EP0405537A1
Expired / Lapsed
EP
⏱️ 0.0 years remaining
N-substituted cycloalkyl and polycycloalkyl alpha-substituted Trp-Phe- and phenethylamine derivatives
Assignee: Warner Lambert Co LLC
•
Filing: 1990-06-28
•
Granted: —
•
Expires: 2010-06-28
Abstract
Abstract Novel unnatural dipeptoids of α-substituted Trp-Phe derivatives useful as agents in the treatment of obesity, hypersecretion of gastric acid in the gut, gastrin-dependent tumors, or as antipsychotics are disclosed. Further the compounds are antianxiety agents and antiulcer agents and are agents useful for preventing the withdrawal response produced by chronic treatment or use followed by chronic treatment followed by withdrawal from nicotine, diazepam, alcohol or cocaine. Also disclosed are pharmaceutical compositions and methods of treatment using the dipeptoids as well as processes for preparing them and novel intermediates useful in their preparation. An additional feature of the invention is the use of the subject compounds to prepare pharmaceutical and diagnostic compositions.
Inventors
- 👤 David Christopher Horwell
- 👤 Martyn Clive Pritchard
- 👤 Reginald Stewart Richardson
- 👤 Edward Roberts
- 👤 Julian Aranda
Bibliographic Details
Application Number
—
Jurisdiction
EP
Data Source
google_patents
Last Synchronized
2026-10-27 12:27
CPC Classifications
C; C07; C07D; C07D403/00; C07D403/02; C07D403/12; A; A61; A61K; A61K31/00; A61K31/33; A61K31/395; A61K31/40; A61P; A61P1/00; A61P1/04; A61P25/00; A61P25/04; A61P25/18; A61P25/20; A61P3/00; A61P3/04; A61P43/00; C07D209/00; C07D209/02; C07D209/04; C07D209/10; C07D209/18; C07D209/20; C07K; C07K5/00; C07K5/04; C07K5/06; C07K5/06139; C07K5/06156; C07K5/08; C07K5/0821; A61K38/00
Claims Analysis
Total Claims: 76
Claim 1
Independent Claim
393 words
A compound of the formula or a pharmaceutically acceptable salt thereof wherein: R¹ is a cycloalkyl or polycycloalkyl hydrocarbon of from three to twelve carbon atoms with from zero to four substituents each independently selected from the group consisting of a straight or branched alkyl of from one to about six carbon atoms, halogen, CN, OR*, SR*, CO₂R*, CF₃, NR⁵R⁶, and -(CH₂) n OR⁵ wherein R* is hydrogen or a straight or branched alkyl of from one to six carbon atoms, R⁵ and R⁶ are each independently hydrogen or alkyl of from one to about six carbon atoms and n is an integer from zero to six; A is -(CH₂) n CO-,-SO₂-, -S(=O)-, -NHCO-, -(CH₂) n -O -, -SCO-, -O-(CH₂) n CO- or -HC=CHCO- wherein n is an integer from zero to six; R² is a straight or branched alkyl of from one to about six carbon atoms, -HC=CH₂, -C≡CH, -CH₂-CH=CH₂, - CH₂C≡CH, -CH₂Ar, -CH₂OR*, -CH₂OAr, -(CH₂) n CO₂R*, or -(CH₂) n NR⁵R⁶ wherein n, R*, R⁵ and R⁶ are as defined above and Ar is as defined below; R³ and R⁴ are each independently selected from hydrogen, R² and -(CH₂) n′ -B-D wherein: n′ is an integer of from zero to three; B is a bond, -OCO(CH₂) n -, -O(CH₂) n -, -NHCO(CH₂) n -, -CONH(CH₂) n -, -NHCOCH=CH-, -COO(CH₂) n -, -CO(CH₂) n -, -S-(CH₂) n -, -S(=O)-(CH₂) n -, -SO₂-(CH₂) n -, wherein R⁷ and R⁸ are independently selected from hydrogen and R² or together form a ring (CH₂) m wherein m is an integer of from 1 to 5 and n is as defined above; D is -COOR*, -CONR⁵R⁶, -CN, -NR⁵R⁶, -OH, -H and acid replacements such as -CH₂OR*, -CHR²OR*, -CH₂SR*, -CHR²SR*, wherein R*, R², R⁵, and R⁶ are as defined above; R⁹ is hydrogen or a straight or branched alkyl of from one to about six carbon atoms, -(CH₂) n CO₂R*, -(CH₂) n OAr′, -(CH₂) n Ar′ or (CH₂) n NR⁵R⁶, wherein n, R*, R⁵, and R⁶ are as defined above or taken from R³ and Ar′ is taken from Ar as defined below; R¹² and R¹³ are each independently hydrogen or are each independently taken with R³ and R⁴ respectively to form a moiety doubly bonded to the carbon atom; and Ar is a mono- or polycyclic unsubstituted or substituted carbo- or heterocyclic aromatic or hydroaromatic moiety.
