103943-63-1

Basic information

• Product Name: D-Tryptophan, N-[(1,1-dimethylethoxy)carbonyl]-1-methyl-
• CAS NO: 103943-63-1
• Molecular Formula: C17H22N2O4
• Molecular Weight: 318.373
• Mol File: 103943-63-1.mol
• Article Data: 15

Chemical Properties

• CAS DataBase Reference: D-Tryptophan, N-[(1,1-dimethylethoxy)carbonyl]-1-methyl-(CAS DataBase Reference)
• NIST Chemistry Reference: D-Tryptophan, N-[(1,1-dimethylethoxy)carbonyl]-1-methyl-(103943-63-1)
• EPA Substance Registry System: D-Tryptophan, N-[(1,1-dimethylethoxy)carbonyl]-1-methyl-(103943-63-1)

Safety Data

• Hazardous Substances Data: 103943-63-1(Hazardous Substances Data)

Usage

General Description

D-Tryptophan, N-[(1,1-dimethylethoxy)carbonyl]-1-methyl- is a chemical compound that is a derivative of the amino acid tryptophan. It is commonly used in the pharmaceutical industry as a building block for the synthesis of peptides and proteins. D-Tryptophan, N-[(1,1-dimethylethoxy)carbonyl]-1-methyl- is often used as a protective group for the amino acid tryptophan, allowing for specific reactions to occur without affecting the rest of the molecule. It is also used in the research and development of new drugs and therapeutic agents. Additionally, it has potential applications in the field of neuroscience and as a precursor to the synthesis of certain neurotransmitters and molecules involved in the regulation of mood and appetite. Overall, D-Tryptophan, N-[(1,1-dimethylethoxy)carbonyl]-1-methyl- is an important chemical compound with several uses in the pharmaceutical and biomedical fields.

Upstream product

• 862403-33-6 benzyl N^α-(tert-butoxycarbonyl)-1-methyl-D-tryptophanate 
• 5241-64-5 Boc-D-Trp-OH 
• 74-88-4 methyl iodide 
• 24424-99-5 di-tert-butyl dicarbonate 
• 110117-83-4 D-(+)-N_a-methyltryptophan 
• 21339-55-9 1-methyl-L-tryptophan 

Downstream Products

• 862403-35-8 (R)-2-t-butoxycarbonylamino-3-(1-methyl-1H-indol-3-yl)-N-benzyloxypropionamide 
• 1416469-50-5 (4aS,8aR)-2-{1-[(2R)-2-amino-3-(1-methyl-1H-indol-3-yl)propanoyl]piperidin-4-yl}-4-(3,4-dimethoxyphenyl)-4a,5,6,7,8,8a-hexahydrophthalazin-1(2H)-one 
• 1416467-94-1 4-[5-(cyclopropylmethoxy)-1,3-benzodioxol-4-yl]-N-[(2R)-1-{4-[(4aS,8aR)-4-(3,4-dimethoxyphenyl)-1-oxo-4a,5,6,7,8,8a-hexahydrophthalazin-2(1H)-yl]piperidin-1-yl}-3-(1-methyl-1H-indol-3-yl)-1-oxopropan-2-yl]-5H-pyrrolo[3,2-d]pyrimidine-7-carboxamide 
• 1416470-20-6 tert-butyl [(2R)-1-{4-[(4aS,8aR)-4-(3,4-dimethoxyphenyl)-1-oxo-4a,5,6,7,8,8a-hexa-hydrophthalazin-2(1H)-yl]piperidin-1-yl}-3-(1-methyl-1H-indol-3-yl)-1-oxopropan-2-yl]carbamate 
• 110117-83-4 D-(+)-N_a-methyltryptophan 
• 862403-33-6 benzyl N^α-(tert-butoxycarbonyl)-1-methyl-D-tryptophanate 
• 128718-74-1 N-tert-butoxycarbonyl-D-phenylalanyl-L-cysteinyl(Acm)-D-tryptophyl(Nⁱⁿ-Me)-L-leucine methyl ester 

Relevant articles and documents

Structure-Activity Relationships of Triple-Action Platinum(IV) Prodrugs with Albumin-Binding Properties and Immunomodulating Ligands

