Batimastat, バチマスタット

Batimastat

バチマスタット

Formula	C23H31N3O4S2
cas	130370-60-4
Mol weight	477.6399

CAS Registry Number: 130370-60-4

CAS Name: (2R,3S)-N4-Hydroxy-N1-[(1S)-2-(methylamino)-2-oxo-1-(phenylmethyl)ethyl]-2-(2-methylpropyl)-3-[(2-thienylthio)methyl]butanediamide

Additional Names: (2S,3R)-5-methyl-3-[[(aS)-a-(methylcarbamoyl)phenethyl]carbamoyl]-2-[(2-thienylthio)methyl]hexanohydroxamic acid; [4-(N-hydroxyamino)-2R-isobutyl-3S-(2-thienylthiomethyl)succinyl]-L-phenylalanine-N-methylamide

Manufacturers’ Codes: BB-94

Molecular Formula: C23H31N3O4S2

Molecular Weight: 477.64

Percent Composition: C 57.84%, H 6.54%, N 8.80%, O 13.40%, S 13.43%

Literature References: Synthetic matrix metalloproteinase inhibitor. Prepn: C. Campion et al., WO 9005719; eidem, US 5240958(1990, 1993 both to British Biotech.). Effect on transplanted human ovarian carcinoma: B. Davies et al., Cancer Res. 53, 2087 (1993). Inhibition of metastasis of transplanted human colorectal carcinoma: X. Wang et al., ibid. 54, 4726 (1994).

Properties: Fine white powder. mp 236-238°.

Melting point: mp 236-238°

Therap-Cat: Antineoplastic adjunct (antimetastatic agent).

Keywords: Antineoplastic Adjunct; Antimetastatic Agent; Matrix Metalloproteinase Inhibitor.

Batimastat (INN/USAN, codenamed BB-94) is an anticancer drug that belongs to the family of drugs called angiogenesis inhibitors. It acts as a matrix metalloproteinase inhibitor (MMPI) by mimicking natural MMPI peptides.

Batimastat was the first MMPI that went into clinical trials. First results of a Phase I trial appeared in 1994. The drug reached Phase III but was never marketed; mainly because it couldn’t be administered orally (as opposed to the newer and chemically similar MMPI marimastat), and injection into the peritoneum caused peritonitis.^[1]

SYN

U.S. Patent 5,453,438

U.S. Patent 5,240,958

U.S. Patent 5,530,161

SYN

US 5240958; US 5310763; WO 9005719

The treatment of D-leucine (I) with NaNO2, H2SO4 and NaBr gives 2(R)-bromo-5-methylpentanoic acid (II), which is esterified with isobutene and H2SO4 to the corresponding tert-butyl ester (III). The condensation of (III) with dibenzyl malonate (IV) by means of potassium tert-butoxide in DMF yields the malonyl derivative (V), which is treated with trifluoroacetic acid to hydrolyze the tert-butyl ester, and without isolation is condensed with L-phenylalanine methyl amide (VI) by means of hydroxybenzotriazole (HOBT) and dicyclohexylcarbodiimide (DCC), affording 4-benzyloxy-3-(benzyloxycarbonyl)-2(R)-isobutylsuccinyl-L-phenylalanine methylamide (VII). The elimination of the benzyl groups of (VII) by hydrogenolysis over Pd/C in ethanol gives the dicarboxylic acid (VIII), which by partial decarboxylation and reaction with aqueous formaldehyde and piperidine yields 4-hydroxy-2(R)-isobutyl-3-methylenesuccinyl-L-phenylalanine methylamide (IX). The addition of thiophene-2-thiol (X) to the double bond of (IX) affords 4-hydroxy-2(R)-isobutyl-3(S)-(2-thienylsulfanylmethyl)succinyl-L-phenylalanine methylamide (XI), which is finally treated with hydroxylamine and hydroxybenzotriazole in dichloromethane/DMF.

SPEC

 

HPLC

References

Batimastat

Clinical data
Pregnancy category	N/A
Routes of administration	Injection into pleural space or abdomen
ATC code	none
Legal status
Legal status	Never marketed
Identifiers
IUPAC name[show]
CAS Number	130370-60-4
PubChem CID	5362422
IUPHAR/BPS	5145
DrugBank	DB03880
ChemSpider	4515033
UNII	BK349F52C9
KEGG	D03061
ChEMBL	ChEMBL279786
ECHA InfoCard	100.222.897
Chemical and physical data
Formula	C23H31N3O4S2
Molar mass	477.64 g/mol g·mol−1
3D model (JSmol)	Interactive image
SMILES[hide] O=C(NC)[C@@H](NC(=O)[C@@H]([C@@H](C(=O)NO)CSc1sccc1)CC(C)C)Cc2ccccc2
InChI[hide] InChI=1S/C23H31N3O4S2/c1-15(2)12-17(18(22(28)26-30)14-32-20-10-7-11-31-20)21(27)25-19(23(29)24-3)13-16-8-5-4-6-9-16/h4-11,15,17-19,30H,12-14H2,1-3H3,(H,24,29)(H,25,27)(H,26,28)/t17-,18+,19+/m1/s1 Key:XFILPEOLDIKJHX-QYZOEREBSA-N

//////////Batimastat, BB-94, バチマスタット  ,

[H][C@@](CC1=CC=CC=C1)(NC(=O)[C@]([H])(CC(C)C)[C@]([H])(CSC1=CC=CS1)C(=O)NO)C(=O)NC