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US4760073A Expired / Lapsed US ⏱️ 0.0 years remaining

Aryl-substituted naphthyridine and pyridopyrazine derivatives, useful as anti-allergic agents

Assignee: Merck Sharp & Dohme LLC
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Filing: 1986-12-23
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Granted: 1988-07-26
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Expires: 2006-12-23
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Abstract

Abstract Aryl-substituted naphthyridines and pyridopyrazines are disclosed which are useful in treating allergic reactions, inflammation, peptic ulcers and/or hyperproliferative skin disease. Pharmaceutical compositions and methods of treatment employing such compounds are also disclosed.

Inventors

  • 👤 David J. Blythin
  • 👤 Ho-Jane Shue

Bibliographic Details

Application Number —
Jurisdiction US
Data Source google_patents
Last Synchronized 2026-10-25 16:51
CPC Classifications
C; C07; C07D; C07D471/00; C07D471/02; C07D471/04; C07D471/12; C07D471/14; C07D495/00; C07D495/12; C07D495/14

Claims Analysis

Total Claims: 36
Claim 1
Independent Claim 351 words
A compound having the structural formula ##STR23## or a pharmaceutically acceptable salt thereof, wherein: X represents CH or N; A represents O or S; m is an ineger of from 0 to 2; n is an integer of from 0 to 2; R 1 and R 2 are the same or different and each is independently selected from H or alkyl containing 1 to 6 carbon atoms; W represents O or --S(O) p -- where p is an integer of from 0 to 2; B represents alkylene having from 2 to 8 carbon atoms, which alkylene may be optionally substituted with a group selected from --OH, --F, alkyl having 1 to 4 carbon atoms, --CH 2 OH, --CHO, --CO 2 H, --COR 3 {wherein R 3 is alkyl of 1 to 6 carbon atoms or --CN}, with the proviso that --OH or --F is not on the carbon atom adjacent to W; Q represents an aryl group containing from 6 to 15 carbon atoms or an aromatic heterocyclic group containing from 3 to 14 carbon atoms and having at least one O, S or N in the ring, which aryl or aromatic heterocyclic group can optionally be substituted with up to 3 substituents Y as defined below; and each Y substituent is independently selected from --OH, hydroxymethyl, alkyl containing from 1 to 6 carbon atoms, halo, --NO 2 , alkoxy containing 1 to 6 carbon atoms, --CF 3 , --CN, cycloalkyl containing 3 to 7 carbon atoms, alkenyloxy containing from 3 to 6 carbon atoms, alkynyloxy containing from 3 to 6 carbon atoms, alkynyloxy containing from 3 to 6 carbon atoms, --S(O) p R 4 {where R 4 and p are as defined above}, --CO--R 5 {wherein R 5 represents --OH, --NH 2 , --NHR 4 , --N(R 4 ) 2 or --OR 4 in which R 4 is as defined above}, --O--D--COR 5 {wherein D represents alkylene having from 1 to 4 carbon atoms and R 5 is as defined above}, --NH 2 , --NHR 4 , --N(R 4 ) 2 {wherein R 4 is as defined above} or --NHCOH.
Claim 2
Dependent Claim 351 words
A compound having the structural formula ##STR23## or a pharmaceutically acceptable salt thereof, wherein: X represents CH or N; A represents O or S; m is an ineger of from 0 to 2; n is an integer of from 0 to 2; R 1 and R 2 are the same or different and each is independently selected from H or alkyl containing 1 to 6 carbon atoms; W represents O or --S(O) p -- where p is an integer of from 0 to 2; B represents alkylene having from 2 to 8 carbon atoms, which alkylene may be optionally substituted with a group selected from --OH, --F, alkyl having 1 to 4 carbon atoms, --CH 2 OH, --CHO, --CO 2 H, --COR 3 {wherein R 3 is alkyl of 1 to 6 carbon atoms or --CN}, with the proviso that --OH or --F is not on the carbon atom adjacent to W; Q represents an aryl group containing from 