US 11,597,733 B2Granted

Compounds and compositions for the treatment of parasitic diseases

AssigneeNovartis AG

InventorsNicole Alice Blaquiere, Richard Yichong Huang, Thomas Martin Kirrane, Jr., Andreas Kordikowski, Anne-Catherine Mata, Christopher Ronald Sarko, Benjamin Robert Taft, Grace Lamprecht Waldron, Fumiaki Yokokawa, Tingying Zhu

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Abstract

The present invention provides a compound of formula (Ia) or a pharmaceutically acceptable salt thereof; a method for manufacturing the compounds of the invention, solid forms, combinations of pharmacologically active agents, pharmaceutical compositions and methods of using such compounds and solid forms thereof to treat or prevent parasitic diseases, for example malaria.

Claims12

Dependent claims

A compound of Formula Ic:

wherein:
Z is N;
Y is C(OH)CH2NH2
R1 is C1-4alkyl;
R2a is C1-4alkyl;
R2b is hydrogen;
R3a is selected from amino, —CO—C1-4alkyl, and 3-6 member, saturated, unsaturated or partially unsaturated heterocyclic ring containing up to three heteroatoms selected from N, NR30, S(O)0-2 and O, wherein the heterocyclic ring of R3a is unsubstituted or substituted with 1 or 2 hydroxy or amino;
R3b, R3c, R3d, and R3e is each independently selected from hydrogen, C1-4alkyl, amino, —X1—R3a, —NH—X1—R3a, hydroxy-substituted-C1-4alkyl, C1-4alkoxy-substituted-C1-4alkyl, hydroxy, oxo, halo, —X1—CO2H, —X1—CO2NH2, —X1—SO2C1-4alkyl, —X1—SO2N(C1-4alkyl)2, and —X1—C3-6-cycloalkyl;
X1 is selected from a bond and C1-4alkylene;
or
a pharmaceutically acceptable salt thereof.

8 more elements

A compound selected from any one of Examples 4-0 to 58-2:

4-(aminomethyl)-1-(5-(6-isopropyl-2-methoxypyridin-3-yl)imidazo[2,1-b][1,3,4]thiadiazol-2-yl)piperidin-4-ol;
3-(aminomethyl)-1-(5-(2-methoxy-4-methylphenyl)imidazo[2,1-b][1,3,4]thiadiazol-2-yl)pyrrolidin-3-ol;
(4-(5-(2-methoxy-4-methylphenyl)imidazo[2,1-b][1,3,4]thiadiazol-2-yl)piperazin-2-yl)methanol;
(4-amino-1-(5-(2-methoxy-4-methylphenyl)imidazo[2,1-b][1,3,4]thiadiazol-2-yl)piperidin-4-yl)methanol;
(3S,5S)-5-amino-1-(5-(4-fluoro-2-methoxyphenyl)imidazo[2,1-b][1,3,4]thiadiazol-2-yl)piperidin-3-ol;
3-(aminomethyl)-1-(5-(6-isopropyl-2-methoxypyridin-3-yl)imidazo[2,1-b][1,3,4]thiadiazol-2-yl)azetidin-3-ol;
4-(aminomethyl)-1-(5-(5-chloro-4-fluoro-2-methoxyphenyl)imidazo[2,1-b][1,3,4]thiadiazol-2-yl)piperidin-4-ol;
4-(aminomethyl)-1-(5-(2-ethoxy-5-methylphenyl)imidazo[2,1-b][1,3,4]thiadiazol-2-yl)piperidin-4-ol;
2-(5-(4-fluoro-2-methoxyphenyl)imidazo[2,1-b][1,3,4]thiadiazol-2-yl)-5-oxa-2,8-diazaspiro[3.5]nonane;
8-(5-(2-methoxy-4-methylphenyl)imidazo[2,1-b][1,3,4]thiadiazol-2-yl)-1-oxa-8-azaspiro[4.5]decan-3-amine;
4-(aminomethyl)-1-(5-(5-fluoro-2-methoxyphenyl)imidazo[2,1-b][1,3,4]thiadiazol-2-yl)piperidin-4-ol;
9-(5-(4-fluoro-2-methoxyphenyl)imidazo[2,1-b][1,3,4]thiadiazol-2-yl)-1-oxa-4,9-diazaspiro[5.5]undecane;
4-(aminomethyl)-1-(5-(2-methoxy-6-methylpyridin-3-yl)imidazo[2,1-b][1,3,4]thiadiazol-2-yl)piperidin-4-ol;
4-(aminomethyl)-1-(5-(3-chloro-2-methoxyphenyl)imidazo[2,1-b][1,3,4]thiadiazol-2-yl)piperidin-4-ol;
4-(aminomethyl)-1-(5-(4-cyclopropyl-2-methoxyphenyl)imidazo[2,1-b][1,3,4]thiadiazol-2-yl)piperidin-4-ol;
(3S,4R)-4-amino-1-(5-(4-fluoro-2-methoxyphenyl)imidazo[2,1-b][1,3,4]thiadiazol-2-yl)piperidin-3-ol;
(3R,4S)-4-amino-1-(5-(4-fluoro-2-methoxyphenyl)imidazo[2,1-b][1,3,4]thiadiazol-2-yl)piperidin-3-ol;
4-(aminomethyl)-1-(5-(3,5-difluoro-2-methoxyphenyl)imidazo[2,1-b][1,3,4]thiadiazol-2-yl)piperidin-4-ol;
4-(aminomethyl)-1-(5-(2,3-dihydrobenzofuran-7-yl)imidazo[2,1-b][1,3,4]thiadiazol-2-yl)piperidin-4-ol;
4-(aminomethyl)-1-(5-(2-methoxy-3-methylphenyl)imidazo[2,1-b][1,3,4]thiadiazol-2-yl)piperidin-4-ol;
(R)-1-(1-(5-(6-isopropyl-2-methoxypyridin-3-yl)imidazo[2,1-b][1,3,4]thiadiazol-2-yl)pyrrolidin-3-yl)cyclopropan-1-amine;
(4-((cyclopropylmethyl)amino)-1-(5-(2-methoxy-4-methylphenyl)imidazo[2,1-b][1,3,4]thiadiazol-2-yl)piperidin-4-yl)methanol;
4-(aminomethyl)-1-(5-(2-methoxy-3-(trifluoromethyl)phenyl)imidazo[2,1-b][1,3,4]thiadiazol-2-yl)piperidin-4-ol;
2-(4-(5-(2-methoxy-4-methylphenyl)imidazo[2,1-b][1,3,4]thiadiazol-2-yl)piperazin-2-yl)ethan-1-ol;
3-(aminomethyl)-1-(5-(2-methoxy-4-methylphenyl)imidazo[2,1-b][1,3,4]thiadiazol-2-yl)azetidin-3-ol;
(3S,4R)-3-fluoro-1-(5-(4-fluoro-2-methoxyphenyl)imidazo[2,1-b][1,3,4]thiadiazol-2-yl)piperidin-4-amine;
(3R,4S)-3-fluoro-1-(5-(4-fluoro-2-methoxyphenyl)imidazo[2,1-b][1,3,4]thiadiazol-2-yl)piperidin-4-amine;
(3S,4R)-4-amino-1-(5-(6-isopropyl-2-methoxypyridin-3-yl)imidazo[2,1-b][1,3,4]thiadiazol-2-yl)pyrrolidin-3-ol;
(4-(5-(6-isopropyl-2-methoxypyridin-3-yl)imidazo[2,1-b][1,3,4]thiadiazol-2-yl)piperazin-2-yl)methanol;
8-(5-(6-isopropyl-2-methoxypyridin-3-yl)imidazo[2,1-b][1,3,4]thiadiazol-2-yl)-1-oxa-8-azaspiro[4.5]decan-3-amine;
8-(5-(4-fluoro-2-methoxyphenyl)imidazo[2,1-b][1,3,4]thiadiazol-2-yl)-1-oxa-8-azaspiro[4.5]decan-3-amine;