Claim 2
Dependent Claim
393 words
A compound of the formula or a pharmaceutically acceptable salt thereof wherein: R¹ is a cycloalkyl or polycycloalkyl hydrocarbon of from three to twelve carbon atoms with from zero to four substituents each independently selected from the group consisting of a straight or branched alkyl of from one to about six carbon atoms, halogen, CN, OR*, SR*, CO₂R*, CF₃, NR⁵R⁶, and -(CH₂) n OR⁵ wherein R* is hydrogen or a straight or branched alkyl of from one to six carbon atoms, R⁵ and R⁶ are each independently hydrogen or alkyl of from one to about six carbon atoms and n is an integer from zero to six; A is -(CH₂) n CO-,-SO₂-, -S(=O)-, -NHCO-, -(CH₂) n -O -, -SCO-, -O-(CH₂) n CO- or -HC=CHCO- wherein n is an integer from zero to six; R² is a straight or branched alkyl of from one to about six carbon atoms, -HC=CH₂, -C≡CH, -CH₂-CH=CH₂, - CH₂C≡CH, -CH₂Ar, -CH₂OR*, -CH₂OAr, -(CH₂) n CO₂R*, or -(CH₂) n NR⁵R⁶ wherein n, R*, R⁵ and R⁶ are as defined above and Ar is as defined below; R³ and R⁴ are each independently selected from hydrogen, R² and -(CH₂) n′ -B-D wherein: n′ is an integer of from zero to three; B is a bond, -OCO(CH₂) n -, -O(CH₂) n -, -NHCO(CH₂) n -, -CONH(CH₂) n -, -NHCOCH=CH-, -COO(CH₂) n -, -CO(CH₂) n -, -S-(CH₂) n -, -S(=O)-(CH₂) n -, -SO₂-(CH₂) n -, wherein R⁷ and R⁸ are independently selected from hydrogen and R² or together form a ring (CH₂) m wherein m is an integer of from 1 to 5 and n is as defined above; D is -COOR*, -CONR⁵R⁶, -CN, -NR⁵R⁶, -OH, -H and acid replacements such as -CH₂OR*, -CHR²OR*, -CH₂SR*, -CHR²SR*, wherein R*, R², R⁵, and R⁶ are as defined above; R⁹ is hydrogen or a straight or branched alkyl of from one to about six carbon atoms, -(CH₂) n CO₂R*, -(CH₂) n OAr′, -(CH₂) n Ar′ or (CH₂) n NR⁵R⁶, wherein n, R*, R⁵, and R⁶ are as defined above or taken from R³ and Ar′ is taken from Ar as defined below; R¹² and R¹³ are each independently hydrogen or are each independently taken with R³ and R⁴ respectively to form a moiety doubly bonded to the carbon atom; and Ar is a mono- or polycyclic unsubstituted or substituted carbo- or heterocyclic aromatic or hydroaromatic moiety.
Claim 3
Dependent Claim
20 words
A compound according to Claim 1 wherein the cycloalkyl or polycycloalkyl has from about six to about ten carbon atoms.
Claim 4
Dependent Claim
21 words
A compound according to Claim 1 wherein each substituent on the cycloalkyl or polycycloalkyl is independently methyl, F, Cl or Br.
Claim 5
Dependent Claim
70 words
A compound according to Claim 1 wherein the polycycloalkyl is selected from the group consisting of wherein W, X, Y, and Z are each independently hydrogen, a straight or branched alkyl of from one to six carbon atoms, CF₃, NR⁵R⁶, -(CH₂) n CO₂R*, CN, F, Cl, Br, OR*, SR*, wherein R*, R⁵ and R⁶ are as defined in Claim 1 and n is an integer of from 1 to 3.
Claim 6
Dependent Claim
16 words
A compound according to claim 1 wherein A is -NHCO-, OC(=O)-, -SO₂-, -S(=O)-, -SCO- or -CH₂CO-.
