Astellas Pharma Gmbh

Sunao Imada

Yutaka Nakajima

Hironori Harada

Kazuyuki Hattori

Kazuya Fujita

Tatsuaki Morokata

Junji Sato

Yoshito Abe

Hideo Tsutsumi

Fumiyuki Shirai

Kazuyuki Tsuchiya

Shunichiro Matsumoto

Keita Nakanishi

Masataka Morita

Takahiro Nigawara

Shohei Shirakami

Yu Harayama

Hiromichi Itani

Eriko Yamamoto

Kaori Kubo

Naohiro Aoyama

Yuji Takasuna

Koji Kato

Takeyuki Nagashima

Kenichi Kawaguchi

Eiji Kawaminami

Hisao Hamaguchi

Toru Asano

Kazuyuki Kuramoto

Tomoyoshi Imaizumi

Mitsuaki Okumura

Hideyuki Watanabe

Kohei Inamura

Junko Maeda

Fumie Takahashi

Yoshihiro Kozuki

Hiroki Ishioka

Tomohiro Yoshinari

Masahiko Shiwaku

Hidehiko Fukahori

Masahiko (deceased) Shiwaku

[Problem] To provide a compound useful as an active ingredient of a pharmaceutical composition for treating pancreatic cancer. [Means for resolution] The present inventors have studied about a compound that is useful as an active ingredient of a pharmaceutical composition for treating pancreatic cancer and have found that a quinazoline compound has an excellent degradation-inducing action on a G12D mutant KRAS protein and a G12D mutant KRAS inhibition activity and can be used as a therapeutic agent for pancreatic cancer, thus completing the present invention. The quinazoline compound or a salt thereof of the present invention can be used as a therapeutic agent for pancreatic cancer.

Quinazoline compound for inducing degradation of G12D mutant KRAS protein

Phenyldifluoromethyl-substituted prolinamide compounds that have a cathepsin S inhibitory effect, and are usable as active ingredients of pharmaceutical compositions for preventing and/or treating autoimmune diseases including systemic lupus erythematosus (SLE) and lupus nephritis, allergies, or graft rejection of an organ, bone marrow or tissue. Such compounds include (4R)&#x2014;N-(1-cyanocyclopropyl)-4-(difluoro{4-[(4-methylpiperazin-1-yl)methyl]-2-(trifluoromethyl)phenyl}methyl)-1-[(1-methylcyclopropyl)carbonyl]-L-prolinamide, (4R)&#x2014;N-(1-cyanocyclopropyl)-4-(difluoro{4-[(4-methylpiperazin-1-yl)methyl]-2-(trifluoromethyl)phenyl}methyl)-1-{[1-(trifluoromethyl)cyclopropyl]carbonyl}-L-prolinamide, (4R)&#x2014;N-(1-cyanocyclopropyl)-4-[{4-[(4-ethylpiperazin-1-yl)methyl]-2-(trifluoromethyl)phenyl}(difluoro)methyl]-1-{[1-(trifluoromethyl)cyclopropyl]carbonyl}-L-prolinamide, (4R)&#x2014;N-(1-cyanocyclopropyl)-4-[{4-[(4-ethylpiperazin-1-yl)methyl]-2-(trifluoromethyl)phenyl}(difluoro)methyl]-1-[(1-methylcyclopropyl)carbonyl]-L-prolinamide, and salts thereof.

Phenyldifluoromethyl-substituted prolinamide compound

On the basis of a cathepsin S inhibitory effect, an excellent agent for treating or preventing autoimmune disease, allergic disease, graft rejection of an organ, bone marrow or tissue, systemic lupus erythematosus, or the like is provided. It was found that a nitrogen-containing bicyclic heterocyclic compound has an excellent cathepsin S inhibitory effect, thereby completing the invention. The compound of the present invention has an cathepsin S inhibitory effect, and can be used as an agent for preventing and/or treating autoimmune disease, allergic disease, graft rejection of an organ, bone marrow or tissue, systemic lupus erythematosus, or the like.

Nitrogen-containing bicyclic aromatic heterocyclic compound

[Problem] On the basis of a cathepsin S inhibitory effect, an excellent agent for treating or preventing autoimmune disease, allergic disease, graft rejection of an organ, bone marrow or tissue, systemic lupus erythematosus, or the like is provided. [Means for Solution] It was found that a nitrogen-containing bicyclic heterocyclic compound has the excellent cathepsin S inhibitory effect, thereby completing the invention. The compound of the present invention has the cathepsin S inhibitory effect, and can be used as an agent for preventing and/or treating autoimmune disease, allergic disease, graft rejection of an organ, bone marrow or tissue, systemic lupus erythematosus, or the like.

Provided is a novel compound which is an agent for treating rejection reactions in various organ transplantations, allergy diseases, autoimmune diseases, and hematologic tumor, and based on a PI3K&#x3b4; selective inhibitory action and/or an IL-2 production inhibitory action and/or a B cell proliferation inhibitory action (including an activation inhibitory action). The provided compound has a PI3K&#x3b4; selective inhibitory action, an IL-2 production inhibitory action, and/or a B cell proliferation inhibitory action, including an activation inhibitory action.

Heterocyclic compound

Provided is a compound which has an excellent S1Pagonist action, and is useful particularly as an active ingredient for an agent for preventing and/or treating a disease induced by undesirable lymphocyte infiltration or a disease induced by abnormal proliferation or accumulation of cells. According to the present invention, a 2H-chromene compound or a derivative thereof which has an excellent S1Pagonist action, and is useful particularly as an active ingredient of an agent for preventing and/or treating a disease induced by undesirable lymphocyte infiltration or a disease induced by abnormal proliferation or accumulation of cells can be provided. The 2H-chromene compound and a derivative thereof which are the compounds of the present invention have an S1Pagonist action, and can be used particularly for prevention and/or treatment of a disease induced by undesirable lymphocyte infiltration or a disease induced by abnormal proliferation or accumulation of cells.

2H-chromene compound and derivative thereof

To provide a useful compound as an active ingredient for a preventing and/or treating agent for rejection in the transplantation of an organ, bone marrow, or a tissue, an autoimmune disease, or the like, which has an excellent S1Pagonist activity. Since the compound of the invention has an S1Pagonist activity, it is useful as an active ingredient for a treating or preventing agent for a disease caused by unfavorable lymphocytic infiltration, for example, an autoimmune disease such as graft rejection in the transplantation of an organ, bone marrow, or a tissue, a graft-versus-host disease, rheumatic arthritis, multiple sclerosis, systemic lupus erythematosus, a nephrotic syndrome, encephalomeningitis, myasthenia gravis, pancreatitis, hepatitis, nephritis, diabetes, pulmonary disorder, asthma, atopic dermatitis, inflammatory bowel disease, atherosclerosis, ischemia-reperfusion injury, or an inflammatory disease, and further, a disease caused by the abnormal growth or accumulation of cells such as cancer and leukemia.

Hetero compound

Growing community of inventors

Tokyo, Japan

Sunao Imada