6 to 15 carbon atoms or an aromatic heterocyclic group containing from 3 to 14 carbon atoms and having at least one O, S or N in the ring, which aryl or aromatic heterocyclic group can optionally be substituted with up to 3 substituents Y as defined below; and each Y substituent is independently selected from --OH, hydroxymethyl, alkyl containing from 1 to 6 carbon atoms, halo, --NO 2 , alkoxy containing 1 to 6 carbon atoms, --CF 3 , --CN, cycloalkyl containing 3 to 7 carbon atoms, alkenyloxy containing from 3 to 6 carbon atoms, alkynyloxy containing from 3 to 6 carbon atoms, alkynyloxy containing from 3 to 6 carbon atoms, --S(O) p R 4 {where R 4 and p are as defined above}, --CO--R 5 {wherein R 5 represents --OH, --NH 2 , --NHR 4 , --N(R 4 ) 2 or --OR 4 in which R 4 is as defined above}, --O--D--COR 5 {wherein D represents alkylene having from 1 to 4 carbon atoms and R 5 is as defined above}, --NH 2 , --NHR 4 , --N(R 4 ) 2 {wherein R 4 is as defined above} or --NHCOH.
Claim 3
Dependent Claim 10 words
A compound according to claim 1 wherein W is oxygen.
Claim 4
Dependent Claim 10 words
A compound according to claim 2 wherein A is oxygen.
Claim 5
Dependent Claim 10 words
A compound according to claim 3 wherein X represents CH.
Claim 6
Dependent Claim 81 words
A compound according to claim 4 wherein -B-W- represents an alkyleneoxy group which may optionally be substituted with a group selected from --OH, --F, --CN, alkyl having 1 to 4 carbon atoms, --CH 2 OH, --CHO, --CO 2 H or --COR 3 wherein R 3 represents --NHR 4 , --N(R 4 ) 2 or --OR 4 and R 4 is alkyl, with the proviso that --OH and --F are not on the carbon adjacent to the oxygen of said alkylenoxy group.
Claim 7
Dependent Claim 20 words
A compound according to claim 5 wherein -B-W- represents --(CH 2 ) 4 --O-- or --(CH 2 ) 3 --O--.
Claim 8
Dependent Claim 10 words
A compound according to claim 6 wherein m equals zero.
Claim 9
Dependent Claim 10 words
A compound according to claim 7 wherein n equal zero.
Claim 10
Dependent Claim 13 words
A compound according to claim 8 wherein Q represents phenyl or substituted phenyl.
Claim 11
Dependent Claim 27 words
A compound according to claim 9 wherein the one to three Y substituents on the O phenyl group are each independently selected from chloro, nitro or trifluoromethyl.
Claim 12
Dependent Claim 48 words
A compound according to claim 1 of the formula ##STR24## wherein A, B, W, Y and n are as defined in claim 23 and q is 0 to 2, and wherein, if n plus p is greater than 1, the Y groups may be the same or different.
Claim 13
Dependent Claim 16 words
A compound according to claim 1 selected from 7-phenyl-1,2,3,4-tetrahydro-oxepine [2,3-c]-[1,8]-naphthyridin-6(7H)-one; 7-(3-chlorophenyl)-1,2,3,4-tetrahydro-oxepine [2,3-c][1,8]-naphathyridin-6(7H)-one; 2,3-dihydro-6-phenyl-1H-pyrano [2,3-c][1,8]-naphthyridin-5(6H)-one; or 1,2-dihydro-5-phenylfuro[2,3-c][1,8]-naphthyridin-4[5-H]-one.
Claim 14
Dependent Claim 1 words
7-(3-Chlorophenyl)-1,2,3,4-tetrahydrooxepino[2,3-c][1,8]-naphthyridin-6(7H)-one.
Claim 15
Dependent Claim 1 words
7-(3-Chlorophenyl)-1,2,3,4-tetrahydrooxepino[2,3-c][1,8]-naphthyridin-6(7H)-one.
Claim 16
Dependent Claim 20 words
A compound according to claim 5 wherein -B-W- represents --(CH 2 ) 4 --O-- or --(CH 2 ) 3 --O--.
Claim 17
Dependent Claim 10 words
A compound according to claim 14 wherein m equals 0.
Claim 18
Dependent Claim 10 words
A compound according to claim 15 wherein n equals 0.
Claim 19
Dependent Claim 13 words
A compound according to claim 17 wherein Q represents phenyl or substituted phenyl.
Claim 20
Dependent Claim 28 words
A compound according to claim 18 wherein the substituted phenyl is substituted with from one to three Y substituent groups each independently selected from chloro, nitro or trifluoromethyl.
