Kyowa Hakko Kirin Co., Limited

Kyowa Kirin Co., Ltd.

Masayoshi Nakoji

Yuichi Takahashi

Tomoyuki Nishikawa

Michihiko Suzuki

Takahiro Nakajima

Junichiro Yamamoto

Jun-ichi Saito

Asana Makino

Fumikazu Shinohara

Taiji Oashi

Kyoichiro Iida

Yukihito Tsukumo

Nobumasa Otsubo

Shuko Okazaki

Yasuo Kouda

An oligonucleotide having improved affinity for AGO2 is disclosed. The oligonucleotide has a nucleotide residue or a nucleoside residue represented by formula (I) wherein Xis an oxygen atom or the like, Ris formula (IIA), wherein Ris halogen or the like, and Ris a hydrogen atom or the like, or formula (IVA) wherein Yis a nitrogen atom or the like, and Yis CH or the like, or the like, Ris a hydrogen atom, hydroxy, halogen, or optionally substituted lower alkoxy, and Ris a hydrogen atom or the like at the 5' end thereof, and the nucleotide residue or the nucleoside residue binds to an adjacent nucleotide residue through the oxygen atom at position 3. A method for improving the knockdown activity of an oligonucleotide wherein the oligonucleotide has a knockdown activity against an mRNA encoding a protein involved in a disease. 

Oligonucleotide

An oligonucleotide having a nucleotide residue or a nucleoside residue represented by formula (I) {wherein Xis an oxygen atom or the like, Ris formula (IIA) (wherein Ris halogen or the like, and Ris a hydrogen atom or the like), formula (IVA) (wherein Yis a nitrogen atom or the like, and Yis CH or the like), or the like, Ris a hydrogen atom, hydroxy, halogen, or optionally substituted lower alkoxy, and Ris a hydrogen atom or the like, or formula (VI) (wherein n2 is 1, 2 or 3)} at the 5' end thereof, wherein the nucleotide residue or the nucleoside residue binds to an adjacent nucleotide residue through the oxygen atom at position 3, is provided. 

Oligonucleotide having non-natural nucleotide at 5'-terminal thereof

Provided are a compound represented by general formula (I), or the pharmaceutically acceptable salt thereof, (wherein Rrepresents a hydrogen atom or the like, Rand Rmay be the same or different, and each represents a hydrogen atom, optionally substituted lower alkyl or cycloalkyl, or Rand Rare combined together with the adjacent nitrogen atom thereto to form nitrogen-containing heterocyclic group, and Z represents a bicyclic heterocyclic group in which optionally substituted two six-membered rings are fused to each other, or the like) and the like.

Pyrimidodiazepinone compound

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Tokyo, Japan

Masayoshi Nakoji