NOVEL SMALL MOLECULE COMPOUND INHIBITING SIGNAL TRANSMISSION PATH OF TLR7 AND TLR9 AND USE THEREOF

• Main Authors: PATRA, Mahesh, CHOI, Sangdun, CHOI, Yang-Seon, MUHAMMAD, Haseeb
• Format: Patent
• Language: English; French; Korean
• Published: 04.02.2021
• Subjects: CHEMISTRY; HETEROCYCLIC COMPOUNDS; HUMAN NECESSITIES; HYGIENE; MEDICAL OR VETERINARY SCIENCE; METALLURGY; ORGANIC CHEMISTRY; PREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES; SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS ORMEDICINAL PREPARATIONS

The present invention relates to a small molecule compound inhibiting a toll-like receptor (TLR) signal transmission path and, more specifically, to a compound having a structure expressed by a particular chemical formula, a TLR inhibitory composition comprising same, and an autoimmune disease or inflammatory disease prevention or therapeutic composition comprising the TLR inhibitory composition. In the present invention, a TLR inhibitory compound TIC10, inhibiting a TLR7- and TLR9-mediated signal transmission path, and a derivative TIC10-7 thereof have been confirmed. The novel compounds block the TNF-α secretion by inhibiting the expression and activation of NF-κB- and MAPK-related proinflammatory genes, and thus can be utilized as a therapeutic agent for many autoimmune diseases, such as systemic lupus erythematosus, psoriasis and psoriatic arthritis, associated with a hyperactivity of a nucleic acid detection TLR. La présente invention concerne un composé à petites molécules inhibant la voie de transmission du signal du récepteur de type Toll (TLR) et, plus particulièrement, un composé ayant une structure exprimée par une formule chimique particulière, une composition inhibitrice de TLR le comprenant, et une composition de prévention ou une composition thérapeutique pour des maladies auto-immunes ou inflammatoires comprenant la composition inhibitrice de TLR. La présente invention concerne un composé TIC10 inhibiteur de TLR, inhibant la voie de transmission du signal induite par TLR7 et TLR9, et un dérivé TIC10-7 de celui-ci. Les nouveaux composés bloquent la sécrétion de TNF-α par inhibition de l'expression et de l'activation de gènes pro-inflammatoires liés à NF-κB et MAPK, et peuvent ainsi être utilisés en tant qu'agent thérapeutique pour de nombreuses maladies auto-immunes, telles que le lupus érythémateux disséminé, le psoriasis et l'arthrite psoriasique, associés à une hyperactivité d'un TLR par détection d'acide nucléique. 본 발명은 톨-유사 수용체(TLR) 신호전달 경로를 억제하는 소분자 화합물에 관한 것으로, 더욱 상세하게는 특정 화학식으로 표시되는 구조를 갖는 화합물과 이를 포함하는 TLR 억제용 조성물 및 상기 TLR 억제용 조성물을 포함하는 자가면역질환 또는 염증성질환의 예방 또는 치료용 조성물에 관한 것이다. 본 발명에서는 TLR7- 및 TLR9-매개 신호전달 경로를 억제하는 TLR 억제 화합물 TIC10 및 이의 유도체 TIC10-7를 확인하였으며, 상기 새로운 화합물들은 NF-κB 및 MAPK 관련 전염증 유전자 발현 및 활성화를 방해함으로써, TNF-α의 분비를 차단하므로, 핵산 감지 TLR의 과다활성과 관련된 전신홍반루프스, 건선 및 건선성 관절염과 같은 수많은 자가면역질환의 치료제로서 유용하게 활용될 수 있다.