヘテロアリーレンおよびヘテロシクリレンから選択される環であり；
各Ｇ１およびＧ２は、独立して、ヘテロアリーレンまたはヘテロシクリレン環であり；
各Ｌ１は、独立して、
Figure 2019212990000003
 から選択され；
Ｌ２およびＬ３は、独立して、存在せず、または、独立して、
Figure 2019212990000004
 から選択され；
各Ｂは、独立して、
Figure 2019212990000005
 から選択され；
各Ｂ１は、独立して、
Figure 2019212990000006
 から選択され、ここで、描かれているＢ１の左側の
Figure 2019212990000007
 結合は、Ａ２、Ｌ３またはＬ１に結合し；ここで、該ヘテロアリーレン、ヘテロシクリレンおよびアリーレンは、それぞれ独立して、場合により、アルキル、ヒドロキシアルキル、ハロアルキル、アルコキシ、ハロゲンまたはヒドロキシルで置換されており；
各Ｒ３は、独立して、Ｈまたは（Ｃ１～Ｃ６）アルキルであり；
各Ｒ４は、独立して、Ｈ、（Ｃ１～Ｃ６）アルキル、ハロゲン、５～１２員ヘテロアリール、５～１２員ヘテロシクリル、（Ｃ６～Ｃ１０）アリールであり、ここで、該ヘテロアリール、ヘテロシクリルおよびアリールは、場合により、－Ｎ（Ｒ３）２、－ＯＲ３、ハロゲン、（Ｃ１～Ｃ６）アルキル、－（Ｃ１～Ｃ６）アルキレン－ヘテロアリール、－（Ｃ１～Ｃ６）アルキレン－ＣＮ、－Ｃ（Ｏ）ＮＲ３－ヘテロアリールまたは－Ｃ（Ｏ）ＮＲ３－ヘテロシクリルで置換されており；
各Ｒ５は、独立して、Ｈ、（Ｃ１～Ｃ６）アルキル、－Ｃ（Ｏ）ＯＲ３または－Ｎ（Ｒ３）２であり、ここで、（Ｃ１～Ｃ６）アルキルのアルキルは、場合により、－Ｎ（Ｒ３
）２または－ＯＲ３で置換されており；
各Ｒ６は、独立して、Ｈ、（Ｃ１～Ｃ６）アルキル、－Ｃ（Ｏ）ＯＲ３または－Ｎ（Ｒ３）２であり、ここで、（Ｃ１～Ｃ６）アルキルのアルキルは、場合により、－Ｎ（Ｒ３）２または－ＯＲ３で置換されており；
各Ｒ７は、独立して、Ｈ、（Ｃ１～Ｃ６）アルキル、－Ｃ（Ｏ）ＯＲ３または－Ｎ（Ｒ３）２であり、ここで、（Ｃ１～Ｃ６）アルキルのアルキルは、場合により、－Ｎ（Ｒ３）２または－ＯＲ３で置換されており；
各Ｒ８は、独立して、Ｈ、（Ｃ１～Ｃ６）アルキル、－Ｃ（Ｏ）ＯＲ３または－Ｎ（Ｒ３）２であり、ここで、（Ｃ１～Ｃ６）アルキルのアルキルは、場合により、－Ｎ（Ｒ３）２または－ＯＲ３で置換されており；
各Ｙは、独立して、Ｃ（Ｒ３）２または結合であり；
各ｎは、独立して、１から１２の整数であり；
各ｏは、独立して、０から３０の整数であり；
各ｐは、独立して、０から１２の整数であり；
各ｑは、独立して、０から３０の整数であり；
各ｒは、独立して、１から６の整数である）、またはその薬学的に許容される塩、互変異性体、立体異性体、もしくはオキセパン異性体。 Compound of formula Ic:
Figure 2019212990000001
 (During the ceremony:
R 32 is -H, = O, -OR 3 , -N 3 or -OC (= Z 1 ) -R 32a ;
R 28 is -H, (C 1 to C 6 ) alkyl or -C (= Z 1 ) -R 28a ;
R 40 is -H or -C (= Z 1 ) -R 40a ;
Here, if R 28 and R 40 are H, then R 32 is not = O;
Here, the compound has the following composition: a) R 32 is -OC (= Z 1 ) -R 32a ; b) R 28 is -C (= Z 1 ) -R 28a . C) R 40 has one, two or three of -C (= Z 1 ) -R 40a :
Each Z 1 is independently O or S;
R 28a , R 32a and R 40a independently have -A 1 -L 1 -A 2 -B; -A 1 -A 2 -B; -L 2 -A 1 -L 1 -A 2 -L 3 -B;
A 1 and A 2 are independent, non-existent, or independent,
Figure 2019212990000002
Selected from;
Here, the bond on the left side of A 1 drawn is bound to -C (= Z 1 )-or L 2 ; where the bond on the right side of the portion A 2 drawn is B or L 3 Combined with;
Each Q is independently one to three rings selected from arylene, cycloalkylene, heteroarylene and heterocyclylene;
Each X is one or two rings independently, non-existent, or selected from arylene, cycloalkylene, heteroarylene and heterocyclylene;
Each X 1 is independently a heteroarylene or heterocyclylene ring;
Each W is one or two rings independently, non-existent, or selected from arylene, cycloalkylene, heteroarylene and heterocyclylene;
Each W1 is independently a heteroarylene or heterocyclylene ring;
Each G is a ring that does not exist independently or is selected from arylene, cycloalkylene, heteroarylene and heterocyclylene;
Each G 1 and G 2 is independently a heteroarylene or heterocyclylene ring;
Each L 1 is independent
Figure 2019212990000003
 Selected from;
L 2 and L 3 are independent, non-existent, or independent,
Figure 2019212990000004
 Selected from;
Each B is independent,
Figure 2019212990000005
 Selected from;
Each B 1 is independent
Figure 2019212990000006
 Selected from, here on the left side of B 1 drawn
Figure 2019212990000007
 The bond is attached to A 2 , L 3 or L 1 ; where the heteroarylene, heterocyclylene and arylene are independent and optionally alkyl, hydroxyalkyl, haloalkyl, alkoxy, halogen or hydroxyl. Has been replaced;
Each R 3 is independently H or ( C 1-6 ) alkyl;
Each R 4 is independently H, (C 1 to C 6 ) alkyl, halogen, 5 to 12-membered heteroaryl, 5 to 12-membered heterocyclyl, (C 6 to C 10 ) aryl, wherein said. Heteroaryl, heterocyclyl and aryl may optionally be -N (R 3 ) 2 , -OR 3 , halogen, (C 1 to C 6 ) alkyl,-(C 1 to C 6 ) alkylene-heteroaryl,-(C). 1 -C 6 ) Substituted with alkylene-CN, -C (O) NR 3 -heteroaryl or -C (O) NR 3 -heterocyclyl;
Each R 5 is independently H, (C 1 to C 6 ) alkyl, -C (O) OR 3 or -N (R 3 ) 2 , where (C 1 to C 6 ) alkyl. Alkyl may be -N (R 3 ), as the case may be.
) Replaced by 2 or -OR 3 ;
Each R 6 is independently H, (C 1 to C 6 ) alkyl, -C (O) OR 3 or -N (R 3 ) 2 , where (C 1 to C 6 ) alkyl. Alkyl is optionally substituted with -N (R 3 ) 2 or -OR 3 ;
Each R 7 is independently H, (C 1 to C 6 ) alkyl, -C (O) OR 3 or -N (R 3 ) 2 , where (C 1 to C 6 ) alkyl. Alkyl is optionally substituted with -N (R 3 ) 2 or -OR 3 ;
Each R 8 is independently H, (C 1 to C 6 ) alkyl, -C (O) OR 3 or -N (R 3 ) 2 , where (C 1 to C 6 ) alkyl. Alkyl is optionally substituted with -N (R 3 ) 2 or -OR 3 ;
Each Y is independently a C (R 3 ) 2 or bond;
Each n is an independently integer from 1 to 12;
Each o is an independent integer from 0 to 30;
Each p is an independent integer from 0 to 12;
Each q is an independent integer from 0 to 30;
Each r is an independently integer from 1 to 6), or a pharmaceutically acceptable salt thereof, tautomer, stereoisomer, or oxepane isomer. Ｒ３２は、＝Ｏである、請求項１に記載の化合物、またはその薬学的に許容される塩、互変異性体、立体異性体、もしくはオキセパン異性体。 R 32 is the compound according to claim 1, or a pharmaceutically acceptable salt thereof, a tautomer, a stereoisomer, or an oxepane isomer, wherein = O. Ｒ３２は、－ＯＲ３である、請求項１に記載の化合物、またはその薬学的に許容される塩、互変異性体、立体異性体、もしくはオキセパン異性体。 R 32 is —OR 3 , the compound according to claim 1, or a pharmaceutically acceptable salt thereof, a tautomer, a stereoisomer, or an oxepane isomer. 式（Ｉ－４０ｂ）：
Figure 2019212990000008
 （式中、Ｒ４０は、－Ｃ（＝Ｚ１）－Ｒ４０ａである）
の構造により表される、請求項１～３のいずれか１項に記載の化合物、またはその薬学的に許容される塩、互変異性体、立体異性体、もしくはオキセパン異性体。 Equation (I-40b):
Figure 2019212990000008
 (In the formula, R 40 is -C (= Z 1 ) -R 40a )
The compound according to any one of claims 1 to 3, or a pharmaceutically acceptable salt, tautomer, stereoisomer, or oxepane isomer thereof, which is represented by the structure of. Ｚ１は、Ｏである、請求項４に記載の化合物、またはその薬学的に許容される塩、互変異性体、立体異性体、もしくはオキセパン異性体。 Z 1 is O, the compound according to claim 4, or a pharmaceutically acceptable salt thereof, a tautomer, a stereoisomer, or an oxepane isomer. 式（Ｉ－２８ｂ）：
Figure 2019212990000009
 （式中、Ｒ２８は、－Ｃ（＝Ｚ１）－Ｒ２８ａである）