4-(aminomethyl)-1-(5-(2-ethoxy-4-(trifluoromethyl)phenyl)imidazo[2,1-b][1,3,4]thiadiazol-2-yl)piperidin-4-ol;
3-(aminomethyl)-1-(5-(2-methoxy-6-methylpyridin-3-yl)imidazo[2,1-b][1,3,4]thiadiazol-2-yl)pyrrolidin-3-ol;
4-(aminomethyl)-1-(5-(4-chloro-2-(2-methoxyethoxy)phenyl)imidazo[2,1-b][1,3,4]thiadiazol-2-yl)piperidin-4-ol;
(S)-3-(aminomethyl)-1-(5-(4-fluoro-2-methoxyphenyl)imidazo[2,1-b][1,3,4]thiadiazol-2-yl)pyrrolidin-3-ol;
(R)-3-(aminomethyl)-1-(5-(4-fluoro-2-methoxyphenyl)imidazo[2,1-b][1,3,4]thiadiazol-2-yl)pyrrolidin-3-ol;
4-(aminomethyl)-1-(5-(4-fluoro-2-(trifluoromethoxy)phenyl)imidazo[2,1-b][1,3,4]thiadiazol-2-yl)piperidin-4-ol;
4-(aminomethyl)-1-(5-(3-fluoro-2-methoxy-4-methylphenyl)imidazo[2,1-b][1,3,4]thiadiazol-2-yl)piperidin-4-ol;
4-(aminomethyl)-1-(5-(2-(cyclopropylmethoxy)-4-fluorophenyl)imidazo[2,1-b][1,3,4]thiadiazol-2-yl)piperidin-4-ol;
4-(aminomethyl)-1-(5-(4-fluoro-2-methoxyphenyl)imidazo[2,1-b][1,3,4]thiadiazol-2-yl)piperidin-4-ol;
4-(aminomethyl)-1-(5-(4-fluoro-5-isopropyl-2-methoxyphenyl)imidazo[2,1-b][1,3,4]thiadiazol-2-yl)piperidin-4-ol;
8-(5-(2-methoxy-6-methylpyridin-3-yl)imidazo[2,1-b][1,3,4]thiadiazol-2-yl)-1-oxa-8-azaspiro[4.5]decan-3-amine;
(4-amino-1-(5-(4-chloro-2-methoxyphenyl)imidazo[2,1-b][1,3,4]thiadiazol-2-yl)piperidin-4-yl)methanol;
4-(aminomethyl)-1-(5-(2,3-dihydrobenzo[b][1,4]dioxin-5-yl)imidazo[2,1-b][1,3,4]thiadiazol-2-yl)piperidin-4-ol;
2-(5-(4-fluoro-2-methoxyphenyl)imidazo[2,1-b][1,3,4]thiadiazol-2-yl)-2-azaspiro[3.3]heptan-5-amine;
(4-(aminomethyl)-1-(5-(4-fluoro-2-methoxyphenyl)imidazo[2,1-b][1,3,4]thiadiazol-2-yl)piperidin-4-yl)methanol;
4-(aminomethyl)-1-(5-(2-ethoxyphenyl)imidazo[2,1-b][1,3,4]thiadiazol-2-yl)piperidin-4-ol;
4-(aminomethyl)-1-(5-(2-methoxypyridin-3-yl)imidazo[2,1-b][1,3,4]thiadiazol-2-yl)piperidin-4-ol;
(S)-(3-amino-1-(5-(4-fluoro-2-methoxyphenyl)imidazo[2,1-b][1,3,4]thiadiazol-2-yl)pyrrolidin-3-yl)methanol;
(R)-(3-amino-1-(5-(4-fluoro-2-methoxyphenyl)imidazo[2,1-b][1,3,4]thiadiazol-2-yl)pyrrolidin-3-yl)methanol;
(3R,5R)-5-fluoro-1-(5-(4-fluoro-2-methoxyphenyl)imidazo[2,1-b][1,3,4]thiadiazol-2-yl)piperidin-3-amine;
(3R,4R)-4-amino-1-(5-(4-fluoro-2-methoxyphenyl)imidazo[2,1-b][1,3,4]thiadiazol-2-yl)piperidin-3-ol;
(3S,4S)-4-amino-1-(5-(4-fluoro-2-methoxyphenyl)imidazo[2,1-b][1,3,4]thiadiazol-2-yl)piperidin-3-ol;
1-(5-(2-methoxy-4-methylphenyl)imidazo[2,1-b][1,3,4]thiadiazol-2-yl)-3-methylpyrrolidin-3-amine;
1-(5-(2-methoxy-6-methylpyridin-3-yl)imidazo[2,1-b][1,3,4]thiadiazol-2-yl)-3-methylpyrrolidin-3-amine;
1-(5-(6-isopropyl-2-methoxypyridin-3-yl)imidazo[2,1-b][1,3,4]thiadiazol-2-yl)-3-methylpyrrolidin-3-amine;
2-((1-(5-(6-isopropyl-2-methoxypyridin-3-yl)imidazo[2,1-b][1,3,4]thiadiazol-2-yl)piperidin-4-yl)amino)ethan-1-ol;
4-(aminomethyl)-1-(5-(2-methoxy-4-(trifluoromethyl)phenyl)imidazo[2,1-b][1,3,4]thiadiazol-2-yl)piperidin-4-ol;
4-amino-1-(5-(4-fluoro-2-methoxyphenyl)imidazo[2,1-b][1,3,4]thiadiazol-2-yl)pyrrolidin-3-ol;
4-(aminomethyl)-1-(5-(3,4-difluoro-2-methoxyphenyl)imidazo[2,1-b][1,3,4]thiadiazol-2-yl)piperidin-4-ol;
(3S,4R)-4-amino-1-(5-(4-fluoro-2-methoxyphenyl)imidazo[2,1-b][1,3,4]thiadiazol-2-yl)pyrrolidin-3-ol;
