US 12,275,714 B2
15-PGDH inhibitors
Shyama Herath, La Jolla, CA (US); Mariangela Urbano, La Jolla, CA (US); Eun-Kyong Kim, La Jolla, CA (US); Chixu Chen, La Jolla, CA (US); Qiang Li, La Jolla, CA (US); Julia Ayers, La Jolla, CA (US); Kaikoo Nakamura, La Jolla, CA (US); Xiuwen Zhu, La Jolla, CA (US); Hugh Rosen, La Jolla, CA (US); Jonathan S. Rosenblum, La Jolla, CA (US); Melissa C. Zhang, La Jolla, CA (US); Yongsheng Liu, La Jolla, CA (US); and Masahiro Ueno, Shimotsuga-gun (JP)
Assigned to KYORIN PHARMACEUTICAL CO., LTD., Chiyoda-ku (JP)
Appl. No. 17/310,268
Filed by KYORIN PHARMACEUTICAL CO., LTD., Chiyoda-ku (JP)
PCT Filed Jan. 29, 2020, PCT No. PCT/US2020/015683
§ 371(c)(1), (2) Date Jul. 27, 2021,
PCT Pub. No. WO2020/160151, PCT Pub. Date Aug. 6, 2020.
Claims priority of provisional application 62/799,361, filed on Jan. 31, 2019.
Prior Publication US 2022/0073494 A1, Mar. 10, 2022
Int. Cl. C07D 401/10 (2006.01); C07D 211/38 (2006.01); C07D 217/24 (2006.01); C07D 401/14 (2006.01); C07D 403/10 (2006.01); C07D 405/14 (2006.01); C07D 409/14 (2006.01); C07D 471/04 (2006.01); C07D 471/10 (2006.01); C07D 487/04 (2006.01); C07D 498/04 (2006.01)
CPC C07D 401/10 (2013.01) [C07D 211/38 (2013.01); C07D 217/24 (2013.01); C07D 401/14 (2013.01); C07D 403/10 (2013.01); C07D 405/14 (2013.01); C07D 409/14 (2013.01); C07D 471/04 (2013.01); C07D 471/10 (2013.01); C07D 487/04 (2013.01); C07D 498/04 (2013.01)] 24 Claims
 
1. A compound of formula (1) or a pharmacologically acceptable salt thereof, wherein the formula (1) is selected from the group consisting of

OG Complex Work Unit Chemistry
where G1 is a phenyl group optionally having at least one substituent selected from group A, a 5-membered aromatic heterocyclic group optionally having at least one substituent selected from the group A, a 6-membered aromatic heterocyclic group optionally having at least one substituent selected from the group A, a bicyclic aromatic heterocyclic group having 8 to 10 atoms and optionally having at least one substituent selected from the group A, a fused heterocyclic group having 9 or 10 atoms and optionally having at least one substituent selected from the group A, C3-C8 cycloalkyl group optionally having at least one substituent selected from the group A or 3 to 8-membered heterocycloalkyl group optionally having at least one substituent selected from the group A;
R3 and R4 are each independently selected from hydrogen, halogen, —CN, —COOY, —NHC(O)Y, C1-C6 alkyl optionally having at least one substituent selected from group C, C1-C6 alkoxy optionally having at least one substituent selected from the group C or C3-C8 cycloalkyl optionally having at least one substituent selected from the group C;
R6 is hydrogen, halogen, —CN, —COOY, —NHC(O)Y, C, C1-C6 alkyl optionally having at least one substituent selected from the group C, C1-C6 alkoxy optionally having at least one substituent selected from the group C or C3-C8 cycloalkyl optionally having at least one substituent selected from the group C;
R7 and R8 are each independently selected from hydrogen, halogen, —CN, —COOY, —NHC(O)Y, C1-C6 alkyl optionally having at least one substituent selected from the group C, C1-C6 alkoxy optionally having at least one substituent selected from the group C or C3-C8 cycloalkyl optionally having at least one substituent selected from the group C;
R10 is hydrogen, halogen, —CN, —COOY, —NHC(O)Y, C1-C6 alkyl optionally having at least one substituent selected from the group C, C1-C6 alkoxy optionally having at least one substituent selected from the group C or C3-C8 cycloalkyl optionally having at least one substituent selected from the group C; Y is independently selected from hydrogen, C1-C6 alkyl optionally having at least one substituent selected from the group C, C1-C6 alkoxy optionally having at least one substituent selected from the group C or C3-C8 cycloalkyl optionally having at least one substituent selected from the group C;