の構造により表される、請求項１～３のいずれか１項に記載の化合物、またはその薬学的に許容される塩、互変異性体、立体異性体、もしくはオキセパン異性体。 Equation (I-28b):
Figure 2019212990000009
 (In the formula, R 28 is -C (= Z 1 ) -R 28a )
The compound according to any one of claims 1 to 3, or a pharmaceutically acceptable salt, tautomer, stereoisomer, or oxepane isomer thereof, which is represented by the structure of. Ｚ１は、Ｏである、請求項６に記載の化合物、またはその薬学的に許容される塩、互変異性体、立体異性体、もしくはオキセパン異性体。 Z 1 is O, the compound according to claim 6, or a pharmaceutically acceptable salt thereof, a tautomer, a stereoisomer, or an oxepane isomer. 式（Ｉ－３２ｂ）：
Figure 2019212990000010
 （式中、Ｒ３２は、－Ｏ－Ｃ（＝Ｚ１）－Ｒ３２ａである）
の構造により表される、請求項１に記載の化合物、またはその薬学的に許容される塩、互変異性体、立体異性体、もしくはオキセパン異性体。 Equation (I-32b):
Figure 2019212990000010
 (In the formula, R 32 is -OC (= Z 1 ) -R 32a )
The compound according to claim 1, or a pharmaceutically acceptable salt, tautomer, stereoisomer, or oxepane isomer thereof, which is represented by the structure of the above. Ｚ１は、Ｏである、請求項８に記載の化合物、またはその薬学的に許容される塩、互変異性体、立体異性体、もしくはオキセパン異性体。 Z 1 is O, the compound according to claim 8, or a pharmaceutically acceptable salt thereof, a tautomer, a stereoisomer, or an oxepane isomer. Ｂは、
Figure 2019212990000011
 である、請求項１～９のいずれか１項に記載の化合物、またはその薬学的に許容される塩、互変異性体、立体異性体、もしくはオキセパン異性体。 B is
Figure 2019212990000011
 The compound according to any one of claims 1 to 9, or a pharmaceutically acceptable salt thereof, a tautomer, a stereoisomer, or an oxepane isomer. Ｂは、
Figure 2019212990000012
 である、請求項１～９のいずれか１項に記載の化合物、またはその薬学的に許容される塩、互変異性体、立体異性体、もしくはオキセパン異性体。 B is
Figure 2019212990000012
 The compound according to any one of claims 1 to 9, or a pharmaceutically acceptable salt thereof, a tautomer, a stereoisomer, or an oxepane isomer. Ｂ１は、
Figure 2019212990000013
 である、請求項１～９のいずれか１項に記載の化合物、またはその薬学的に許容される塩、互変異性体、立体異性体、もしくはオキセパン異性体。 B 1 is
Figure 2019212990000013
 The compound according to any one of claims 1 to 9, or a pharmaceutically acceptable salt thereof, a tautomer, a stereoisomer, or an oxepane isomer. Ｂ１は、
Figure 2019212990000014
 である、請求項１～９のいずれか１項に記載の化合物、またはその薬学的に許容される塩、互変異性体、立体異性体、もしくはオキセパン異性体。 B 1 is
Figure 2019212990000014
 The compound according to any one of claims 1 to 9, or a pharmaceutically acceptable salt thereof, a tautomer, a stereoisomer, or an oxepane isomer. Ｒ４は、場合により－Ｎ（Ｒ３）２、－ＯＲ３、ハロゲン、（Ｃ１～Ｃ６）アルキル、－（Ｃ１～Ｃ６）アルキレン－ヘテロアリール、－（Ｃ１～Ｃ６）アルキレン－ＣＮまたはＣ（Ｏ）ＮＲ３－ヘテロアリールで置換されている５～１２員ヘテロアリールである、請求項１～９のいずれか１項に記載の化合物、またはその薬学的に許容される塩、互変異性体、立体異性体、もしくはオキセパン異性体。 R 4 may be -N (R 3 ) 2 , -OR 3 , halogen, (C 1 to C 6 ) alkyl,-(C 1 to C 6 ) alkylene-heteroaryl,-(C 1 to C 6 ). The compound according to any one of claims 1-9, which is a 5- to 12-membered heteroaryl substituted with alkylene-CN or C (O) NR 3 -heteroaryl, or pharmaceutically acceptable thereof. Salt, tautomer, stereoisomer, or oxepane isomer. 以下の式：
Figure 2019212990000015
 を有する、請求項１～１４のいずれか１項に記載の化合物、またはその薬学的に許容される塩、互変異性体、立体異性体、もしくはオキセパン異性体。 The following formula:
Figure 2019212990000015
 The compound according to any one of claims 1 to 14, or a pharmaceutically acceptable salt thereof, a tautomer, a stereoisomer, or an oxepane isomer having the above.
Figure 2019212990000016
Figure 2019212990000017
Figure 2019212990000018
Figure 2019212990000019
Figure 2019212990000020
Figure 2019212990000021
Figure 2019212990000022
Figure 2019212990000023
Figure 2019212990000024
Figure 2019212990000025
Figure 2019212990000026
Figure 2019212990000027
Figure 2019212990000028
Figure 2019212990000029
Figure 2019212990000030
Figure 2019212990000031
 からなる群から選択される化合物、またはその薬学的に許容される塩、互変異性体、立体異性体、もしくはオキセパン異性体。
Figure 2019212990000016
Figure 2019212990000017
Figure 2019212990000018
Figure 2019212990000019
Figure 2019212990000020
Figure 2019212990000021
Figure 2019212990000022
Figure 2019212990000023
Figure 2019212990000024
Figure 2019212990000025
Figure 2019212990000026
Figure 2019212990000027
Figure 2019212990000028
Figure 2019212990000029
Figure 2019212990000030
Figure 2019212990000031
 A compound selected from the group consisting of, or a pharmaceutically acceptable salt thereof, a tautomer, a stereoisomer, or an oxepane isomer. 以下：
Figure 2019212990000032
Figure 2019212990000033
Figure 2019212990000034
Figure 2019212990000035
Figure 2019212990000036
Figure 2019212990000037
Figure 2019212990000038
Figure 2019212990000039
Figure 2019212990000040
Figure 2019212990000041
Figure 2019212990000042
Figure 2019212990000043
Figure 2019212990000044
Figure 2019212990000045
 からなる群から選択される化合物、またはその薬学的に許容される塩、互変異性体、立体異性体、もしくはオキセパン異性体。 Less than:
Figure 2019212990000032
Figure 2019212990000033
Figure 2019212990000034
Figure 2019212990000035
Figure 2019212990000036
Figure 2019212990000037
Figure 2019212990000038
Figure 2019212990000039
Figure 2019212990000040
Figure 2019212990000041
Figure 2019212990000042
Figure 2019212990000043
Figure 2019212990000044
Figure 2019212990000045
A compound selected from the group consisting of, or a pharmaceutically acceptable salt thereof, a tautomer, a stereoisomer, or an oxepane isomer.
Figure 2019212990000046
Figure 2019212990000047
Figure 2019212990000048
Figure 2019212990000049
 からなる群から選択される化合物、またはその薬学的に許容される塩、互変異性体、立体異性体、もしくはオキセパン異性体。
Figure 2019212990000046
Figure 2019212990000047
Figure 2019212990000048
Figure 2019212990000049
A compound selected from the group consisting of, or a pharmaceutically acceptable salt thereof, a tautomer, a stereoisomer, or an oxepane isomer. 式：
Figure 2019212990000050
 を有する化合物、またはその立体異性体。 formula:
Figure 2019212990000050
 A compound having the above, or a stereoisomer thereof. 式：
Figure 2019212990000051
 を有する化合物、またはその互変異性体。 formula:
Figure 2019212990000051
 A compound having, or a tautomer thereof. 式：
Figure 2019212990000052
 を有する化合物、またはそのオキセパン異性体。 formula:
Figure 2019212990000052
 A compound having, or an oxepane isomer thereof. 式：
Figure 2019212990000053
 を有する化合物、またはその立体異性体。 formula:
Figure 2019212990000053
 A compound having the above, or a stereoisomer thereof. 式：
Figure 2019212990000054
 を有する化合物、またはその互変異性体。 formula:
Figure 2019212990000054
