US2008261920A1PendingUtilityA1
2-Aminooxazolines as TAAR1 ligands
Est. expiryFeb 2, 2027(~0.6 yrs left)· nominal 20-yr term from priority
A61P 3/06A61P 9/00A61P 3/04A61P 25/16A61P 25/06A61P 25/24A61P 25/30A61P 25/08A61P 3/10A61P 3/00A61P 25/28A61P 25/18A61P 25/20A61P 25/22A61P 25/00C07F 7/0812C07D 413/04C07D 413/06C07D 263/28C07D 413/12A61K 31/421A61K 31/422
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Claims
Abstract
The invention relates to compounds of formula I wherein X, Y, R 1 , R 2 , and n are as defined herein or to a pharmaceutically suitable acid addition salt thereof. The invention also relates to pharmaceutical compositions containing such compounds and methods for the treatment of diseases related to the biological function of the trace amine associated receptors, which diseases include depression, anxiety disorders, bipolar disorder, attention deficit hyperactivity disorder, stress-related disorders, psychotic disorders, schizophrenia, neurological diseases, Parkinson's disease, neurodegenerative disorders, Alzheimer's disease, epilepsy, migraine, substance abuse and metabolic disorders, eating disorders, diabetes, diabetic complications, obesity, dyslipidemia, disorders of energy consumption and assimilation, disorders and malfunction of body temperature homeostasis, disorders of sleep and circadian rhythm, and cardiovascular disorders.
Claims
exact text as granted — not AI-modified1 . A method of treating a disorder selected from the group consisting of depression, anxiety disorders, bipolar disorder, attention deficit hyperactivity disorder, stress-related disorders, psychotic disorders, schizophrenia, neurological diseases, Parkinson's disease, neurodegenerative disorders, Alzheimer's disease, epilepsy, migraine, substance abuse and metabolic disorders, eating disorders, diabetes, diabetic complications, obesity, dyslipidemia, disorders of energy consumption and assimilation, disorders and malfunction of body temperature homeostasis, disorders of sleep and circadian rhythm, and cardiovascular disorders comprising administering to an individual a therapeutically effective amount of a compound of formula I
wherein
R 1 is hydrogen, deuterium, tritium, lower alkyl, lower alkoxy, lower alkyl substituted by halogen, lower alkoxy substituted by halogen, halogen, phenyl optionally substituted by halogen, phenyloxy, benzyl, benzyloxy, —COO-lower alkyl, —O—(CH 2 ) o —O-lower alkyl, NH-cycloalkyl, cycloalkyl or tetrahydropyran-4-yloxy, wherein the substituents for n>1 are the same or different;
X is a bond, —CHR—, —CHRCHR′—, —OCH 2 —, —CH 2 OCHR—, —CH 2 CH 2 CH 2 —, —SCH 2 —, —S(O) 2 CH 2 —, —CH 2 SCH 2 —, —CH 2 N(R)CH 2 —, -cycloalkyl-CH 2 — or SiRR′—CH 2 —;
R and R′ are each independently hydrogen, lower alkyl or lower alkyl substituted by halogen;
R 2 is hydrogen, phenyl or lower alkyl;
Y is phenyl, naphthyl, thiophenyl, pyridinyl, cycloalkyl, 1,2,3,4-tetrahydro-naphthalen-2-yl, 2,3-dihydrobenzo[1,4]dioxin-6-yl or benzo[1,3]dioxol-5-yl;
n is 0, 1, 2 or 3; and
o is 2 or 3;
or of a pharmaceutically suitable acid addition salt thereof.
2 . The method of claim 1 , wherein X is a bond.
3 . The method of claim 2 , wherein Y is phenyl, substituted by one or more halogen atoms.
4 . The method of claim 3 , wherein the compound administered is selected from the group consisting of
(S)-4-(2-chloro-phenyl)-4,5-dihydro-oxazol-2-ylamine,
(RS)-4-(4-chloro-phenyl)-4,5-dihydro-oxazol-2-ylamine,
(RS)-4-(2,4-difluoro-phenyl)-4,5-dihydro-oxazol-2-ylamine,
(S)-4-(2,3-difluoro-phenyl)-4,5-dihydro-oxazol-2-ylamine,
(RS)-4-(3,4-dichlorophenyl)-4,5-dihydro-oxazol-2-ylamine,
(RS)-4-(2,5-difluoro-phenyl)-4,5-dihydro-oxazol-2-ylamine,
(RS)-4-(2,3,4-trifluoro-phenyl)-4,5-dihydro-oxazol-2-ylamine,
(RS)-4-(3-chloro-2-fluoro-phenyl)-4,5-dihydro-oxazol-2-ylamine,
(RS)-4-(5-chloro-2-fluoro-phenyl)-4,5-dihydro-oxazol-2-ylamine,
(RS)-4-(4-bromo-phenyl)-4,5-dihydro-oxazol-2-ylamine,
(S)-4-(3-bromo-2,4-difluoro-phenyl)-4,5-dihydro-oxazol-2-ylamine,
(S)-4-(2,4-difluoro-phenyl)-4,5-dihydro-oxazol-2-ylamine,
(S)-4-(3,4-dichloro-phenyl)-4,5-dihydro-oxazol-2-ylamine,
(S)-4-(2,5-difluoro-phenyl)-4,5-dihydro-oxazol-2-ylamine,
(S)-4-(4-bromo-phenyl)-4,5-dihydro-oxazol-2-ylamine,
(S)-4-(2,4,5-trifluoro-phenyl)-4,5-dihydro-oxazol-2-ylamine,
(S)-4-(3-chloro-2-fluoro-phenyl)-4,5-dihydro-oxazol-2-ylamine,
(S)-4-(2,3,5-trifluoro-phenyl)-4,5-dihydro-oxazol-2-ylamine,
(S)-4-(3,4-dichloro-phenyl)-4-methyl-4,5-dihydro-oxazol-2-ylamine,
(S)-4-(4-chloro-phenyl)-4-methyl-4,5-dihydro-oxazol-2-ylamine, (S)-4-(3,4-difluoro-phenyl)-4,5-dihydro-oxazol-2-ylamine,
(S)-4-(2,3-dichloro-phenyl)-4,5-dihydro-oxazol-2-ylamine;
(S)-4-(4-chloro-phenyl)-4,5-dihydro-oxazol-2-ylamine,
(S)-4-(3,4,5-trifluoro-phenyl)-4,5-dihydro-oxazol-2-ylamine,
(S)-4-(3-chloro-4-fluoro-phenyl)-4,5-dihydro-oxazol-2-ylamine,
(S)-4-(4-chloro-3-fluoro-phenyl)-4,5-dihydro-oxazol-2-ylamine,
(S)-4-(3,5-difluoro-phenyl)-4,5-dihydro-oxazol-2-ylamine,
(S)-4-(3-chloro-5-fluoro-phenyl)-4,5-dihydro-oxazol-2-ylamine,
(S)-4-(2-chloro-phenyl)-4-methyl-4,5-dihydro-oxazol-2-ylamine,
(RS)-4-(3-chloro-phenyl)-4,5-dihydro-oxazol-2-ylamine,
(RS)-4-(3-bromo-phenyl)-4,5-dihydro-oxazol-2-ylamine,
(S)-4-(2,5-difluoro-phenyl)-4-methyl-4,5-dihydro-oxazol-2-ylamine,
(RS)-4-(3-fluoro-phenyl)-4,5-dihydro-oxazol-2-ylamine,
(RS)-4-(3,5-dichloro-phenyl)-4,5-dihydro-oxazol-2-ylamine,
(+)-(S)-4-(5-chloro-2-fluoro-phenyl)-4,5-dihydro-oxazol-2-ylamine,
(+)-(S)-4-(3-chloro-phenyl)-4,5-dihydro-oxazol-2-ylamine,
(S)-4-(2-fluoro-phenyl)-4-methyl-4,5-dihydro-oxazol-2-ylamine,
(+)-(S)-4-(3-bromo-phenyl)-4,5-dihydro-oxazol-2-ylamine,
(+)-(S)-4-(3-fluoro-phenyl)-4,5-dihydro-oxazol-2-ylamine,
(+)-(S)-4-(3,5-dichloro-phenyl)-4,5-dihydro-oxazol-2-ylamine,
(S)-4-(2,4-difluoro-phenyl)-4-methyl-4,5-dihydro-oxazol-2-ylamine,
(RS)-4-methyl-4-(2,3,5-trifluoro-phenyl)-4,5-dihydro-oxazol-2-ylamine,
(S)-4-(4-bromo-phenyl)-4-methyl-4,5-dihydro-oxazol-2-ylamine,
(RS)-4-(2,4-dichloro-phenyl)-4,5-dihydro-oxazol-2-ylamine;
(S)-4-(4-chloro-3-fluoro-phenyl)-4-methyl-4,5-dihydro-oxazol-2-ylamine,
(RS)-4-(2-bromo-phenyl)-4,5-dihydro-oxazol-2-ylamine,
(RS)-4-methyl-4-(2,4,5-trifluoro-phenyl)-4,5-dihydro-oxazol-2-ylamine,
(RS)-4-(4-bromo-3-fluoro-phenyl)-4,5-dihydro-oxazol-2-ylamine,
(RS)-4-(2,5-dichloro-phenyl)-4,5-dihydro-oxazol-2-ylamine,
(+)-(S)-4-(2-bromo-phenyl)-4,5-dihydro-oxazol-2-ylamine,
(S)-4-(3-chloro-5-fluoro-phenyl)-4-methyl-4,5-dihydro-oxazol-2-ylamine,
(RS)-4-methyl-4-(2,3,4-trifluoro-phenyl)-4,5-dihydro-oxazol-2-ylamine,
(S)-4-(5-chloro-2-fluoro-phenyl)-4-methyl-4,5-dihydro-oxazol-2-ylamine,
(RS)-4-methyl-4-(4-chloro-2,5-difluoro-phenyl)-4,5-dihydro-oxazol-2-ylamine,
(RS)-4-methyl-4-(3,4,5-trifluoro-phenyl)-4,5-dihydro-oxazol-2-ylamine,
(S)-4-(3-chloro-4-fluoro-phenyl)-4-methyl-4,5-dihydro-oxazol-2-ylamine,
(S)-4-(4-chloro-2,5-difluoro-phenyl)-4-methyl-4,5-dihydro-oxazol-2-ylamine,
(RS)-4-(4-bromo-2-chloro-phenyl)-4,5-dihydro-oxazol-2-ylamine,
(RS)-4-(2,4-dichloro-phenyl)-4-methyl-4,5-dihydro-oxazol-2-ylamine,
(−)-(R)-4-(2,4-dichloro-phenyl)-4,5-dihydro-oxazol-2-ylamine,
(+)-(S)-4-(2,4-dichloro-phenyl)-4,5-dihydro-oxazol-2-ylamine,
(+)-(S)-4-(2,5-dichloro-phenyl)-4,5-dihydro-oxazol-2-ylamine,
(RS)-4-(2,5-dichloro-phenyl)-4-methyl-4,5-dihydro-oxazol-2-ylamine,
(+)-(S)-4-(2,3,4-trifluoro-phenyl)-4,5-dihydro-oxazol-2-ylamine,
(S)-4-methyl-4-(3,4,5-trifluoro-phenyl)-4,5-dihydro-oxazol-2-ylamine,
(RS)-4-(3-chloro-2-fluoro-phenyl)-4-methyl-4,5-dihydro-oxazol-2-ylamine,
(S)-4-(4-chloro-phenyl)-4-ethyl-4,5-dihydro-oxazol-2-ylamine,
(−)-(R)-4-(4-bromo-2-chloro-phenyl)-4,5-dihydro-oxazol-2-ylamine,
(+)-(S)-4-(4-bromo-2-chloro-phenyl)-4,5-dihydro-oxazol-2-ylamine,
(RS)-4-(2-chloro-4-fluoro-phenyl)-4-methyl-4,5-dihydro-oxazol-2-ylamine,
(+)-(S)-4-(4-bromo-3-fluoro-phenyl)-4,5-dihydro-oxazol-2-ylamine,
(RS)-4-(4-bromo-3-chloro-phenyl)-4,5-dihydro-oxazol-2-ylamine,
(S)-4-(3,4-dichloro-phenyl)-4-ethyl-4,5-dihydro-oxazol-2-ylamine,
(+)-(S)-4-(4-bromo-3-chloro-phenyl)-4,5-dihydro-oxazol-2-ylamine,
(RS)-4-(4-bromo-2-fluoro-phenyl)-4,5-dihydro-oxazol-2-ylamine, and
(S)-4-(4-bromo-2-fluoro-phenyl)-4,5-dihydro-oxazol-2-ylamine.
