185540-75-4

Basic information

• Product Name: (S)-2-{[4-(Toluene-4-sulfonyl)-3,4-dihydro-2H-benzo[1,4]thiazine-7-carbonyl]-amino}-pentanedioic acid diethyl ester
• CAS NO: 185540-75-4
• Molecular Weight: 534.654
• Mol File: 185540-75-4.mol
• Article Data: 1

Chemical Properties

• CAS DataBase Reference: (S)-2-{[4-(Toluene-4-sulfonyl)-3,4-dihydro-2H-benzo[1,4]thiazine-7-carbonyl]-amino}-pentanedioic acid diethyl ester(CAS DataBase Reference)
• NIST Chemistry Reference: (S)-2-{[4-(Toluene-4-sulfonyl)-3,4-dihydro-2H-benzo[1,4]thiazine-7-carbonyl]-amino}-pentanedioic acid diethyl ester(185540-75-4)
• EPA Substance Registry System: (S)-2-{[4-(Toluene-4-sulfonyl)-3,4-dihydro-2H-benzo[1,4]thiazine-7-carbonyl]-amino}-pentanedioic acid diethyl ester(185540-75-4)

Safety Data

• Hazardous Substances Data: 185540-75-4(Hazardous Substances Data)

Upstream product

• 185540-73-2 3-(2-Chloro-ethylsulfanyl)-4-(toluene-4-sulfonylamino)-benzoic acid methyl ester 
• 185540-74-3 4-(Toluene-4-sulfonyl)-3,4-dihydro-2H-benzo[1,4]thiazine-7-carboxylic acid methyl ester 
• 156578-98-2 4-tosyl-3,4-dihydro-2H-benzo[b][1,4]-thiazine-7-carboxylic acid 
• 98-59-9 p-toluenesulfonyl chloride 
• 1571-66-0 4-amino-3-mercaptobenzoic acid hydrochloride 
• 185540-71-0 4-Amino-3-(2-chloro-ethylsulfanyl)-benzoic acid 

Relevant articles and documents

Antirheumatic agents: Novel methotrexate derivatives bearing a benzoxazine or benzothiazine moiety

Novel methotrexate (MTX) derivatives bearing dihydro-2H-1,4- benzothiazine or dihydro-2H-1,4-benzoxazine were synthesized and tested for in vitro antiproliferative activities against human synovial cells (hSC) and human peripheral blood mononuclear cells (hPBMC) obtained from patients with rheumatoid arthritis and healthy volunteers, respectively. In vivo antiarthritic activities of these derivatives were also evaluated in a rat adjuvant arthritis model. N-[[4-[(2,4-Diaminopteridin-6-yl)methyl]-3,4- dihydro-2H-1,4-benzothiazin-7-yl]carbonyl]-L-glutamic acid (3c) exhibited more potent antiproliferative activities in hSC and hPBMC than MTX in vitro. Antiproliferative activities of N-[[4-[(2,4-diaminopteridin-6-yl)methyl]- 3,4-dihydro-2H-1,4-benzoxazin-7-yl]carbonyl]-L-homoglutamic acid (3b) and N- [[4-[(2,4-diaminopteridin-6-yl)methyl]-3,4-dihydro-2H-1,4-benzothiazin-7- yl]carbonyl]-L-homoglutamic acid (3d) (MX-68) were comparable to that of MTX in these in vitro assays. Compounds 3b,d (MX-68) significantly suppressed progression of the adjuvant arthritis in a dose-dependent manner ranging from 0.5 to 2.5 mg/kg (po). In addition, 3d (MX-68) completely suppressed this progression at the dose of 2.5 mg/kg (po). Importantly, 3d (MX-68) having benzothiazine and homoglutamate, as expected, did not undergo polyglutamation, a process which may be responsible for the associated side effects of MTX. These results suggest that 3d (MX-68) is a potent and safe candidate antirheumatic agent, absent of the side effects of MTX.