 A compound having, or a tautomer thereof. 式：
Figure 2019212990000055
 を有する化合物。 formula:
Figure 2019212990000055
 Compounds with. 式：
Figure 2019212990000056
 を有する化合物。 formula:
Figure 2019212990000056
 Compounds with.
Figure 2019212990000057
 またはその立体異性体もしくは互変異性体と
Figure 2019212990000058
 またはその立体異性体もしくは互変異性体との
混合物を含む組成物。
Figure 2019212990000057
 Or with its stereoisomer or tautomer
Figure 2019212990000058
 Or a composition comprising a mixture thereof with its stereoisomer or tautomer.
Figure 2019212990000059
 との混合物を含む組成物。
Figure 2019212990000059
 A composition comprising a mixture with. 請求項１～２７のいずれか１項に記載の化合物、またはその薬学的に許容される塩、互変異性体、立体異性体、もしくはオキセパン異性体、および薬学的に許容される担体、希釈剤または賦形剤のうちの少なくとも１つを含む医薬組成物。 The compound according to any one of claims 1 to 27, or a pharmaceutically acceptable salt, tautomer, stereoisomer, or oxepan isomer thereof, and a pharmaceutically acceptable carrier or diluent. Alternatively, a pharmaceutical composition comprising at least one of the excipients. ｍＴＯＲにより介在される疾患または障害を処置する方法で使用するための、請求項２８に記載の医薬組成物であって、該方法は、ｍＴＯＲにより介在される疾患または障害に罹患している、またはそれを発症しやすい対象に、治療有効量の該医薬組成物を投与する工程を含む、上記医薬組成物。 28. The pharmaceutical composition of claim 28 for use in a method of treating a disease or disorder mediated by mTOR, wherein the method is suffering from or suffering from a disease or disorder mediated by mTOR. The pharmaceutical composition comprising a step of administering a therapeutically effective amount of the pharmaceutical composition to a subject who is prone to develop it. ｍＴＯＲにより介在される疾患または障害を防止する方法で使用するための、請求項２８に記載の医薬組成物であって、該方法は、ｍＴＯＲにより介在される疾患または障害に罹患している、またはそれを発症しやすい対象に、治療有効量の該医薬組成物を投与する工程を含む、上記医薬組成物。 28. The pharmaceutical composition of claim 28 for use in a method of preventing a disease or disorder mediated by mTOR, wherein the method is suffering from or suffering from a disease or disorder mediated by mTOR. The pharmaceutical composition comprising a step of administering a therapeutically effective amount of the pharmaceutical composition to a subject who is prone to develop it. 疾患は癌であり、該癌は、脳および神経血管腫瘍、頭頸部癌、乳癌、肺癌、中皮腫、リンパ系癌、胃癌、腎臓癌、腎臓癌、肝臓癌、卵巣癌、卵巣子宮内膜症、精巣癌、消化管癌、前立腺癌、膠芽腫、皮膚癌、黒色腫、神経癌、脾臓癌、膵臓癌、血液増殖障害、リンパ腫、白血病、子宮内膜癌、子宮頸癌、外陰癌、前立腺癌、陰茎癌、骨癌、筋肉癌、軟部組織癌、腸または直腸癌、肛門癌、膀胱癌、胆管癌、眼癌、消化管間質腫瘍および神経内分泌腫瘍から選択される、請求項２９または３０に記載の医薬組成物。 The disease is cancer, which is brain and neurovascular tumor, head and neck cancer, breast cancer, lung cancer, mesopharyngeal tumor, lymphoid cancer, gastric cancer, kidney cancer, kidney cancer, liver cancer, ovarian cancer, ovarian endometrial. Disease, testicular cancer, gastrointestinal cancer, prostate cancer, glioblastoma, skin cancer, melanoma, nerve cancer, spleen cancer, pancreatic cancer, blood growth disorder, lymphoma, leukemia, endometrial cancer, cervical cancer, genital cancer , Prostate cancer, penis cancer, bone cancer, muscle cancer, soft tissue cancer, intestinal or rectal cancer, anal cancer, bladder cancer, bile duct cancer, eye cancer, gastrointestinal stromal tumor and neuroendocrine tumor, claim. 29 or 30. The pharmaceutical composition. 癌を処置する方法で使用するための、請求項２８に記載の医薬組成物であって、該方法は、対象に、治療有効量の該医薬組成物を投与する工程を含む、上記医薬組成物。 28. The pharmaceutical composition for use in a method of treating cancer, wherein the method comprises the step of administering to the subject a therapeutically effective amount of the pharmaceutical composition. .. 癌は、脳および神経血管腫瘍、頭頸部癌、乳癌、肺癌、中皮腫、リンパ系癌、胃癌、腎臓癌、腎臓癌、肝臓癌、卵巣癌、卵巣子宮内膜症、精巣癌、消化管癌、前立腺癌、膠芽腫、皮膚癌、黒色腫、神経癌、脾臓癌、膵臓癌、血液増殖障害、リンパ腫、白血病、子宮内膜癌、子宮頸癌、外陰癌、前立腺癌、陰茎癌、骨癌、筋肉癌、軟部組織癌、腸または直腸癌、肛門癌、膀胱癌、胆管癌、眼癌、消化管間質腫瘍および神経内分泌腫瘍から選択される、請求項３２に記載の医薬組成物。 Cancers include brain and neurovascular tumors, head and neck cancers, breast cancers, lung cancers, mesothelomas, lymphoid cancers, gastric cancers, kidney cancers, kidney cancers, liver cancers, ovarian cancers, ovarian endometriosis, testicular cancers, gastrointestinal tract. Cancer, prostate cancer, glioblastoma, skin cancer, melanoma, nerve cancer, spleen cancer, pancreatic cancer, blood growth disorder, lymphoma, leukemia, endometrial cancer, cervical cancer, genital cancer, prostate cancer, penis cancer, 32. The pharmaceutical composition according to claim 32, which is selected from bone cancer, muscle cancer, soft tissue cancer, intestinal or rectal cancer, anal cancer, bladder cancer, bile duct cancer, eye cancer, gastrointestinal stromal tumor and neuroendocrine tumor. .. ｍＴＯＲにより介在される疾患または状態の危険性を処置する、防止する、または低下させるのに使用するための、請求項１～２７のいずれか１項に記載の化合物、またはその薬学的に許容される塩、互変異性体、立体異性体、もしくはオキセパン異性体。 The compound according to any one of claims 1-27, or pharmaceutically acceptable thereof, for use in treating, preventing, or reducing the risk of a disease or condition mediated by mTOR. Salt, tautomer, stereoisomer, or oxepane isomer. ｍＴＯＲにより介在される疾患または障害の危険性を処置する、防止する、または低下させるための医薬の生産における、請求項１～２７のいずれか１項に記載の化合物、またはその薬学的に許容される塩、互変異性体、立体異性体、もしくはオキセパン異性体の使用。 The compound according to any one of claims 1-27, or pharmaceutically acceptable thereof, in the production of a pharmaceutical agent for treating, preventing or reducing the risk of a disease or disorder mediated by mTOR. Use of salt, tautomer, steric isomer, or oxepane isomer. 癌を処置するのに使用するための、請求項１～２７のいずれか１項に記載の化合物、またはその薬学的に許容される塩、互変異性体、立体異性体、もしくはオキセパン異性体。 The compound according to any one of claims 1 to 27, or a pharmaceutically acceptable salt thereof, a tautomer, a stereoisomer, or an oxepane isomer for use in treating cancer. 癌を処置するための医薬の生産における、請求項１～２７のいずれか１項に記載の化合物、またはその薬学的に許容される塩、互変異性体、立体異性体、もしくはオキセパン異性体の使用。 The compound according to any one of claims 1 to 27, or a pharmaceutically acceptable salt, tautomer, stereoisomer, or oxepane isomer thereof in the production of a pharmaceutical agent for treating cancer. use.
JP2020561074A 2018-05-01 2019-04-29 C40-, C28- and C-32-linked rapamycin analogs as MTOR inhibitors Active JP7358387B2 (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
JP2023164097A JP2023182654A (en) 2018-05-01 2023-09-27 C40-, c28-, and c-32-linked rapamycin analogs as mtor inhibitors