5 . The method of claim 2 , wherein Y is phenyl substituted by CH 3 , CF 3 , OCH 3 , OCF 3 or OCH 2 -phenyl.
6 . The method of claim 5 , which compound administered is selected from the group consisting of
(RS)-4-(2-trifluoromethyl-phenyl)-4,5-dihydro-oxazol-2-ylamine,
(RS)-4-o-tolyl-4,5-dihydro-oxazol-2-ylamine,
(RS)-4-(4-trifluoromethoxy-phenyl)-4,5-dihydro-oxazol-2-ylamine,
(RS)-4-(4-methoxy-3-methyl-phenyl)-4,5-dihydro-oxazol-2-ylamine,
(S)-4-o-tolyl-4,5-dihydro-oxazol-2-ylamine,
(RS)-4-(4-benzyloxy-phenyl)-4,5-dihydro-oxazol-2-ylamine,
(S)-4-(2-trifluoromethyl-phenyl)-4,5-dihydro-oxazol-2-ylamine,
(S)-4-(4-methoxy-3-methyl-phenyl)-4,5-dihydro-oxazol-2-ylamine,
(S)-4-methyl-4-(4-trifluoromethyl-phenyl)-4,5-dihydro-oxazol-2-ylamine,
(S)-4-(3-trifluoromethyl-phenyl)-4,5-dihydro-oxazol-2-ylamine,
(S)-4-methyl-4-p-tolyl-4,5-dihydro-oxazol-2-ylamine,
(S)-4-methyl-4-(3-trifluoromethyl-phenyl)-4,5-dihydro-oxazol-2-ylamine,
(RS)-4-(4-methoxy-2-trifluoromethyl-phenyl)-4,5-dihydro-oxazol-2-ylamine, and
(+)-(S)-4-(4-methoxy-2-trifluoromethyl-phenyl)-4,5-dihydro-oxazol-2-ylamine.
7 . The method of claim 2 , wherein Y is phenyl substituted by phenyl, which is optionally substituted by halogen.
8 . The method of claim 7 , which compound administered is selected from the group consisting of
(RS)-4-biphenyl-4-yl-4,5-dihydro-oxazol-2-ylamine,
(S)-4-biphenyl-4-yl-4,5-dihydro-oxazol-2-ylamine, and
(RS)-4-(4′-chloro-biphenyl-4-yl)-4,5-dihydro-oxazol-2-ylamine.
9 . The method of claim 2 , wherein Y is phenyl substituted by OCH 3 or by halogen and CF 3 , halogen and CH 3 , halogen and cycloalkyl or by halogen and OCH 3 .
10 . The method of claim 9 , wherein the compound administered is selected from the group consisting of
(RS)-4-(3-chloro-4-methoxyphenyl)-4,5-dihydro-oxazol-2-ylamine,
(S)-4-(3-chloro-4-methoxy-phenyl)-4,5-dihydro-oxazol-2-ylamine,
(S)-4-(2-fluoro-4-trifluoromethyl-phenyl)-4-methyl-4,5-dihydro-oxazol-2-ylamine,
(RS)-4-(4-fluoro-2-trifluoromethyl-phenyl)-4,5-dihydro-oxazol-2-ylamine,
(RS)-4-(5-chloro-2-trifluoromethyl-phenyl)-4,5-dihydro-oxazol-2-ylamine,
(RS)-4-(4-chloro-2-trifluoromethyl-phenyl)-4,5-dihydro-oxazol-2-ylamine,
(RS)-4-(4,5-dichloro-2-trifluoromethyl-phenyl)-4,5-dihydro-oxazol-2-ylamine,
(+)-(S)-4-(4-chloro-2-trifluoromethyl-phenyl)-4,5-dihydro-oxazol-2-ylamine,
(+)-(S)-4-(4,5-dichloro-2-trifluoromethyl-phenyl)-4,5-dihydro-oxazol-2-ylamine,
(−)-(R)-4-(4,5-dichloro-2-trifluoromethyl-phenyl)-4,5-dihydro-oxazol-2-ylamine,
(+)-(S)-4-(4-fluoro-2-trifluoromethyl-phenyl)-4,5-dihydro-oxazol-2-ylamine,
(RS)-4-(5-fluoro-2-trifluoromethyl-phenyl)-4,5-dihydro-oxazol-2-ylamine,
(RS)-4-(5-fluoro-2-methyl-phenyl)-4,5-dihydro-oxazol-2-ylamine,
(+)-(S)-4-(5-fluoro-2-trifluoromethyl-phenyl)-4,5-dihydro-oxazol-2-ylamine,
(RS)-4-(4-chloro-3-methyl-phenyl)-4-methyl-4,5-dihydro-oxazol-2-ylamine,
(RS)-4-(5-chloro-2-methyl-phenyl)-4,5-dihydro-oxazol-2-ylamine,
(RS)-4-(4-chloro-2-fluoro-5-methyl-phenyl)-4-methyl-4,5-dihydro-oxazol-2-ylamine,
(S)-4-(4-chloro-3-methyl-phenyl)-4-methyl-4,5-dihydro-oxazol-2-ylamine,
(RS)-4-(4-bromo-2-trifluoromethyl-phenyl)-4,5-dihydro-oxazol-2-ylamine,
(S)-4-(4-chloro-2-fluoro-5-methyl-phenyl)-4-methyl-4,5-dihydro-oxazol-2-ylamine,
(+)-(S)-4-(5-chloro-2-methyl-phenyl)-4,5-dihydro-oxazol-2-ylamine,
(RS)-4-(4-fluoro-2-methyl-phenyl)-4,5-dihydro-oxazol-2-ylamine,
(+)-(S)-4-(4-bromo-2-trifluoromethyl-phenyl)-4,5-dihydro-oxazol-2-ylamine,
(+)-(S)-4-(5-chloro-2-trifluoromethyl-phenyl)-4,5-dihydro-oxazol-2-ylamine,
(RS)-4-(4-chloro-2-ethyl-phenyl)-4,5-dihydro-oxazol-2-ylamine,
(+)-(S)-4-(4-fluoro-2-methyl-phenyl)-4,5-dihydro-oxazol-2-ylamine,
(RS)-4-(3-chloro-4-methyl-phenyl)-4,5-dihydro-oxazol-2-ylamine,
(RS)-4-(4-chloro-2-cyclopropyl-phenyl)-4,5-dihydro-oxazol-2-ylamine,
(S)-4-(4-chloro-2-ethyl-phenyl)-4,5-dihydro-oxazol-2-ylamine,
(RS)-4-(3-fluoro-2-methyl-phenyl)-4,5-dihydro-oxazol-2-ylamine,
(S)-4-(4-chloro-2-cyclopropyl-phenyl)-4,5-dihydro-oxazol-2-ylamine,
(RS)-4-(3-fluoro-2-trifluoromethyl-phenyl)-4,5-dihydro-oxazol-2-ylamine, and
(S)-4-(3-chloro-4-methyl-phenyl)-4,5-dihydro-oxazol-2-ylamine.
11 . The method of claim 1 , wherein X is CHR and Y is phenyl.
12 . The method of claim 11 , wherein the compound administered is selected from the group consisting of
(S)-4-(2-chloro-benzyl)-4,5-dihydro-oxazol-2-ylamine,
(S)-4-(3-trifluoromethyl-benzyl)-4,5-dihydro-oxazol-2-ylamine, and
(RS)-4-(2-fluoro-5-methyl-benzyl)-4,5-dihydro-oxazol-2-ylamine.
13 . The method of claim 1 , wherein X is CHRCHR′ and Y is phenyl.
14 . The method of claim 13 , wherein the compound administered is selected from the group consisting of (R)-4-phenethyl-4,5-dihydro-oxazol-2-ylamine,
(S)-4-phenethyl-4,5-dihydro-oxazol-2-ylamine,
(RS)-4-methyl-4-phenethyl-4,5-dihydro-oxazol-2-ylamine,
(S)-4-methyl-4-phenethyl-4,5-dihydro-oxazol-2-ylamine,
(RS)-4-phenethyl-4,5-dihydro-oxazol-2-ylamine,
(S)-4-[2-(4-fluoro-phenyl)-ethyl]-4,5-dihydro-oxazol-2-ylamine,
(S)-4-[2-(4-fluoro-3-methoxy-phenyl)-ethyl]-4,5-dihydro-oxazol-2-ylamine,
((S)-4-[2-(2,4-difluoro-phenyl)-ethyl]-4,5-dihydro-oxazol-2-ylamine,
(S)-4-[2-(3,4-difluoro-phenyl)-ethyl]-4,5-dihydro-oxazol-2-ylamine,
(S)-4-[2-(2-trifluoromethyl-phenyl)-ethyl]-4,5-dihydro-oxazol-2-ylamine,
(S)-4-[2-(2-fluoro-phenyl)-ethyl]-4,5-dihydro-oxazol-2-ylamine,
(S)-4-[2-(3-fluoro-phenyl)-ethyl]-4,5-dihydro-oxazol-2-ylamine,
(S)-4-[2-(3,5-difluoro-phenyl)-ethyl]-4,5-dihydro-oxazol-2-ylamine,
(S)-4-(2-o-tolyl-ethyl)-4,5-dihydro-oxazol-2-ylamine,
(S)-4-(2-m-tolyl-ethyl)-4,5-dihydro-oxazol-2-ylamine,
(S)-4-(2-p-tolyl-ethyl)-4,5-dihydro-oxazol-2-ylamine,
(S)-4-[2-(4-trifluoromethyl-phenyl)-ethyl]-4,5-dihydro-oxazol-2-ylamine,
(S)-4-[2-(3-trifluoromethyl-phenyl)-ethyl]-4,5-dihydro-oxazol-2-ylamine,
(R)-4-[2-(3,4-dichloro-phenyl)-ethyl]-4,5-dihydro-oxazol-2-ylamine,
(S)-4-[2-(3,4-dichloro-phenyl)-ethyl]-4,5-dihydro-oxazol-2-ylamine,
(S)-4-[2-(4-chloro-2-fluoro-phenyl)-ethyl]-4,5-dihydro-oxazol-2-ylamine,
(S)-4-[2-(4-fluoro-3-trifluoromethyl-phenyl)-ethyl]-4,5-dihydro-oxazol-2-ylamine,
(S)-4-[2-(3-fluoro-4-trifluoromethyl-phenyl)-ethyl]-4,5-dihydro-oxazol-2-ylamine,
(S)-4-[2-(3,5-dichloro-phenyl)-ethyl]-4,5-dihydro-oxazol-2-ylamine,
(S)-4-[2-(2-chloro-4-fluoro-phenyl)-ethyl]-4,5-dihydro-oxazol-2-ylamine,
(S)-4-[2-(4-fluoro-3-methyl-phenyl)-ethyl]-4,5-dihydro-oxazol-2-ylamine,
(S)-4-{2-[3-(1,1,2,2-tetrafluoro-ethoxy)-phenyl]-ethyl}-4,5-dihydro-oxazol-2-ylamine,
(S)-4-[2-(2-fluoro-3-trifluoromethyl-phenyl)-ethyl]-4,5-dihydro-oxazol-2-ylamine,
(S)-4-[2-(3-bromo-phenyl)-ethyl]-4,5-dihydro-oxazol-2-ylamine,
(S)-4-[2-(4-chloro-3-trifluoromethyl-phenyl)-ethyl]-4,5-dihydro-oxazol-2-ylamine,
(S)-4-[2-(3-fluoro-4-trifluoromethoxy-phenyl)-ethyl]-4,5-dihydro-oxazol-2-ylamine,
(S)-4-[2-(4-fluoro-3-trifluoromethoxy-phenyl)-ethyl]-4,5-dihydro-oxazol-2-ylamine,
(S)-4-[2-(2,3-dichloro-phenyl)-ethyl]-4,5-dihydro-oxazol-2-ylamine,
(S)-4-[2-(3-chloro-4-trifluoromethoxy-phenyl)-ethyl]-4,5-dihydro-oxazol-2-ylamine,
(S)-4-[2-(2-chloro-3-trifluoromethyl-phenyl)-ethyl]-4,5-dihydro-oxazol-2-ylamine,