(3S,4R)-4-amino-1-(5-(4-fluoro-2-methoxyphenyl)imidazo[2,1-b][1,3,4]thiadiazol-2-yl)pyrrolidin-3-ol;
4-(aminomethyl)-1-(5-(4-chloro-2-methoxyphenyl)imidazo[2,1-b][1,3,4]thiadiazol-2-yl)piperidin-4-ol;
4-(aminomethyl)-1-(5-(4,5-difluoro-2-methoxyphenyl)imidazo[2,1-b][1,3,4]thiadiazol-2-yl)piperidin-4-ol;
(R)-(3-amino-1-(5-(2-ethoxy-4-fluorophenyl)imidazo[2,1-b][1,3,4]thiadiazol-2-yl)pyrrolidin-3-yl)methanol;
(S)-(3-amino-1-(5-(2-ethoxy-4-fluorophenyl)imidazo[2,1-b][1,3,4]thiadiazol-2-yl)pyrrolidin-3-yl)methanol;
4-(aminomethyl)-1-(5-(2-methoxy-4,5-dimethylphenyl)imidazo[2,1-b][1,3,4]thiadiazol-2-yl)piperidin-4-ol;
(3S,4R)-3-amino-1-(5-(4-fluoro-2-methoxyphenyl)imidazo[2,1-b][1,3,4]thiadiazol-2-yl)piperidin-4-ol;
(3R,4S)-3-amino-1-(5-(4-fluoro-2-methoxyphenyl)imidazo[2,1-b][1,3,4]thiadiazol-2-yl)piperidin-4-ol;
2-(4-(5-(6-isopropyl-2-methoxypyridin-3-yl)imidazo[2,1-b][1,3,4]thiadiazol-2-yl)piperazin-1-yl)ethan-1-ol;
3-(aminomethyl)-1-(5-(6-isopropyl-2-methoxypyridin-3-yl)imidazo[2,1-b][1,3,4]thiadiazol-2-yl)pyrrolidin-3-ol;
4-(aminomethyl)-1-(5-(2-methoxy-4-(tetrahydro-2H-pyran-4-yl)phenyl)imidazo[2,1-b][1,3,4]thiadiazol-2-yl)piperidin-4-ol;
4-(2-(4-(aminomethyl)-4-hydroxypiperidin-1-yl)imidazo[2,1-b][1,3,4]thiadiazol-5-yl)-3-methoxybenzonitrile;
4-(aminomethyl)-1-(5-(2,6-dimethoxypyridin-3-yl)imidazo[2,1-b][1,3,4]thiadiazol-2-yl)piperidin-4-ol;
(4-amino-1-(5-(4-chloro-2-(2-methoxyethoxy)phenyl)imidazo[2,1-b][1,3,4]thiadiazol-2-yl)piperidin-4-yl)methanol;
3-(aminomethyl)-1-(5-(4-fluoro-2-methoxyphenyl)imidazo[2,1-b][1,3,4]thiadiazol-2-yl)azetidin-3-ol;
4-(aminomethyl)-1-(5-(2-ethoxy-4-fluorophenyl)imidazo[2,1-b][1,3,4]thiadiazol-2-yl)piperidin-4-ol;
4-(aminomethyl)-1-(5-(6-isopropyl-2-(2-methoxyethoxy)pyridin-3-yl)imidazo[2,1-b][1,3,4]thiadiazol-2-yl)piperidin-4-ol;
4-(aminomethyl)-1-(5-(3-fluoro-2-methoxyphenyl)imidazo[2,1-b][1,3,4]thiadiazol-2-yl)piperidin-4-ol;
4-(aminomethyl)-1-(5-(3-methoxynaphthalen-2-yl)imidazo[2,1-b][1,3,4]thiadiazol-2-yl)piperidin-4-ol;
(3S,4S)-3-amino-1-(5-(4-fluoro-2-methoxyphenyl)imidazo[2,1-b][1,3,4]thiadiazol-2-yl)piperidin-4-ol;
(3R,4R)-3-amino-1-(5-(4-fluoro-2-methoxyphenyl)imidazo[2,1-b][1,3,4]thiadiazol-2-yl)piperidin-4-ol;
(4aR,8aR)-6-(5-(2-methoxy-4-methylphenyl)imidazo[2,1-b][1,3,4]thiadiazol-2-yl)octahydro-2H-pyrido[4,3-b][1,4]oxazine;
1-(5-(6-isopropyl-2-methoxypyridin-3-yl)imidazo[2,1-b][1,3,4]thiadiazol-2-yl)-[1,3′-biazetidin]-3-ol;
(4-amino-1-(5-(6-isopropyl-2-methoxypyridin-3-yl)imidazo[2,1-b][1,3,4]thiadiazol-2-yl)piperidin-4-yl)methanol;
4-(aminomethyl)-1-(5-(5-chloro-2-methoxyphenyl)imidazo[2,1-b][1,3,4]thiadiazol-2-yl)piperidin-4-ol;
4-(aminomethyl)-1-(5-(2-methoxyphenyl)imidazo[2,1-b][1,3,4]thiadiazol-2-yl)piperidin-4-ol;
4-(aminomethyl)-1-(5-(4-fluoro-2-isopropoxyphenyl)imidazo[2,1-b][1,3,4]thiadiazol-2-yl)piperidin-4-ol;
4-(1-(5-(6-isopropyl-2-methoxypyridin-3-yl)imidazo[2,1-b][1,3,4]thiadiazol-2-yl)piperidin-4-yl)morpholine;
4-(aminomethyl)-1-(5-(2-(trifluoromethoxy)phenyl)imidazo[2,1-b][1,3,4]thiadiazol-2-yl)piperidin-4-ol;
3-(aminomethyl)-1-(5-(2-ethoxy-4-fluorophenyl)imidazo[2,1-b][1,3,4]thiadiazol-2-yl)pyrrolidin-3-ol;
1-(1-(5-(6-isopropyl-2-methoxypyridin-3-yl)imidazo[2,1-b][1,3,4]thiadiazol-2-yl)piperidin-4-yl)azetidin-3-ol;