Applications Claiming Priority (7)

Application Number Priority Date Filing Date Title
US201862665435P 2018-05-01 2018-05-01
US62/665,435 2018-05-01
US201862752874P 2018-10-30 2018-10-30
US62/752,874 2018-10-30
US201962836036P 2019-04-18 2019-04-18
US62/836,036 2019-04-18
PCT/US2019/029737 WO2019212990A1 (en) 2018-05-01 2019-04-29 C40-, c28-, and c-32-linked rapamycin analogs as mtor inhibitors

Related Child Applications (1)

Application Number Title Priority Date Filing Date
JP2023164097A Division JP2023182654A (en) 2018-05-01 2023-09-27 C40-, c28-, and c-32-linked rapamycin analogs as mtor inhibitors

Publications (3)

Publication Number Publication Date
JP2021523112A JP2021523112A (en) 2021-09-02
JPWO2019212990A5 true JPWO2019212990A5 (en) 2022-05-02
JP7358387B2 JP7358387B2 (en) 2023-10-10

Family

ID=66484166

Family Applications (2)

Application Number Title Priority Date Filing Date
JP2020561074A Active JP7358387B2 (en) 2018-05-01 2019-04-29 C40-, C28- and C-32-linked rapamycin analogs as MTOR inhibitors
JP2023164097A Pending JP2023182654A (en) 2018-05-01 2023-09-27 C40-, c28-, and c-32-linked rapamycin analogs as mtor inhibitors

Family Applications After (1)

Application Number Title Priority Date Filing Date
JP2023164097A Pending JP2023182654A (en) 2018-05-01 2023-09-27 C40-, c28-, and c-32-linked rapamycin analogs as mtor inhibitors

Country Status (28)

