AMIDATION OF HYALURONIC ACID WITH A METHOTREXATE-DERIVED AMINE: OPTIMIZATION OF THE KEY REACTION FOR THE SYNTHESIS OF A CANDIDATE DRUG FOR THE TREATMENT OF OSTEOARTHRITIS

被引：0

作者：

Homma, Akie ^{[1
]}

Ishizawa, Takenori ^{[2
]}

Sato, Haruhiko ^{[2
]}

Okamachi, Akira ^{[2
]}

Emura, Takashi ^{[2
]}

Kato, Tatsuya ^{[2
]}

Matsuura, Tetsu ^{[2
]}

Sato, Shigeo ^{[2
]}

Ikemi, Masahisa ^{[3
]}

Kitagawa, Hironoshin ^{[3
]}

Morikawa, Tadashi ^{[3
]}

Ikeya, Hitoshi ^{[3
]}

Takahashi, Koichi ^{[3
]}

机构：

[1] Chugai Pharmaceut Co Ltd, API Proc Dept, Kita Ku, Tokyo 1158543, Japan

[2] Chugai Pharmaceut Co Ltd, Div Res, Shizuoka 4128513, Japan

[3] Denki Kagaku Kogyo KK, Cent Res Inst, Tokyo 1948560, Japan

来源：

HETEROCYCLES | 2010年 / 82卷 / 01期

关键词：

High Molecular Weight HA; Degradation of HA; Gel Permeation Chromatography; Acetyltryptophan; CARBODIIMIDES;

D O I：

10.3987/COM-10-S(E)41

中图分类号：

O62 [有机化学];

学科分类号：

070303 ; 081704 ;

摘要：

Optimal amidation conditions between hyaluronic acid (HA) and a methotrexate (MTX)-derived amine that gave rise to a HA-MTX conjugate having a molecular weight of similar to 2000 kDa have been established based on a model experiment using a tryptophan-derived amine in aqueous THF. This method is robust and provides a conjugate with properties of primary importance for efficacy-MW and amine binding ratio-that satisfy the criteria for a HA-MTX conjugate to be a good candidate.

引用

页码：273 / 279

页数：7

共 1 条

[1] Synthesis and optimization of hyaluronic acid-methotrexate conjugates to maximize benefit in the treatment of osteoarthritis
Homma, Akie
Sato, Haruhiko
Tamura, Tatsuya
Okamachi, Akira
Emura, Takashi
Ishizawa, Takenori
Kato, Tatsuya
Matsuura, Tetsu
Sato, Shigeo
Higuchi, Yoshinobu
Watanabe, Tomoyuki
Kitamura, Hidetomo
Asanuma, Kentaro
Yamazaki, Tadao
Ikemi, Masahisa
Kitagawa, Hironoshin
Morikawa, Tadashi
Ikeya, Hitoshi
Maeda, Kazuaki
Takahashi, Koichi
Nohmi, Kenji
Izutani, Noriyuki
Kanda, Makoto
Suzuki, Ryohchi
BIOORGANIC & MEDICINAL CHEMISTRY, 2010, 18 (03) : 1062 - 1075

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