the group A is halogen, hydroxyl, carbonyl, nitrile, carboxyl, formyl, C1-C6 alkyl optionally having at least one substituent selected from group A1, C1-C6 alkylcarbonyl optionally having at least one substituent selected from the group A1, C1-C6 alkoxy optionally having at least one substituent selected from the group A1, C1-C6 alkoxycarbonyl optionally having at least one substituent selected from the group A1, C1-C6 alkylsulfonyl optionally having at least one substituent selected from the group A1, C1-C6 alkylsulfonylamino optionally having at least one substituent selected from the group A1, C3-C8 cycloalkyl optionally having at least one substituent selected from the group A1, C3-C8 cycloalkylcarbonyl optionally having at least one substituent selected from the group A1, C3-C8 cycloalkoxy optionally having at least one substituent selected from the group A1, C3-C8 cycloalkylsulfonyl optionally having at least one substituent selected from the group A1, C3-C8 cycloalkylsulfonylamino optionally having at least one substituent selected from the group A1, C5-C7 heterocycloalkyl optionally having at least one substituent selected from the group A1, C5-C7 heterocycloalkylcarbonyl optionally having at least one substituent selected from the group A1, C5-C7 heterocycloalkylamino optionally having at least one substituent selected from the group A1, C5-C7 heterocycloalkylaminocarbonyl optionally having at least one substituent selected from the group A1, aminocarbonyl optionally substituted with one or two C1-C6 alkyl optionally at least one having substituent selected from the group A1, aminosulfonyl optionally substituted with one or two C1-C6 alkyl optionally having at least one substituent selected from the group A1, amino optionally substituted with one or two C1-C6 alkyl optionally having at least one substituent selected from the group A1, phenyl optionally having at least one substituent selected from the group B, 5-membered aromatic heterocyclic group optionally having at least one substituent selected from the group B, 6-membered aromatic heterocyclic group optionally having at least one substituent selected from the group B or heterocyclic group optionally having substituent(s) selected from the group B;
the group A1 is halogen, hydroxyl, amino, carbonyl, nitrile, carboxyl, formyl, C1-C6 alkyl optionally having at least one substituent selected from group A2, C1-C6 alkylcarbonyl optionally having at least one substituent selected from the group A2, C1-C6 alkoxy optionally having at least one substituent selected from the group A2, C1-C6 alkoxycarbonyl optionally having at least one substituent selected from the group A2, C1-C6 alkylsulfonyl optionally having at least one substituent selected from the group A2, C1-C6 alkylsulfonylamino optionally having at least one substituent selected from the group A2, C3-C8 cycloalkyl optionally having at least one substituent selected from the group A2, C5-C7 heterocycloalkyl optionally having at least one substituent selected from the group A2, C5-C7 heterocycloalkylcarbonyl optionally having at least one substituent selected from the group A2, C5-C7 heterocycloalkylamino optionally having at least one substituent selected from the group A2, C5-C7 heterocycloalkylaminocarbonyl optionally having at least one substituent selected from the group A2, aminocarbonyl optionally substituted with one or two C1-C6 alkyl optionally having at least one substituent selected from the group A2, amino optionally substituted with one or two C1-C6 alkyl optionally having at least one substituent selected from the group A2, 5-membered aromatic heterocyclic group optionally having at least one substituent selected from the group B, 6-membered aromatic heterocyclic group optionally having at least one substituent selected from the group B or heterocyclic group optionally having at least one substituent selected from the group B;
the group A2 is halogen, hydroxyl, nitrile, carboxyl, formyl, C1-C6 alkyl, C1-C6 alkylcarbonyl, C1-C6 alkoxy, C1-C6 alkoxycarbonyl, C1-C6 alkylsulfonylamino, 5-membered aromatic heterocyclic group, 6-membered aromatic heterocyclic group, heterocyclic group or 5 to 7-membered heterocycloalkyl group;
the group B is halogen, hydroxyl, carbonyl, carboxyl, C1-C6 alkyl, halo-C1-C6 alkyl, hydroxy-C1-C6 alkyl, C1-C6 alkylcarbonyl, C1-C6 alkoxy, halo-C1-C6 alkoxy, C1-C6 alkoxycarbonyl, C1-C6 alkyl substituted with C1-C6 alkoxy, C1-C6 alkyl substituted with C1-C6 alkoxycarbonyl, C3-C8 cycloalkyl, C3-C8 cycloalkylcarbonyl, C3-C8 cycloalkoxy, aminocarbonyl optionally substituted with one or two C1-C6 alkyl, C1-C6 alkylsulfonyl, aminosulfonyl optionally substituted with one or two C1-C6 alkyl, C1-C6 alkylsulfonylamino, amino optionally substituted with one or two C1-C6 alkyl or 5 to 7-membered heterocycloalkyl group;
the group C is halogen, hydroxyl, carboxyl, C1-C6 alkylcarbonyl, C1-C6 alkoxy, C1-C6 alkoxycarbonyl, aminocarbonyl optionally substituted with one or two C1-C6 alkyl, amino optionally substituted with one or two C1-C6 alkyl or 5 to 7-membered heterocycloalkyl group; and
R11, R12 and R13 are the same or different and are hydrogen, halogen, C1-C6 alkyl, halo (C1-C6) alkyl, C1-C6 alkoxy or halo (C1-C6) alkoxy, and n is an integer of 1 to 3.