(S)-4-(1-methyl-2-phenyl-ethyl)-4,5-dihydro-oxazol-2-ylamine,
(S)-4-[2-(2-fluoro-5-trifluoromethyl-phenyl)-ethyl]-4,5-dihydro-oxazol-2-ylamine,
(S)-4-[2-(3-fluoro-5-trifluoromethyl-phenyl)-ethyl]-4,5-dihydro-oxazol-2-ylamine,
(S)-4-[2-(2,5-bis-trifluoromethyl-phenyl)-ethyl]-4,5-dihydro-oxazol-2-ylamine,
(S)-4-[2-(4-chloro-phenyl)-butyl]-4,5-dihydro-oxazol-2-ylamine,
(S)-4-(2-phenyl-butyl)-4,5-dihydro-oxazol-2-ylamine,
(S)-4-[2-(4-trifluoromethyl-phenyl)-propyl]-4,5-dihydro-oxazol-2-ylamine,
(S)-4-[2-(4-trifluoromethyl-phenyl)-butyl]-4,5-dihydro-oxazol-2-ylamine,
(S)-4-[2-(3-trifluoromethyl-phenyl)-propyl]-4,5-dihydro-oxazol-2-ylamine,
(S)-4-[2-(3-trifluoromethyl-phenyl)-butyl]-4,5-dihydro-oxazol-2-ylamine,
(S)-4-[2-(3,5-difluoro-phenyl)-propyl]-4,5-dihydro-oxazol-2-ylamine,
(S)-4-[2-(3,5-difluoro-phenyl)-butyl]-4,5-dihydro-oxazol-2-ylamine,
(S)-4-[2-(4-fluoro-phenyl)-butyl]-4,5-dihydro-oxazol-2-ylamine,
(S)-4-[2-(3,4-difluoro-phenyl)-butyl]-4,5-dihydro-oxazol-2-ylamine,
(S)-4-[2-(2-fluoro-phenyl)-propyl]-4,5-dihydro-oxazol-2-ylamine,
(S)-4-[2-(3,4-dichloro-phenyl)-propyl]-4,5-dihydro-oxazol-2-ylamine,
(S)-4-[2-(3,4-dichloro-phenyl)-butyl]-4,5-dihydro-oxazol-2-ylamine,
(S)-4-[2-(2-fluoro-phenyl)-butyl]-4,5-dihydro-oxazol-2-ylamine,
(S)-4-[2-(2-chloro-phenyl)-ethyl]-4-methyl-4,5-dihydro-oxazol-2-ylamine,
(S)-4-[2-(3-chloro-phenyl)-ethyl]-4,5-dihydro-oxazol-2-ylamine,
(S)-4-[2-(4-chloro-phenyl)-ethyl]-4-methyl-4,5-dihydro-oxazol-2-ylamine,
(S)-4-[2-(3-chloro-phenyl)-ethyl]-4-methyl-4,5-dihydro-oxazol-2-ylamine,
(S)-4-[2-(4-fluoro-phenyl)-ethyl]-4-methyl-4,5-dihydro-oxazol-2-ylamine,
(S)-4-[2-(4-chloro-phenyl)-ethyl]-4,5-dihydro-oxazol-2-ylamine,
(S)-4-[2-(2-chloro-phenyl)-ethyl]-4,5-dihydro-oxazol-2-ylamine,
(S)-4-[2-(3-chloro-phenyl)-butyl]-4,5-dihydro-oxazol-2-ylamine,
(S)-4-((S)-2-phenyl-butyl)-4,5-dihydro-oxazol-2-ylamine,
(S)-4-((R)-2-phenyl-butyl)-4,5-dihydro-oxazol-2-ylamine,
(S)-4-[2-(2-chloro-6-fluoro-phenyl)-ethyl]-4,5-dihydro-oxazol-2-ylamine,
(S)-4-[2-(2,4-dichloro-phenyl)-ethyl]-4-methyl-4,5-dihydro-oxazol-2-ylamine,
(S)-4-[2-(2-bromo-phenyl)-ethyl]-4,5-dihydro-oxazol-2-ylamine,
(S)-4-[2-(2,5-dichloro-phenyl)-ethyl]-4,5-dihydro-oxazol-2-ylamine,
(S)-4-[2-(3-fluoro-phenyl)-butyl]-4,5-dihydro-oxazol-2-ylamine,
(S)-4-[2-(3-chloro-2-fluoro-phenyl)-butyl]-4,5-dihydro-oxazol-2-ylamine,
(S)-4-[2-(3-chloro-4-fluoro-phenyl)-butyl]-4,5-dihydro-oxazol-2-ylamine,
(S)-4-[2-(3-chloro-5-fluoro-phenyl)-butyl]-4,5-dihydro-oxazol-2-ylamine, and
(S)-4-[2-(5-chloro-2-fluoro-phenyl)-butyl]-4,5-dihydro-oxazol-2-ylamine.
15 . The method of claim 1 , wherein X is OCH 2 and Y is phenyl.
16 . The method of claim 15 , wherein the compound administered is selected from the group consisting of
(S)-4-(4-fluoro-phenoxymethyl)-4,5-dihydro-oxazol-2-ylamine,
(S)-4-(4-chloro-phenoxymethyl)-4,5-dihydro-oxazol-2-ylamine,
(S)-4-(3,4-dichloro-phenoxymethyl)-4,5-dihydro-oxazol-2-ylamine,
(S)-4-(3,5-dichloro-phenoxymethyl)-4,5-dihydro-oxazol-2-ylamine,
(S)-4-(4-bromo-phenoxymethyl)-4,5-dihydro-oxazol-2-ylamine,
(S)-4-(3-chloro-phenoxymethyl)-4,5-dihydro-oxazol-2-ylamine,
(S)-4-(2,4-difluoro-phenoxymethyl)-4,5-dihydro-oxazol-2-ylamine, and
(S)-4-(2-fluoro-phenoxymethyl)-4,5-dihydro-oxazol-2-ylamine.
17 . The method of claim 1 , wherein X is CH 2 OCHR and Y is phenyl.
18 . The method of claim 17 , wherein the compound administered is
(S)-4-benzyloxymethyl-4,5-dihydro-oxazol-2-ylamine.
19 . The method of claim 1 , wherein X is
—(CH 2 ) 3 — and Y is phenyl.
20 . The method of claim 19 , wherein the compound administered is selected from the group consisting of
(S)-4-(3-phenyl-propyl)-4,5-dihydro-oxazol-2-ylamine and
(R)-4-(3-phenyl-propyl)-4,5-dihydro-oxazol-2-ylamine.
21 . The method of claim 1 , wherein X is —SCH 2 —, —S(O) 2 CH 2 —, or —CH 2 SCH 2 — and Y is phenyl.
22 . The method of claim 21 , wherein the compound administered is selected from the group consisting of
(R)-4-phenylsulfanylmethyl-4,5-dihydro-oxazol-2-ylamine,
(R)-4-benzenesulfonylmethyl-4,5-dihydro-oxazol-2-ylamine,
(R)-4-benzylsulfanylmethyl-4,5-dihydro-oxazol-2-ylamine, and
(R)-4-(4-chloro-phenylsulfanylmethyl)-4,5-dihydro-oxazol-2-ylamine.
23 . The method of claim 1 , wherein X is
—CH 2 N(R)CH 2 —, cycloalkyl-CH 2 — or SiRR′—CH 2 — and Y is phenyl.
24 . The method of claim 23 , wherein the compound administered is selected from the group consisting of
(S)-4-[1-(4-chloro-phenyl)-cyclopropylmethyl]-4,5-dihydro-oxazol-2-ylamine,
(S)-4-[1-(4-chloro-phenyl)-cyclobutylmethyl]-4,5-dihydro-oxazol-2-ylamine,
(S)-4-(1-phenyl-cyclopropylmethyl)-4,5-dihydro-oxazol-2-ylamine,
(S)-4-[(benzyl-ethyl-amino)-methyl]-4,5-dihydro-oxazol-2-ylamine, and
(R)-4-[(dimethyl-phenyl-silanyl)-methyl]-4,5-dihydro-oxazol-2-ylamine.
25 . The method of claim 1 , wherein Y is naphthyl, pyridyl, cyclohexyl, 2,3-dihydrobenzo[1,4]dioxin or 1,2,3,4-tetrahydronaphthalen.
26 . The method of claim 25 , wherein the compound administered is selected from the group consisting of
(RS)-4-(2,3-dihydro-benzo[1,4]dioxin-6-yl)-4,5-dihydro-oxazol-2-ylamine,
(RS)-4-naphthalen-2-yl-4,5-dihydro-oxazol-2-ylamine,
(RS)-4-naphthalen-1-yl-4,5-dihydro-oxazol-2-ylamine,
(R)-4-naphthalen-1-ylmethyl-4,5-dihydro-oxazol-2-ylamine,
(S)-4-naphthalen-1-ylmethyl-4,5-dihydro-oxazol-2-ylamine,
(S)-4-naphthalen-2-ylmethyl-4,5-dihydro-oxazol-2-ylamine,
(RS)-4-(1,2,3,4-tetrahydro-naphthalen-2-yl)-4,5-dihydro-oxazol-2-ylamine,
(S)-4-naphthalen-2-yl-4,5-dihydro-oxazol-2-ylamine,
(S)-4-[2-(3-fluoro-pyridin-4-yl)-ethyl]-4,5-dihydro-oxazol-2-ylamine,
(S)-4-[2-(6-trifluoromethyl-pyridin-2-yl)-ethyl]-4,5-dihydro-oxazol-2-ylamine,
(S)-4-[2-(2-methyl-pyridin-4-yl)-ethyl]-4,5-dihydro-oxazol-2-ylamine, and
(S)-4-(2-cyclohexyl-ethyl)-4,5-dihydro-oxazol-2-ylamine.
27 . A compound of formula I
wherein
R 1 is hydrogen, deuterium, tritium, lower alkyl, lower alkoxy, lower alkyl substituted by halogen, lower alkoxy substituted by halogen, halogen, phenyl optionally substituted by halogen, phenyloxy, benzyl, benzyloxy, —COO-lower alkyl, —O—(CH 2 ) o —O-lower alkyl, NH-cycloalkyl, cycloalkyl or tetrahydropyran-4-yloxy, wherein the substituents for n>1 are the same or different;
X is a bond, —CHR—, —CHRCHR′—, —OCH 2 —, —CH 2 OCHR—, —CH 2 CH 2 CH 2 —, —SCH 2 —, —S(O) 2 CH 2 —, —CH 2 SCH 2 —, —CH 2 N(R)CH 2 —, -cycloalkyl-CH 2 — or SiRR′—CH 2 —;
R and R′ are each independently hydrogen, lower alkyl or lower alkyl substituted by halogen;
R 2 is hydrogen, phenyl or lower alkyl;
Y is phenyl, naphthyl, thiophenyl, pyridinyl, cycloalkyl, 1,2,3,4-tetrahydro-naphthalen-2-yl, 2,3-dihydrobenzo[1,4]dioxin-6-yl or benzo[1,3]dioxol-5-yl;
n is 0, 1, 2 or 3; and
o is 2 or 3;
or of a pharmaceutically suitable acid addition salt thereof.
28 . The compound of claim 1 , having formula I-A
wherein
R 1 is halogen, for n>1 the halogen atom is the same or different;
R 2 is hydrogen, phenyl or lower alkyl; and
n is 1, 2 or 3;
or a pharmaceutically suitable acid addition salt thereof.
