Journal of Medicinal Chemistry p. 2426 - 2431 (1989)
Update date:2022-08-04
Topics:
Kralovec
Spencer
Blair
Mammen
Singh
Ghose
In order to increase the retention of drug activity, regiospecific coupling has been used to synthesize conjugates of methotrexate (MTX, 1) with normal rabbit IgG (NRG) and a mouse anti-human renal cancer monoclonal IgG (Dal K-20). MTX γ-methyl ester (4) was produced either by selective esterification of MTX or by coupling of 4-amino-4-deoxy-N10-methylpteroic acid (2) with suitable glutamic acid derivatives. The MTX γ-methyl ester (4) was then converted to the corresponding hydrazide 6. An amide-linked conjugate was formed when the MTX γ-hydrazide (6) was converted to reactive acylating species 7 by using tert-butyl nitrite or trifluoroacetaldehyde, which were reacted with nucleophilic centers, presumably ε-amino groups, in native IgG. A hydrazone-linked conjugate was formed when MTX γ-hydrazide (6) was reacted directly with IgG that had first been oxidized with periodate to form polyaldehyde IgG. The regiospecifically synthesized conjugates were somewhat more effective inhibitors in vitro of dihydrofolate reductase and of colony formation by human renal cancer (Caki-1) cells than were control nonregiospecific conjugates.
View MoreNanjing Chemlin Chemical Co., Ltd.
website:http://www.echemlin.cn
Contact:+86-25-83697070
Address:Rm.902 Longyin Plaza, No. 217 Zhongshan Rd.(N) Nanjing 210009,China
Beyond Pharmaceutical Co., Ltd
Contact:+86-571-8195-3185
Address:No. 13-1, Liansheng Road, Yuhang District
Chengdu Biopurify Phytochemicals Ltd.
website:http://www.phytopurify.com
Contact:+86-28-82633397
Address:2F,No.11 Building,No.388 Rongtaidadao CNSTP,Wenjiang Zone,Chengdu,Sichuan, China
Contact:86-574-26865651
Address:529 YuanBaoShan Road, Beilun District
Contact:+86-25-8776 0031
Address:3-2001 Jiaye Int'l Town, 158 Lushan Road,Nanjing, 210019, China
Doi:10.1002/oms.1210280203
(1993)Doi:10.1016/S0020-1693(98)00299-0
(1999)Doi:10.1080/15257779908043072
(1999)Doi:10.1021/ja9834881
(1999)Doi:10.1016/S0960-894X(98)00692-1
(1999)Doi:10.1016/S0040-4039(01)87713-3
(1969)