Chemotherapy with platinum complexes is essential for clinical anticancer therapy. However, due to side effects and drug resistance, further drug improvement is urgently needed. Herein, we report on triple-action platinum(IV) prodrugs, which, in addition to tumor targeting via maleimide-mediated albumin binding, release the immunomodulatory ligand 1-methyl-d-tryptophan (1-MDT). Unexpectedly, structure-activity relationship analysis showed that the mode of 1-MDT conjugation distinctly impacts the reducibility and thus activation of the prodrugs. This in turn affected ligand release, pharmacokinetic properties, efficiency of immunomodulation, and the anticancer activity in vitro and in a mouse model in vivo. Moreover, we could demonstrate that the design of albumin-targeted multi-modal prodrugs using platinum(IV) is a promising strategy to enhance the cellular uptake of bioactive ligands with low cell permeability (1-MDT) and to improve their selective delivery into the malignant tissue. This will allow tumor-specific anticancer therapy supported by a favorably tuned immune microenvironment.

A Pt(IV) Pro-drug Preferentially Targets Indoleamine-2,3-dioxygenase, Providing Enhanced Ovarian Cancer Immuno-Chemotherapy

Expression of indoleamine-2,3-dioxygenase (IDO), an immunosuppressive enzyme in human tumors, leads to immune evasion and tumor tolerance. IDO is therefore a tumor immunotherapeutic target, and several IDO inhibitors are currently undergoing clinical trials. IDO inhibitors can enhance the efficacy of common cancer chemotherapeutics. Here we investigate Pt(IV)-(D)-1-methyltryptophan conjugates 1 and 2 for combined immunomodulation and DNA cross-link-triggered apoptosis for cancer "immuno-chemotherapy". Compound 2 effectively kills hormone-dependent, cisplatin-resistant human ovarian cancer cells, inhibiting IDO by transcriptional deregulation of the autocrine-signaling loop IDO-AHR-IL6, which blocks kynurenine production and promotes T-cell proliferation. Additionally, 1 and 2 display low toxicity in mice and are stable in blood. To our knowledge, this construct is the first Pt drug candidate with immune checkpoint blockade properties.

Preparation method and application of compounds and anticancer drugs

The invention provides compounds, which are twin drugs formed by a platinum drug and a small molecule drug covalently connected to the axial position of the platinum drug and having an immune negative modulation relieving function, and have structures as shown in a formula I: wherein the structure of the platinum drug is in a dotted frame; R1 and R2 are the same or different small molecule drugs with the function of relieving immune negative regulation; or one of R1 and R2 is a small molecule medicine with an immune negative regulation relieving function, and the other one is hydroxyl. According to the invention, the small molecule drug with the function of relieving the negative immune regulation is covalently linked to the axial position of the platinum drug to form the twin drug, so that the tumor killing effect of the platinum drug and the function of relieving the negative immune regulation of the small molecule drug are simultaneously exerted at the tumor site; the twin drugs are combined with immunotherapy for use, so that the response of immunotherapy can be effectively improved, and the treatment effect on tumors is remarkably improved. The platinum anticancer twin drug are simple in preparation method, low in cost and suitable for industrial production, and has clinical transformation potential.

Dual-functional conjugates improving cancer immunochemotherapy by inhibiting tubulin polymerization and indoleamine-2,3-dioxygenase

A series of novel conjugates comprising tublin and IDO inhibitors were designed, synthesized and evaluated for their antiproliferative activity. Among them, HI5, composed of combretastatin A-4 (CA-4) and (D)-1-methyltryptophan (D-MT) by a linker, exhibited the most potent antitumor activity, in particular with higher IC50 value (0.07 μM) than CA-4 (0.21 μM) against HeLa cancer cell line. Mechanism studies indicated that HI5 can inhibit tubulin polymerization and cell migration, cause G2/M phase arrest, concurrent induce apoptosis via the mitochondrial dependent apoptosis pathway and cause reactive oxidative stress generation in HeLa cells. Furthermore, HI5 can inhibit IDO expression and decrease kynurenine production, leading to stimulating T cells activation and proliferation to enhance antitumor immunity in vitro. Interestingly, HI5 can effectively limit the tumor growth in the HeLa xenograft mice models without causing significant loss of body weight. Consequently, such a conjugation can be a potent and safe immunochemotherapeutic method for improving cancer therapy.