US 12,336,977 B2
Nitenin analogue compounds and their use in the treatment of chronic and acute pain
Pedro Afonso Dos Santos Baltazar De Lima, Cascais (PT); Beatriz Szwarc Dos Santos, Lisbon (PT); Ana Rosa Maço Abreu, Pombal (PT); André Emanuel Pinheiro Bastos, Lisbon (PT); Rui Gomes, São Domingos de Rana (PT); Marisa Isabel Lopes De Sousa, Benavente (PT); Joana Maria Monteiro Serrão, Charneca da Caparica (PT); Sílvia Patrícia Pena Lino, Lisbon (PT); Patrícia Isabel Da Silveira Máximo, Lisbon (PT); Luísa Maria Pinto Ferreira, Mem Martins (PT); Paula Cristina De Sério Branco, Igreja Nova MFR (PT); Henrique Sovela Mourão, Costa de Caparica (PT); Vanessa Alexandra Rosado Sabino, São Salvador da Aramenha (PT); Ming Him Tong, Aberdeen (GB); Laurent Alain Claudetrembleau, Danestone Aberdeen (GB); Ana Maria Ferreira Da Costa Lourenço, Lisbon (PT); and Miguel Angelo Segão Mondragão, Linda-a-Velha (PT)
Assigned to SEA4US—BIOTECNOLOGIA E RECURSOS MARINHOS, LDA., Sagres (PT)
Appl. No. 17/631,135
Filed by SEA4US-BIOTECNOLOGIA E RECURSOS MARINHOS, LDA., Sagres (PT)
PCT Filed Jul. 22, 2020, PCT No. PCT/IB2020/056915
§ 371(c)(1), (2) Date Jan. 28, 2022,
PCT Pub. No. WO2021/019373, PCT Pub. Date Feb. 4, 2021.
Claims priority of application No. 115685 (PT), filed on Jul. 31, 2019.
Prior Publication US 2022/0288017 A1, Sep. 15, 2022
Int. Cl. A61K 31/365 (2006.01); A61K 31/353 (2006.01); A61P 25/04 (2006.01); C07D 307/28 (2006.01); C07D 307/36 (2006.01)
CPC A61K 31/365 (2013.01) [A61K 31/353 (2013.01); A61P 25/04 (2018.01); C07D 307/28 (2013.01); C07D 307/36 (2013.01)] 15 Claims
OG exemplary drawing
 
1. A compound of formula I, II, or III, or a pharmaceutically acceptable salt thereof,

OG Complex Work Unit Chemistry
wherein
custom character represents a carbon-carbon single bond or a carbon-carbon double bond;
X is selected from O, NH, CH2;
Y is selected from CH, CH2;
Z is selected from C, N;
G is selected from O;
T is selected from, SH;
One of R1 and R2 is H, and then R1 is selected from alkenyl, cycloalkyl or —CH2—R3 or R2 is selected from alkyl, alkenyl, cycloalkyl, aryl or —CH2—R3; wherein for R1, R3 is selected from, cycloalkyl, heteroaryl, —R4-R5 and for R2, R3 is selected from aryl, cycloalkyl, heteroaryl, —R4-R5; wherein R4 is selected from alkyl, alkenyl; wherein R5 is selected from aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted gama-lactone;
Q is selected from C, CH;
D is selected from C, CH;
One of A and E is H and the other is selected from OH, SH, C4 or C7-C12 alkyl, alkenyl, R6-R7, wherein R6 is selected from C2-C12 alkyl, alkenyl, and R7 is selected from substituted or unsubstituted aryl, except phenyl, substituted or unsubstituted heteroaryl, substituted or unsubstituted gama-lactone;
J is selected from H, OH, SH, NH2, and halogen;
wherein the compound is not nitenin, dihydronitenin nor their respective, enantiomers, and stereoisomers; wherein aryl refers to a monovalent aromatic hydrocarbon radical comprising 6-20 carbon atoms (C6-C20) that is derived by removing a hydrogen atom from an aromatic ring; alkyl refers to a saturated monovalent hydrocarbon radical comprising one to four carbon atoms (C1-C4) and may be linear, or cyclic; heteroaryl refers to a monovalent aromatic radical comprising 5 to 20 atoms, one or more 5-,6-, or 7-membered rings, and one or more heteroatoms independently chosen from nitrogen, oxygen, phosphorous, and sulfur; cycloalkyl is a cyclic alkyl; and alkenyl refers to a monovalent hydrocarbon radical comprising four to eight carbon atoms (C2-C8) with at least one site of unsaturation.