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1. WO2014156196 - THERAPEUTIC AGENT FOR TYPE 2 DIABETES

Publication Number WO/2014/156196
Publication Date 02.10.2014
International Application No. PCT/JP2014/001853
International Filing Date 28.03.2014
Chapter 2 Demand Filed 10.10.2014
IPC
A61K 31/138 2006.01
AHUMAN NECESSITIES
61MEDICAL OR VETERINARY SCIENCE; HYGIENE
KPREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
31Medicinal preparations containing organic active ingredients
13Amines, e.g. amantadine
135having aromatic rings, e.g. methadone
138Aryloxyalkylamines, e.g. propranolol, tamoxifen, phenoxybenzamine
A61K 31/135 2006.01
AHUMAN NECESSITIES
61MEDICAL OR VETERINARY SCIENCE; HYGIENE
KPREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
31Medicinal preparations containing organic active ingredients
13Amines, e.g. amantadine
135having aromatic rings, e.g. methadone
A61K 31/4453 2006.01
AHUMAN NECESSITIES
61MEDICAL OR VETERINARY SCIENCE; HYGIENE
KPREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
31Medicinal preparations containing organic active ingredients
33Heterocyclic compounds
395having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
435having six-membered rings with one nitrogen as the only ring hetero atom
44Non-condensed pyridines; Hydrogenated derivatives thereof
445Non-condensed piperidines, e.g. piperocaine
4453only substituted in position 1, e.g. propipocaine, diperodon
A61K 31/47 2006.01
AHUMAN NECESSITIES
61MEDICAL OR VETERINARY SCIENCE; HYGIENE
KPREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
31Medicinal preparations containing organic active ingredients
33Heterocyclic compounds
395having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
435having six-membered rings with one nitrogen as the only ring hetero atom
47Quinolines; Isoquinolines
A61K 31/495 2006.01
AHUMAN NECESSITIES
61MEDICAL OR VETERINARY SCIENCE; HYGIENE
KPREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
31Medicinal preparations containing organic active ingredients
33Heterocyclic compounds
395having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
495having six-membered rings with two nitrogen atoms as the only ring hetero atoms, e.g. piperazine
A61K 31/496 2006.01
AHUMAN NECESSITIES
61MEDICAL OR VETERINARY SCIENCE; HYGIENE
KPREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
31Medicinal preparations containing organic active ingredients
33Heterocyclic compounds
395having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
495having six-membered rings with two nitrogen atoms as the only ring hetero atoms, e.g. piperazine
496Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene
CPC
A61K 31/192
AHUMAN NECESSITIES
61MEDICAL OR VETERINARY SCIENCE; HYGIENE
KPREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
31Medicinal preparations containing organic active ingredients
185Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic, hydroximic acids
19Carboxylic acids, e.g. valproic acid
192having aromatic groups, e.g. sulindac, 2-arylpropionic acids, ethacrynic acid
A61K 31/197
AHUMAN NECESSITIES
61MEDICAL OR VETERINARY SCIENCE; HYGIENE
KPREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
31Medicinal preparations containing organic active ingredients
185Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic, hydroximic acids
19Carboxylic acids, e.g. valproic acid
195having an amino group
197the amino and the carboxyl groups being attached to the same acyclic carbon chain, e.g. gamma-aminobutyric acid [GABA], beta-alanine, epsilon-aminocaproic acid, pantothenic acid
A61K 31/4545
AHUMAN NECESSITIES
61MEDICAL OR VETERINARY SCIENCE; HYGIENE
KPREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
31Medicinal preparations containing organic active ingredients
33Heterocyclic compounds
395having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
435having six-membered rings with one nitrogen as the only ring hetero atom
44Non condensed pyridines; Hydrogenated derivatives thereof
445Non condensed piperidines, e.g. piperocaine
4523containing further heterocyclic ring systems