29 . The compound of claim 28 , which is selected from the group consisting of
(S)-4-(2-chloro-phenyl)-4,5-dihydro-oxazol-2-ylamine,
(RS)-4-(4-chloro-phenyl)-4,5-dihydro-oxazol-2-ylamine,
(RS)-4-(2,4-difluoro-phenyl)-4,5-dihydro-oxazol-2-ylamine,
(S)-4-(2,3-difluoro-phenyl)-4,5-dihydro-oxazol-2-ylamine,
(RS)-4-(3,4-dichlorophenyl)-4,5-dihydro-oxazol-2-ylamine,
(RS)-4-(2,5-difluoro-phenyl)-4,5-dihydro-oxazol-2-ylamine,
(RS)-4-(2,3,4-trifluoro-phenyl)-4,5-dihydro-oxazol-2-ylamine,
(RS)-4-(3-chloro-2-fluoro-phenyl)-4,5-dihydro-oxazol-2-ylamine,
(RS)-4-(5-chloro-2-fluoro-phenyl)-4,5-dihydro-oxazol-2-ylamine,
(RS)-4-(4-bromo-phenyl)-4,5-dihydro-oxazol-2-ylamine,
(S)-4-(3-bromo-2,4-difluoro-phenyl)-4,5-dihydro-oxazol-2-ylamine,
(S)-4-(2,4-difluoro-phenyl)-4,5-dihydro-oxazol-2-ylamine,
(S)-4-(3,4-dichloro-phenyl)-4,5-dihydro-oxazol-2-ylamine,
(S)-4-(2,5-difluoro-phenyl)-4,5-dihydro-oxazol-2-ylamine,
(S)-4-(4-bromo-phenyl)-4,5-dihydro-oxazol-2-ylamine,
(S)-4-(2,4,5-trifluoro-phenyl)-4,5-dihydro-oxazol-2-ylamine,
(S)-4-(3-chloro-2-fluoro-phenyl)-4,5-dihydro-oxazol-2-ylamine,
(S)-4-(2,3,5-trifluoro-phenyl)-4,5-dihydro-oxazol-2-ylamine,
(S)-4-(3,4-dichloro-phenyl)-4-methyl-4,5-dihydro-oxazol-2-ylamine,
(S)-4-(4-chloro-phenyl)-4-methyl-4,5-dihydro-oxazol-2-ylamine,
(S)-4-(3,4-difluoro-phenyl)-4,5-dihydro-oxazol-2-ylamine,
(S)-4-(2,3-dichloro-phenyl)-4,5-dihydro-oxazol-2-ylamine,
(S)-4-(4-chloro-phenyl)-4,5-dihydro-oxazol-2-ylamine,
(S)-4-(3,4,5-trifluoro-phenyl)-4,5-dihydro-oxazol-2-ylamine,
(S)-4-(3-chloro-4-fluoro-phenyl)-4,5-dihydro-oxazol-2-ylamine,
(S)-4-(4-chloro-3-fluoro-phenyl)-4,5-dihydro-oxazol-2-ylamine,
(S)-4-(3,5-difluoro-phenyl)-4,5-dihydro-oxazol-2-ylamine,
(S)-4-(3-chloro-5-fluoro-phenyl)-4,5-dihydro-oxazol-2-ylamine,
(S)-4-(2-chloro-phenyl)-4-methyl-4,5-dihydro-oxazol-2-ylamine,
(RS)-4-(3-chloro-phenyl)-4,5-dihydro-oxazol-2-ylamine,
(RS)-4-(3-bromo-phenyl)-4,5-dihydro-oxazol-2-ylamine,
(S)-4-(2,5-difluoro-phenyl)-4-methyl-4,5-dihydro-oxazol-2-ylamine,
(RS)-4-(3-fluoro-phenyl)-4,5-dihydro-oxazol-2-ylamine,
(RS)-4-(3,5-dichloro-phenyl)-4,5-dihydro-oxazol-2-ylamine,
(+)-(S)-4-(5-chloro-2-fluoro-phenyl)-4,5-dihydro-oxazol-2-ylamine,
(+)-(S)-4-(3-chloro-phenyl)-4,5-dihydro-oxazol-2-ylamine,
(S)-4-(2-fluoro-phenyl)-4-methyl-4,5-dihydro-oxazol-2-ylamine,
(+)-(S)-4-(3-bromo-phenyl)-4,5-dihydro-oxazol-2-ylamine,
(+)-(S)-4-(3-fluoro-phenyl)-4,5-dihydro-oxazol-2-ylamine,
(+)-(S)-4-(3,5-dichloro-phenyl)-4,5-dihydro-oxazol-2-ylamine,
(S)-4-(2,4-difluoro-phenyl)-4-methyl-4,5-dihydro-oxazol-2-ylamine,
(RS)-4-methyl-4-(2,3,5-trifluoro-phenyl)-4,5-dihydro-oxazol-2-ylamine,
(S)-4-(4-bromo-phenyl)-4-methyl-4,5-dihydro-oxazol-2-ylamine,
(RS)-4-(2,4-dichloro-phenyl)-4,5-dihydro-oxazol-2-ylamine,
(S)-4-(4-chloro-3-fluoro-phenyl)-4-methyl-4,5-dihydro-oxazol-2-ylamine,
(RS)-4-(2-bromo-phenyl)-4,5-dihydro-oxazol-2-ylamine,
(RS)-4-methyl-4-(2,4,5-trifluoro-phenyl)-4,5-dihydro-oxazol-2-ylamine,
(RS)-4-(4-bromo-3-fluoro-phenyl)-4,5-dihydro-oxazol-2-ylamine,
(RS)-4-(2,5-dichloro-phenyl)-4,5-dihydro-oxazol-2-ylamine,
(+)-(S)-4-(2-bromo-phenyl)-4,5-dihydro-oxazol-2-ylamine,
(S)-4-(3-chloro-5-fluoro-phenyl)-4-methyl-4,5-dihydro-oxazol-2-ylamine,
(RS)-4-methyl-4-(2,3,4-trifluoro-phenyl)-4,5-dihydro-oxazol-2-ylamine,
(S)-4-(5-chloro-2-fluoro-phenyl)-4-methyl-4,5-dihydro-oxazol-2-ylamine,
(RS)-4-methyl-4-(4-chloro-2,5-difluoro-phenyl)-4,5-dihydro-oxazol-2-ylamine,
(RS)-4-methyl-4-(3,4,5-trifluoro-phenyl)-4,5-dihydro-oxazol-2-ylamine,
(S)-4-(3-chloro-4-fluoro-phenyl)-4-methyl-4,5-dihydro-oxazol-2-ylamine,
(S)-4-(4-chloro-2,5-difluoro-phenyl)-4-methyl-4,5-dihydro-oxazol-2-ylamine,
(RS)-4-(4-bromo-2-chloro-phenyl)-4,5-dihydro-oxazol-2-ylamine,
(RS)-4-(2,4-dichloro-phenyl)-4-methyl-4,5-dihydro-oxazol-2-ylamine,
(−)-(R)-4-(2,4-dichloro-phenyl)-4,5-dihydro-oxazol-2-ylamine,
(+)-(S)-4-(2,4-dichloro-phenyl)-4,5-dihydro-oxazol-2-ylamine,
(+)-(S)-4-(2,5-dichloro-phenyl)-4,5-dihydro-oxazol-2-ylamine,
(RS)-4-(2,5-dichloro-phenyl)-4-methyl-4,5-dihydro-oxazol-2-ylamine,
(+)-(S)-4-(2,3,4-trifluoro-phenyl)-4,5-dihydro-oxazol-2-ylamine,
(S)-4-methyl-4-(3,4,5-trifluoro-phenyl)-4,5-dihydro-oxazol-2-ylamine,
(RS)-4-(3-chloro-2-fluoro-phenyl)-4-methyl-4,5-dihydro-oxazol-2-ylamine,
(S)-4-(4-chloro-phenyl)-4-ethyl-4,5-dihydro-oxazol-2-ylamine,
(−)-(R)-4-(4-bromo-2-chloro-phenyl)-4,5-dihydro-oxazol-2-ylamine,
(+)-(S)-4-(4-bromo-2-chloro-phenyl)-4,5-dihydro-oxazol-2-ylamine,
(RS)-4-(2-chloro-4-fluoro-phenyl)-4-methyl-4,5-dihydro-oxazol-2-ylamine,
(+)-(S)-4-(4-bromo-3-fluoro-phenyl)-4,5-dihydro-oxazol-2-ylamine,
(RS)-4-(4-bromo-3-chloro-phenyl)-4,5-dihydro-oxazol-2-ylamine,
(S)-4-(3,4-dichloro-phenyl)-4-ethyl-4,5-dihydro-oxazol-2-ylamine,
(+)-(S)-4-(4-bromo-3-chloro-phenyl)-4,5-dihydro-oxazol-2-ylamine,
(RS)-4-(4-bromo-2-fluoro-phenyl)-4,5-dihydro-oxazol-2-ylamine, and
(S)-4-(4-bromo-2-fluoro-phenyl)-4,5-dihydro-oxazol-2-ylamine.
30 . The compound of claim 27 , having formula I-B
R 1 is CH 3 , CF 3 , OCH 3 , OCF 3 or OCH 2 -phenyl, wherein the substituents for n>1 are the same or different;
R 2 is hydrogen, phenyl or lower alkyl;
n is 1, 2 or 3;
or a pharmaceutically suitable acid addition salt thereof.
31 . The compound of claim 30 , which is selected from the group consisting of
(RS)-4-(2-trifluoromethyl-phenyl)-4,5-dihydro-oxazol-2-ylamine,
(RS)-4-o-tolyl-4,5-dihydro-oxazol-2-ylamine,
(RS)-4-(4-trifluoromethoxy-phenyl)-4,5-dihydro-oxazol-2-ylamine,
(RS)-4-(4-methoxy-3-methyl-phenyl)-4,5-dihydro-oxazol-2-ylamine,
(S)-4-o-tolyl-4,5-dihydro-oxazol-2-ylamine,
(RS)-4-(4-benzyloxy-phenyl)-4,5-dihydro-oxazol-2-ylamine,
(S)-4-(2-trifluoromethyl-phenyl)-4,5-dihydro-oxazol-2-ylamine,
(S)-4-(4-methoxy-3-methyl-phenyl)-4,5-dihydro-oxazol-2-ylamine,
(S)-4-methyl-4-(4-trifluoromethyl-phenyl)-4,5-dihydro-oxazol-2-ylamine,
(S)-4-(3-trifluoromethyl-phenyl)-4,5-dihydro-oxazol-2-ylamine,
(S)-4-methyl-4-p-tolyl-4,5-dihydro-oxazol-2-ylamine,
(S)-4-methyl-4-(3-trifluoromethyl-phenyl)-4,5-dihydro-oxazol-2-ylamine,
(RS)-4-(4-methoxy-2-trifluoromethyl-phenyl)-4,5-dihydro-oxazol-2-ylamine, and
(+)-(S)-4-(4-methoxy-2-trifluoromethyl-phenyl)-4,5-dihydro-oxazol-2-ylamine.
32 . The compound of claim 27 , having formula I-C
wherein
R 2 is hydrogen, phenyl or lower alkyl;
or a pharmaceutically suitable acid addition salt thereof.
33 . The compound of claim 32 , which is selected from the group consisting of
(RS)-4-biphenyl-4-yl-4,5-dihydro-oxazol-2-ylamine,
(S)-4-biphenyl-4-yl-4,5-dihydro-oxazol-2-ylamine, and
(RS)-4-(4′-chloro-biphenyl-4-yl)-4,5-dihydro-oxazol-2-ylamine.
34 . The compound of claim 27 , having formula I-D
wherein
R 1 is halogen and CF 3 , halogen and CH 3 , halogen and cycloalkyl, or is halogen and OCH 3 ; and
R 2 is hydrogen, phenyl or lower alkyl;
or a pharmaceutically suitable acid addition salt thereof.