Claim 7
Dependent Claim
42 words
A compound according to claim 1 wherein Ar is 2- or 3-thienyl, 2- or 3-furanyl, 2-, 3- or 4-pyridinyl or an unsubstituted or substituted phenyl whose substituents if any are each independently hydrogen, fluorine, chlorine, bromine, iodine, methyl, methoxy, trifluoromethyl or nitro.
Claim 8
Dependent Claim
43 words
A compound according to claim 1 wherein: R¹ is 2-adamantyl or 1-(S)-2-endobornyl; A is -NHCO-, -OCO-, -SO₂-, -S(=O)- or -CH₂CO-; R² is -CH₃, -CH₂CO₂H or -CH₂C≡CH; R³ is -CH₂-B-D or H; R⁴ is -(CH₂) n -B-D or H; R⁹ is hydrogen or methyl.
Claim 9
Dependent Claim
37 words
A compound according to claim 1 wherein: R is 2-adamantyl or 1-(S)-2-endobornyl; A is -OC(=O)-; R² is -CH₃; R³ is H, CH₂OH, CH₂OCOCH₂CH₂CO₂H, CH₂OCOCH=CHCO₂H, CH₂NHCOCH₂CH₂CO₂H, or CH₂NHCOCH=CHCO₂H R⁴ is H, -NHCOCH₂CH₂CO₂H ([D] configuration) or NHCOCH=CHCO2H ([D] configuration).
Claim 10
Dependent Claim
8 words
A compound according to Claim 1 named (±)-trans-2-chlorocyclohexyl[1-(1H-indol-3-ylmethyl)-1-methyl-2-oxo-2-[(2-phenylethyl)amino]ethyl]carbamate.
Claim 11
Dependent Claim
8 words
A compound according to Claim 1 named 2-chlorocyclohexyl[2-[[1-(hydroxymethyl)-2-phenylethyl]amino]-1-(1H-indol-3-ylmethyl)-1-methyl-2-oxoethyl]carbamate.
Claim 12
Dependent Claim
9 words
A compound according to Claim 1 named 2-[[2-[[[(2-chlorocyclohexyl)oxy]carbonyl]amino]-3-(1H-indol-3-yl)-2-methyl-1-oxopropyl]amino]-3-phenylpropyl butanedioate.
Claim 13
Dependent Claim
9 words
A compound according to Claim 1 named 2-[[2-[[[(2-methylcyclohexyl)oxy]carbonyl]amino]-3-(1H-indol-3-yl)-2-methyl-1-oxopropyl]amino]-3-phenylpropyl butanedioate.
Claim 14
Dependent Claim
11 words
A compound according to Claim 1 named (±)-tricyclo[3.3.1.1 3,7 ]dec-2-yl [1-(1H-indol-3-ylmethyl)-1-methyl-2-oxo-2-[(2-phenylethyl)amino]ethyl]carbamate.
Claim 15
Dependent Claim
11 words
A compound according to Claim 1 named (+) or (-)-2-chlorocyclohexyl[1-(1H-indol-3-ylmethyl)-1-methyl-2-oxo-2-[(2-phenylethyl)amino]ethyl] carbamate.
Claim 16
Dependent Claim
12 words
A compound according to Claim 1 named tricyclo[3.3.1.1 3,7 ]dec-2-yl [2-[[1-(hydroxymethyl)-2-phenylethyl]amino]-1-(1H-indol-3-ylmethyl)-1-methyl-2-oxoethyl] carbamate.
Claim 17
Dependent Claim
11 words
A compound according to Claim 1 named 2-[[3-(1H-indol-3-yl)-2-methyl-1-oxo-2-[[(tricyclo[3.3.1.1 3,7 ]dec-2-yloxy)carbonyl]amino]propyl]amino]-3-phenylpropyl butanedioate.
Claim 18
Dependent Claim
11 words
A compound according to Claim 1 named 2-[[3-(1H-indol-3-yl)-2-methyl-1-oxo-2-[[(tricyclo[3.3.1.1 3,7 ]dec-2-yloxy)carbonyl]amino]propyl]amino]-1-phenylethyl butanedioate.
Claim 19
Dependent Claim
12 words
A compound according to Claim 1 named [R-(R*,R*)]-4-[[2-[[3-(1H-indol-3-yl)-2-methyl-1-oxo-2-[[(tricyclo[3.3.1.1 3,7 ]dec-2-yloxy) carbonyl]amino]propyl]-amino]-1-phenylethyl]-amino]-4-oxobutanoic acid.