4545containing a six-membered ring with nitrogen as a ring hetero atom, e.g. pipamperone, anabasine
A61K 31/495
AHUMAN NECESSITIES
61MEDICAL OR VETERINARY SCIENCE; HYGIENE
KPREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
31Medicinal preparations containing organic active ingredients
33Heterocyclic compounds
395having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
495having six-membered rings with two ; or more; nitrogen atoms as the only ring heteroatoms, e.g. piperazine ; or tetrazines
A61K 31/496
AHUMAN NECESSITIES
61MEDICAL OR VETERINARY SCIENCE; HYGIENE
KPREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
31Medicinal preparations containing organic active ingredients
33Heterocyclic compounds
395having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
495having six-membered rings with two ; or more; nitrogen atoms as the only ring heteroatoms, e.g. piperazine ; or tetrazines
496Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene
A61K 45/06
AHUMAN NECESSITIES
61MEDICAL OR VETERINARY SCIENCE; HYGIENE
KPREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
45Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
06Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
Applicants
  • 国立大学法人熊本大学 NATIONAL UNIVERSITY CORPORATION KUMAMOTO UNIVERSITY [JP]/[JP]
  • 学校法人銀杏学園 熊本保健科学大学 KUMAMOTO HEALTH SCIENCE UNIVERSITY [JP]/[JP]
Inventors
  • 富澤 一仁 TOMIZAWA, Kazuhito
  • 魏 范研 WEI, Fanyan
  • 井上 謙吾 INOUE, Kengo
  • 大川原 正 OKAWARA, Tadashi
Agents
  • 廣田 雅紀 HIROTA, Masanori
Priority Data
2013-07239129.03.2013JP
Publication Language Japanese (JA)
Filing Language Japanese (JA)
Designated States
Title
(EN) THERAPEUTIC AGENT FOR TYPE 2 DIABETES
(FR) AGENT THÉRAPEUTIQUE POUR LE DIABÈTE DE TYPE 2
(JA) 2型糖尿病治療剤
Abstract
(EN)
The present invention addresses the problem of providing a novel therapeutic agent for patients with type 2 diabetes, one of the causes thereof being abnormal synthesis of insulin due to aberrant modification of tRNALys(UUU) in a pancreatic β cell with mutation in the Cdkal1 gene. By employing (1) a screening system using escherichia coli in which when a reading frame is shifted when a mistranslation occurs during protein translation, luciferase is translated correctly, (2) a screening system using pancreatic islets isolated from pancreatic β cell specific Cdkal1 knockout mice, and (3) a screening system using pancreatic β cell specific Cdkal1 knockout mice, it was found that compounds represented by formulas (I) to (III) can be therapeutic agents for patients with type 2 diabetes whose insulin secretion capability is reduced due to mutation in the Cdkal1 gene.
(FR)
La présente invention concerne le problème de la fourniture d'un nouvel agent thérapeutique pour des patients souffrant du diabète de type 2, dont une des causes est la synthèse anormale de l'insuline due à une modification aberrante d'ARNtlys(UUU) dans une cellule pancréatique β avec mutation dans le gène Cdkal1. En utilisant (1) un système de criblage utilisant des Escherichia coli où, quand un cadre de lecture est déplacé quand une erreur de translation apparaît durant la translation de la protéine, la luciférase est translatée correctement, (2) un système de criblage utilisant les îlots pancréatiques isolés des cellules pancréatiques β spécifiques des souris knock-out Cdkal1, et (3) un système de criblage utilisant des cellules pancréatiques β spécifiques des souris knock-out Cdkal1, on a découvert que les composés représentés par les formules (I) à (III) peuvent être des agents thérapeutiques pour des patients souffrant de diabète de type 2 dont la capacité à sécréter de l'insuline est réduite en raison d'une mutation dans le gène Cdkal1.
(JA)
 本発明の課題は、Cdkal1遺伝子が変異した膵臓β細胞における、tRNALys(UUU)の修飾異常によるインスリンの合成異常を原因のひとつとする2型糖尿病患者に対し、新規治療薬を提供することである。 (1)タンパク翻訳時に誤翻訳が起こり、読み枠がずれた場合にルシフェラーゼが正しく翻訳される大腸菌を用いたスクリーニング系、(2)膵臓β細胞特異的Cdkal1欠損マウスより単離した膵臓ランゲルハンス島を用いたスクリーニング系、(3)膵臓β細胞特異的Cdkal1欠損マウスを用いたスクリーニング系を用い、以下の式(I)~(III)で表される化合物がCdkal1遺伝子が変異することによりインスリン分泌能が低下した2型糖尿病患者に対する治療薬となりうることを発見した。
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