35 . The compound of claim 34 , which is selected from the group consisting of
(RS)-4-(3-chloro-4-methoxyphenyl)-4,5-dihydro-oxazol-2-ylamine,
(S)-4-(3-chloro-4-methoxy-phenyl)-4,5-dihydro-oxazol-2-ylamine,
(S)-4-(2-fluoro-4-trifluoromethyl-phenyl)-4-methyl-4,5-dihydro-oxazol-2-ylamine,
(RS)-4-(4-fluoro-2-trifluoromethyl-phenyl)-4,5-dihydro-oxazol-2-ylamine,
(RS)-4-(5-chloro-2-trifluoromethyl-phenyl)-4,5-dihydro-oxazol-2-ylamine,
(RS)-4-(4-chloro-2-trifluoromethyl-phenyl)-4,5-dihydro-oxazol-2-ylamine,
(RS)-4-(4,5-dichloro-2-trifluoromethyl-phenyl)-4,5-dihydro-oxazol-2-ylamine,
(+)-(S)-4-(4-chloro-2-trifluoromethyl-phenyl)-4,5-dihydro-oxazol-2-ylamine,
(+)-(S)-4-(4,5-dichloro-2-trifluoromethyl-phenyl)-4,5-dihydro-oxazol-2-ylamine,
(−)-(R)-4-(4,5-dichloro-2-trifluoromethyl-phenyl)-4,5-dihydro-oxazol-2-ylamine,
(+)-(S)-4-(4-fluoro-2-trifluoromethyl-phenyl)-4,5-dihydro-oxazol-2-ylamine,
(RS)-4-(5-fluoro-2-trifluoromethyl-phenyl)-4,5-dihydro-oxazol-2-ylamine,
(RS)-4-(5-fluoro-2-methyl-phenyl)-4,5-dihydro-oxazol-2-ylamine,
(+)-(S)-4-(5-fluoro-2-trifluoromethyl-phenyl)-4,5-dihydro-oxazol-2-ylamine,
(RS)-4-(4-chloro-3-methyl-phenyl)-4-methyl-4,5-dihydro-oxazol-2-ylamine,
(RS)-4-(5-chloro-2-methyl-phenyl)-4,5-dihydro-oxazol-2-ylamine,
(RS)-4-(4-chloro-2-fluoro-5-methyl-phenyl)-4-methyl-4,5-dihydro-oxazol-2-ylamine,
(S)-4-(4-chloro-3-methyl-phenyl)-4-methyl-4,5-dihydro-oxazol-2-ylamine,
(RS)-4-(4-bromo-2-trifluoromethyl-phenyl)-4,5-dihydro-oxazol-2-ylamine,
(S)-4-(4-chloro-2-fluoro-5-methyl-phenyl)-4-methyl-4,5-dihydro-oxazol-2-ylamine,
(+)-(S)-4-(5-chloro-2-methyl-phenyl)-4,5-dihydro-oxazol-2-ylamine,
(RS)-4-(4-fluoro-2-methyl-phenyl)-4,5-dihydro-oxazol-2-ylamine,
(+)-(S)-4-(4-bromo-2-trifluoromethyl-phenyl)-4,5-dihydro-oxazol-2-ylamine,
(+)-(S)-4-(5-chloro-2-trifluoromethyl-phenyl)-4,5-dihydro-oxazol-2-ylamine,
(RS)-4-(4-chloro-2-ethyl-phenyl)-4,5-dihydro-oxazol-2-ylamine,
(+) (S)-4-(4-fluoro-2-methyl-phenyl)-4,5-dihydro-oxazol-2-ylamine,
(RS)-4-(3-chloro-4-methyl-phenyl)-4,5-dihydro-oxazol-2-ylamine, and
(RS)-4-(4-chloro-2-cyclopropyl-phenyl)-4,5-dihydro-oxazol-2-ylamine.
(S)-4-(4-chloro-2-ethyl-phenyl)-4,5-dihydro-oxazol-2-ylamine
(RS)-4-(3-fluoro-2-methyl-phenyl)-4,5-dihydro-oxazol-2-ylamine
(S)-4-(4-chloro-2-cyclopropyl-phenyl)-4,5-dihydro-oxazol-2-ylamine
(RS)-4-(3-fluoro-2-trifluoromethyl-phenyl)-4,5-dihydro-oxazol-2-ylamine or
(S)-4-(3-chloro-4-methyl-phenyl)-4,5-dihydro-oxazol-2-ylamine.
36 . The compound of claim 27 , having formula I-E
wherein
R 1 is halogen, CF 3 or CH 3 , wherein the substituents for n>1 are the same or different;
R 2 is hydrogen, phenyl or lower alkyl;
R is hydrogen, lower alkyl or lower alkyl substituted by halogen; and
n is 1 or 2;
or a pharmaceutically suitable acid addition salt thereof.
37 . The compound of claim 36 , which is selected from the group consisting of
(S)-4-(2-chloro-benzyl)-4,5-dihydro-oxazol-2-ylamine,
(S)-4-(3-trifluoromethyl-benzyl)-4,5-dihydro-oxazol-2-ylamine, and
(RS)-4-(2-fluoro-5-methyl-benzyl)-4,5-dihydro-oxazol-2-ylamine.
38 . The compound of claim 27 , having formula I-F
wherein
R 1 is hydrogen, lower alkyl, lower alkoxy, lower alkyl substituted by halogen, lower alkoxy substituted by halogen or is halogen, wherein the substituents for n>1 are the same or different;
R and R′ are each independently hydrogen, lower alkyl or lower alkyl substituted by halogen;
R 2 is hydrogen, phenyl or lower alkyl; and
n is 0, 1, 2 or 3;
or a pharmaceutically suitable acid addition salt thereof.
39 . The compound of claim 38 , which is selected from the group consisting of
(R)-4-phenethyl-4,5-dihydro-oxazol-2-ylamine,
(S)-4-phenethyl-4,5-dihydro-oxazol-2-ylamine,
(RS)-4-methyl-4-phenethyl-4,5-dihydro-oxazol-2-ylamine,
(S)-4-methyl-4-phenethyl-4,5-dihydro-oxazol-2-ylamine,
(S)-4-[2-(4-fluoro-phenyl)-ethyl]-4,5-dihydro-oxazol-2-ylamine,
(S)-4-[2-(4-fluoro-3-methoxy-phenyl)-ethyl]-4,5-dihydro-oxazol-2-ylamine,
((S)-4-[2-(2,4-difluoro-phenyl)-ethyl]-4,5-dihydro-oxazol-2-ylamine,
(S)-4-[2-(3,4-difluoro-phenyl)-ethyl]-4,5-dihydro-oxazol-2-ylamine,
(S)-4-[2-(2-trifluoromethyl-phenyl)-ethyl]-4,5-dihydro-oxazol-2-ylamine,
(S)-4-[2-(2-fluoro-phenyl)-ethyl]-4,5-dihydro-oxazol-2-ylamine,
(S)-4-[2-(3-fluoro-phenyl)-ethyl]-4,5-dihydro-oxazol-2-ylamine,
(S)-4-[2-(3,5-difluoro-phenyl)-ethyl]-4,5-dihydro-oxazol-2-ylamine,
(S)-4-(2-o-tolyl-ethyl)-4,5-dihydro-oxazol-2-ylamine,
(S)-4-(2-m-tolyl-ethyl)-4,5-dihydro-oxazol-2-ylamine,
(S)-4-(2-p-tolyl-ethyl)-4,5-dihydro-oxazol-2-ylamine,
(S)-4-[2-(4-trifluoromethyl-phenyl)-ethyl]-4,5-dihydro-oxazol-2-ylamine,
(S)-4-[2-(3-trifluoromethyl-phenyl)-ethyl]-4,5-dihydro-oxazol-2-ylamine,
(R)-4-[2-(3,4-dichloro-phenyl)-ethyl]-4,5-dihydro-oxazol-2-ylamine,
(S)-4-[2-(3,4-dichloro-phenyl)-ethyl]-4,5-dihydro-oxazol-2-ylamine,
(S)-4-[2-(4-chloro-2-fluoro-phenyl)-ethyl]-4,5-dihydro-oxazol-2-ylamine,
(S)-4-[2-(4-fluoro-3-trifluoromethyl-phenyl)-ethyl]-4,5-dihydro-oxazol-2-ylamine,
(S)-4-[2-(3-fluoro-4-trifluoromethyl-phenyl)-ethyl]-4,5-dihydro-oxazol-2-ylamine,
(S)-4-[2-(3,5-dichloro-phenyl)-ethyl]-4,5-dihydro-oxazol-2-ylamine,
(S)-4-[2-(2-chloro-4-fluoro-phenyl)-ethyl]-4,5-dihydro-oxazol-2-ylamine,
(S)-4-[2-(4-fluoro-3-methyl-phenyl)-ethyl]-4,5-dihydro-oxazol-2-ylamine,
(S)-4-{2-[3-(1,1,2,2-tetrafluoro-ethoxy)-phenyl]-ethyl}-4,5-dihydro-oxazol-2-ylamine,
(S)-4-[2-(2-fluoro-3-trifluoromethyl-phenyl)-ethyl]-4,5-dihydro-oxazol-2-ylamine,
(S)-4-[2-(3-bromo-phenyl)-ethyl]-4,5-dihydro-oxazol-2-ylamine,
(S)-4-[2-(4-chloro-3-trifluoromethyl-phenyl)-ethyl]-4,5-dihydro-oxazol-2-ylamine,
(S)-4-[2-(3-fluoro-4-trifluoromethoxy-phenyl)-ethyl]-4,5-dihydro-oxazol-2-ylamine,
(S)-4-[2-(4-fluoro-3-trifluoromethoxy-phenyl)-ethyl]-4,5-dihydro-oxazol-2-ylamine,
(S)-4-[2-(2,3-dichloro-phenyl)-ethyl]-4,5-dihydro-oxazol-2-ylamine,
(S)-4-[2-(3-chloro-4-trifluoromethoxy-phenyl)-ethyl]-4,5-dihydro-oxazol-2-ylamine,
(S)-4-[2-(2-chloro-3-trifluoromethyl-phenyl)-ethyl]-4,5-dihydro-oxazol-2-ylamine,
(S)-4-(1-methyl-2-phenyl-ethyl)-4,5-dihydro-oxazol-2-ylamine,
(S)-4-[2-(2-fluoro-5-trifluoromethyl-phenyl)-ethyl]-4,5-dihydro-oxazol-2-ylamine,
(S)-4-[2-(3-fluoro-5-trifluoromethyl-phenyl)-ethyl]-4,5-dihydro-oxazol-2-ylamine,
(S)-4-[2-(2,5-bis-trifluoromethyl-phenyl)-ethyl]-4,5-dihydro-oxazol-2-ylamine,
(S)-4-[2-(4-chloro-phenyl)-butyl]-4,5-dihydro-oxazol-2-ylamine,
(S)-4-(2-phenyl-butyl)-4,5-dihydro-oxazol-2-ylamine,
(S)-4-[2-(4-trifluoromethyl-phenyl)-propyl]-4,5-dihydro-oxazol-2-ylamine,
(S)-4-[2-(4-trifluoromethyl-phenyl)-butyl]-4,5-dihydro-oxazol-2-ylamine,
(S)-4-[2-(3-trifluoromethyl-phenyl)-propyl]-4,5-dihydro-oxazol-2-ylamine,
(S)-4-[2-(3-trifluoromethyl-phenyl)-butyl]-4,5-dihydro-oxazol-2-ylamine,
(S)-4-[2-(3,5-difluoro-phenyl)-propyl]-4,5-dihydro-oxazol-2-ylamine,
(S)-4-[2-(3,5-difluoro-phenyl)-butyl]-4,5-dihydro-oxazol-2-ylamine,
(S)-4-[2-(4-fluoro-phenyl)-butyl]-4,5-dihydro-oxazol-2-ylamine,
(S)-4-[2-(3,4-difluoro-phenyl)-butyl]-4,5-dihydro-oxazol-2-ylamine,
(S)-4-[2-(2-fluoro-phenyl)-propyl]-4,5-dihydro-oxazol-2-ylamine,
(S)-4-[2-(3,4-dichloro-phenyl)-propyl]-4,5-dihydro-oxazol-2-ylamine,
(S)-4-[2-(3,4-dichloro-phenyl)-butyl]-4,5-dihydro-oxazol-2-ylamine,
(S)-4-[2-(2-fluoro-phenyl)-butyl]-4,5-dihydro-oxazol-2-ylamine,
(S)-4-[2-(2-chloro-phenyl)-ethyl]-4-methyl-4,5-dihydro-oxazol-2-ylamine,
(S)-4-[2-(3-chloro-phenyl)-ethyl]-4,5-dihydro-oxazol-2-ylamine,
(S)-4-[2-(4-chloro-phenyl)-ethyl]-4-methyl-4,5-dihydro-oxazol-2-ylamine,
(S)-4-[2-(3-chloro-phenyl)-ethyl]-4-methyl-4,5-dihydro-oxazol-2-ylamine,
(S)-4-[2-(4-fluoro-phenyl)-ethyl]-4-methyl-4,5-dihydro-oxazol-2-ylamine,
(S)-4-[2-(4-chloro-phenyl)-ethyl]-4,5-dihydro-oxazol-2-ylamine,
(S)-4-[2-(2-chloro-phenyl)-ethyl]-4,5-dihydro-oxazol-2-ylamine,
(S)-4-[2-(3-chloro-phenyl)-butyl]-4,5-dihydro-oxazol-2-ylamine,
(S)-4-((S)-2-phenyl-butyl)-4,5-dihydro-oxazol-2-ylamine,
(S)-4-((R)-2-phenyl-butyl)-4,5-dihydro-oxazol-2-ylamine,
(S)-4-[2-(2-chloro-6-fluoro-phenyl)-ethyl]-4,5-dihydro-oxazol-2-ylamine,
(S)-4-[2-(2,4-dichloro-phenyl)-ethyl]-4-methyl-4,5-dihydro-oxazol-2-ylamine,
(S)-4-[2-(2-bromo-phenyl)-ethyl]-4,5-dihydro-oxazol-2-ylamine,
(S)-4-[2-(2,5-dichloro-phenyl)-ethyl]-4,5-dihydro-oxazol-2-ylamine,
(S)-4-[2-(3-fluoro-phenyl)-butyl]-4,5-dihydro-oxazol-2-ylamine,
(S)-4-[2-(3-chloro-2-fluoro-phenyl)-butyl]-4,5-dihydro-oxazol-2-ylamine,
(S)-4-[2-(3-chloro-4-fluoro-phenyl)-butyl]-4,5-dihydro-oxazol-2-ylamine,
(S)-4-[2-(3-chloro-5-fluoro-phenyl)-butyl]-4,5-dihydro-oxazol-2-ylamine, and
(S)-4-[2-(5-chloro-2-fluoro-phenyl)-butyl]-4,5-dihydro-oxazol-2-ylamine.