Claim 21
Dependent Claim 43 words
A compound having the formula ##STR25## wherein A, B, W, Y and n are as defined in claim 1, q is 0 to 2, and wherein if n plus q is greater than 1, the Y groups may be the same or different.
Claim 22
Dependent Claim 23 words
An anti-allergic, anti-inflammatory, cytoprotective or anti-hyperproliferative skin disease pharamceutical composition comprising a compound of formula I in combination with a pharmaceutically acceptable carrier.
Claim 23
Dependent Claim 23 words
An anti-allergic, anti-inflammatory, cytoprotective or anti-hyperproliferative skin disease pharamceutical composition comprising a compound of formula I in combination with a pharmaceutically acceptable carrier.
Claim 24
Dependent Claim 31 words
A method of treating an allergic reaction in a mammal which comprises administering to said mammal an anti-allergic effective amount of a compound of formula I as defined in claim 1.
Claim 25
Dependent Claim 29 words
A method of treating inflammation in a mammal which comprises administering to said mammal an anti-inflammatory effective amount of a compound of formula I as defined in claim 1.
Claim 26
Dependent Claim 30 words
A method of treating peptic ulcers in a mammal which comprises administering to said mammal a cytoprotective effective amount of a compound of formula I as defined in claim 1.
Claim 27
Dependent Claim 31 words
A method of treating hyperproliferative skin disease in a mammal which comprises topically administering to said mammal an effective amount of a compound of formula I as defined in claim 1.
Claim 28
Dependent Claim 16 words
The method of claim 24 wherein the disease treated is psoriasis, lichenified eczema or seborrheic dermatitis.
Claim 29
Dependent Claim 11 words
The method of claim 25 wherein the disease treated is psoriasis.
Claim 30
Dependent Claim 27 words
A method for treating allergic reactions in a mammal which comprises administering an anti-allergic effective amount of the pharmaceutical composition defined in claim 1 to said mammal.
Claim 31
Dependent Claim 26 words
A method for treating inflammation in a mammal which comprises administering an anti-inflammatory effective amount of the pharmaceutical composition defined in claim 1 to said mammal.
Claim 32
Dependent Claim 27 words
A method for treating peptic ulcers in a mammal which comprises administering a cytoprotective effective amount of the pharmaceutical composition defined in claim 23 to said mammal.
Claim 33
Dependent Claim 28 words
A method for treating hyperproliferative skin diseases in a mammal which comprises topically administering an effective amount of a pharmaceutical composition defined in claim 1 to said mammal.
Claim 34
Dependent Claim 16 words
A method according to claim 30 wherein the disease is psoriasis, lichenified eczema or seborrhoeic dermatitis.
Claim 35
Dependent Claim 11 words
A method according to claim 31 wherein the disease is psoriasis.
Claim 36
Dependent Claim 29 words
A method for treating a mammal suffering from a hyperproliferative skin disease which comprises administering an effective amount of a compound as defined in claim 1 to said mammal.

References Cited (Backward Citations)

JPS5724233A Cited
JPS5823755A Cited
EP0127135A2 Cited
GB2142013A Cited
US4596809A Cited

USPTO Annuity & Maintenance Windows

Annuity Stage Window Opens Payment Deadline Surcharge Period Until Estimated Fee Status
3.5 Years (Year 4) 1991-07-26 1992-01-25 1992-07-26 $2000.00 Window Closed / Lapsed
7.5 Years (Year 8) 1995-07-26 1996-01-25 1996-07-26 $3760.00 Window Closed / Lapsed
11.5 Years (Year 12) 1999-07-26 2000-01-25 2000-07-26 $7700.00 Window Closed / Lapsed

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