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US 12,103,902 B2Granted
Bicyclic compounds
AssigneeVivace Therapeutics, Inc.
InventorsAndrei W. Konradi, Tracy Tzu-Ling Tang Lin
Life of this patent
Estimating the term…
Abstract
Provided herein are compounds and pharmaceutical compositions comprising said compounds that are useful for treating diseases, such as cancers. Specific cancers include those that are mediated by YAP/TAZ or those that are modulated by the interaction between YAP/TAZ and TEAD.
Claims17
A method of treating a cancer mediated by activation of transcriptional coactivator with PDZ binding motif/Yes-associated protein transcription coactivator (TAZ/YAP) in a subject in need thereof comprising administering to the subject in need thereof a therapeutically effective amount of a compound of Formula (I), or a pharmaceutically acceptable salt thereof,
- wherein,
- X1 is CRX;
- and each X2 and X3 is CRY;
- each X4, X5, and X6, is independently N or CRX;
- each RX is independently hydrogen, halogen, nitro, —OR3, —SR3, —CN, —C(═O)R3, —C(═O)N(R3)2, —C(═O)OR3, —S(═O)R3, —S(═O)2R3, —N(R3)2, —NR3S(═O)2R3, —NR3C(═O)R3, —NR3C(═O)OR3, substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted C1-C6fluoroalkyl, substituted or unsubstituted C2-C4alkenyl, substituted or unsubstituted C2-C4alkynyl, substituted or unsubstituted C1-C6heteroalkyl, substituted or unsubstituted C3-C10cycloalkyl, substituted or unsubstituted C2-C10heterocycloalkyl, substituted or unsubstituted aralkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl;
- each RY is independently hydrogen, halogen, nitro, —CN, —C(═O)R3, —C(═O)N(R3)2 , —C(═O)OR3, —S(═O)R3, —S(═O)2R3, —N(R3)2, —NR3S(═O)2R3, —NR3C(═O)R3, —NR3C(═O)OR3, substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted C1-C6fluoroalkyl, substituted or unsubstituted C2-C4alkenyl, substituted or unsubstituted C2-C4alkynyl, substituted or unsubstituted C1-C6heteroalkyl, substituted or unsubstituted C3-C10cycloalkyl, substituted or unsubstituted C2-C10heterocycloalkyl, substituted or unsubstituted aralkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl;
- R is halogen, nitro, —CN, —OR3, —SR3, —C(═O)R3, —C(═O)N(R3)2, —C(═O)OR3, —S(═O)R3, —S(═O)2R3, —N(R3)2, —NR3S(═O)2R3, —NR3C(═O)R3, —NR3C(═O)OR3, or substituted or unsubstituted C1-C6fluoroalkyl;
- R1 is C1-C10alkyl substituted with —OR3;
- and R3 is hydrogen, substituted or unsubstituted C1-C6alkyl, substituted or unsubstituted C1-C6fluoroalkyl, or substituted or unsubstituted C3-C10cycloalkyl;
- each R2 is independently halogen, nitro, —N3, —CN, —OR3, —SR3, —S(═O)2R3, —N(R3)2, —C(═O)OR3, substituted or unsubstituted C1-C6alkyl, substituted or unsubstituted C1-C6fluoroalkyl, substituted or unsubstituted C1-C6heteroalkyl, substituted or unsubstituted C3-C10cycloalkyl, substituted or unsubstituted C2-C10heterocycloalkyl, substituted or unsubstituted aralkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl;
- each R3 is independently hydrogen, substituted or unsubstituted C1-C6alkyl, substituted or unsubstituted C1-C6fluoroalkyl, substituted or unsubstituted C1-C6heteroalkyl, substituted or unsubstituted C3-C10cycloalkyl, substituted or unsubstituted C2-C10heterocycloalkyl, substituted or unsubstituted aralkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl;
- or if two R3 are on the same nitrogen atom, then two R3 are taken together with the nitrogen atom to which they are attached to form a substituted or unsubstituted C3-C7 heterocycloalkyl;
- and
- n is 0, 1, 2, 3, or 4;
- and
- wherein the cancer is selected from uveal melanoma, mesothelioma, esophageal cancer, liver cancer, breast cancer, hepatocellular carcinoma, lung adenocarcinoma, glioma, colon cancer, colorectal cancer, gastric cancer, medulloblastoma, ovarian cancer, esophageal squamous cell carcinoma, sarcoma, Ewing sarcoma-, head and neck cancer, prostate cancer, and meningioma, and wherein the treatment is for therapeutic benefit.