40 . The compound of claim 27 , having formula I-G
wherein
R 1 is lower alkyl, lower alkyl substituted by halogen or halogen, wherein the substituents for n>1 are the same or different;
R 2 is hydrogen, phenyl or lower alkyl; and
n is 0, 1, 2 or 3;
or a pharmaceutically suitable acid addition salt thereof.
41 . The compound of claim 40 , which is selected from the group consisting of
(S)-4-(4-fluoro-phenoxymethyl)-4,5-dihydro-oxazol-2-ylamine,
(S)-4-(4-chloro-phenoxymethyl)-4,5-dihydro-oxazol-2-ylamine,
(S)-4-(3,4-dichloro-phenoxymethyl)-4,5-dihydro-oxazol-2-ylamine,
(S)-4-(3,5-dichloro-phenoxymethyl)-4,5-dihydro-oxazol-2-ylamine,
(S)-4-(4-bromo-phenoxymethyl)-4,5-dihydro-oxazol-2-ylamine,
(S)-4-(3-chloro-phenoxymethyl)-4,5-dihydro-oxazol-2-ylamine,
(S)-4-(2,4-difluoro-phenoxymethyl)-4,5-dihydro-oxazol-2-ylamine, and
(S)-4-(2-fluoro-phenoxymethyl)-4,5-dihydro-oxazol-2-ylamine.
42 . The compound of claim 27 , having formula I-H
wherein
R 1 is hydrogen or halogen; and
n is 0 or 1;
or a pharmaceutically suitable acid addition salt thereof.
43 . The compound of claim 42 , which is
(S)-4-benzyloxymethyl-4,5-dihydro-oxazol-2-ylamine.
44 . The compound of claim 27 , wherein X is —(CH 2 ) 3 — and Y is phenyl.
45 . The compound of claim 44 , which is selected from the group consisting of
(S)-4-(3-Phenyl-propyl)-4,5-dihydro-oxazol-2-ylamine and
(R)-4-(3-Phenyl-propyl)-4,5-dihydro-oxazol-2-ylamine.
46 . The compound of claim 27 , wherein X is —SCH 2 —, —S(O) 2 CH 2 —, —CH 2 S(O) 2 CH 2 — or —CH 2 SCH 2 — and Y is phenyl.
47 . The compound of claim 46 , which is selected from the group consisting of
(R)-4-phenylsulfanylmethyl-4,5-dihydro-oxazol-2-ylamine,
(R)-4-benzenesulfonylmethyl-4,5-dihydro-oxazol-2-ylamine,
(R)-4-benzylsulfanylmethyl-4,5-dihydro-oxazol-2-ylamine, and
(R)-4-(4-chloro-phenylsulfanylmethyl)-4,5-dihydro-oxazol-2-ylamine.
48 . The compound of claim 27 , wherein X is —CH 2 N(R)CH 2 —, cycloalkyl-CH 2 — or SiRR′—CH 2 — and Y is phenyl.
49 . The compound of claim 48 , which is selected from the group consisting of
(S)-4-[1-(4-chloro-phenyl)-cyclopropylmethyl]-4,5-dihydro-oxazol-2-ylamine,
(S)-4-[1-(4-chloro-phenyl)-cyclobutylmethyl]-4,5-dihydro-oxazol-2-ylamine,
(S)-4-(1-phenyl-cyclopropylmethyl)-4,5-dihydro-oxazol-2-ylamine,
(S)-4-[(benzyl-ethyl-amino)-methyl]-4,5-dihydro-oxazol-2-ylamine, and
(R)-4-[(dimethyl-phenyl-silanyl)-methyl]-4,5-dihydro-oxazol-2-ylamine.
50 . The compound of claim 27 , wherein Y is naphthyl, pyridyl, cyclohexyl, 2,3-dihydrobenzo[1,4]dioxin or 1,2,3,4-tetrahydronaphthalen.
51 . The compound of claim 50 , which is selected from the group consisting of
(RS)-4-(2,3-dihydro-benzo[1,4]dioxin-6-yl)-4,5-dihydro-oxazol-2-ylamine,
(RS)-4-naphthalen-2-yl-4,5-dihydro-oxazol-2-ylamine,
(RS)-4-naphthalen-1-yl-4,5-dihydro-oxazol-2-ylamine,
(R)-4-naphthalen-1-ylmethyl-4,5-dihydro-oxazol-2-ylamine,
(S)-4-naphthalen-1-ylmethyl-4,5-dihydro-oxazol-2-ylamine,
(S)-4-naphthalen-2-ylmethyl-4,5-dihydro-oxazol-2-ylamine,
(RS)-4-(1,2,3,4-tetrahydro-naphthalen-2-yl)-4,5-dihydro-oxazol-2-ylamine,
(S)-4-naphthalen-2-yl-4,5-dihydro-oxazol-2-ylamine,
(S)-4-[2-(3-fluoro-pyridin-4-yl)-ethyl]-4,5-dihydro-oxazol-2-ylamine,
(S)-4-[2-(6-trifluoromethyl-pyridin-2-yl)-ethyl]-4,5-dihydro-oxazol-2-ylamine,
(S)-4-[2-(2-methyl-pyridin-4-yl)-ethyl]-4,5-dihydro-oxazol-2-ylamine, and
(S)-4-(2-cyclohexyl-ethyl)-4,5-dihydro-oxazol-2-ylamine.
52 . A pharmaceutical composition comprising a therapeutically effective amount of a compound of formula I
wherein
R 1 is hydrogen, deuterium, tritium, lower alkyl, lower alkoxy, lower alkyl substituted by halogen, lower alkoxy substituted by halogen, halogen, phenyl optionally substituted by halogen, phenyloxy, benzyl, benzyloxy, —COO-lower alkyl, —O—(CH 2 ) o —O-lower alkyl, NH-cycloalkyl, cycloalkyl or tetrahydropyran-4-yloxy, wherein the substituents for n>1 are the same or different;
X is a bond, —CHR—, —CHRCHR′—, —OCH 2 —, —CH 2 OCHR—, —CH 2 CH 2 CH 2 —, —SCH 2 —, —S(O) 2 CH 2 —, —CH 2 SCH 2 —, —CH 2 N(R)CH 2 —, -cycloalkyl-CH 2 — or SiRR′—CH 2 —;
R and R′ are each independently hydrogen, lower alkyl or lower alkyl substituted by halogen;
R 2 is hydrogen, phenyl or lower alkyl;
Y is phenyl, naphthyl, thiophenyl, pyridinyl, cycloalkyl, 1,2,3,4-tetrahydro-naphthalen-2-yl, 2,3-dihydrobenzo[1,4]dioxin-6-yl or benzo[1,3]dioxol-5-yl;
n is 0, 1, 2 or 3; and
o is 2 or 3;
or of a pharmaceutically suitable acid addition salt thereof and a pharmaceutically acceptable carrier.
53 . The composition of claim 52 , wherein the compound of formula I is selected from the group consisting of
(S)-4-(2-chloro-phenyl)-4,5-dihydro-oxazol-2-ylamine,
(RS)-4-(4-chloro-phenyl)-4,5-dihydro-oxazol-2-ylamine,
(RS)-4-(2,4-difluoro-phenyl)-4,5-dihydro-oxazol-2-ylamine,
(S)-4-(2,3-difluoro-phenyl)-4,5-dihydro-oxazol-2-ylamine,
(RS)-4-(3,4-dichlorophenyl)-4,5-dihydro-oxazol-2-ylamine,
(RS)-4-(2,5-difluoro-phenyl)-4,5-dihydro-oxazol-2-ylamine,
(RS)-4-(2,3,4-trifluoro-phenyl)-4,5-dihydro-oxazol-2-ylamine,
(RS)-4-(3-chloro-2-fluoro-phenyl)-4,5-dihydro-oxazol-2-ylamine,
(RS)-4-(5-chloro-2-fluoro-phenyl)-4,5-dihydro-oxazol-2-ylamine,
(RS)-4-(4-bromo-phenyl)-4,5-dihydro-oxazol-2-ylamine,
(S)-4-(3-bromo-2,4-difluoro-phenyl)-4,5-dihydro-oxazol-2-ylamine,
(S)-4-(2,4-difluoro-phenyl)-4,5-dihydro-oxazol-2-ylamine,
(S)-4-(3,4-dichloro-phenyl)-4,5-dihydro-oxazol-2-ylamine,
(S)-4-(2,5-difluoro-phenyl)-4,5-dihydro-oxazol-2-ylamine,
(S)-4-(4-bromo-phenyl)-4,5-dihydro-oxazol-2-ylamine,
(S)-4-(2,4,5-trifluoro-phenyl)-4,5-dihydro-oxazol-2-ylamine,
(S)-4-(3-chloro-2-fluoro-phenyl)-4,5-dihydro-oxazol-2-ylamine,
(S)-4-(2,3,5-trifluoro-phenyl)-4,5-dihydro-oxazol-2-ylamine,
(S)-4-(3,4-dichloro-phenyl)-4-methyl-4,5-dihydro-oxazol-2-ylamine,
(S)-4-(4-chloro-phenyl)-4-methyl-4,5-dihydro-oxazol-2-ylamine,
(S)-4-(3,4-difluoro-phenyl)-4,5-dihydro-oxazol-2-ylamine,
(S)-4-(2,3-dichloro-phenyl)-4,5-dihydro-oxazol-2-ylamine,
(S)-4-(4-chloro-phenyl)-4,5-dihydro-oxazol-2-ylamine,
(S)-4-(3,4,5-trifluoro-phenyl)-4,5-dihydro-oxazol-2-ylamine,
(S)-4-(3-chloro-4-fluoro-phenyl)-4,5-dihydro-oxazol-2-ylamine,
(S)-4-(4-chloro-3-fluoro-phenyl)-4,5-dihydro-oxazol-2-ylamine,
(S)-4-(3,5-difluoro-phenyl)-4,5-dihydro-oxazol-2-ylamine,
(S)-4-(3-chloro-5-fluoro-phenyl)-4,5-dihydro-oxazol-2-ylamine,
(S)-4-(2-chloro-phenyl)-4-methyl-4,5-dihydro-oxazol-2-ylamine,
(RS)-4-(3-chloro-phenyl)-4,5-dihydro-oxazol-2-ylamine,
(RS)-4-(3-bromo-phenyl)-4,5-dihydro-oxazol-2-ylamine,
(S)-4-(2,5-difluoro-phenyl)-4-methyl-4,5-dihydro-oxazol-2-ylamine,
(RS)-4-(3-fluoro-phenyl)-4,5-dihydro-oxazol-2-ylamine,
(RS)-4-(3,5-dichloro-phenyl)-4,5-dihydro-oxazol-2-ylamine,
(+)-(S)-4-(5-chloro-2-fluoro-phenyl)-4,5-dihydro-oxazol-2-ylamine,
