120205-48-3

Basic information

• Product Name: (3R,4S,5S)-tert-butyl 3-Methoxy-5-Methyl-4-(MethylaMino)heptanoate hydroc hloride
• Synonyms: (3R,4S,5S)-tert-butyl 3-Methoxy-5-Methyl-4-(MethylaMino)heptanoate hydroc hloride;(3R,4S,5S)-3-Methoxy-5-methyl-4-(methylamino)heptanoic Acid 1,1-Dimethylethyl Ester Hydrochloride;(3R,4S,5S)-tert-butyl 3-Methoxy-5-Methyl-4-(MethylaMino)heptanoate hydrochloride (Dil-HCl);Dolaisoleucine Hydrochloride (DIL-HCl);2-Methyl-2-propanyl (3R,4S,5S)-3-methoxy-5-methyl-4-(methylamino) heptanoate hydrochloride (1:1);3R,4S,5S-tert-butyl 3-methoxy-5-methyl-4-;methylaminoheptanoatehydrochloride;tert-Butyl (3R,4S,5S)-3-methoxy-5-methyl-4-(methylamino)heptanoate hydrochloride
• CAS NO: 120205-48-3
• Molecular Formula: C₁₄H₂₉NO₃*ClH
• Molecular Weight: 296
• Mol File: 120205-48-3.mol

Chemical Properties

• Appearance: /
• Storage Temp.: Inert atmosphere,Room Temperature
• CAS DataBase Reference: (3R,4S,5S)-tert-butyl 3-Methoxy-5-Methyl-4-(MethylaMino)heptanoate hydroc hloride(CAS DataBase Reference)
• NIST Chemistry Reference: (3R,4S,5S)-tert-butyl 3-Methoxy-5-Methyl-4-(MethylaMino)heptanoate hydroc hloride(120205-48-3)
• EPA Substance Registry System: (3R,4S,5S)-tert-butyl 3-Methoxy-5-Methyl-4-(MethylaMino)heptanoate hydroc hloride(120205-48-3)

Safety Data

• Hazardous Substances Data: 120205-48-3(Hazardous Substances Data)

Usage

Uses

(3R,4S,5S)-3-Methoxy-5-methyl-4-(methylamino)heptanoic Acid 1,1-Dimethylethyl Ester is an β-methoxy-γ-amino acid component of dolastatin 10, an antineoplastic agent.

Upstream product

• 154633-73-5 tert-Butyl (3S,4S,5S)-3-methoxy-4--5-methylheptanoate 
• 1859-49-0 (2S,3S)-2-(benzylamino)-3-methylpentanoic acid 
• 73-32-5 L-isoleucine 
• 74786-02-0 1-(tert-butyldimethylsilyloxy)-1-tert-butoxyethylene 
• 870640-61-2 (2S,3S)-N-benzyl-1,1-dimethoxy-N,3-dimethylpentan-2-amine 
• 870640-63-4 (2S,3S)-2-(benzyl(methyl)amino)-3-methylpentanal 
• 870640-62-3 (2S,3 S)-2-[benzyl(methyl)amino]-3-methylpentan-1-ol 
• 4125-97-7 (2S,3S)-2-(benzyl(methyl)amino)-3-methylpentanoic acid 
• 42417-66-3 (2S,3S)-3-methyl-2-(methyl{[(phenylmethyl)oxy]carbonyl}amino)pentanoic acid 
• 120205-58-5 tert-Butyl (3R,4S,5S)-3-methoxy-4--5-methylheptanoate 
• 120294-43-1 tert-Butyl (3R,4S,5S)-3-hydroxy-4--5-methylheptanoate 
• 870640-64-5 tert-butyl (3R,4S,5S)-4-[benzyl(methyl)amino]-3-methoxy-5-methyl heptanoate 
• 120205-56-3 benzyl methyl[(2S,3S)-3-methyl-1-oxopentan-2-yl]carbamate 
• 120205-55-2 benzyl [(2S,3S)-1-hydroxy-3-methylpentan-2-yl]methylcarbamate 

