US 11,999,732 B2
P2X3 receptor antagonists
Davide Graziani, Milan (IT); Sergio Menegon, Milan (IT); Patrizia Angelico, Milan (IT); and Carlo Riva, Milan (IT)
Assigned to RECORDATI INDUSTRIA CHIMICA E FARMACEUTICA SPA, Milan (IT)
Appl. No. 17/259,511
Filed by RECORDATI INDUSTRIA CHIMICA E FARMACEUTICA SPA, Milan (IT)
PCT Filed Jul. 11, 2019, PCT No. PCT/EP2019/068681
§ 371(c)(1), (2) Date Jan. 11, 2021,
PCT Pub. No. WO2020/011921, PCT Pub. Date Jan. 16, 2020.
Claims priority of application No. 1811452 (GB), filed on Jul. 12, 2018.
Prior Publication US 2021/0246139 A1, Aug. 12, 2021
Int. Cl. C07D 471/14 (2006.01); A61K 31/519 (2006.01); C07D 487/14 (2006.01); C07D 491/22 (2006.01); C07D 519/00 (2006.01)
CPC C07D 471/14 (2013.01) [C07D 487/14 (2013.01); C07D 491/22 (2013.01); C07D 519/00 (2013.01)] 16 Claims
 
1. A compound according to formula I:

OG Complex Work Unit Chemistry
or an enantiomer, diastereomer, N-oxide, or a pharmaceutically acceptable salt or combinations thereof, wherein:
one or two of the A groups comprise nitrogen atoms, and the remaining A groups each comprises carbon atom;
X—Y represents a N—C group;
each R1 independently represents 2-oxa-6-azaspiro[3.3]heptan-6-yl, 3-methoxymethylazetidin-1-yl, 3-methoxypyrrolidin-1-yl, 4-acetylpiperazin-1-yl, 4-aminopiperidin-1-yl, 4-hydroxypiperidin-1-yl, 4-hydroxypiperidin-1-yl-carbonyl, 4-methoxypiperidin-1-yl, 4-morpholinyl, dimethylaminopiperidin-1-yl, hydroxymethylpiperidin-1-yl, morpholin-4-ylcarbonyl, tetrahydro-2H-pyran-4-ylamino or tetrahydro-2H-pyran-4-ylaminocarbonyl, (oxetan-3-ylmethyl)amino, 4-(hydroxyacetyl)piperazin-1-yl;
R2 is an optionally substituted, C1-C6 alkyl group, C1-C6 alkoxy group, C4-C14 arylalkyl group, C4-C14 heteroarylalkyl group, C3-C7 cycloalkyl group, a mono-, bi- or tricyclic C6-C14 aryl group or a mono-, bi- or tricyclic C1-C13 heterocyclic group containing from 1 to 5 heteroatoms selected from N, O or S;
groups R3 and R4 are linked to each other to form a five-membered heterocyclic ring containing 2 or 3 nitrogen atoms or a six-membered heterocyclic ring containing 2 nitrogen atoms, substituted with one or more groups R6;
R5 is O double-bonded directly to the X—Y containing ring;
each R6 independently represents a halogen atom selected from F, Cl, Br or I; or an, optionally substituted, carbonyl, oxo, C1-C6 alkyl, C1-C6 alkoxy or C3-C7 cycloalkyl group, an, optionally substituted, mono-, bi- or tricyclic C6-C14 aryl group or an, optionally substituted, mono-, bi- or tricyclic C1-C13 heterocyclic group containing from 1 to 5 heteroatoms selected from N, O or S or alternatively, two R6 groups are linked to each other to form a group of the formula -(Zp)- wherein p is an integer of from 3 to 5 and each Z independently represents an oxygen atom or an optionally substituted methylene group, provided that no two adjacent Z moieties represent oxygen atoms; and
n is an integer independently selected from 0 to 3.