13 more elements
A method of inhibiting an interaction of transcriptional enhancer associate domain (TEAD) transcription factors with transcriptional coactivator with PDZ binding motif/Yes-associated protein transcription coactivator (TAZ/YAP) in a mammal comprising administering to a subject in need thereof a therapeutically effective amount of a compound of Formula (I), or a pharmaceutically acceptable salt thereof,
- wherein,
- X1 is CRX;
- and each X2 and X3 is CRY;
- each X4, X5, and X6, is independently N or CRX;
- each RX is independently hydrogen, halogen, nitro, —OR3, —SR3, —CN, —C(═O)R3, —C(═O)N(R3)2, —C(═O)OR3, —S(═O)R3, —S(═O)2R3, —N(R3)2, —NR3S(═O)2R3, —NR3C(═O)R3, —NR3C(—O)OR3, substituted or unsubstituted C1-C6alkyl, substituted or unsubstituted C1-C6fluoroalkyl, substituted or unsubstituted C2-C4alkenyl, substituted or unsubstituted C2-C4alkynyl, substituted or unsubstituted C1-C6heteroalkyl, substituted or unsubstituted C3-C10cycloalkyl, substituted or unsubstituted C2-C10heterocycloalkyl, substituted or unsubstituted aralkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl;
- each RY is independently hydrogen, halogen, nitro, —CN, —C(O═O)R3, —C(═O)N(R3)2, —C(═O)OR3, —S(═O)R3, —S(═O)2R3, —N(R3)2, —NR3S(═O)2R3, —NR3C(═O)R3, —NR3C(═O)OR3, substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted C1-C6fluoroalkyl, substituted or unsubstituted C2-C4alkenyl, substituted or unsubstituted C2-C4alkynyl, substituted or unsubstituted C1-C6heteroalkyl, substituted or unsubstituted C3-C10cycloalkyl, substituted or unsubstituted C2-C10heterocycloalkyl, substituted or unsubstituted aralkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl;
- R is halogen, nitro, —CN, —OR3, —SR3, —C(═O)R3, -C(—O)N(R3)2, —C(═O)OR3, —S(═O)R3, —S(═O)2R3, —N(R3)2, —NR3S(—O)2R3, —NR3C(—O)R3, —NR3C(═O)OR3, or substituted or unsubstituted C1-C6fluoroalkyl;
- R1 is C1-C6alkyl substituted with —OR3;
- and R3 is hydrogen, substituted or unsubstituted C1-C6alkyl, substituted or unsubstituted C1-C6fluoroalkyl, or substituted or unsubstituted C3-C10cycloalkyl;
- each R2 is independently halogen, nitro, —N3, —CN, —OR3, —SR3, —S(═O)2R3, —N(R3)2, —C(═O)OR3, substituted or unsubstituted C1-C6alkyl, substituted or unsubstituted C1-C10fluoroalkyl, substituted or unsubstituted C1-C6heteroalkyl, substituted or unsubstituted C3-C10cycloalkyl, substituted or unsubstituted C2-C10heterocycloalkyl, substituted or unsubstituted aralkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl,
- each R3 is independently hydrogen, substituted or unsubstituted C1-C6alkyl, substituted or unsubstituted C1-C6fluoroalkyl, substituted or unsubstituted C1-C6heteroalkyl, substituted or unsubstituted C3-C10cycloalkyl, substituted or unsubstituted C2-C10heterocycloalkyl, substituted or unsubstituted aralkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl;
- or if two R3 are on the same nitrogen atom, then two R3 are taken together with the nitrogen atom to which they are attached to form a substituted or unsubstituted C3-C7 heterocycloalkyl;
- and
- n is 0, 1, 2, 3, or 4.
11 more elements
Dependencies are inferred from the claim text.