Downstream Products

• 120205-52-9 tert-butyl (3R,4S,5S)-4-[(2S)-2-[[(benzyloxy)carbonyl]amino]-N,3-dimethylbutanamido]-3-methoxy-5-methylheptanoate 
• 646502-53-6 4-((S)-2-((S)-2-(6-(2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)hexanamido)-3-methylbutanamido)-5-ureidopentanamido)benzyl((S)-1-(((S)-1-(((3R,4S,5S)-1-((S)-2-((1R,2R)-3-(((1S,2R)-1-hydroxy-1-phenylpropan-2-yl)amino)-1-methoxy-2-methyl-3-oxopropyl)pyrrolidin-1-yl)-3-methoxy-5-methyl-1-oxoheptan-4-yl)(methyl)amino)-3-methyl-1-oxobutan-2-yl)amino)-3-methyl-1-oxobutan-2-yl)(methyl)carbamate 
• 474645-27-7 [3H]-Vedotin 
• 863971-44-2 (5S,8S,11S,12R)-11-((S)-sec-butyl)-1-(9H-fluoren-9-yl)-5,8-diisopropyl-12-methoxy-4,10-dimethyl-3,6,9-trioxo-2-oxa-4,7,10-triazatetradecan-14-oic acid 
• 474645-25-5 tert-butyl (5S,8S,11S,12R)-11-((S)-sec-butyl)-1-(9H-fluoren-9-yl)-5,8-diisopropyl-12-methoxy-4,10-dimethyl-3,6,9-trioxo-2-oxa-4,7,10-triazatetradecan-14-oate 

Relevant articles and documents

Rational Design of Azastatin as a Potential ADC Payload with Reduced Bystander Killing

Auristatins are a class of ultrapotent microtubule inhibitors, whose growing clinical popularity in oncology is based upon their use as payloads in antibody-drug conjugates (ADCs). The most widely utilized auristatin, MMAE, has however been shown to cause apoptosis in non-pathological cells proximal to the tumour (“bystander killing”). Herein, we introduce azastatins, a new class of auristatin derivatives encompassing a side chain amine for antibody conjugation. The synthesis of Cbz-azastatin methyl ester, which included the C2-elongation and diastereoselective reduction of two proteinogenic amino acids as key transformations, was accomplished in 22 steps and 0.76 % overall yield. While Cbz-protected azastatin methyl ester (0.13–3.0 nM) inhibited proliferation more potently than MMAE (0.47–6.5 nM), removal of the Cbz-group yielded dramatically increased IC50-values (9.8–170 nM). We attribute the reduced apparent cytotoxicity of the deprotected azastatin methyl esters to a lack of membrane permeability. These results clearly establish the azastatins as a novel class of cytotoxic payloads ideally suited for use in next-generation ADC development.

COMPOSITION FOR THE TREATMENT OF IGF-1R EXPRESSING CANCER

The present invention relates to a method for the treatment of IGF-IR expressing cancers as well as to a compositions and a kit for said traitment. From one aspect, the invention reates to the combined use of a first antibody for the determination of the IGF-IR status of a cancer and a second antibody used as an ADC for the treatment of said cancer.

CONJUGATE OF MONOMETHYL AURISTATIN F AND TRASTUZUMAB AND ITS USE FOR THE TREATMENT OF CANCER

The present invention relates to an antibody-drug-conjugate or pharmaceutical composition comprising the same. From one aspect, the invention relates to an antibody-drug-conjugate (ADC) comprising an antibody consisting of the Trastuzumab or a biosimilar thereof, said antibody being conjugated to at least one drug consisting of a monomethyl auristatin F derivative. The invention also comprises method of treatment of cancer comprising administering to the subject an effective amount of said antibody-drug-conjugate or composition comprising the same.