4-(aminomethyl)-1-(5-(2-methoxy-6-(trifluoromethyl)pyridin-3-yl)imidazo[2,1-b][1,3,4]thiadiazol-2-yl)piperidin-4-ol;
(4-(aminomethyl)-1-(5-(2-methoxy-4-methylphenyl)imidazo[2,1-b][1,3,4]thiadiazol-2-yl)piperidin-4-yl)methanol;
4-(1-(5-(6-isopropyl-2-methoxypyridin-3-yl)imidazo[2,1-b][1,3,4]thiadiazol-2-yl)piperidin-4-yl)thiomorpholine 1,1-dioxide;
(4-amino-1-(5-(2-methoxy-6-methylpyridin-3-yl)imidazo[2,1-b][1,3,4]thiadiazol-2-yl)piperidin-4-yl)methanol;
(4-amino-1-(5-(4-fluoro-2-methoxyphenyl)imidazo[2,1-b][1,3,4]thiadiazol-2-yl)piperidin-4-yl)methanol;
4-(aminomethyl)-1-(5-(4-fluoro-2-methoxy-5-methylphenyl)imidazo[2,1-b][1,3,4]thiadiazol-2-yl)piperidin-4-ol;
(4-amino-1-(5-(2-ethoxy-4-fluorophenyl)imidazo[2,1-b][1,3,4]thiadiazol-2-yl)piperidin-4-yl)methanol;
4-(aminomethyl)-1-(5-(2,4-dimethoxyphenyl)imidazo[2,1-b][1,3,4]thiadiazol-2-yl)piperidin-4-ol;
N-((3aR,7aR)-2-(5-(4-fluoro-2-methoxyphenyl)imidazo[2,1-b][1,3,4]thiadiazol-2-yl)octahydro-3aH-pyrrolo[3,4-c]pyridin-3a-yl)acetamide;
2-(5-(2-methoxy-4-methylphenyl)imidazo[2,1-b][1,3,4]thiadiazol-2-yl)-5-oxa-2,7-diazaspiro[3.4]oct-6-en-6-amine;
8-(5-(4-fluoro-2-methoxyphenyl)imidazo[2,1-b][1,3,4]thiadiazol-2-yl)-1-oxa-3,8-diazaspiro[4.5]dec-2-en-2-amine;
8-(5-(4-fluoro-2-methoxyphenyl)imidazo[2,1-b][1,3,4]thiadiazol-2-yl)-3-oxa-1,8-diazaspiro[4.5]dec-1-en-2-amine;
8-(5-(2-methoxy-4-methylphenyl)imidazo[2,1-b][1,3,4]thiadiazol-2-yl)-1-oxa-3,8-diazaspiro[4.5]dec-2-en-2-amine;
(3aS,5S,6S,7aR)-6-amino-2-(5-(6-isopropyl-2-methoxypyridin-3-yl)imidazo[2,1-b][1,3,4]thiadiazol-2-yl)octahydro-1H-isoindol-5-ol;
(3aS,5S,6S,7aR)-6-amino-2-(5-(6-isopropyl-2-methoxypyridin-3-yl)imidazo[2,1-b][1,3,4]thiadiazol-2-yl)octahydro-1H-isoindol-5-ol;
(3aS,5S,6S,7aR)-6-amino-2-(5-(4-fluoro-2-methoxyphenyl)imidazo[2,1-b][1,3,4]thiadiazol-2-yl)octahydro-1H-isoindol-5-ol;
(9-(5-(4-fluoro-2-methoxyphenyl)imidazo[2,1-b][1,3,4]thiadiazol-2-yl)-2-oxa-9-azaspiro[5.5]und;
ecan-3-yl)methanamine;
(3-amino-1-(5-(6-isopropyl-2-methoxypyridin-3-yl)imidazo[2,1-b][1,3,4]thiadiazol-2-yl)azetidin-3-yl)methanol;
(3-fluoro-1-(5-(4-fluoro-2-methoxyphenyl)imidazo[2,1-b][1,3,4]thiadiazol-2-yl)piperidin-3-yl)methanamine;
(8-(5-(4-fluoro-2-methoxyphenyl)imidazo[2,1-b][1,3,4]thiadiazol-2-yl)-1-oxa-8-azaspiro[4.5]decan-2-yl)methanamine;
2-(5-(4-fluoro-2-methoxyphenyl)imidazo[2,1-b][1,3,4]thiadiazol-2-yl)-5-oxa-2-azaspiro[3.4]octan-7-amine;
(3S,4S)-8-(5-(4-fluoro-2-methoxyphenyl)imidazo[2,1-b][1,3,4]thiadiazol-2-yl)-3-methyl-2-oxa-8-azaspiro[4.5]decan-4-amine;
4-(aminomethyl)-1-(5-(2-(dimethylamino)-6-methylpyridin-3-yl)imidazo[2,1-b][1,3,4]thiadiazol-2-yl)piperidin-4-ol;
4-(aminomethyl)-1-(5-(6-methyl-2-(methylthio)pyridin-3-yl)imidazo[2,1-b][1,3,4]thiadiazol-2-yl)piperidin-4-ol;
3-(aminomethyl)-1-(5-(4-fluoro-2-methoxyphenyl)imidazo[2,1-b][1,3,4]thiadiazol-2-yl)piperidin-3-ol;
8-(5-(4-fluoro-2-methoxyphenyl)imidazo[2,1-b][1,3,4]thiadiazol-2-yl)-2-oxa-8-azaspiro[4.5]decan-4-amine;
3-amino-1-(9-(5-(4-fluoro-2-methoxyphenyl)imidazo[2,1-b][1,3,4]thiadiazol-2-yl)-1,4,9-triazaspiro[5.5]undecan-4-yl)-3-methylbutan-1-one;
5-(6-isopropyl-2-methoxypyridin-3-yl)-2-(1,4,9-triazaspiro[5.5]undecan-9-yl)imidazo[2,1-b][1,3,4]thiadiazole;
5-(4-fluoro-2-methoxyphenyl)-2-(1,4,9-triazaspiro[5.5]undecan-9-yl)imidazo[2,1-b][1,3,4]thiadiazole;