(+)-(S)-4-(3-chloro-phenyl)-4,5-dihydro-oxazol-2-ylamine,
(S)-4-(2-fluoro-phenyl)-4-methyl-4,5-dihydro-oxazol-2-ylamine,
(+)-4-(3-bromo-phenyl)-4,5-dihydro-oxazol-2-ylamine,
(+)-(S)-4-(3-fluoro-phenyl)-4,5-dihydro-oxazol-2-ylamine,
(+)-(S)-4-(3,5-dichloro-phenyl)-4,5-dihydro-oxazol-2-ylamine,
(S)-4-(2,4-difluoro-phenyl)-4-methyl-4,5-dihydro-oxazol-2-ylamine,
(RS)-4-methyl-4-(2,3,5-trifluoro-phenyl)-4,5-dihydro-oxazol-2-ylamine,
(S)-4-(4-bromo-phenyl)-4-methyl-4,5-dihydro-oxazol-2-ylamine,
(RS)-4-(2,4-dichloro-phenyl)-4,5-dihydro-oxazol-2-ylamine,
(S)-4-(4-chloro-3-fluoro-phenyl)-4-methyl-4,5-dihydro-oxazol-2-ylamine,
(RS)-4-(2-bromo-phenyl)-4,5-dihydro-oxazol-2-ylamine,
(RS)-4-methyl-4-(2,4,5-trifluoro-phenyl)-4,5-dihydro-oxazol-2-ylamine,
(RS)-4-(4-bromo-3-fluoro-phenyl)-4,5-dihydro-oxazol-2-ylamine,
(RS)-4-(2,5-dichloro-phenyl)-4,5-dihydro-oxazol-2-ylamine,
(+)-(S)-4-(2-bromo-phenyl)-4,5-dihydro-oxazol-2-ylamine,
(S)-4-(3-chloro-5-fluoro-phenyl)-4-methyl-4,5-dihydro-oxazol-2-ylamine,
(RS)-4-methyl-4-(2,3,4-trifluoro-phenyl)-4,5-dihydro-oxazol-2-ylamine,
(S)-4-(5-chloro-2-fluoro-phenyl)-4-methyl-4,5-dihydro-oxazol-2-ylamine,
(RS)-4-methyl-4-(4-chloro-2,5-difluoro-phenyl)-4,5-dihydro-oxazol-2-ylamine,
(RS)-4-methyl-4-(3,4,5-trifluoro-phenyl)-4,5-dihydro-oxazol-2-ylamine,
(S)-4-(3-chloro-4-fluoro-phenyl)-4-methyl-4,5-dihydro-oxazol-2-ylamine,
(S)-4-(4-chloro-2,5-difluoro-phenyl)-4-methyl-4,5-dihydro-oxazol-2-ylamine,
(RS)-4-(4-bromo-2-chloro-phenyl)-4,5-dihydro-oxazol-2-yl amine,
(RS)-4-(2,4-dichloro-phenyl)-4-methyl-4,5-dihydro-oxazol-2-ylamine,
(−)-(R)-4-(2,4-dichloro-phenyl)-4,5-dihydro-oxazol-2-ylamine,
(+)-(S)-4-(2,4-dichloro-phenyl)-4,5-dihydro-oxazol-2-ylamine,
(+)-(S)-4-(2,5-dichloro-phenyl)-4,5-dihydro-oxazol-2-ylamine,
(RS)-4-(2,5-dichloro-phenyl)-4-methyl-4,5-dihydro-oxazol-2-ylamine,
(+)-(S)-4-(2,3,4-trifluoro-phenyl)-4,5-dihydro-oxazol-2-ylamine,
(S)-4-methyl-4-(3,4,5-trifluoro-phenyl)-4,5-dihydro-oxazol-2-ylamine,
(RS)-4-(3-chloro-2-fluoro-phenyl)-4-methyl-4,5-dihydro-oxazol-2-ylamine,
(S)-4-(4-chloro-phenyl)-4-ethyl-4,5-dihydro-oxazol-2-ylamine,
(−)-(R)-4-(4-bromo-2-chloro-phenyl)-4,5-dihydro-oxazol-2-ylamine,
(+)-(S)-4-(4-bromo-2-chloro-phenyl)-4,5-dihydro-oxazol-2-ylamine,
(RS)-4-(2-chloro-4-fluoro-phenyl)-4-methyl-4,5-dihydro-oxazol-2-ylamine,
(+)-(S)-4-(4-bromo-3-fluoro-phenyl)-4,5-dihydro-oxazol-2-ylamine,
(RS)-4-(4-bromo-3-chloro-phenyl)-4,5-dihydro-oxazol-2-ylamine,
(S)-4-(3,4-dichloro-phenyl)-4-ethyl-4,5-dihydro-oxazol-2-ylamine,
(+)-(S)-4-(4-bromo-3-chloro-phenyl)-4,5-dihydro-oxazol-2-ylamine,
(RS)-4-(4-bromo-2-fluoro-phenyl)-4,5-dihydro-oxazol-2-ylamine,
(S)-4-(4-bromo-2-fluoro-phenyl)-4,5-dihydro-oxazol-2-ylamine,
(RS)-4-(2-trifluoromethyl-phenyl)-4,5-dihydro-oxazol-2-ylamine,
(RS)-4-o-tolyl-4,5-dihydro-oxazol-2-ylamine,
(RS)-4-(4-trifluoromethoxy-phenyl)-4,5-dihydro-oxazol-2-ylamine,
(RS)-4-(4-methoxy-3-methyl-phenyl)-4,5-dihydro-oxazol-2-ylamine,
(S)-4-o-tolyl-4,5-dihydro-oxazol-2-ylamine,
(RS)-4-(4-benzyloxy-phenyl)-4,5-dihydro-oxazol-2-ylamine,
(S)-4-(2-trifluoromethyl-phenyl)-4,5-dihydro-oxazol-2-ylamine,
(S)-4-(4-methoxy-3-methyl-phenyl)-4,5-dihydro-oxazol-2-ylamine,
(S)-4-methyl-4-(4-trifluoromethyl-phenyl)-4,5-dihydro-oxazol-2-ylamine,
(S)-4-(3-trifluoromethyl-phenyl)-4,5-dihydro-oxazol-2-ylamine,
(S)-4-methyl-4-p-tolyl-4,5-dihydro-oxazol-2-ylamine,
(S)-4-methyl-4-(3-trifluoromethyl-phenyl)-4,5-dihydro-oxazol-2-ylamine,
(RS)-4-(4-methoxy-2-trifluoromethyl-phenyl)-4,5-dihydro-oxazol-2-ylamine,
(+)-(S)-4-(4-methoxy-2-trifluoromethyl-phenyl)-4,5-dihydro-oxazol-2-ylamine,
(RS)-4-biphenyl-4-yl-4,5-dihydro-oxazol-2-ylamine,
(S)-4-biphenyl-4-yl-4,5-dihydro-oxazol-2-ylamine,
(RS)-4-(4′-chloro-biphenyl-4-yl)-4,5-dihydro-oxazol-2-ylamine,
(RS)-4-(3-chloro-4-methoxyphenyl)-4,5-dihydro-oxazol-2-ylamine,
(S)-4-(3-chloro-4-methoxy-phenyl)-4,5-dihydro-oxazol-2-ylamine,
(S)-4-(2-fluoro-4-trifluoromethyl-phenyl)-4-methyl-4,5-dihydro-oxazol-2-ylamine,
(RS)-4-(4-fluoro-2-trifluoromethyl-phenyl)-4,5-dihydro-oxazol-2-ylamine,
(RS)-4-(5-chloro-2-trifluoromethyl-phenyl)-4,5-dihydro-oxazol-2-ylamine,
(RS)-4-(4-chloro-2-trifluoromethyl-phenyl)-4,5-dihydro-oxazol-2-ylamine,
(RS)-4-(4,5-dichloro-2-trifluoromethyl-phenyl)-4,5-dihydro-oxazol-2-ylamine,
(+)-(S)-4-(4-chloro-2-trifluoromethyl-phenyl)-4,5-dihydro-oxazol-2-ylamine,
(+)-(S)-4-(4,5-dichloro-2-trifluoromethyl-phenyl)-4,5-dihydro-oxazol-2-ylamine,
(−)-(R)-4-(4,5-dichloro-2-trifluoromethyl-phenyl)-4,5-dihydro-oxazol-2-ylamine,
(+)-(S)-4-(4-fluoro-2-trifluoromethyl-phenyl)-4,5-dihydro-oxazol-2-ylamine,
(RS)-4-(5-fluoro-2-trifluoromethyl-phenyl)-4,5-dihydro-oxazol-2-ylamine,
(RS)-4-(5-fluoro-2-methyl-phenyl)-4,5-dihydro-oxazol-2-ylamine,
(+)-(S)-4-(5-fluoro-2-trifluoromethyl-phenyl)-4,5-dihydro-oxazol-2-ylamine,
(RS)-4-(4-chloro-3-methyl-phenyl)-4-methyl-4,5-dihydro-oxazol-2-ylamine,
(RS)-4-(5-chloro-2-methyl-phenyl)-4,5-dihydro-oxazol-2-ylamine,
(RS)-4-(4-chloro-2-fluoro-5-methyl-phenyl)-4-methyl-4,5-dihydro-oxazol-2-ylamine,
(S)-4-(4-chloro-3-methyl-phenyl)-4-methyl-4,5-dihydro-oxazol-2-ylamine,
(RS)-4-(4-bromo-2-trifluoromethyl-phenyl)-4,5-dihydro-oxazol-2-ylamine,
(S)-4-(4-chloro-2-fluoro-5-methyl-phenyl)-4-methyl-4,5-dihydro-oxazol-2-ylamine,
(+)-(S)-4-(5-chloro-2-methyl-phenyl)-4,5-dihydro-oxazol-2-ylamine,
(RS)-4-(4-fluoro-2-methyl-phenyl)-4,5-dihydro-oxazol-2-ylamine,
(+)-(S)-4-(4-bromo-2-trifluoromethyl-phenyl)-4,5-dihydro-oxazol-2-ylamine,
(+)-(S)-4-(5-chloro-2-trifluoromethyl-phenyl)-4,5-dihydro-oxazol-2-ylamine,
(RS)-4-(4-chloro-2-ethyl-phenyl)-4,5-dihydro-oxazol-2-ylamine,
((S)-4-(4-fluoro-2-methyl-phenyl)-4,5-dihydro-oxazol-2-ylamine,
(RS)-4-(3-chloro-4-methyl-phenyl)-4,5-dihydro-oxazol-2-ylamine,
(RS)-4-(4-chloro-2-cyclopropyl-phenyl)-4,5-dihydro-oxazol-2-ylamine,
(S)-4-(4-chloro-2-ethyl-phenyl)-4,5-dihydro-oxazol-2-ylamine,
(RS)-4-(3-fluoro-2-methyl-phenyl)-4,5-dihydro-oxazol-2-ylamine,
(S)-4-(4-chloro-2-cyclopropyl-phenyl)-4,5-dihydro-oxazol-2-ylamine,
(RS)-4-(3-fluoro-2-trifluoromethyl-phenyl)-4,5-dihydro-oxazol-2-ylamine,
(S)-4-(3-chloro-4-methyl-phenyl)-4,5-dihydro-oxazol-2-ylamine,
(S)-4-(2-chloro-benzyl)-4,5-dihydro-oxazol-2-ylamine,
(S)-4-(3-trifluoromethyl-benzyl)-4,5-dihydro-oxazol-2-ylamine,
(RS)-4-(2-fluoro-5-methyl-benzyl)-4,5-dihydro-oxazol-2-ylamine,
(R)-4-phenethyl-4,5-dihydro-oxazol-2-ylamine,
(S)-4-phenethyl-4,5-dihydro-oxazol-2-ylamine,
(RS)-4-methyl-4-phenethyl-4,5-dihydro-oxazol-2-ylamine,
(S)-4-methyl-4-phenethyl-4,5-dihydro-oxazol-2-ylamine,
(S)-4-[2-(4-fluoro-phenyl)-ethyl]-4,5-dihydro-oxazol-2-ylamine,
(S)-4-[2-(4-fluoro-3-methoxy-phenyl)-ethyl]-4,5-dihydro-oxazol-2-ylamine,
((S)-4-[2-(2,4-difluoro-phenyl)-ethyl]-4,5-dihydro-oxazol-2-ylamine,