CONJUGATE OF MONOMETHYL AURISTATIN F AND TRASTUZUMAB AND ITS USE FOR THE TREATMENT OF CANCER

The present invention relates to an antibody-drug-conjugate. From one aspect, the invention relates to an antibody-drug-conjugate comprising an antibody consisting of the Trastuzumab, said antibody being conjugated to at least one drug consisting of a monomethyl auristatin F derivative. The invention also comprises method of treatment and the use of said antibody-drug-conjugate for the treatment of cancer.

ANTIBODY-DRUG-CONJUGATE AND ITS USE FOR THE TREATMENT OF CANCER

The present invention relates to an antibody-drug-conjugate. From one aspect, the invention relates to an antibody-drug-conjugate comprising an antibody capable of binding to a Target, said antibody being conjugated to at least one drug selected from derivatives of dolastatin 10 and auristatins. The invention also comprises method of treatment and the use of said antibody-drug-conjugate for the treatment of cancer.

DERIVATIVES OF DOLASTATIN 10 AND AURISTATINS

The present invention concerns a compound of following formula (I): where: - R1 is H or OH, - R2 is a (C1-C6)alkyl, COOH, COO-((C1-C6)alkyl) or thiazolyl group, - R3 is H or a (C1-C6)alkyl group, and - R4 is: ■ a straight-chain or branched, saturated or unsaturated hydrocarbon group having 1 to 8 carbon atoms substituted by one or more groups chosen from among OH and NR5R6, ■ -(CH2CH2X1)(CH2CH2X2)a2(CH2CH2X3)a3(CH2CH2X4)a4(CH2CH2X5)a5R7, ■ an aryl-(C1-C8)alkyl group substituted by one or more groups chosen from among OH and NR9R10 groups, or ■ a heterocycle-(C1-C8)alkyl group optionally substituted by one or more groups chosen from among (C1-C6)alkyl, OH and NR12R13 groups, or a pharmaceutically acceptable salt, hydrate or solvate thereof, and its uses in particular for the treatment of cancer, pharmaceutical compositions containing the same and the preparation methods thereof.

DERIVATIVES OF DOLASTATIN 10 AND AURISTATINS

The present invention concerns a compound of following formula (I) where: - R1 is H or OH, - R2 is a (C1-C6)alkyl, COOH, COO-((C1-C6)alkyl) or thiazolyl group, - R3 is H or a (C1-C6)alkyl group, and - R4 is an aryl-(C1-C8)alkyl group substituted by one or more groups chosen from among OH and NR9R10 groups, or a pharmaceutically acceptable salt, hydrate or solvate thereof, and its uses in particular for the treatment of cancer, pharmaceutical compositions containing the same and the preparation methods thereof.

DERIVATIVES OF DOLASTATIN 10 AND AURISTATINS

The present invention concerns a compound of following formula (I) where: - R1 is H or OH, - R2 is a (C1-C6)alkyl, COOH, COO-((C1-C6)alkyl) or thiazolyl group, - R3 is H or a (C1-C6)alkyl group, and - R4 is: - an aryl-(C1-C8)alkyl group substituted by one or more groups chosen from among OH and NR9R10 groups, or - a heterocycle-(C1-C8)alkyl group optionally substituted by one or more groups chosen from among (C1-C6)alkyl, OH and NR12R13 groups, or a pharmaceutically acceptable salt, hydrate or solvate thereof, and its uses in particular for the treatment of cancer, pharmaceutical compositions containing the same and the preparation methods thereof.

CYTOTOXIC PEPTIDES AND ANTIBODY DRUG CONJUGATES THEREOF

The present invention is directed to cytotoxic pentapeptides, to antibody drug conjugates thereof, and to methods for using the same to treat cancer.

Synthesis of alpha-amino-beta-alkoxy-carboxylic acid esters

Compounds of formula I and a process for the preparation of such compounds are disclosed.