1-(5-(4-fluoro-2-methoxyphenyl)imidazo[2,1-b][1,3,4]thiadiazol-2-yl)-4-(morpholinomethyl)piperidin-4-amine;
7-(5-(4-fluoro-2-methoxyphenyl)imidazo[2,1-b][1,3,4]thiadiazol-2-yl)-5,6,7,8-tetrahydroimidazo[1,5-a]pyrazin-3-amine;
(1-(5-(4-fluoro-2-methoxyphenyl)imidazo[2,1-b][1,3,4]thiadiazol-2-yl)-4-((oxetan-3-ylmethyl)amino)piperidin-4-yl)methanol;
(1-(5-(4-fluoro-2-methoxyphenyl)imidazo[2,1-b][1,3,4]thiadiazol-2-yl)-4-((2-morpholinoethyl)amino)piperidin-4-yl)methanol;
4-((3-aminopropyl)amino)-1-(5-(4-fluoro-2-methoxyphenyl)imidazo[2,1-b][1,3,4]thiadiazol-2-yl)piperidin-4-yl)methanol;
6-(aminomethyl)-2-(5-(4-fluoro-2-methoxyphenyl)imidazo[2,1-b][1,3,4]thiadiazol-2-yl)-2-azaspiro[3.3]heptan-6-ol;
(S)-3-(aminomethyl)-1-(5-(6-isopropyl-2-methoxypyridin-3-yl)imidazo[2,1-b][1,3,4]thiadiazol-2-yl)pyrrolidin-3-ol;
(R)-3-(aminomethyl)-1-(5-(6-isopropyl-2-methoxypyridin-3-yl)imidazo[2,1-b][1,3,4]thiadiazol-2-yl)pyrrolidin-3-ol;
(S)-3-(aminomethyl)-1-(5-(2-methoxy-6-methylpyridin-3-yl)imidazo[2,1-b][1,3,4]thiadiazol-2-yl)pyrrolidin-3-ol;
(R)-3-(aminomethyl)-1-(5-(2-methoxy-6-methylpyridin-3-yl)imidazo[2,1-b][1,3,4]thiadiazol-2-yl)pyrrolidin-3-ol;
3-(aminomethyl)-1-(5-(6-isopropyl-2-methoxypyridin-3-yl)imidazo[2,1-b][1,3,4]thiadiazol-2-yl)pyrrolidin-3-ol;
(3S,4S)-4-amino-1-(5-(2-methoxy-4-methylphenyl)imidazo[2,1-b][1,3,4]thiadiazol-2-yl)-4-methylpiperidin-3-ol;
(3R,4R)-4-amino-1-(5-(2-methoxy-4-methylphenyl)imidazo[2,1-b][1,3,4]thiadiazol-2-yl)-4-methylpiperidin-3-ol;
(3R,4R)-4-amino-1-(5-(6-isopropyl-2-methoxypyridin-3-yl)imidazo[2,1-b][1,3,4]thiadiazol-2-yl)-4-methylpiperidin-3-ol;
(3S,4S)-4-amino-1-(5-(6-isopropyl-2-methoxypyridin-3-yl)imidazo[2,1-b][1,3,4]thiadiazol-2-yl)-4-methylpiperidin-3-ol;
(3R,4R)-4-amino-1-(5-(4-fluoro-2-methoxyphenyl)imidazo[2,1-b][1,3,4]thiadiazol-2-yl)-4-methylpiperidin-3-ol;
(3S,4S)-4-amino-1-(5-(4-fluoro-2-methoxyphenyl)imidazo[2,1-b][1,3,4]thiadiazol-2-yl)-4-methylpiperidin-3-ol;
(3R,4R)-4-amino-1-(5-(2-methoxy-6-methylpyridin-3-yl)imidazo[2,1-b][1,3,4]thiadiazol-2-yl)-4-methylpiperidin-3-ol;
(3S,4S)-4-amino-1-(5-(2-methoxy-6-methylpyridin-3-yl)imidazo[2,1-b][1,3,4]thiadiazol-2-yl)-4-methylpiperidin-3-ol;
(3S,4S)-3-amino-1-(5-(4-fluoro-2-methoxyphenyl)imidazo[2,1-b][1,3,4]thiadiazol-2-yl)-4-methylpiperidin-4-ol;
(3R,4R)-3-amino-1-(5-(4-fluoro-2-methoxyphenyl)imidazo[2,1-b][1,3,4]thiadiazol-2-yl)-4-methylpiperidin-4-ol;
(3R,4R)-4-amino-1-(5-(4-fluoro-2-methoxyphenyl)imidazo[2,1-b][1,3,4]thiadiazol-2-yl)-4-methylpiperidin-3-ol;
4-(aminomethyl)-1-(5-(4-fluoro-2-methoxyphenyl)imidazo[2,1-b][1,3,4]thiadiazol-2-yl)piperidine-4-carboxamide;
N-((1-aminocyclopropyl)methyl)-4-(aminomethyl)-1-(5-(4-fluoro-2-methoxyphenyl)imidazo[2,1-b][1,3,4]thiadiazol-2-yl)piperidine-4-carboxamide;
N-(2-amino-2-methylpropyl)-8-(5-(4-fluoro-2-methoxyphenyl)imidazo[2,1-b][1,3,4]thiadiazol-2-yl)-1-thia-8-azaspiro[4.5]decane-4-carboxamide 1,1-dioxide;
2-(4-amino-1-(5-(4-fluoro-2-methoxyphenyl)imidazo[2,1-b][1,3,4]thiadiazol-2-yl)piperidin-4-yl)propan-2-ol;
2-(4-amino-1-(5-(4-fluoro-2-methoxyphenyl)imidazo[2,1-b][1,3,4]thiadiazol-2-yl)piperidin-4-yl)propan-2-ol;
4-(aminomethyl)-1-(5-(4-(1-hydroxycyclobutyl)-2-methoxyphenyl)imidazo[2,1-b][1,3,4]thiadiazol-2-yl)piperidin-4-ol;
