174602-80-3

Upstream product

• 24424-99-5 di-tert-butyl dicarbonate 
• 882980-43-0 2-benzyloxy-1-methylpyridinium triflate 
• 45170-31-8 Boc-N-Me-Val-OH 
• 72-18-4 L-valine 
• 13734-41-3 t-Boc-L-valine 
• 100-39-0 benzyl bromide 
• 66447-55-0 ((S)-1-benzylcarbamoyl-2-methyl-propyl)-carbamic acid tert-butyl ester 
• 74-88-4 methyl iodide 

Downstream Products

• 177607-73-7 (S)-2-[((2S,3R)-3-Acetoxy-2-tert-butoxycarbonylamino-butyryl)-methyl-amino]-3-methyl-butyric acid benzyl ester 
• 119603-16-6 majusculamide D 

Relevant academic research and scientific papers

Highly Convergent Total Synthesis and Assignment of Absolute Configuration of Majusculamide D, a Potent and Selective Cytotoxic Metabolite from Moorea sp.

The total synthesis of majusculamide D (MJS-D) is described, a lipopentapeptide originally isolated from Lyngbya majuscula and reisolated from a Moorea sp. MJS-D possesses selective and potent cancer cell toxicity. A scalable and convergent strategy with a minimal number of purifications produced significant quantities of MJM-D for in vivo evaluations. The absolute configuration of the 1,3-dimethyl-octanamide motif was determined by synthesis of this fragment via ZACA chemistry.

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.

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. 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.

IGF-1R ANTIBODY-DRUG-CONJUGATE AND ITS USE FOR THE TREATMENT OF CANCER

The present invention relates to an antibody-drug-conjugate capable of binding IGF-1R. From one aspect, the invention relates to an antibody-drug-conjugate comprising an antibody capable of binding to IGF-1R, 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.

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.

1-Ethyl 2-halopyridinium salts, highly efficient coupling reagents for hindered peptide synthesis both in solution and the solid-phase

1-Ethyl-2-halopyridinium salts, BEP, FEP, BEPH and FEPH, were synthesized and proved to be very effective for the synthesis of hindered peptides containing N-methylated or C(α),C(α)-dialkylated amino acid residues. HPLC monitoring of model reactions indicated that these pyridinium salts demonstrated higher reactivities, lower racemization than the commonly used halogenated uronium and phosphonium salts. The efficiency of these pyridinium type coupling reagents was further proved by the synthesis of a series of hindered oligopeptides and active esters with good yields and convenient workup. The 8-11 tetrapeptide fragment of Cyclosporin A (CsA) and the pentapeptide moiety of Dolastatin 15 were also successfully synthesized using these pyridinium salts. The efficiency of these pyridinium type coupling reagents for SPPS was also demonstrated by the solid-phase synthesis of the extremely hindered 8-11 peptide segment of CsA and the linear undecapeptide of CsO. The mechanism of the pyridinium salt mediated coupling reactions was also studied by 1H NMR, IR and HPLC. It was proposed that the major reactive intermediates were the corresponding acyl halide and acyloxypyridinium salts of the N-protected amino acid or peptide. (C) 2000 Elsevier Science Ltd.