1246532-96-6

Basic information

• Product Name: Tert-butyl 4-(4-aMino-3-Methoxyphenyl)piperazine-1-carboxylate
• Synonyms: Tert-butyl 4-(4-aMino-3-Methoxyphenyl)piperazine-1-carboxylate
• CAS NO: 1246532-96-6
• Molecular Weight: 307.393
• Mol File: 1246532-96-6.mol

Chemical Properties

• CAS DataBase Reference: Tert-butyl 4-(4-aMino-3-Methoxyphenyl)piperazine-1-carboxylate(CAS DataBase Reference)
• NIST Chemistry Reference: Tert-butyl 4-(4-aMino-3-Methoxyphenyl)piperazine-1-carboxylate(1246532-96-6)
• EPA Substance Registry System: Tert-butyl 4-(4-aMino-3-Methoxyphenyl)piperazine-1-carboxylate(1246532-96-6)

Safety Data

• Hazardous Substances Data: 1246532-96-6(Hazardous Substances Data)

Usage

Uses

Used in Pharmaceutical Research and Development:
Tert-butyl 4-(4-amino-3-methoxyphenyl)piperazine-1-carboxylate is used as a potential therapeutic agent for its ability to modulate specific biological targets in the body, which may contribute to the treatment of various diseases and disorders.
Used in the Treatment of Neurological and Psychiatric Conditions:
In the field of medicine, Tert-butyl 4-(4-amino-3-methoxyphenyl)piperazine-1-carboxylate is used as a potential treatment for neurological and psychiatric conditions due to its interaction with biological targets that may be implicated in these disorders.
Used in Drug Mechanism and Interaction Studies:
Tert-butyl 4-(4-amino-3-methoxyphenyl)piperazine-1-carboxylate is utilized as a valuable tool in studying the mechanisms of action of certain drugs and their interactions with target proteins in the body, which can aid in the development of more effective medications.

Upstream product

• 448-19-1 4-fluoro-2-methoxy-1-nitrobenzene 
• 57260-71-6 1-t-Butoxycarbonylpiperazine 
• 1017782-79-4 tert-butyl 4-(3-methoxy-4-nitrophenyl)piperazine-1-carboxylate 

Downstream Products

• 1246532-97-7 C₃₂H₄₆N₈O₄ 
• 1254783-97-5 tert-butyl 4-(4-(5-chloro-4-(3-nitrophenoxy)pyrimidin-2-ylamino)-3-methoxyphenyl)piperazine-1-carboxylate 

Relevant articles and documents

Discovery and structure ? activity relationship exploration of pyrazolo[1,5-a]pyrimidine derivatives as potent FLT3-ITD inhibitors

Internal tandem duplications of FLT3 (FLT3-ITD) occur in approximately 25% of all acute myeloid leukemia (AML) cases and confer a poor prognosis. Optimization of the screening hit 1 from our in-house compound library led to the discovery of a series of pyrazolo[1,5-a]pyrimidine derivatives as potent and selective FLT3-ITD inhibitors. Compounds 17 and 19 displayed potent FLT3-ITD activities both with IC50 values of 0.4 nM and excellent antiproliferative activities against AML cell lines. Especially, compounds 17 and 19 inhibited the quizartinib resistance- conferring mutations, FLT3D835Y, both with IC50 values of 0.3 nM. Moreover, western blot analysis indicated that compounds 17 and 19 potently inhibited the phosphorylation of FLT3 and attenuated downstream signaling in AML cells. These results indicated that pyrazolo[1,5-a]pyrimidine derivatives could be promising FLT3-ITD inhibitors for the treatment AML.

COMPOUNDS AND METHODS FOR THE TARGETED DEGRADATION OF INTERLEUKIN-1 RECEPTOR-ASSOCIATED KINASE 1 PROTEINS

The present invention relates to compounds comprising an interleukin-1 receptor-associated kinase 1 (IRAK1) protein binding moiety and a Von Hippel-Lindau (VHL) E3 ubiquitin ligase binding moiety, and associated methods of use. The compounds are useful as modulators of targeted ubiquitination, especially with respect to IRAK1, which is degraded by the compounds according to the invention.

PROTEIN DEGRADATION TARGETING COMPOUND, ANTI-TUMOR APPLICATION, INTERMEDIATE THEREOF AND USE OF INTERMEDIATE

The present disclosure relates to compounds of formula (I) and their anti-tumor uses, and their intermediates of formula (III), intermediates of formula (IV), and uses of the intermediates. The compound of formula (I) has a degrading effect on a specific target protein, which is mainly composed of three parts. The first part is a small molecule compound (SMBP, Small Molecules Binding Protein) that can bind to a protein, the second part LIN is a linker, and the three-part ULM is a ubiquitin ligand (ULM, Ubiquitin Ligase Binding Moiety), wherein SMBP is covalently bound to LIN, and LIN is covalently bound to ULM. A series of compounds designed and synthesized in the present disclosure have a wide range of pharmacological activities, including the functions of degrading specific proteins and/or inhibiting activities of specific proteins, and thus can be used in related tumor treatments.

Discovery of Highly Potent and Selective IRAK1 Degraders to Probe Scaffolding Functions of IRAK1 in ABC DLBCL

MyD88 gene mutation has been identified as one of the most prevalent driver mutations in the activated B-cell-like diffuse large B-cell lymphoma (ABC DLBCL). The published literature suggests that interleukin-1 receptor-associated kinase 1 (IRAK1) is an essential gene for ABC DLBCL harboring MyD88 mutation. Importantly, the scaffolding function of IRAK1, rather than its kinase activity, is required for tumor cell survival. Herein, we present our design, synthesis, and biological evaluation of a novel series of potent and selective IRAK1 degraders. One of the most potent compounds, Degrader-3 (JNJ-1013), effectively degraded cellular IRAK1 protein with a DC50 of 3 nM in HBL-1 cells. Furthermore, JNJ-1013 potently inhibited IRAK1 downstream signaling pathways and demonstrated strong anti-proliferative effects in ABC DLBCL cells with MyD88 mutation. This work suggests that IRAK1 degraders have the potential for treating cancers that are dependent on the IRAK1 scaffolding function.