((1-(5-(4-fluoro-2-methoxyphenyl)imidazo[2,1-b][1,3,4]thiadiazol-2-yl)-4-((methylsulfonyl)methyl)piperidin-4-yl)methanamine;
1-(4-(aminomethyl)-1-(5-(4-fluoro-2-methoxyphenyl)imidazo[2,1-b][1,3,4]thiadiazol-2-yl)piperidin-4-yl)-N,N-dimethylmethanesulfonamide;
((3R,5S)-5-amino-1-(5-(4-fluoro-2-methoxyphenyl)imidazo[2,1-b][1,3,4]thiadiazol-2-yl)piperidin-3-ol;
(4S,4aR,7aS)-6-(5-(2-ethoxy-6-isopropylpyridin-3-yl)imidazo[2,1-b][1,3,4]thiadiazol-2-yl)octahydropyrano[2,3-c]pyrrol-4-amine;
(4S,4aR,7aS)-6-(5-(2-methoxy-4-(trifluoromethyl)phenyl)imidazo[2,1-b][1,3,4]thiadiazol-2-yl)octahydropyrano[2,3-c]pyrrol-4-amine;
(4R,4aS,7aR)-6-(5-(2-methoxy-4-(trifluoromethyl)phenyl)imidazo[2,1-b][1,3,4]thiadiazol-2-yl)octahydropyrano[2,3-c]pyrrol-4-amine;
(4S,4aR,7aS)-6-(5-(6-isopropyl-2-methoxypyridin-3-yl)imidazo[2,1-b][1,3,4]thiadiazol-2-yl)octahydropyrano[2,3-c]pyrrol-4-amine;
(4R,4aS,7aR)-6-(5-(6-isopropyl-2-methoxypyridin-3-yl)imidazo[2,1-b][1,3,4]thiadiazol-2-yl)octahydropyrano[2,3-c]pyrrol-4-amine;
(4S,4aR,7aS)-6-(5-(4-fluoro-2-methoxyphenyl)imidazo[2,1-b][1,3,4]thiadiazol-2-yl)octahydropyrano[2,3-c]pyrrol-4-amine;
(4R,4aS,7aR)-6-(5-(4-fluoro-2-methoxyphenyl)imidazo[2,1-b][1,3,4]thiadiazol-2-yl)octahydropyrano[2,3-c]pyrrol-4-amine;
((4S,4aS,7aR)-6-(5-(4-fluoro-2-methoxyphenyl)imidazo[2,1-b][1,3,4]thiadiazol-2-yl)octahydropyrano[2,3-c]pyrrol-4-amine;
(4S,4aS,7aR)-6-(5-(6-isopropyl-2-methoxypyridin-3-yl)imidazo[2,1-b][1,3,4]thiadiazol-2-yl)octahydropyrano[2,3-c]pyrrol-4-amine;
(4R,4aR,7aS)-6-(5-(6-isopropyl-2-methoxypyridin-3-yl)imidazo[2,1-b][1,3,4]thiadiazol-2-yl)octahydropyrano[2,3-c]pyrrol-4-amine;
4S,4aR,7aR)-6-(5-(6-isopropyl-2-methoxypyridin-3-yl)imidazo[2,1-b][1,3,4]thiadiazol-2-yl)octahydropyrano[2,3-c]pyrrol-4-amine;
(3aS,5R,7R,7aR)-7-amino-2-(5-(6-isopropyl-2-methoxypyridin-3-yl)imidazo[2,1-b][1,3,4]thiadiazol-2-yl)octahydro-1H-isoindol-5-ol;
(3aR,4S,5S,7aS)-4-amino-2-(5-(6-isopropyl-2-methoxypyridin-3-yl)imidazo[2,1-b][1,3,4]thiadiazol-2-yl)octahydro-1H-isoindol-5-ol;
(3aR,4S,5R,7aS)-4-amino-2-(5-(2-methoxy-6-methylpyridin-3-yl)imidazo[2,1-b][1,3,4]thiadiazol-2-yl)octahydro-1H-isoindol-5-ol;
(3aR,4S,5R,7aS)-4-amino-2-(5-(6-isopropyl-2-methoxypyridin-3-yl)imidazo[2,1-b][1,3,4]thiadiazol-2-yl)octahydro-1H-isoindol-5-ol;
(3aR,4S,5R,7aS)-4-amino-2-(5-(4-fluoro-2-methoxyphenyl)imidazo[2,1-b][1,3,4]thiadiazol-2-yl)octahydro-1H-isoindol-5-ol;
(3aR,4R,7aS)-2-(5-(6-isopropyl-2-methoxypyridin-3-yl)imidazo[2,1-b][1,3,4]thiadiazol-2-yl)-2,3,3a,4,7,7a-hexahydro-1H-isoindol-4-amine:
4-(aminomethyl)-1-(5-(4-chloro-5-fluoro-2-methoxyphenyl)imidazo[2,1-b][1,3,4]thiadiazol-2-yl)piperidin-4-ol;
4-(aminomethyl)-1-(5-(2-isopropoxy-6-isopropylpyridin-3-yl)imidazo[2,1-b][1,3,4]thiadiazol-2-yl)piperidin-4-ol;
4-(aminomethyl)-1-(5-(2-ethoxy-6-isopropylpyridin-3-yl)imidazo[2,1-b][1,3,4]thiadiazol-2-yl)piperidin-4-ol;
(4-amino-1-(5-(2-ethoxy-6-isopropylpyridin-3-yl)imidazo[2,1-b][1,3,4]thiadiazol-2-yl)piperidin-4-yl)methanol;
3-(aminomethyl)-1-(5-(2-ethoxy-6-isopropylpyridin-3-yl)imidazo[2,1-b][1,3,4]thiadiazol-2-yl)azetidin-3-ol;
(4-amino-1-(5-(4-(1,2-difluoroethyl)-2-methoxyphenyl)imidazo[2,1-b][1,3,4]thiadiazol-2-yl)piperidin-4-yl)methanol;
