Patent EA-001740-B1 (EA)
Title: Treament of the common cold or allergic rhinitis
Inventor: JOHNSON KIRK W
IPC: C07D401/04
Filed: 1997-08-12
Abstract: 1. A method for the treatment or amelioration of the symptoms of the common cold or allergic rhinitis in a mammal which comprises administering to a mammal in need thereof an effective amount of a serotonin 5-HT1F  agonist. 2. A method of Claim 1 where the serotonin 5-HT1F agonist is selective for the 5-HT1F  receptor relative to other receptors. 3. A method as claimed in Claim 1 in which the serotonin 5-HT 1F  agonist is a compound of Formula I:   in which A-B is -CH-CH2- or -C=CH-; X is H, halo, C1-C4 alkoxy, C1-C4 alkylthio, C1-C4 alkyl, benzyloxy, hydroxy or carboxamido; n is 1-4; Ar is pyridinyl, pyrrolyl or a structure of Formula II:   where R<1> is H, C1-C6 alkyl, C3-C7 cycloalkyl, C3-C7 cycloalkylmethyl, benzyl, phenyl or substituted phenyl. 4. A method as claimed in Claim 1 in which the serotonin 5-HT1F  agonist is a compound of Formula III:   in which A-B is -CH-CH2- or -C=CH-; X is H, halo, C1-C4 alkoxy, C1-C4 alkylthio, C1-C4 alkyl, benzyloxy, hydroxy or carboxamido; Y is O, S or a bond; n is 1-4; Ar is 1-naphthyl, 2-naphthyl, phenyl or phenyl monosubstituted with a substituent selected from the group consisting of halo, C1-C4 alkoxy, C1-C4 alkylthio, C1-C4 alkyl, benzyloxy, hydroxy or trifluoromethyl. 5. A method as claimed in Claim 1 in which the serotonin 5-HT1F  agonist is a compound of Formula IV:   in which A-B is -CH-CH2- or -C=CH-; R is H or C1-C6 alkyl; R<1> is H or C1-C4 alkyl; X is -S-R<2>, -C(O)R<3>, -C(O)NR<4>R<15>, -NR<5>R<6>, -NR<7>SO2R<8>, -NHC(Q)NR<10>R<11>, -NHC(O)OR<12> or -NR<13>C(O)R<14>; wherein Q is O, or S; R<2> is phenyl, substituted phenyl, phenyl(C1-C4 alkylene), phenyl(C1-C4 alkylene) substituted in the phenyl ring, or pyridinyl; R<3> is C1-C6 alkyl, phenyl(C1-C4 alkylene), phenyl(C1-C4 alkylene) substituted in the phenyl ring, naphthyl, N-methyl-N-methoxyamino, heteroaryl, substituted heteroaryl, heteroaryl(C1-C4 alkyl), or substituted heteroaryl(C1-C4 alkyl); R<4> is heteroaryl, substituted heteroaryl, heteroaryl(C1-C4 alkyl), or substituted heteroaryl(C1-C4 alkyl); R<4> and R<15> taken together with the nitrogen atom form a pyrrolidine, piperidine, substituted piperidine, piperazine, 4-substituted piperazine, morpholine or thiomorpholine ring; R<5> and R<6> are both trifluoromethanesulfonyl; R<7> is H or C1-C4 alkyl; R<8> is C1-C4 alkyl, phenyl, substituted phenyl, or di(C1-C4 alkyl)amino; R<10> and R<11> are independently selected from the group consisting of C1-C6 alkyl, C3-C6 alkenyl, C3-C8 cycloalkyl, phenyl, substituted phenyl, phenyl(C1-C4 alkylene), phenyl(C1-C4 alkylene) substituted in the phenyl ring, ((C1-C4 alkyl or C1-C4 alkoxycarbonyl substituted)C1-C4 alkyl)phenyl, C1-C4 alkyl, α-position substituted with C1-C4 alkoxycarbonyl; or R<10> and R<11> taken together with the nitrogen atom form a pyrrolidine, piperidine, piperazine, 4-substituted piperazine, morpholine or thiomorpholine ring; R<12> is C1-C6 alkyl, C3-C6 alkenyl, phenyl, substituted phenyl, C3-C8 cycloalkyl, C1-C4 alkyl ω-position substituted with C1-C4 alkoxy; R<13> is H or C1-C4 alkyl; R<14> is C1-C10 alkyl substituted with up to three substituents selected from the group consisting of hydroxy, C1-C4 alkoxy, halo, aryloxy, C1-C4 alkoxycarbonyl and heteroaryloxy, C2-C10 alkenyl, C2-C10 alkynyl, C3-C8 cycloalkyl, phenyl, substituted phenyl, naphthyl, phenyl(C1-C4 alkylene), phenyl(C1-C4 alkylene) substituted on the phenyl ring, 2-phenylethylen-1-yl, diphenylmethyl, conjugated with benzene ring C4-C8 cycloalkyl, C1-C4 alkylene ω-position substituted with C3-C6 cycloalkyl, or a heterocycle; and R<15> is H or C1-C6 alkyl. 6. A method as claimed in Claim 5 in which the serotonin 5-HT1F  agonist is N-(4-fluorobenzoyl)-5-amino-3-(1-methylpiperidin-4-yl)-1H-indole. 7. A method as claimed in Claim 1 in which the serotonin 5-HT1F  agonist is a compound of Formula V:   wherein: R<1> and R<2> are independently hydrogen, C1-C4 alkyl, or -CH2CH2-aryl where aryl is phenyl, phenyl mono-substituted with halo, or 1-(C1-C6 alkyl)pyrazol-4-yl; X is -OH, -NHC(O)R<3>, -NHC(Y)NHR<4>, -NHC(O)OR<5>, -C(O)R<6> or -NHSO2R<7>; R<3> is C1-C6 alkyl, C2-C6 alkenyl, C3-C8 cycloalkyl, phenyl, substituted phenyl, naphthyl, (C1-C4 alkylene)phenyl, thienylmethyl, or a heterocycle; R<4> is C1-C6 alkyl, phenyl, or phenyl di-substituted with halo; R<5> is C1-C6 alkyl, C2-C6 alkenyl, benzyl or phenyl mono-substituted with halo; R<6> is C1-C6 alkyl, phenyl, or phenyl mono-substituted with halo or C1-C4 alkoxy; R<7> is dimethylamino, phenyl or phenyl mono-substituted with halo or C1-C4 alkyl; m is 0 or 1; n is 1 or 2; and Y is S or O. 8. A method as claimed in Claim 1 in which the serotonin 5-HT1F  agonist is a compound of Formula VI:   in which R<1> is C1-C4 alkyl; R<2> is C1-C4 alkyl, cycloalkyl-(C1-C3 alkylene), aryl-(C1-C3 alkylene), or heteroaryl-(C1-C3 alkylene); R<3> is C1-C4 alkyl or phenyl; R<4> is C1-C4 alkyl, C3-C7 cycloalkyl, phenyl, substituted phenyl, biphenylyl, naphthyl, or a heterocycle; and pharmaceutically acceptable acid addition salts thereof. 9. A method of any of Claims 1-8 wherein the mammal is a human.