863781-33-3

Upstream product

• 13139-15-6 N-tert-butoxycarbonyl-L-leucine 
• 13734-41-3 t-Boc-L-valine 
• 15136-32-0 (N-(tert-butoxycarbonyl)-L-leucinyl)-L-phenylalanine methyl ester 
• 2577-90-4 methyl (2S)-2-amino-3-phenylpropanoate 
• 38155-18-9 L-leucyl-L-phenylalanine methyl ester 

Downstream Products

• 1190394-25-2 Boc-Leu(N-Me)-Lys(Cbz)-Val-Leu-Phe-OMe 
• 73401-65-7 (S)-2-((S)-2-tert-Butoxycarbonylamino-4-methyl-pentanoylamino)-4-methyl-pentanoic acid 
• 909108-87-8 (S)-2-((S)-2-{(S)-2-[(S)-2-((R)-2-tert-Butoxycarbonylamino-4-methyl-pentanoylamino)-4-methyl-pentanoylamino]-3-methyl-butyrylamino}-4-methyl-pentanoylamino)-3-phenyl-propionic acid methyl ester 
• 1006104-42-2 (S)-2-[(S)-2-((S)-2-{(S)-2-[((R)-2-Amino-4-methyl-pentanoyl)-methyl-amino]-4-methyl-pentanoylamino}-3-methyl-butyrylamino)-4-methyl-pentanoylamino]-3-phenyl-propionic acid 
• 1006104-46-6 (S)-2-((S)-2-{(S)-2-[(R)-2-((R)-2-Amino-4-methyl-pentanoylamino)-4-methyl-pentanoylamino]-3-methyl-butyrylamino}-4-methyl-pentanoylamino)-3-phenyl-propionic acid 
• 909108-89-0 (S)-2-((S)-2-{(S)-2-[(R)-2-((R)-2-tert-Butoxycarbonylamino-4-methyl-pentanoylamino)-4-methyl-pentanoylamino]-3-methyl-butyrylamino}-4-methyl-pentanoylamino)-3-phenyl-propionic acid methyl ester 
• 909108-83-4 (S)-2-((S)-2-{(S)-2-[(R)-2-((S)-2-tert-Butoxycarbonylamino-4-methyl-pentanoylamino)-4-methyl-pentanoylamino]-3-methyl-butyrylamino}-4-methyl-pentanoylamino)-3-phenyl-propionic acid methyl ester 
• 909108-88-9 (S)-2-[(S)-2-((S)-2-{(S)-2-[((R)-2-tert-Butoxycarbonylamino-4-methyl-pentanoyl)-methyl-amino]-4-methyl-pentanoylamino}-3-methyl-butyrylamino)-4-methyl-pentanoylamino]-3-phenyl-propionic acid methyl ester 
• 863781-34-4 (S)-2-((S)-2-{(S)-2-[(S)-2-((S)-2-tert-Butoxycarbonylamino-4-methyl-pentanoylamino)-4-methyl-pentanoylamino]-3-methyl-butyrylamino}-4-methyl-pentanoylamino)-3-phenyl-propionic acid methyl ester 
• 863781-62-8 (S)-2-[(S)-2-((S)-2-{(S)-2-[(S)-2-(tert-Butoxycarbonyl-methyl-amino)-4-methyl-pentanoylamino]-4-methyl-pentanoylamino}-3-methyl-butyrylamino)-4-methyl-pentanoylamino]-3-phenyl-propionic acid methyl ester 
• 909108-57-2 (S)-2-((S)-4-Methyl-2-{(S)-3-methyl-2-[(S)-4-methyl-2-((S)-4-methyl-2-methylamino-pentanoylamino)-pentanoylamino]-butyrylamino}-pentanoylamino)-3-phenyl-propionic acid 

Relevant academic research and scientific papers

Design and synthesis of Hsp90 inhibitors: Exploring the SAR of Sansalvamide A derivatives

Utilizing the structure-activity relationship we have developed during the synthesis of the first two generations and mechanism of action studies that point to the interaction of these molecules with the key oncogenic protein Hsp90, we report here the design of 32 new Sansalvamide A derivatives and their synthesis. Our new structures, designed from previously reported potent compounds, were tested for cytotoxicity on the HCT116 colon cancer cell line, and their binding to the biological target was analyzed using computational studies involving blind docking of derivatives using Autodock. Further, we show new evidence that our molecules bind directly to Hsp90 and modulate Hsp90's binding with client proteins. Finally, we demonstrate that we have integrated good ADME properties into a new derivative.

A comprehensive study of Sansalvamide A derivatives: The structure-activity relationships of 78 derivatives in two pancreatic cancer cell lines

We report an extensive structure-activity relationship (SAR) of 78 compounds active against two pancreatic cancer cell lines. Our comprehensive evaluation of these compounds utilizes SAR that allow us to evaluate which features of potent compounds play a

Comprehensive study of sansalvamide A derivatives and their structure-activity relationships against drug-resistant colon cancer cell lines

We report an extensive structure-activity relationship (SAR) of 62 compounds active against two drug-resistant colon cancer cell lines. Our comprehensive evaluation of two generations of compounds utilizes SAR, NMR, and molecular modeling to evaluate the

Synthesis and cytotoxicity of a new class of potent decapeptide macrocycles

(Chemical Equation Presented) Described are the syntheses of five decapeptides that are C-2-symmetrical derivatives of the natural product pentapeptide sansalvamide A. Derivatives were made using a succinct convergent synthesis. These analogues share no s

Synthesis of second-generation Sansalvamide A derivatives: Novel templates as potential antitumor agents

We report the synthesis of 34 second-generation Sansalvamide A derivatives. San A derivatives have unique anticancer properties and target multiple cancers, including colon, pancreatic, breast, prostate, and melanoma. As novel templates, the derivatives d

MACROCYCLIC PEPTIDES AND METHODS FOR MAKING AND USING THEM

The invention provides novel macrocyclic peptides and methods for their preparation. The invention also provides pharmaceutical compositions and methods to treat, prevent or ameliorate a cell proliferative disease or conditions, e.g., a cancer, in a subje

High-yielding macrocyclization conditions used in the synthesis of novel Sansalvamide A derivatives

Described are the syntheses of nine Sansalvamide A derivatives using new, high-yielding, in situ deprotection-cyclization conditions that are general for this series of macrocycles, 55% average for both steps. This is 10-fold greater than previously repor

Synthesis of Sansalvamide A derivatives and their cytotoxicity in the MSS colon cancer cell line HT-29

We report the synthesis of thirty-six Sansalvamide A derivatives, and their biological activity against colon cancer HT-29 cell line, a microsatellite stable (MSS) colon cancer cell-line. The thirty-six compounds can be divided into three subsets, where t

Synthesis and cytotoxicity of novel Sansalvamide A derivatives

(Chemical Equation Presented) Described are the syntheses of 14 derivatives of the natural product Sansalvamide A, where two are more active against HCT 116 colon cancer cell lines than the natural product. These derivatives were synthesized using a combi