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US 2023/0406849 A1Published application
Kras inhibitors for treatment of cancers
AssigneeTyligand Bioscience (Shanghai) Limited
InventorsErchang SHANG, Boyu ZHONG, Tony Yantao ZHANG, Guanglin SONG, Ruixiang WANG, Bingqing TANG, Xubo HU
Life of this patent
Estimating the term…
Abstract
Compounds which have the structure represented by formula (I) and can be used as KRas inhibitors, pharmaceutical compositions comprising this type of compounds, a method of preparing this type of compounds, and uses of these compounds in the treatment of cancers.
Claims24
A compound of formula (I),
- wherein,
- A is selected from C—Ra or N, wherein Ra is selected from halogen, CN, nitro, C3-6 cycloalkyl or C1-6 alkyl optionally substituted by halogen;
- R1, R2 and R3 are each independently selected from H, halogen or C1-6 alkyl, wherein the alkyl is optionally substituted by a group independently selected from halogen, —N(Rc)2, —ORc or 3-8 membered heterocycloalkyl;
- Rb at each occurrence is independently selected from H, halogen, CN, or C1-6 alkyl optionally substituted by halogen or CN;
- X is selected from a bond, —O— or —NH—;
- R4 is selected from H, halogen, C1-6 alkyl, —C0-6 alkyl-C6-10 aryl, —C0-6 alkyl-C3-8 cycloalkyl, —C0-6 alkyl-C3-8 cycloalkenyl, —C0-6 alkyl-3-8 membered heterocycloalkyl, —C0-6 alkyl-3-8 membered heterocycloalkenyl, —C0-6 alkyl-5-10 membered heteroaryl, wherein the alkyl, aryl, cycloalkyl, cycloalkenyl, heterocycloalkyl, heterocycloalkenyl and heteroaryl groups are optionally substituted by one or more groups independently selected from halogen, C1-6 alkyl optionally substituted by halogen, —(CRcRc)0-6—SRc, —(CRcRc)0-6—(CO)0-1—ORc, —(CRcRc)0-6—(CO)0-1—N(Rc)2, wherein the —(CRcRc)0-6—(CO)0-1—N(Rc)2 attached to the aryl, cycloalkyl, cycloalkenyl, heterocycloalkyl, heterocycloalkenyl or heteroaryl, via the group connected to N and together with the ring atom to which it is attached and the adjacent atom, optionally form a 4-7 membered nitrogen-containing heterocyclic ring;
- Rc at each occurrence is independently selected from H or C1-6 alkyl optionally substituted by halogen, or wherein two Rc attached to the same carbon or nitrogen atom, together with the carbon atom or nitrogen atom to which they are attached, independently form a 3-6 membered cyclic group;
- E is selected from halogen, —O—Rd or —N(Rd)2—, wherein each Rd is independently H or C1-6 alkyl optionally substituted by halogen;
- R5 is
- m is 0 or 1;
- represents an aromatic ring;
- B and D are each independently selected from N or C;
- Z, G and Y are each independently selected from C, N, O or S;
- R6, R7 and R8 are each independently selected from H, halogen and C1-6 alkyl optionally substituted by halogen;
- with the proviso that B and D are not both N;
- and at most three of Z, G, Y, D and B are not C;
- or an isomer, a pharmaceutically acceptable salt or a solvate thereof.
14 more elements
A compound of formula (II) or an isomer, a pharmaceutically acceptable salt or a solvate thereof,
- wherein:
- A is selected from C—Ra or N, wherein Ra is selected from halogen;
- R1, R2 and R3 are each independently selected from H, halogen or C1-6 alkyl;
- Rb at each occurrence is independently selected from H, halogen, CN, or C1-6 alkyl optionally substituted by halogen or CN;
- X is selected from a bond, —O— or —NH—;
- R4 is selected from H, halogen, C1-6 alkyl, —C0-3 alkyl-C6-10 aryl, —C0-3 alkyl-C3-8 cycloalkyl, —C0-3 alkyl-C3-8 cycloalkenyl, —C0-3 alkyl-3-8 membered heterocycloalkyl comprising 1, 2 or 3 heteroatoms independently selected from N, O or S, —C0-3 alkyl-3-8 membered heterocycloalkenyl comprising 1, 2 or 3 heteroatoms independently selected from N, O or S, —C0-3 alkyl-5-10 membered heteroaryl comprising 1, 2 or 3 heteroatoms independently selected from N, O or S, wherein the alkyl, aryl, cycloalkyl, cycloalkenyl, heterocycloalkyl, heterocycloalkenyl and heteroaryl are optionally substituted by 1, 2 or 3 groups independently selected from halogen, C1-6 alkyl optionally substituted by halogen, —(CRcRc)0-6—ORc, —(CRcRc)0-6—N(Rc)2, where the —(CRcRc)0-6—N(Rc)2 attached to the aryl, cycloalkyl, cycloalkenyl, heterocycloalkyl, heterocycloalkenyl or heteroaryl, via the group connected to N and together with the ring atom to which it is attached and the adjacent atom, optionally form a 4-7 membered nitrogen-containing heterocyclic ring;
- Rc at each occurrence is independently selected from H or C1-6 alkyl optionally substituted by halogen;
- E is selected from halogen, —O—Rd or —N(Rd)2—, wherein each Rd is independently H or C1-6 alkyl optionally substituted by halogen;
- R6, R7 and R8 are each independently selected from H, halogen and C1-6 alkyl optionally substituted by halogen;
- or an isomer, a pharmaceutically acceptable salt or a solvate thereof.
7 more elements
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A compound selected from
- or an isomer, a pharmaceutically acceptable salt or a solvate thereof.
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Dependencies are inferred from the claim text.