1239461-22-3

Usage

Uses

Used in Pharmaceutical Research:
Methyl 2-amino-4-bromothiophene-3-carboxylate is used as a key intermediate in the design and synthesis of novel, orally active, brain-penetrant, and tri-substituted thiophene-based JNK inhibitors. These inhibitors are being studied for their potential therapeutic applications in various neurological disorders and conditions involving the activation of the c-Jun N-terminal kinase (JNK) signaling pathway.
Used in Medicinal Chemistry:
In the field of medicinal chemistry, methyl 2-amino-4-bromothiophene-3-carboxylate serves as a valuable building block for the development of new chemical entities with potential therapeutic properties. Its unique structural features allow for the creation of diverse molecular frameworks that can be tailored to target specific biological receptors or enzymes, making it a versatile compound for drug discovery efforts.
Used in Drug Design:
Methyl 2-amino-4-bromothiophene-3-carboxylate is utilized in drug design to create new molecules with improved pharmacological properties, such as enhanced potency, selectivity, and bioavailability. By incorporating methyl 2-amino-4-bromothiophene-3-carboxylate into the molecular structure of potential drug candidates, researchers can explore its effects on various biological targets and optimize its therapeutic potential.
Used in Chemical Synthesis:
In addition to its applications in medicinal chemistry and drug design, methyl 2-amino-4-bromothiophene-3-carboxylate is also used as a synthetic building block in the preparation of other organic compounds. Its unique functional groups and structural features make it a useful starting material for the synthesis of a wide range of chemical products, including pharmaceuticals, agrochemicals, and specialty chemicals.

Upstream product

• 1239461-56-3 methyl 2-(((9H-fluoren-9-yl)methoxy)carbonylamino)-4-bromothiophene-3-carboxylate 
• 32807-28-6 Methyl 4-chloroacetoacetate 

Relevant academic research and scientific papers

Discovery of QCA570 as an Exceptionally Potent and Efficacious Proteolysis Targeting Chimera (PROTAC) Degrader of the Bromodomain and Extra-Terminal (BET) Proteins Capable of Inducing Complete and Durable Tumor Regression

Proteins of the bromodomain and extra-terminal (BET) family are epigenetics "readers" and promising therapeutic targets for cancer and other human diseases. We describe herein a structure-guided design of [1,4]oxazepines as a new class of BET inhibitors and our subsequent design, synthesis, and evaluation of proteolysis-targeting chimeric (PROTAC) small-molecule BET degraders. Our efforts have led to the discovery of extremely potent BET degraders, exemplified by QCA570, which effectively induces degradation of BET proteins and inhibits cell growth in human acute leukemia cell lines even at low picomolar concentrations. QCA570 achieves complete and durable tumor regression in leukemia xenograft models in mice at well-tolerated dose-schedules. QCA570 is the most potent and efficacious BET degrader reported to date.

BET BROMODOMAIN PROTEIN DEGRADERS WITH CLEAVABLE LINKERS

The present disclosure provides compounds represented by Formula (I): Formula (I) and the pharmaceutically acceptable salts and solvates thereof, wherein R1, R2a, R2b, R3a, R3b, R4, Y, =, Ar, W, L, and B are as defined as set forth in the specification. The present disclosure also provides compounds of Formula (I)I for use to treat a condition or disorder responsive to inhibition and/or degradation of BET bromodomains such as cancer.

FUSED 1,4-OXAZEPINES AS BET PROTEIN DEGRADERS

The present disclosure provides compounds represented by Formula I and the pharmaceutically acceptable salts, hydrates, and solvates thereof, wherein R1, R2a, R2b, R3a, R3b, R4, Ar, L, X, Y, and B are as defined as set forth in the specification. The present disclosure also provids compounds of Formula I for use to treat a condition or disorder responsive to degradation of BET bromodomains such as cancer.

FUSED 1,4-OXAZEPINES AND RELATED ANALOGS AS BET BROMODOMAIN INHIBITORS

The present disclosure provides fused 1,4-oxazepines and related analogs represented by Formula (I) and the pharmaceutically acceptable salts, hydrates, and solvates thereof, wherein R1, R2a, R2b, R3a, R3b, R4, R5, A, and Y are as defined as set forth in the specification. The present disclosure is also directed to the use of compounds of Formula (I) to treat a condition or disorder responsive to inhibition of BET bromodomains such as cancer.

Design and synthesis of a novel, orally active, brain penetrant, tri-substituted thiophene based JNK inhibitor

The SAR of a series of tri-substituted thiophene JNK3 inhibitors is described. By optimizing both the N-aryl acetamide region of the inhibitor and the 4-position of the thiophene we obtained single digit nanomolar compounds, such as 47, which demonstrated an in vivo effect on JNK activity when dosed orally in our kainic acid mouse model as measured by phospho-c-jun reduction.

INHIBITORS OF JUN N-TERMINAL KINASE

The present disclosure provides inhibitors of c-Jun N-terminal kinases (JNK) having a structure according to the following formula (I): or a salt or solvate thereof, wherein ring A, Ca, Cb, Z, R5, W and Cy are defined herein. The disclosure further provides pharmaceutical compositions including the compounds of the present disclosure and methods of making and using the compounds and compositions of the present disclosure, e.g., in the treatment and prevention of various disorders, such as Alzheimer's disease.