Country Link
US (4) US20190336609A1 (en)
EP (2) EP3788049B1 (en)
JP (2) JP7358387B2 (en)
KR (1) KR20210018244A (en)
CN (1) CN112771054A (en)
AU (2) AU2019262978B2 (en)
BR (1) BR112020022201A2 (en)
CA (1) CA3098692A1 (en)
CL (1) CL2020002827A1 (en)
CO (1) CO2020013865A2 (en)
CR (2) CR20200578A (en)
DK (1) DK3788049T3 (en)
ES (1) ES2945560T3 (en)
FI (1) FI3788049T3 (en)
HR (1) HRP20230488T1 (en)
HU (1) HUE062352T2 (en)
IL (2) IL300091A (en)
LT (1) LT3788049T (en)
MX (2) MX2020011565A (en)
PE (1) PE20212112A1 (en)
PH (1) PH12020551795A1 (en)
PL (1) PL3788049T3 (en)
PT (1) PT3788049T (en)
RS (1) RS64272B1 (en)
SG (1) SG11202010559UA (en)
SI (1) SI3788049T1 (en)
TW (1) TW202014208A (en)
WO (1) WO2019212990A1 (en)

Families Citing this family (31)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
SG11201900157RA (en) 2016-07-12 2019-02-27 Revolution Medicines Inc 2,5-disubstituted 3-methyl pyrazines and 2,5,6-trisubstituted 3-methyl pyrazines as allosteric shp2 inhibitors
EP3571189B1 (en) 2017-01-23 2023-03-29 Revolution Medicines, Inc. Pyridine compounds as allosteric shp2 inhibitors
JP7240319B2 (en) 2017-01-23 2023-03-15 レヴォリューション・メディスンズ，インコーポレイテッド Bicyclic compounds as allosteric SHP2 inhibitors
WO2019075265A1 (en) 2017-10-12 2019-04-18 Revolution Medicines, Inc. Pyridine, pyrazine, and triazine compounds as allosteric shp2 inhibitors
MX2020006273A (en) 2017-12-15 2020-09-14 Revolution Medicines Inc Polycyclic compounds as allosteric shp2 inhibitors.
CA3098692A1 (en) 2018-05-01 2019-11-07 Revolution Medicines, Inc. C40-, c28-, and c-32-linked rapamycin analogs as mtor inhibitors
MX2020011564A (en) 2018-05-01 2021-01-29 Revolution Medicines Inc C26-linked rapamycin analogs as mtor inhibitors.
CN113767100A (en) 2019-03-01 2021-12-07 锐新医药公司 Bicyclic heteroaryl compounds and uses thereof
WO2020180770A1 (en) 2019-03-01 2020-09-10 Revolution Medicines, Inc. Bicyclic heterocyclyl compounds and uses thereof
TW202132315A (en) 2019-11-04 2021-09-01 美商銳新醫藥公司 Ras inhibitors
BR112022008565A2 (en) 2019-11-04 2022-08-09 Revolution Medicines Inc COMPOUND, PHARMACEUTICAL COMPOSITION, CONJUGATE, METHODS TO TREAT CANCER AND A RAS PROTEIN-RELATED DISORDER
JP2022553859A (en) 2019-11-04 2022-12-26 レボリューション メディシンズ インコーポレイテッド RAS inhibitor
CN114901662A (en) 2019-11-08 2022-08-12 锐新医药公司 Bicyclic heteroaryl compounds and uses thereof
CN114980976A (en) 2019-11-27 2022-08-30 锐新医药公司 Covalent RAS inhibitors and uses thereof
IL299131A (en) 2020-06-18 2023-02-01 Revolution Medicines Inc Methods for delaying, preventing, and treating acquired resistance to ras inhibitors
WO2022020114A2 (en) 2020-07-10 2022-01-27 Ting Therapeutics Llc Methods for the prevention and treatment of hearing loss
EP4208261A1 (en) 2020-09-03 2023-07-12 Revolution Medicines, Inc. Use of sos1 inhibitors to treat malignancies with shp2 mutations
EP4214209A1 (en) 2020-09-15 2023-07-26 Revolution Medicines, Inc. Indole derivatives as ras inhibitors in the treatment of cancer
AR124449A1 (en) 2020-12-22 2023-03-29 Qilu Regor Therapeutics Inc SOS1 INHIBITORS AND USES THEREOF
AU2022253019A1 (en) * 2021-04-09 2023-11-16 Revolution Medicines, Inc. Synthesis of rapamycin analog compounds
EP4334321A1 (en) 2021-05-05 2024-03-13 Revolution Medicines, Inc. Ras inhibitors
CN117616031A (en) 2021-05-05 2024-02-27 锐新医药公司 RAS inhibitors for the treatment of cancer
WO2022235866A1 (en) 2021-05-05 2022-11-10 Revolution Medicines, Inc. Covalent ras inhibitors and uses thereof
CN117337297A (en) * 2021-05-12 2024-01-02 锐新医药公司 Use of SOS1 inhibitors and MTOR inhibitors for the treatment of cancer
CN114044775B (en) * 2021-08-30 2023-04-07 杭州医学院 Compound for target ubiquitination induction of BCR-ABL protein degradation and application thereof
AR127308A1 (en) 2021-10-08 2024-01-10 Revolution Medicines Inc RAS INHIBITORS
WO2023114954A1 (en) 2021-12-17 2023-06-22 Genzyme Corporation Pyrazolopyrazine compounds as shp2 inhibitors
EP4227307A1 (en) 2022-02-11 2023-08-16 Genzyme Corporation Pyrazolopyrazine compounds as shp2 inhibitors
WO2023172940A1 (en) 2022-03-08 2023-09-14 Revolution Medicines, Inc. Methods for treating immune refractory lung cancer
WO2023240263A1 (en) 2022-06-10 2023-12-14 Revolution Medicines, Inc. Macrocyclic ras inhibitors
GB202212000D0 (en) * 2022-08-17 2022-09-28 Mironid Ltd Compounds and their use as PDE4 activators

