US 11,655,235 B2
Pyrrolidine and piperidine compounds
Tae Han Dong, Yongin-si (KR); Yoo Hoi Park, Suwon-si (KR); Tae Kyun Kim, Hwaseong-si (KR); Jae Eun Joo, Yongin-si (KR); Eun Hye Jung, Yongin-si (KR); Jae Won Jeong, Hwaseong-si (KR); Hyun Seung Lee, Yongin-si (KR); Do Hoon Kim, Yongin-si (KR); Ji Eun Yang, Yongin-si (KR); Jun Chui Park, Yongin-si (KR); Sang Myoun Lim, Seoul (KR); Na Ry Ha, Seoul (KR); Da In Chung, Seoul (KR); and Ji Yeong Gal, Suwon-si (KR)
Assigned to YUHAN CORPORATION, Seoul (KR)
Filed by YUHAN CORPORATION, Seoul (KR)
Filed on Nov. 5, 2020, as Appl. No. 17/90,552.
Claims priority of provisional application 62/931,554, filed on Nov. 6, 2019.
Prior Publication US 2021/0147386 A1, May 20, 2021
Int. Cl. A61P 1/16 (2006.01); A61P 35/00 (2006.01); C07D 207/16 (2006.01); C07D 401/14 (2006.01); C07D 403/14 (2006.01); C07D 405/14 (2006.01); C07D 409/14 (2006.01); C07D 413/14 (2006.01); C07D 471/04 (2006.01); C07D 491/048 (2006.01); C07D 495/04 (2006.01); A61K 31/4545 (2006.01); A61K 31/4709 (2006.01); A61K 31/5377 (2006.01); A61K 31/4725 (2006.01); A61K 31/519 (2006.01); A61K 31/423 (2006.01); A61K 31/517 (2006.01); A61K 31/4365 (2006.01); A61K 31/4025 (2006.01); A61K 31/4355 (2006.01)
CPC C07D 401/14 (2013.01) [C07D 207/16 (2013.01); C07D 403/14 (2013.01); C07D 405/14 (2013.01); C07D 409/14 (2013.01); C07D 413/14 (2013.01); C07D 471/04 (2013.01); C07D 491/048 (2013.01); C07D 495/04 (2013.01); A61K 31/4025 (2013.01); A61K 31/423 (2013.01); A61K 31/4355 (2013.01); A61K 31/4365 (2013.01); A61K 31/4545 (2013.01); A61K 31/4709 (2013.01); A61K 31/4725 (2013.01); A61K 31/517 (2013.01); A61K 31/519 (2013.01); A61K 31/5377 (2013.01); A61P 1/16 (2018.01); A61P 35/00 (2018.01)] 28 Claims
 
1. A compound of Formula 1:

OG Complex Work Unit Chemistry
or a stereoisomer, a mixture of stereoisomers, or a pharmaceutically acceptable salt thereof,
wherein:
n is 1 or 2;
R1 is selected from the group consisting of Formulas I, II, III, IV, and V:

OG Complex Work Unit Chemistry
R2 is a hydrogen or a C1-3alkyl;
R3 is: a 5- to 12-membered heteroaryl, wherein said heteroaryl contains 1 to 3 heteroatoms independently selected from O, N, and S and is optionally substituted by 1 to 3 Z,
a 3- to 12-membered non-aromatic heterocycle, wherein said heterocycle contains 1 to 3 heteroatoms independently selected from O, N, and S and is optionally substituted by 1 to 3 Z,
—NR4R5, —OR4, —C(O)NHR4, —NHC(O)(CH2)mR4, —NHS(O)2R4, —(CH2)mCH2R4, or —(CH2)mNHR4,
wherein m is 0 or 1;
R4 is: a phenyl substituted with 1 to 3 Z,
a heterocycle selected from the group consisting of benzo[d][1,3]dioxolyl, dihydrobenzo[1,4]dioxinyl, 2,3-dihydrobenzofuranyl, 2-oxo-1,2-dihydroquinolinyl, and 2-oxo-1,2,3,4-tetrahydroquinolinyl, wherein said heterocycle is optionally substituted with 1 to 3 Z,
a naphthyl optionally substituted with 1 to 3 Z, or
a heteroaryl selected from the group consisting of pyridinyl, pyrimidinyl, pyrazinyl, imidazolyl, pyrazolyl, triazolyl, oxazolyl, thiazolyl, furanyl, pyrrolyl, thiophenyl, quinolinyl, isoquinolinyl, chromenonyl, quinazolinyl, benzoxazolyl, benzofuranyl, benzothiophenyl, indolyl, indolinyl, benzimidazolyl, benzoxazolyl, benzothiazolyl, indazolyl, furo[3,2-c]pyridinyl, thieno[2,3-d]pyrimidinyl, thieno[3,2-c]pyridinyl, isoxazolyl, acridinyl, and naphthyridinyl, wherein said heteroaryl is optionally substituted with 1 to 3 Z;
R5 is a hydrogen or a C1-3alkyl;
each Z is independently selected from the group consisting of hydroxy, amino, halogen, cyano, nitro, carboxylic acid, C1-5alkyl optionally substituted by 1 to 3 Z1, C2-6alkenyl optionally substituted by Z1, C2-6alkynyl optionally substituted by Z1, C1-5alkoxy optionally substituted by 1 to 3 Z1, C1-5alkylthio optionally substituted by Z1, mono- or di-C1-5 alkylamino optionally substituted by Z1, piperazinyl optionally substituted by Z1, C1-5 alkylsulfonylamino optionally substituted by Z1, C1-5alkylcarbonylamino optionally substituted by Z1, aminosulfonyl optionally substituted by Z1, aminocarbonyl optionally substituted by Z1, C1-5alkylaminocarbonyl optionally substituted by Z1, phenyl optionally substituted by Z1, phenoxy optionally substituted by Z1, benzyl optionally substituted by Z1, benzoyl optionally substituted by Z1, phenylaminocarbonyl optionally substituted by Z1, pyrazolyl optionally substituted by Z1, benzoxazolyl optionally substituted by Z1, C1-5 alkoxycarbonyl optionally substituted by Z1, benzyloxy optionally substituted by Z1, C1-5 alkylsulfonyl optionally substituted by Z1, acetyl, morpholinyl optionally substituted by Z1, —NR6C(O)R7, and —C(O)NR6R7;
wherein each Z1 is independently selected from halogen, hydroxyl, amino, C1-5 alkylamino, cyano, acetyl, C1-5 alkyl, C1-5 haloalkyl, C3-6 carbocycle, and C3-6 heterocycle, wherein said C3-6 carbocycle and said C3-6 heterocycle are optionally substituted with halogen, hydroxyl, C1-5alkyl, or C1-5 haloalkyl;
R6 is hydrogen or a C1-3alkyl group;
R7 is: a C1-3alkyl group optionally substituted with phenyl,
a phenyl optionally substituted with 1 to 3 Z2, or
a heteroaryl selected from the group consisting of pyridinyl, pyrimidinyl, pyrazinyl, imidazolyl, pyrazolyl, triazolyl, oxazolyl, thiazolyl, furanyl, pyrrolyl, thiophenyl, quinolinyl, isoquinolinyl, chromenonyl, quinazolinyl, benzoxazolyl, benzofuranyl, benzothiophenyl, indolyl, indolinyl, benzimidazolyl, benzoxazolyl, benzothiazolyl, indazolyl, furo[3,2-c]pyridinyl, thieno[2,3-d]pyrimidinyl, thieno[3,2-c]pyridinyl, isoxazolyl, acridinyl, and naphthyridinyl, wherein said heteroaryl is optionally substituted with 1 to 3 Z2; and
each Z2 is independently selected from the group consisting of hydroxy, amino, halogen, cyano, nitro, hydroxycarbonyl, C1-5alkyl optionally substituted by 1 to 3 Z3, C2-6alkenyl, C2-6alkynyl, C1-5alkoxy optionally substituted by 1 to 3 Z3, C1-5alkylthio, mono- or di-C1-5alkylamino, piperazinyl optionally substituted by Z3, C1-5alkylsulfonylamino, C1-5alkylcarbonylamino, aminosulfonyl, aminocarbonyl, C1-5alkylaminocarbonyl, phenyl, phenoxy, benzyl, benzoyl, phenylaminocarbonyl, pyrazolyl, and benzoxazolyl;
wherein each Z3 is independently selected from halogen, amino, and acetyl.