US 12,404,247 B2
3, 5-disubstituted pyridine and 3, 5-disubstituted pyridazine derivatives and pharmaceutical use of same
Taichi Takahashi, Osaka (JP); Hisayuki Takamatsu, Osaka (JP); Daisuke Iijima, Osaka (JP); and Shuzo Takeda, Osaka (JP)
Assigned to MITSUBISHI TANABE PHARMA CORPORATION, Osaka (JP)
Filed by MITSUBISHI TANABE PHARMA CORPORATION, Osaka (JP)
Filed on Mar. 13, 2024, as Appl. No. 18/603,405.
Application 18/603,405 is a division of application No. 17/258,682, granted, now 11,958,812, previously published as PCT/JP2019/029366, filed on Jul. 26, 2019.
Claims priority of application No. 2018-141254 (JP), filed on Jul. 27, 2018.
Prior Publication US 2024/0239756 A1, Jul. 18, 2024
Int. Cl. C07D 237/14 (2006.01); A61P 11/00 (2006.01); C07D 213/89 (2006.01); C07D 237/08 (2006.01); C07D 401/04 (2006.01); C07D 413/04 (2006.01)
CPC C07D 237/14 (2013.01) [A61P 11/00 (2018.01); C07D 213/89 (2013.01); C07D 237/08 (2013.01); C07D 401/04 (2013.01); C07D 413/04 (2013.01)] 22 Claims
 
1. A method for treating a disease involving autotaxin, comprising:
administering an effective amount of a carboxylic acid compound of formula (1)

OG Complex Work Unit Chemistry
or a pharmacologically acceptable salt thereof to a patient in need thereof,
wherein R1 in the formula (1) is

OG Complex Work Unit Chemistry
where X1a is —C(R1a)2— where plural R1a are the same or different and each R1a is a hydrogen atom, a halogen atom, C1-C2 perfluoroalkyl, C1-C2 perfluoroalkoxy or C1-C6 alkyl, or plural R1a are bonded to form 1,1-C3-C6 cycloalkylene or —NR1b— where R1b is a hydrogen atom or C1-C2 perfluoroalkyl,
X1b and X1c are the same or different and each of X1b and X1c is —O— or —CH2— provided X1b and X1c are not simultaneously —O—, R1c is a hydrogen atom, a halogen atom, C1-C2 perfluoroalkyl, C1-C2 perfluoroalkoxy, C1-C6 alkyl or C1-C2 perfluoroalkylthio, R1d is a hydrogen atom, a halogen atom or C1-C6 alkyl, and R1e is a hydrogen atom, C1-C2 perfluoroalkyl or C1-C2 perfluoroalkoxy,
X in the formula (1) is —N═ or —CH═,
ring A in the formula (1) is

OG Complex Work Unit Chemistry
where X2a is —N═ or —CR2a═ where R2a is a hydrogen atom, a halogen atom, C1-C6 alkyl or C1-C6 alkoxy, R2b is a hydrogen atom, a halogen atom, C1-C6 alkyl or C1-C6 alkoxy,
R2c is a hydrogen atom or C1-C6 alkyl, X2b is —O—, —NR2d— where R2d is a hydrogen atom or C1-C2 perfluoroalkyl or —CHR2e— where R2e is a hydrogen atom or C1-C6 alkyl,
X2c is —(CH2)n′— where n′ is 0 or 1 or —O—, and
L in the formula (1) is —(CHR3a)n— where n is 0, 1, 2 or 3, plural R3a are the same or different and each R3a is a hydrogen atom or a C1-C6 alkyl, —(CH2)m—O—(CH2)m′— where m and m′ are the same or different and each of m and m′ is 0, 1 or 2, C2-C3 alkenylene,

OG Complex Work Unit Chemistry
where R3b and R3c are the same or different and each of R3b and R3c is a hydrogen atom or C1-C6 alkyl, R3d is a hydrogen atom, C1-C6 alkoxy, C1-C6 alkyl or C1-C2 perfluoroalkyl, R3e is a hydrogen atom, C1-C6 alkoxy, C1-C6 alkyl or C1-C2 perfluoroalkyl,
wherein the disease involving autotaxin is cancer or tumor, a fibrotic disease, an inflammatory disease, an ophthalmic disease, a urological disease, type II diabetes-related obesity or an acute coronary syndrome,
the cancer or tumor is malignant melanoma, brain tumor, neuroblastoma, glioblastoma multiforme, EBV positive Hodgkin lymphoma, glioblastoma, non-small cell lung cancer, lung tumor, breast tumor, ovary tumor, pancreas tumor, prostate intraepithelial tumor, prostate tumor, thyroid gland tumor, follicular lymphoma, liver tumor or renal cell carcinoma,
the fibrotic disease is lung fibrosis, scleroderma, hepatic fibrosis, renal fibrosis, diabetic nephropathy or atherosclerosis,
the inflammatory disease is asthma, COPD, rheumatoid arthritis, arthritis deformans, NASH, NAFLD, inflammatory bowel disease, Crohn's disease, ulcerative colitis, neuropathic pain or pruritus,
the acute coronary syndrome is angina pectoris or myocardial infarction,
the ophthalmic disease is glaucoma, and
the urological disease is prostatomegaly.