4-(aminomethyl)-1-(5-(2-(2-hydroxyethoxy)-6-isopropylpyridin-3-yl)imidazo[2,1-b][1,3,4]thiadiazol-2-yl)piperidin-4-ol;
(4-amino-1-(5-(4-(1,2-difluoroethyl)-2-methoxyphenyl)imidazo[2,1-b][1,3,4]thiadiazol-2-yl)piperidin-4-yl)methanol;
4-(aminomethyl)-1-(5-(4-(1,2-difluoroethyl)-2-methoxyphenyl)imidazo[2,1-b][1,3,4]thiadiazol-2-yl)piperidin-4-ol;
4-(aminomethyl)-1-(5-(2-(2,2-difluoroethoxy)phenyl)imidazo[2,1-b][1,3,4]thiadiazol-2-yl)piperidin-4-ol;
4-(aminomethyl)-1-(5-(4-isopropyl-2-methoxyphenyl)imidazo[2,1-b][1,3,4]thiadiazol-2-yl)piperidin-4-ol;
4-(aminomethyl)-1-(5-(2-ethoxy-4-isopropylphenyl)imidazo[2,1-b][1,3,4]thiadiazol-2-yl)piperidin-4-ol;
4-(aminomethyl)-1-(5-(2-methoxy-4-(tetrahydrofuran-3-yl)phenyl)imidazo[2,1-b][1,3,4]thiadiazol-2-yl)piperidin-4-ol;
4-(aminomethyl)-1-(5-(2-methoxy-4-(1-methoxycyclopropyl)phenyl)imidazo[2,1-b][1,3,4]thiadiazol-2-yl)piperidin-4-ol;
4-(aminomethyl)-1-(5-(2-methoxy-4-(1-methoxycyclobutyl)phenyl)imidazo[2,1-b][1,3,4]thiadiazol-2-yl)piperidin-4-ol;
(4-amino-1-(5-(2-(2-fluoroethoxy)phenyl)imidazo[2,1-b][1,3,4]thiadiazol-2-yl)piperidin-4-yl)methanol;
4-(aminomethyl)-1-(5-(2-(2-fluoroethoxy)phenyl)imidazo[2,1-b][1,3,4]thiadiazol-2-yl)piperidin-4-ol;
(4-amino-1-(5-(2-(2,2-difluoroethoxy)phenyl)imidazo[2,1-b][1,3,4]thiadiazol-2-yl)piperidin-4-yl)methanol;
4-(aminomethyl)-1-(5-(2-(2,2-difluoroethoxy)phenyl)imidazo[2,1-b][1,3,4]thiadiazol-2-yl)piperidin-4-ol;
(4-amino-1-(5-(2-(2,3-difluoropropoxy)phenyl)imidazo[2,1-b][1,3,4]thiadiazol-2-yl)piperidin-4-yl)methanol;
4-(aminomethyl)-1-(5-(2-(2,3-difluoropropoxy)phenyl)imidazo[2,1-b][1,3,4]thiadiazol-2-yl)piperidin-4-ol;
4-(aminomethyl)-1-(5-(4-chloro-5-isopropyl-2-methoxyphenyl)imidazo[2,1-b][1,3,4]thiadiazol-2-yl)piperidin-4-ol;
4-amino-8-(5-(6-isopropyl-2-methoxypyridin-3-yl)imidazo[2,1-b][1,3,4]thiadiazol-2-yl)-1-thia-8-azaspiro[4.5]decane 1,1-dioxide;
1-(5-(4-fluoro-2-methoxyphenyl)imidazo[2,1-b][1,3,4]thiadiazol-2-yl)-4-(methoxymethyl)piperidin-4-amine;
2-(3-amino-1-(5-(4-fluoro-2-methoxyphenyl)imidazo[2,1-b][1,3,4]thiadiazol-2-yl)pyrrolidin-3-yl)propan-2-ol;
3-amino-1-(5-(4-fluoro-2-methoxyphenyl)imidazo[2,1-b][1,3,4]thiadiazol-2-yl)-4-methylpiperidin-4-ol;
(3R,4r,5S)-4-amino-1-(5-(4-fluoro-2-methoxyphenyl)imidazo[2,1-b][1,3,4]thiadiazol-2-yl)-4-methylpiperidine-3,5-diol;
and ((3S,4S)-4-amino-1-(5-(4-fluoro-2-methoxyphenyl)imidazo[2,1-b][1,3,4]thiadiazol-2-yl)piperidin-3-yl)methanol.

195 more elements

Dependencies are inferred from the claim text.

Facts

Application: 17/076,126Filed 21 Oct 2020 · us provisional application
Priority: 21 Oct 2019
Published: US 2021/0115065 A122 Apr 2021
Granted: 7 Mar 2023
Term ends: Not estimatedThe source records don’t support an estimate.

Classification23 codes

C07D 513/04
In which the condensed system contains two hetero rings: ortho-condensed systems
A61K 31/433
Having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole: thidiazoles
A61K 31/438
Having six-membered rings with one nitrogen as the only ring hetero atom: the ring being spiro-condensed with carbocyclic or heterocyclic ring systems
A61K 31/4439
Containing further heterocyclic ring systems: containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole