US 12,337,007 B2
Patentiflorin A analogs as antiviral agents
Hongjie Zhang, Hong Kong (CN); Wanfei Li, Hong Kong (CN); and Nga Yi Tsang, Hong Kong (CN)
Assigned to Hong Kong Baptist University, Hong Kong (CN)
Filed by Hong Kong Baptist University, Hong Kong (CN)
Filed on Feb. 24, 2023, as Appl. No. 18/173,865.
Application 18/173,865 is a division of application No. 16/947,935, filed on Aug. 25, 2020, granted, now 11,638,713.
Claims priority of provisional application 62/891,441, filed on Aug. 26, 2019.
Prior Publication US 2023/0248754 A1, Aug. 10, 2023
Int. Cl. A61K 31/69 (2006.01); A61K 31/365 (2006.01); A61K 31/381 (2006.01); A61K 31/443 (2006.01); A61K 31/506 (2006.01); A61K 31/5377 (2006.01); A61K 31/7048 (2006.01); A61K 31/706 (2006.01); A61P 31/16 (2006.01); A61P 31/18 (2006.01)
CPC A61K 31/69 (2013.01) [A61K 31/365 (2013.01); A61K 31/381 (2013.01); A61K 31/443 (2013.01); A61K 31/506 (2013.01); A61K 31/5377 (2013.01); A61K 31/7048 (2013.01); A61K 31/706 (2013.01); A61P 31/16 (2018.01); A61P 31/18 (2018.01)] 7 Claims
OG exemplary drawing
 
1. A method of treating a viral infection in a subject in need thereof, the method comprising administering a therapeutically effective amount of a compound to the subject, wherein the compound has the Formula (I):

OG Complex Work Unit Chemistry
or a pharmaceutically acceptable salt or pro-drug thereof wherein,
X is oxygen;
R1 is heteroaryl, —OR15, —OC(O)R15, —N(R17)R18, —N(R17)C(O)R18, —N═C(R17)R18, pinacolboryl, —OS(O)2CF3, heterocyclcyl optionally substituted with 1 or 2 group(s) independently selected from R16, or alkynyl optionally substituted with a trialkylsilane: or R1 is —O(CH2)m-cyano, —O(CH2)m—C(O)N(R17)R18, or —O(CH2)m—C(O)OR17, wherein m is a whole number elected from 1-4;
R2, R5, R6, R7, R10, R13, and R14 are each hydrogen;
R3 and R4 are each independently —O-alkyl;
R8 and R9 taken together with the carbon atoms to which they are attached form a methylenedioxy ring;
R11 and R12 taken together form oxo;
R15 is a glycosidic group represented by the Formula (V):

OG Complex Work Unit Chemistry
wherein, each of R19, R21, R23 and R25 is hydrogen;
R20 is selected from the group consisting of —OR27, —OC(O)R27, —OC(O)N(R27)R27, and —OC(O)OR27;
R22 is selected from the group) consisting of —OR27, —OC(O)R27, —OC(O)N(R27)R27, and —OC(O)OR27;
at least one of R20, R22 and R24 is selected from the group consisting of —OC(O)R27, —OC(O)N(R27)R27, and —OC(O)OR27;
at least one of R20, R22, and R24 is hydroxyl;
R26 is hydrogen or methyl; R27 for each occurrence is independently selected from the group consisting of hydrogen, halogen, trichloromethyl, trifluoromethyl, cyano, nitro —OR29, —C(O)R30, —C(O)N(R29)R30, —C(O)OR29, —OC(O)R29, —S(O)2R29, —S(O)2N(R29)R30, —N(R29)R30, —N(R29)N(R29)R30, —N(R29)C(O)R30, —N(R29)S(O)2R30, hydrocarbyl optionally substituted with 1, 2, 3, 4 or 5 group(s) independently selected from R4, heterocyclyl optionally substituted with 1, 2, 3, 4 or 5 group(s) independently selected from R28, and —(CH)k-heterocyclyl optionally substituted with 1, 2, 3, 4 or 5 group(s) independently selected from R28, wherein k is an integer between 1-6;
R28 for each occurrence is independently selected from halogen, trichloromethyl, trifluoromethyl, cyano, nitro, oxo, ═NR29, —OR29, —C(O)R30, —C(O)N(R29)R30, —C(O)OR29, —OC(O)R29, —S(O)2R29, —S(O)2N(R29)R30, —N(R29)R30, —N(R29)N(R29)R30, —N(R29)R30, —N(R29)C(O)R30 and —N(R29)S(O)2R30; and
R29 and R30 for each occurrence are each independently hydrogen or selected from hydrocarbyl and heterocyclyl, either of which is optionally substituted with 1, 2, 3, 4 or 5 group(s) independently selected from halogen, cyano, amino, hydroxy, C1-6 alkyl and C1-6 alkoxy;
R16 for each occurrence is independently selected from the group consisting of alkynyl, halogen, trichloromethyl, trifluoromethyl, cyano, nitro, oxo, ═NR17, —OR17, —C(O)R18, —C(O)N(R17)R18, —C(O)OR17, —OC(O)R17, —S(O)2R17, —S(O)2N(R17)R18, —N(R17)R18, —N(R17)N(R17)R18, —N(R17)C(O)R18 and —N(R17)S(O)2R18; and
R17 and R18 for each occurrence are independently hydrogen, alkyl, alkynyl, cycloalkyl, aryl, or heteroaryl, or selected from hydrocarbyl and heterocyclyl, either of which is optionally substituted with 1, 2, 3, 4 or 5 group(s) independently selected from the group consisting of halogen, cyano, amino, hydroxy, C1-6 alkyl and C1-6 alkoxy, wherein the viral infection is selected from the group consisting of HIV, coronaviruses, influenza viruses, Ebola virus, and Marburg virus.