Family Cites Families (147)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
ZA737247B (en) 1972-09-29 1975-04-30 Ayerst Mckenna & Harrison Rapamycin and process of preparation
GB1459571A (en) 1974-09-12 1976-12-22 Pfizer Ltd Thiophene-2-sulphonamide derivatives and their use as therapeutic agents sheet orienting apparatus
US4316885A (en) 1980-08-25 1982-02-23 Ayerst, Mckenna And Harrison, Inc. Acyl derivatives of rapamycin
US4513135A (en) 1982-03-05 1985-04-23 Eli Lilly And Company Diaryl-pyrazine derivatives affecting GABA binding
US4911920A (en) 1986-07-30 1990-03-27 Alcon Laboratories, Inc. Sustained release, comfort formulation for glaucoma therapy
FR2588189B1 (en) 1985-10-03 1988-12-02 Merck Sharp & Dohme LIQUID-GEL PHASE TRANSITION PHARMACEUTICAL COMPOSITION
US4650803A (en) 1985-12-06 1987-03-17 University Of Kansas Prodrugs of rapamycin
JPH0249775A (en) 1988-05-19 1990-02-20 Nippon Soda Co Ltd Heterocyclic compound having 6-membered or 7-membered ring and production thereof
US5120726A (en) 1991-03-08 1992-06-09 American Home Products Corporation Rapamycin hydrazones
US5023264A (en) 1990-07-16 1991-06-11 American Home Products Corporation Rapamycin oximes
US5023263A (en) 1990-08-09 1991-06-11 American Home Products Corporation 42-oxorapamycin
JPH04112877A (en) 1990-09-04 1992-04-14 Nippon Soda Co Ltd New cyanopyrazine derivative and production thereof
PT98990A (en) 1990-09-19 1992-08-31 American Home Prod PROCESS FOR THE PREPARATION OF CARBOXYLIC ACID ESTERS OF RAPAMICIN
US5221670A (en) 1990-09-19 1993-06-22 American Home Products Corporation Rapamycin esters
US5130307A (en) 1990-09-28 1992-07-14 American Home Products Corporation Aminoesters of rapamycin
US5233036A (en) 1990-10-16 1993-08-03 American Home Products Corporation Rapamycin alkoxyesters
DE69212850T2 (en) 1991-01-15 1997-03-06 Alcon Lab Inc Use of carrageenan in topical ophthalmic compositions
GB9103430D0 (en) 1991-02-19 1991-04-03 Smithkline Beecham Plc Novel compound
US5212162A (en) 1991-03-27 1993-05-18 Alcon Laboratories, Inc. Use of combinations gelling polysaccharides and finely divided drug carrier substrates in topical ophthalmic compositions
US5120842A (en) 1991-04-01 1992-06-09 American Home Products Corporation Silyl ethers of rapamycin
US5100883A (en) 1991-04-08 1992-03-31 American Home Products Corporation Fluorinated esters of rapamycin
US5118678A (en) 1991-04-17 1992-06-02 American Home Products Corporation Carbamates of rapamycin
US5118677A (en) 1991-05-20 1992-06-02 American Home Products Corporation Amide esters of rapamycin
US5162333A (en) 1991-09-11 1992-11-10 American Home Products Corporation Aminodiesters of rapamycin
US5151413A (en) 1991-11-06 1992-09-29 American Home Products Corporation Rapamycin acetals as immunosuppressant and antifungal agents
GB9125660D0 (en) 1991-12-03 1992-01-29 Smithkline Beecham Plc Novel compound
US5221740A (en) 1992-01-16 1993-06-22 American Home Products Corporation Oxepane isomers of rapamycin useful as immunosuppressive agents
US5177203A (en) 1992-03-05 1993-01-05 American Home Products Corporation Rapamycin 42-sulfonates and 42-(N-carboalkoxy) sulfamates useful as immunosuppressive agents
ZA935111B (en) 1992-07-17 1994-02-04 Smithkline Beecham Corp Rapamycin derivatives
ZA935112B (en) 1992-07-17 1994-02-08 Smithkline Beecham Corp Rapamycin derivatives
US5256790A (en) 1992-08-13 1993-10-26 American Home Products Corporation 27-hydroxyrapamycin and derivatives thereof
GB9221220D0 (en) 1992-10-09 1992-11-25 Sandoz Ag Organic componds
US5489680A (en) 1992-10-13 1996-02-06 American Home Products Corporation Carbamates of rapamycin
US5480989A (en) * 1992-10-13 1996-01-02 American Home Products Corporation Carbamates of rapamycin
US5480988A (en) 1992-10-13 1996-01-02 American Home Products Corporation Carbamates of rapamycin
US5302584A (en) * 1992-10-13 1994-04-12 American Home Products Corporation Carbamates of rapamycin
US5411967A (en) 1992-10-13 1995-05-02 American Home Products Corporation Carbamates of rapamycin
US5262423A (en) 1992-10-29 1993-11-16 American Home Products Corporation Rapamycin arylcarbonyl and alkoxycarbonyl carbamates as immunosuppressive and antifungal agents
US5262564A (en) 1992-10-30 1993-11-16 Octamer, Inc. Sulfinic acid adducts of organo nitroso compounds useful as retroviral inactivating agents anti-retroviral agents and anti-tumor agents
US5258389A (en) * 1992-11-09 1993-11-02 Merck & Co., Inc. O-aryl, O-alkyl, O-alkenyl and O-alkynylrapamycin derivatives
US5260300A (en) * 1992-11-19 1993-11-09 American Home Products Corporation Rapamycin carbonate esters as immuno-suppressant agents
US5252579A (en) 1993-02-16 1993-10-12 American Home Products Corporation Macrocyclic immunomodulators
US5504091A (en) 1993-04-23 1996-04-02 American Home Products Corporation Biotin esters of rapamycin
AU6711994A (en) * 1993-04-23 1994-11-21 American Home Products Corporation Rapamycin conjugates and antibodies
US5387680A (en) * 1993-08-10 1995-02-07 American Home Products Corporation C-22 ring stabilized rapamycin derivatives
US5373014A (en) 1993-10-08 1994-12-13 American Home Products Corporation Rapamycin oximes
US5391730A (en) 1993-10-08 1995-02-21 American Home Products Corporation Phosphorylcarbamates of rapamycin and oxime derivatives thereof
US5378836A (en) 1993-10-08 1995-01-03 American Home Products Corporation Rapamycin oximes and hydrazones
US5527907A (en) 1993-11-19 1996-06-18 Abbott Laboratories Macrolide immunomodulators
CA2175215C (en) * 1993-11-19 2008-06-03 Yat Sun Or Semisynthetic analogs of rapamycin (macrolides) being immunomodulators
US5385909A (en) 1993-11-22 1995-01-31 American Home Products Corporation Heterocyclic esters of rapamycin
US5385910A (en) 1993-11-22 1995-01-31 American Home Products Corporation Gem-distributed esters of rapamycin
US5385908A (en) 1993-11-22 1995-01-31 American Home Products Corporation Hindered esters of rapamycin
SG64372A1 (en) 1993-12-17 1999-04-27 Novartis Ag Rapamycin derivatives
US5389639A (en) 1993-12-29 1995-02-14 American Home Products Company Amino alkanoic esters of rapamycin
US5362718A (en) 1994-04-18 1994-11-08 American Home Products Corporation Rapamycin hydroxyesters
US5463048A (en) 1994-06-14 1995-10-31 American Home Products Corporation Rapamycin amidino carbamates
US5491231A (en) 1994-11-28 1996-02-13 American Home Products Corporation Hindered N-oxide esters of rapamycin
US5563145A (en) 1994-12-07 1996-10-08 American Home Products Corporation Rapamycin 42-oximes and hydroxylamines
US6323201B1 (en) 1994-12-29 2001-11-27 The Regents Of The University Of California Compounds for inhibition of ceramide-mediated signal transduction
US5741677A (en) 1995-06-07 1998-04-21 Geron Corporation Methods for measuring telomere length
HU228234B1 (en) 1995-06-09 2013-02-28 Novartis Ag Rapamycin derivatives, pharmaceutical compositions containing them and their use
US5780462A (en) 1995-12-27 1998-07-14 American Home Products Corporation Water soluble rapamycin esters
WO1997048694A1 (en) 1996-06-20 1997-12-24 Board Of Regents, The University Of Texas System Compounds and methods for providing pharmacologically active preparations and uses thereof
CA2293400A1 (en) 1997-06-13 1998-12-17 Gerald Mcmahon Novel heteroaryl compounds for the modulation of protein tyrosine enzyme related cellular signal transduction
US6342507B1 (en) * 1997-09-05 2002-01-29 Isotechnika, Inc. Deuterated rapamycin compounds, method and uses thereof
WO1999036553A2 (en) 1998-01-15 1999-07-22 Ariad Gene Therapeutics, Inc. Regulation of biological events using multimeric chimeric proteins
EP1212331B1 (en) 1999-08-24 2004-04-21 Ariad Gene Therapeutics, Inc. 28-epirapalogs
US6277983B1 (en) 2000-09-27 2001-08-21 American Home Products Corporation Regioselective synthesis of rapamycin derivatives
SI2762140T1 (en) 2001-02-19 2017-07-31 Novartis Ag Treatment of solid brain tumours with a rapamycin derivative
BR0314139A (en) 2002-09-12 2005-07-12 Pharmacia & Upjohn Co Llc Substituted 1,4-pyrazine derivatives
JP2004161716A (en) 2002-11-15 2004-06-10 Takeda Chem Ind Ltd Jnk inhibitor
US7160867B2 (en) * 2003-05-16 2007-01-09 Isotechnika, Inc. Rapamycin carbohydrate derivatives
GB0314057D0 (en) 2003-06-18 2003-07-23 Astrazeneca Ab Therapeutic agents
US7429596B2 (en) 2003-06-20 2008-09-30 The Regents Of The University Of California 1H-pyrrolo [2,3-D] pyrimidine derivatives and methods of use thereof
EP1678160A1 (en) 2003-10-27 2006-07-12 Astellas Pharma Inc. Pyrazine derivatives and pharmaceutical use thereof
