Water-Soluble Antitumor Agents. I. Synthesis and Biological Activity of 6-S-Aminoacyloxymethyl Mercaptopurine Derivatives

• Published in: Chemical & pharmaceutical bulletin Vol. 43; no. 10; pp. 1793 - 1796
• Main Authors: KASHIDA, Tatsuo, TANAKA, Takashi, TSUJIHARA, Kenji, NARASAKI, Naoko, OHOHASHI, Motoaki, HASHIYAMA, Tomiki, ODA, Kouji, HARADA, Naoyuki, HONGU, MITSUYA
• Format: Journal Article
• Language: English
• Published: Tokyo The Pharmaceutical Society of Japan 01.10.1995; 公益社団法人日本薬学会; Maruzen; Japan Science and Technology Agency
• Subjects: 6-mercaptopurine derivative; Animals; Antineoplastic agents; Antineoplastic Agents - chemical synthesis; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; antitumor activity; Biological and medical sciences; Colonic Neoplasms - pathology; double grafted tumor system; Fibrosarcoma - pathology; General aspects; Magnetic Resonance Spectroscopy; Medical sciences; Mercaptopurine - analogs & derivatives; Mercaptopurine - chemical synthesis; Mercaptopurine - pharmacology; Mice; Mice, Inbred BALB C; Neoplasm Transplantation; Pharmacology. Drug treatments; Sarcoma - pathology; Solubility; tumor immunity; Water - chemistry; water-soluble; Antineoplastic agent; Solid tumor; Purine derivatives; Rodentia; Malignant tumor; α-Aminoacid; Vertebrata; Immunostimulant agent; Experimental disease; Mammalia; Structure activity relation; Mouse; Animal; Water solubility; Chemical synthesis
• ISSN: 0009-2363; 1347-5223; 1347-5223
• DOI: 10.1248/cpb.43.1793

In an attempt to improve the effectiveness and bioavailability of 6-mercaptopurine, various kinds of water-soluble analogues, such as 6-S-aminoacyloxymethyl mercaptopurine derivatives (3a-m) and 6-S, 9-disubstituted derivatives (7a, b and 9a, b), were synthesized. These compounds were evaluated for activity to augment antitumor immunity by using a double grafted tumor system. Antitumor activities against solid tumors (sarcoma 180 and colon 26) were also evaluated. Many compounds exhibited potent activities in both test systems. In particular, the aminopropionate derivative (3a) and the L-glutamate derivative (3f) showed significant enhancement of antitumor immunity together with potent antitumor activities.