(S)-4-[2-(3,4-difluoro-phenyl)-ethyl]-4,5-dihydro-oxazol-2-ylamine,
(S)-4-[2-(2-trifluoromethyl-phenyl)-ethyl]-4,5-dihydro-oxazol-2-ylamine,
(S)-4-[2-(2-fluoro-phenyl)-ethyl]-4,5-dihydro-oxazol-2-ylamine,
(S)-4-[2-(3-fluoro-phenyl)-ethyl]-4,5-dihydro-oxazol-2-ylamine,
(S)-4-[2-(3,5-difluoro-phenyl)-ethyl]-4,5-dihydro-oxazol-2-ylamine,
(S)-4-(2-o-tolyl-ethyl)-4,5-dihydro-oxazol-2-ylamine,
(S)-4-(2-m-tolyl-ethyl)-4,5-dihydro-oxazol-2-ylamine,
(S)-4-(2-p-tolyl-ethyl)-4,5-dihydro-oxazol-2-ylamine,
(S)-4-[2-(4-trifluoromethyl-phenyl) y -ethyl]-4,5-dihydro-oxazol-2-ylamine,
(S)-4-[2-(3-trifluoromethyl-phenyl)-ethyl]-4,5-dihydro-oxazol-2-ylamine,
(R)-4-[2-(3,4-dichloro-phenyl)-ethyl]-4,5-dihydro-oxazol-2-ylamine,
(S)-4-[2-(3,4-dichloro-phenyl)-ethyl]-4,5-dihydro-oxazol-2-ylamine,
(S)-4-[2-(4-chloro-2-fluoro-phenyl)-ethyl]-4,5-dihydro-oxazol-2-ylamine,
(S)-4-[2-(4-fluoro-3-trifluoromethyl-phenyl)-ethyl]-4,5-dihydro-oxazol-2-ylamine,
(S)-4-[2-(3-fluoro-4-trifluoromethyl-phenyl)-ethyl]-4,5-dihydro-oxazol-2-ylamine,
(S)-4-[2-(3,5-dichloro-phenyl)-ethyl]-4,5-dihydro-oxazol-2-ylamine,
(S)-4-[2-(2-chloro-4-fluoro-phenyl)-ethyl]-4,5-dihydro-oxazol-2-ylamine,
(S)-4-[2-(4-fluoro-3-methyl-phenyl)-ethyl]-4,5-dihydro-oxazol-2-ylamine,
(S)-4-{2-[3-(1,1,2,2-tetrafluoro-ethoxy)-phenyl]-ethyl}-4,5-dihydro-oxazol-2-ylamine,
(S)-4-[2-(2-fluoro-3-trifluoromethyl-phenyl)-ethyl]-4,5-dihydro-oxazol-2-ylamine,
(S)-4-[2-(3-bromo-phenyl)-ethyl]-4,5-dihydro-oxazol-2-ylamine,
(S)-4-[2-(4-chloro-3-trifluoromethyl-phenyl)-ethyl]-4,5-dihydro-oxazol-2-ylamine,
(S)-4-[2-(3-fluoro-4-trifluoromethoxy-phenyl)-ethyl]-4,5-dihydro-oxazol-2-ylamine,
(S)-4-[2-(4-fluoro-3-trifluoromethoxy-phenyl)-ethyl]-4,5-dihydro-oxazol-2-ylamine,
(S)-4-[2-(2,3-dichloro-phenyl)-ethyl]-4,5-dihydro-oxazol-2-ylamine,
(S)-4-[2-(3-chloro-4-trifluoromethoxy-phenyl)-ethyl]-4,5-dihydro-oxazol-2-ylamine,
(S)-4-[2-(2-chloro-3-trifluoromethyl-phenyl)-ethyl]-4,5-dihydro-oxazol-2-ylamine,
(S)-4-(1-methyl-2-phenyl-ethyl)-4,5-dihydro-oxazol-2-ylamine,
(S)-4-[2-(2-fluoro-5-trifluoromethyl-phenyl)-ethyl]-4,5-dihydro-oxazol-2-ylamine,
(S)-4-[2-(3-fluoro-5-trifluoromethyl-phenyl)-ethyl]-4,5-dihydro-oxazol-2-ylamine,
(S)-4-[2-(2,5-bis-trifluoromethyl-phenyl)-ethyl]-4,5-dihydro-oxazol-2-ylamine,
(S)-4-[2-(4-chloro-phenyl)-butyl]-4,5-dihydro-oxazol-2-ylamine,
(S)-4-(2-phenyl-butyl)-4,5-dihydro-oxazol-2-ylamine,
(S)-4-[2-(4-trifluoromethyl-phenyl)-propyl]-4,5-dihydro-oxazol-2-ylamine,
(S)-4-[2-(4-trifluoromethyl-phenyl)-butyl]-4,5-dihydro-oxazol-2-ylamine,
(S)-4-[2-(3-trifluoromethyl-phenyl)-propyl]-4,5-dihydro-oxazol-2-ylamine,
(S)-4-[2-(3-trifluoromethyl-phenyl)-butyl]-4,5-dihydro-oxazol-2-ylamine,
(S)-4-[2-(3,5-difluoro-phenyl)-propyl]-4,5-dihydro-oxazol-2-ylamine,
(S)-4-[2-(3,5-difluoro-phenyl)-butyl]-4,5-dihydro-oxazol-2-ylamine,
(S)-4-[2-(4-fluoro-phenyl)-butyl]-4,5-dihydro-oxazol-2-ylamine,
(S)-4-[2-(3,4-difluoro-phenyl)-butyl]-4,5-dihydro-oxazol-2-ylamine,
(S)-4-[2-(2-fluoro-phenyl)-propyl]-4,5-dihydro-oxazol-2-ylamine,
(S)-4-[2-(3,4-dichloro-phenyl)-propyl]-4,5-dihydro-oxazol-2-ylamine,
(S)-4-[2-(3,4-dichloro-phenyl)-butyl]-4,5-dihydro-oxazol-2-ylamine,
(S)-4-[2-(2-fluoro-phenyl)-butyl]-4,5-dihydro-oxazol-2-ylamine,
(S)-4-[2-(2-chloro-phenyl)-ethyl]-4-methyl-4,5-dihydro-oxazol-2-ylamine,
(S)-4-[2-(3-chloro-phenyl)-ethyl]-4,5-dihydro-oxazol-2-ylamine,
(S)-4-[2-(4-chloro-phenyl)-ethyl]-4-methyl-4,5-dihydro-oxazol-2-ylamine,
(S)-4-[2-(3-chloro-phenyl)-ethyl]-4-methyl-4,5-dihydro-oxazol-2-ylamine,
(S)-4-[2-(4-fluoro-phenyl)-ethyl]-4-methyl-4,5-dihydro-oxazol-2-ylamine,
(S)-4-[2-(4-chloro-phenyl)-ethyl]-4,5-dihydro-oxazol-2-ylamine,
(S)-4-[2-(2-chloro-phenyl)-ethyl]-4,5-dihydro-oxazol-2-ylamine,
(S)-4-[2-(3-chloro-phenyl)-butyl]-4,5-dihydro-oxazol-2-ylamine,
(S)-4-((S)-2-phenyl-butyl)-4,5-dihydro-oxazol-2-ylamine,
(S)-4-((R)-2-phenyl-butyl)-4,5-dihydro-oxazol-2-ylamine,
(S)-4-[2-(2-chloro-6-fluoro-phenyl)-ethyl]-4,5-dihydro-oxazol-2-ylamine,
(S)-4-[2-(2,4-dichloro-phenyl)-ethyl]-4-methyl-4,5-dihydro-oxazol-2-ylamine,
(S)-4-[2-(2-bromo-phenyl)-ethyl]-4,5-dihydro-oxazol-2-ylamine,
(S)-4-[2-(2,5-dichloro-phenyl)-ethyl]-4,5-dihydro-oxazol-2-ylamine,
(S)-4-[2-(3-fluoro-phenyl)-butyl]-4,5-dihydro-oxazol-2-ylamine,
(S)-4-[2-(3-chloro-2-fluoro-phenyl)-butyl]-4,5-dihydro-oxazol-2-ylamine,
(S)-4-[2-(3-chloro-4-fluoro-phenyl)-butyl]-4,5-dihydro-oxazol-2-ylamine,
(S)-4-[2-(3-chloro-5-fluoro-phenyl)-butyl]-4,5-dihydro-oxazol-2-ylamine,
(S)-4-[2-(5-chloro-2-fluoro-phenyl)-butyl]-4,5-dihydro-oxazol-2-ylamine,
(S)-4-(4-fluoro-phenoxymethyl)-4,5-dihydro-oxazol-2-ylamine,
(S)-4-(4-chloro-phenoxymethyl)-4,5-dihydro-oxazol-2-ylamine,
(S)-4-(3,4-dichloro-phenoxymethyl)-4,5-dihydro-oxazol-2-ylamine,
(S)-4-(3,5-dichloro-phenoxymethyl)-4,5-dihydro-oxazol-2-ylamine,
(S)-4-(4-bromo-phenoxymethyl)-4,5-dihydro-oxazol-2-ylamine,
(S)-4-(3-chloro-phenoxymethyl)-4,5-dihydro-oxazol-2-ylamine,
(S)-4-(2,4-difluoro-phenoxymethyl)-4,5-dihydro-oxazol-2-ylamine,
(S)-4-(2-fluoro-phenoxymethyl)-4,5-dihydro-oxazol-2-ylamine,
(S)-4-benzyloxymethyl-4,5-dihydro-oxazol-2-ylamine,
(S)-4-(3-Phenyl-propyl)-4,5-dihydro-oxazol-2-ylamine,
(R)-4-(3-Phenyl-propyl)-4,5-dihydro-oxazol-2-ylamine,
(R)-4-phenylsulfanylmethyl-4,5-dihydro-oxazol-2-ylamine,
(R)-4-benzenesulfonylmethyl-4,5-dihydro-oxazol-2-ylamine,
(R)-4-benzylsulfanylmethyl-4,5-dihydro-oxazol-2-ylamine,
(R)-4-(4-chloro-phenylsulfanylmethyl)-4,5-dihydro-oxazol-2-ylamine,
(S)-4-[1-(4-chloro-phenyl)-cyclopropylmethyl]-4,5-dihydro-oxazol-2-ylamine,
(S)-4-[1-(4-chloro-phenyl)-cyclobutylmethyl]-4,5-dihydro-oxazol-2-ylamine,
(S)-4-(1-phenyl-cyclopropylmethyl)-4,5-dihydro-oxazol-2-ylamine,
(S)-4-[(benzyl-ethyl-amino)-methyl]-4,5-dihydro-oxazol-2-ylamine,
(R)-4-[(dimethyl-phenyl-silanyl)-methyl]-4,5-dihydro-oxazol-2-ylamine,
(RS)-4-(2,3-dihydro-benzo[1,4]dioxin-6-yl)-4,5-dihydro-oxazol-2-ylamine,
(RS)-4-naphthalen-2-yl-4,5-dihydro-oxazol-2-ylamine,
(RS)-4-naphthalen-1-yl-4,5-dihydro-oxazol-2-ylamine,
(R)-4-naphthalen-1-ylmethyl-4,5-dihydro-oxazol-2-ylamine,
(S)-4-naphthalen-1-ylmethyl-4,5-dihydro-oxazol-2-ylamine,
(S)-4-naphthalen-2-ylmethyl-4,5-dihydro-oxazol-2-ylamine,
(RS)-4-(1,2,3,4-tetrahydro-naphthalen-2-yl)-4,5-dihydro-oxazol-2-ylamine,
(S)-4-naphthalen-2-yl-4,5-dihydro-oxazol-2-ylamine,
(S)-4-[2-(3-fluoro-pyridin-4-yl)-ethyl]-4,5-dihydro-oxazol-2-ylamine,
(S)-4-[2-(6-trifluoromethyl-pyridin-2-yl)-ethyl]-4,5-dihydro-oxazol-2-ylamine,
(S)-4-[2-(2-methyl-pyridin-4-yl)-ethyl]-4,5-dihydro-oxazol-2-ylamine, and
(S)-4-(2-cyclohexyl-ethyl)-4,5-dihydro-oxazol-2-ylamine or a pharmaceutically suitable acid addition salt thereof.Cited by (0)
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