US7220755B2 (en) 2003-11-12 2007-05-22 Biosensors International Group, Ltd. 42-O-alkoxyalkyl rapamycin derivatives and compositions comprising same
EP1571151B1 (en) 2004-03-01 2008-12-24 Terumo Kabushiki Kaisha Process for production of O-alkylated rapamycin derivatives
JP4848286B2 (en) 2004-04-30 2011-12-28 武田薬品工業株式会社 Heterocyclic amide compounds and their use as MMP-13 inhibitors
CN100516195C (en) 2004-07-19 2009-07-22 汕头市双骏生物科技有限公司 New strain and method of producing pacilitaxel using said strain
EP1831225A2 (en) 2004-11-19 2007-09-12 The Regents of the University of California Anti-inflammatory pyrazolopyrimidines
US7241771B2 (en) 2005-03-07 2007-07-10 Wyeth Oxepane isomer of 42-O-(2-hydroxy)ethyl-rapamycin
CA2606288A1 (en) 2005-04-18 2006-10-26 Neurogen Corporation Subtituted heteroaryl cb1 antagonists
US7189582B2 (en) 2005-04-27 2007-03-13 Dade Behring Inc. Compositions and methods for detection of sirolimus
GB0525546D0 (en) * 2005-12-15 2006-01-25 Novartis Ag Organic compounds
PT2004654E (en) 2006-04-04 2013-08-27 Univ California Pyrazolopyrimidine derivatives for use as kinase antagonists
US20090274739A1 (en) 2006-04-13 2009-11-05 The Trustees Of Columbia University In The City Of New York Methods and compositions for treating neointimal hyperplasia
WO2007121453A2 (en) 2006-04-17 2007-10-25 The Regents Of The University Of California 2-hydroxy-1-oxo 1,2 dihydro isoquinoline chelating agents
RU2445312C2 (en) 2006-08-23 2012-03-20 Кудос Фармасьютиклз Лимитед 2-METHYLMORPHOLINE PYRIDO-, PYRAZO- AND PYRIMIDO-PYRIMIDINE DERIVATIVES AS mTOR INHIBITORS
EP2298772A1 (en) 2006-10-18 2011-03-23 Takeda Pharmaceutical Company Limited Fused heterocyclic compounds
EP1916006A1 (en) 2006-10-19 2008-04-30 Albert Schömig Implant coated with a wax or a resin
JP5456321B2 (en) 2006-11-27 2014-03-26 テルモ株式会社 Process for producing O-alkylated rapamycin derivative and O-alkylated rapamycin derivative
US20080234262A1 (en) 2007-03-21 2008-09-25 Wyeth Pyrazolopyrimidine analogs and their use as mtor kinase and pi3 kinase inhibitors
CA2678415A1 (en) 2007-04-05 2008-10-16 Wyeth Wortmannin-rapamycin conjugate and uses thereof
JPWO2008156174A1 (en) 2007-06-21 2010-08-26 大正製薬株式会社 Pyrazineamide compound
US20090074831A1 (en) 2007-09-18 2009-03-19 Robert Falotico LOCAL VASCULAR DELIVERY OF mTOR INHIBITORS IN COMBINATION WITH PEROXISOME PROLIFERATORS-ACTIVATED RECEPTOR STIMULATORS
WO2009046436A1 (en) 2007-10-04 2009-04-09 Memorial Sloan-Kettering Cancer Center Methods for inhibiting senescence of epithelial cells
AU2009204483B2 (en) 2008-01-04 2014-03-13 Intellikine, Llc Certain chemical entities, compositions and methods
US8193182B2 (en) 2008-01-04 2012-06-05 Intellikine, Inc. Substituted isoquinolin-1(2H)-ones, and methods of use thereof
US7842475B2 (en) 2008-01-08 2010-11-30 Siemens Healthcare Diagnostics Inc. Stabilization of solid support assay reagents
WO2009114874A2 (en) 2008-03-14 2009-09-17 Intellikine, Inc. Benzothiazole kinase inhibitors and methods of use
US20090253733A1 (en) * 2008-04-02 2009-10-08 Biointeractions, Ltd. Rapamycin carbonate esters
US20110098241A1 (en) * 2008-04-14 2011-04-28 Poniard Pharmaceuticals, Inc. Rapamycin analogs as anti-cancer agents
TW200948361A (en) 2008-05-26 2009-12-01 Chunghwa Chemical Synthesis & Biotech Co Ltd Method for synthesizing Biolimus A9 and the like and method for improving stability of the same
AU2009268611B2 (en) 2008-07-08 2015-04-09 Intellikine, Llc Kinase inhibitors and methods of use
US20110224223A1 (en) 2008-07-08 2011-09-15 The Regents Of The University Of California, A California Corporation MTOR Modulators and Uses Thereof
US20100055145A1 (en) 2008-08-29 2010-03-04 Biosensors International Group Stent coatings for reducing late stent thrombosis
EP2346508B1 (en) 2008-09-26 2016-08-24 Intellikine, LLC Heterocyclic kinase inhibitors
JP5819195B2 (en) 2008-10-16 2015-11-18 ザ リージェンツ オブ ザ ユニバーシティ オブ カリフォルニア Fusion ring heteroaryl kinase inhibitors
CN102256966B (en) 2008-10-17 2016-02-10 白头生物医学研究所 Solubility mTOR mixture and its conditioning agent
US8110578B2 (en) 2008-10-27 2012-02-07 Signal Pharmaceuticals, Llc Pyrazino[2,3-b]pyrazine mTOR kinase inhibitors for oncology indications and diseases associated with the mTOR/PI3K/Akt pathway
US8476431B2 (en) 2008-11-03 2013-07-02 Itellikine LLC Benzoxazole kinase inhibitors and methods of use
US20110269779A1 (en) 2008-11-18 2011-11-03 Intellikine, Inc. Methods and compositions for treatment of ophthalmic conditions
CA2760791C (en) 2009-05-07 2017-06-20 Intellikine, Inc. Heterocyclic compounds and uses thereof
CA2771532C (en) 2009-08-17 2021-03-23 Intellikine, Inc. Heterocyclic compounds and uses thereof
AU2010284255B2 (en) 2009-08-17 2016-11-17 Memorial Sloan-Kettering Cancer Center Heat shock protein binding compounds, compositions, and methods for making and using same
WO2011047384A2 (en) 2009-10-16 2011-04-21 The Regents Of The University Of California Methods of inhibiting ire1
WO2011146882A1 (en) 2010-05-21 2011-11-24 Intellikine, Inc. Chemical compounds, compositions and methods for kinase modulation
CN103140494A (en) 2010-08-04 2013-06-05 美利奴生命科学有限公司 Process for preparation of novel 42-0-(heteroalkoxyalkyl) rapamycin compounds with anti-proliferative properties
JP5847386B2 (en) 2010-09-15 2016-01-20 関東化學株式会社 Method for producing amine compound
GB201106829D0 (en) 2011-04-21 2011-06-01 Proximagen Ltd Heterocyclic compounds
EP2640730B1 (en) 2010-11-19 2019-08-07 Biocon Limited Processes for preparation of everolimus and intermediates thereof
EP2670756B1 (en) 2011-02-04 2017-06-21 Synthon BV Process for making everolimus
CN106619647A (en) 2011-02-23 2017-05-10 因特利凯有限责任公司 Combination of mtor inhibitors and pi3-kinase inhibitors and uses thereof
JP6047149B2 (en) 2011-05-04 2016-12-21 インテリカイン， エルエルシー Combined pharmaceutical composition and use thereof
CN103796655A (en) 2011-05-06 2014-05-14 加利福尼亚大学董事会 Treatment of polycystic disease
US9358229B2 (en) 2011-08-10 2016-06-07 Novartis Pharma Ag JAK PI3K/mTOR combination therapy
MX370814B (en) 2011-09-02 2020-01-08 Univ California Substituted pyrazolo[3,4-d]pyrimidines and uses thereof.
WO2013105063A1 (en) 2012-01-13 2013-07-18 Novartis Ag Fused piperidines as ip receptor agonists for the treatment of pulmonary arterial hypertension (pah) and related disorders
WO2014082286A1 (en) 2012-11-30 2014-06-05 Hangzhou Zylox Pharma Co., Ltd. Rafamycin analogs and methods for making same
WO2014121885A1 (en) 2013-02-07 2014-08-14 Merck Patent Gmbh Substituted quinoxaline derivatives and their use as positive allosteric modulators of mglur4
ES2699351T3 (en) 2014-01-17 2019-02-08 Novartis Ag Derivatives of 1-pyridazin / triazin-3-yl-piper (-azine) / idine / pyrolidine and compositions thereof to inhibit the activity of SHP2
JO3517B1 (en) 2014-01-17 2020-07-05 Novartis Ag N-azaspirocycloalkane substituted n-heteroaryl compounds and compositions for inhibiting the activity of shp2
US9815813B2 (en) 2014-01-17 2017-11-14 Novartis Ag 1-(triazin-3-yl/pyridazin-3-yl)-piper(-azine)idine derivatives and compositions therefor for inhibiting the activity of SHP2
CN105461738B (en) 2014-06-03 2019-03-08 中国人民解放军军事医学科学院毒物药物研究所 A kind of rapamycin derivative, preparation method, its pharmaceutical composition and purposes
KR101668590B1 (en) 2014-06-19 2016-10-25 전남대학교병원 Bioactive Peptide-coated Stent Promotes Endothelial Cell Proliferation and Prevents Stent Thrombosis
CN107073066B (en) 2014-09-11 2021-09-17 加利福尼亚大学董事会 mTORC1 inhibitors
WO2016100116A1 (en) 2014-12-17 2016-06-23 Siemens Healthcare Diagnostics Inc. Sandwich assay design for small molecules
US20160279108A1 (en) * 2015-02-24 2016-09-29 University Of Kansas Targeted mtor inhibitors
CN106188093B (en) * 2015-05-08 2018-06-12 上海医药工业研究院 A kind of rapamycin structure analog and preparation method thereof
CN112625028A (en) 2015-06-19 2021-04-09 诺华股份有限公司 Compounds and compositions for inhibiting SHP2 activity
US10683308B2 (en) 2015-09-11 2020-06-16 Navitor Pharmaceuticals, Inc. Rapamycin analogs and uses thereof
AU2016385839B2 (en) 2016-01-11 2021-05-27 Merck Patent Gmbh Quinolin-2-one derivatives
CN110770243A (en) * 2017-05-02 2020-02-07 锐新医药公司 Rapamycin analogs as MTOR inhibitors
UY37900A (en) * 2017-09-26 2019-04-30 Novartis Ag NEW DERIVATIVES OF RAPAMYCIN
MX2020011564A (en) 2018-05-01 2021-01-29 Revolution Medicines Inc C26-linked rapamycin analogs as mtor inhibitors.
CA3098692A1 (en) 2018-05-01 2019-11-07 Revolution Medicines, Inc. C40-, c28-, and c-32-linked rapamycin analogs as mtor inhibitors