Discovery of the First Examples of Threonine Tyrosine Kinase PROTAC Degraders

The first examples of threonine tyrosine kinase (TTK) PROTACs were designed and synthesized. Two of the most potent molecules, 8e and 8j, demonstrated strong TTK degradation in COLO-205 human colorectal cancer cells with DC50 values of 1.7 and 3.1 nM, respectively. Proteasome-mediated degradation by the compounds could last for approximately 8 h after washout. The degraders 8e and 8j demonstrated improved antiproliferative activities comparing with the structurally similar inhibitor counterparts 8q and 8r. Degraders 8e and 8j also demonstrated reasonable PK profiles and exhibited potent target degradation and in vivo anticancer efficacy in a xenograft mouse model of COLO-205 human colorectal cancer cells upon i.p. administration.

Discovery of a Pyrimidothiazolodiazepinone as a Potent and Selective Focal Adhesion Kinase (FAK) Inhibitor

Focal adhesion kinase (FAK) is a tyrosine kinase with prominent roles in protein scaffolding, migration, angiogenesis, and anchorage-independent cell survival and is an attractive target for the development of cancer therapeutics. However, current FAK inhibitors display dual kinase inhibition and/or significant activity on several kinases. Although multitargeted activity is at times therapeutically advantageous, such behavior can also lead to toxicity and confound chemical-biology studies. We report a novel series of small molecules based on a tricyclic pyrimidothiazolodiazepinone core that displays both high potency and selectivity for FAK. Structure-activity relationship (SAR) studies explored modifications to the thiazole, diazepinone, and aniline "tail,"which identified lead compound BJG-03-025. BJG-03-025 displays potent biochemical FAK inhibition (IC50 = 20 nM), excellent kinome selectivity, activity in 3D-culture breast and gastric cancer models, and favorable pharmacokinetic properties in mice. BJG-03-025 is a valuable chemical probe for evaluation of FAK-dependent biology.

Development of a Brigatinib degrader (SIAIS117) as a potential treatment for ALK positive cancer resistance

EML4-ALK and NPM-ALK fusion proteins possess constitutively activated ALK (anaplastic lymphoma kinase) activity, which in turn leads to the development of non-small cell lung cancer and anaplastic large-cell lymphomas (ALCLs). FDA-approved ALK inhibitor drugs cause significant cancer regression. However, drug resistance eventually occurs and it becomes a big obstacle in clinic. Novel proteolysis targeting chimera (PROTAC) technology platform provides a potential therapeutic strategy for drug resistance. Herein, we designed and synthesized a series of ALK PROTACs based on Brigatinib and VHL-1 conjunction, and screened SIAIS117 as the best degrader which not only blocked the growth of SR and H2228 cancer cell lines, but also degraded ALK protein. In addition, SIAIS117 also showed much better growth inhibition effect than Brigatinib on 293T cell line that exogenously expressed G1202R-resistant ALK proteins. Furthermore, it also degraded G1202R mutant ALK protein in vitro. At last, it has the potentially anti-proliferation ability of small cell lung cancer. Thus, we have successfully generated the degrader SIAIS117 that can potentially overcome resistance in cancer targeted therapy.

Compounds for targeted degradation of focal adhesion kinase and application of the compounds in medicine

The invention relates to the field of biomedicine and drug synthesis, in particular to compounds for targeted degradation of focal adhesion kinase (FAK) protein, pharmaceutically acceptable salts, hydrates, solvates or prodrugs of the compounds, preparation methods of the compounds and the pharmaceutically acceptable salts, hydrates, solvates or prodrugs, and application of the compounds as therapeutic agents, especially as FAK degradation agents. The structures of the compounds, and the geometric isomers or pharmaceutically acceptable salts, hydrates, solvates or prodrugs thereof are shown inthe specification. The compounds provided by the invention have a good degradation effect on FAK kinase, and can be used for preventing, treating or adjunctively treating various diseases related tothe expression or activity of FAK kinase.

Design and Optimization Leading to an Orally Active TTK Protein Kinase Inhibitor with Robust Single Agent Efficacy

Triple negative breast cancer (TNBC) is an aggressive disease with high relapse rates and few treatment options. Outlined in previous publications, we identified a series of potent, dual TTK/CLK2 inhibitors with strong efficacy in TNBC xenograft models. P

ALK (anaplastic lymphoma kinase) protein degradation agent and anti-tumor application thereof

The invention discloses a compound in a formula (I) and an anti-tumor application thereof. The compound in the formula (I) has degradation and inhabitation functions on ALK target protein and mainly comprises four parts, the first part ALK-TKIs is a compound with ALK tyrosine kinase inhabitation activity; the second part LIN is different linkers; the third part ULM (ubiquitin ligase binding moiety) of VHL, CRBN or other protease micromolecular ligand with a ubiquitination function; the fourth part group A is carboxyl or deficiency and covalently binds ALK-TKIs with LIN and covalently binds LINwith ULM. A series of designed and synthesized compounds have wide pharmacological activity, have functions of degrading ALK protein and inhibiting ALK activity and can be applied to related tumor therapy.