Similar Documents

Publication Publication Date Title
JPWO2019212990A5 (en)
JPWO2019212991A5 (en)
KR101882328B1 (en) Dual inhibitors of met and vegf for the treatment of castration-resistant prostate cancer and osteoblastic bone metastases
JP2021508686A5 (en)
JP2019535744A5 (en)
JP2019514882A5 (en)
JP2020533277A5 (en)
CN112752759A (en) 1H-pyrazolo [4,3-d ] pyrimidine compounds as Toll-like receptor 7(TLR7) agonists, and methods and uses thereof
JP2016523973A5 (en)
RU2007116987A (en) NEW COMPOUNDS
JP2014193925A5 (en)
KR102014478B1 (en) Novel piperidine-2,6-dione derivatives and use thereof
JP2008508298A5 (en)
JPWO2019191470A5 (en)
JP2014518544A5 (en)
JP2020534300A5 (en)
JP2021152063A5 (en)
JP2012520321A5 (en)
RU2020113749A (en) ANALOGUES OF THAILANSTATIN
JPWO2020260252A5 (en)
JP2019522681A5 (en)
CN110240587A (en) A kind of aryl difluorobenzyl ether compound, Preparation method and use
JPWO2021055295A5 (en)
JPWO2020051356A5 (en)
US10093609B2 (en) TAK1 kinase inhibitors, compositions, and uses related thereto