Claim 20
Dependent Claim
9 words
A compound according to Claim 1 named [1S-[1α,2β[S*(S*)],4α]]-4-[[2-[[3-(1H-indol-3-yl)-2-methyl-1-oxo-2-[[[(1,7,7-trimethylbicyclo-2.2.1]hept-2-yl)amino]carbonyl]amino]propyl]amino]-1-phenylethyl]amino]-4-oxobutanoic acid.
Claim 21
Dependent Claim
11 words
A compound according to Claim 1 named [R-[R*,S*-(E)]]-4-[[2-[[3-(1H-indol-3-yl)-2-methyl-1-oxo-2-[[tricyclo[3.3.1.1 3,7 ]dec-2-yloxy)carbonyl]amino]propyl]amino]-3-phenylpropyl]amino]-4-oxo-2-butenoic acid.
Claim 22
Dependent Claim
11 words
A compound according to Claim 1 named [R-(R*,S*)]-4-[[2-[[3-(1H-indol-3-yl)-2-methyl-1-oxo-2-[[(tricyclo[3.3.1.1 3,7 ]dec-2-yloxy)carbonyl]amino]propyl]amino]-3-phenylpropyl]amino]-4-oxo-butanoic acid.
Claim 23
Dependent Claim
10 words
A compound according to Claim 1 named (R)-tricyclo[3.3.1.1 3,7 ]dec-2-yl-[1-(1H-indol-3-ylmethyl)-1-methyl-2-[methyl-(2-phenylethyl)amino]-2-oxoethylcarbamate.
Claim 24
Dependent Claim
11 words
A compound according to Claim 1 named [R-(R*,S*)]-2-[[2-[[3-(1H-indol-3-yl)-2-methyl-1-oxo-2-[[(tricyclo[3.3.1.1 3,7 ]dec-2-yloxy)carbonyl]amino]propyl]amino]-3-phenylpropyl]sulfinyl]acetic acid.
Claim 25
Dependent Claim
11 words
A compound according to Claim 1 named [R-(R*,S*)]-[[2-[[3-(1H-indol-3-yl)-2-methyl-1-oxo-2-[[(tricyclo[3.3.1.1 3,7 ]dec-2-yloxy)]carbonyl]amino]propyl]amino]-3-phenylpropyl]sulfonyl]acetic acid.
Claim 26
Dependent Claim
13 words
A compound according to Claim 1 named [R-(R*,S*]]-[[2-[[3-(1H-indol-3-yl)-2-methyl-1-oxo-2-[[(tricyclo[3.3.1.1 3,7 ]dec-2-yloxy)carbonyl]amino]propyl]amino]-3-phenylpropyl]sulfinyl]acetic acid, ethyl ester.
Claim 27
Dependent Claim
11 words
A compound according to Claim 1 named [R-(R*,S*)]-[[2-[[3-(1H-indol-3-yl)-2-methyl-1-oxo-2-[[(tricyclo[3.3.1.1 3,7 ]dec-2-yloxy)]carbonyl]amino]propyl]amino]-3-phenylpropyl]sulfonyl]acetic acid.
Claim 28
Dependent Claim
11 words
A compound according to Claim 1 named [R-[R*,R*-(E)]]-4-[[2-[[3-(1H-indol-3-yl)-2-methyl-1-oxo2-[[(tricyclo[3.3.1.1 3,7 ]dec-2-ylloxy)carbonyl]amino]propyl]amino]-1-phenylethyl]amino]-4-oxo-2-butenoic acid.
Claim 29
Dependent Claim
11 words
A compound according to Claim 1 named [R-(R*,S*)]-[[2-[[2-[3-(1H-indol-3-yl)-2-methyl-1-oxo-2-[[(tricyclo[3.3.1.1 3,7 ]dec-2-yloxy)-carbonyl]amino]propyl]amino]-3-phenylpropyl]thio]acetic acid.
Claim 30
Dependent Claim
15 words
A compound according to Claim 1 named [1S-[1α,2β[S*[S*(E)]],4α]]-4-[[2-[[3-(1H-indol-3-yl)-2-methyl-1-oxo-2-[[[(1,7,7-trimethylbicyclo[2.2.1]hept-2-yl)oxy]carbonyl]amino]propyl]amino]-1-phenylethyl]amino]-4-oxo-2-butenoic acid, methyl ester, (bicyclo system is 1S-endo).
Claim 31
Dependent Claim
13 words
A compound according to Claim 1 named [1S-[1α,2β[S*[S*(E)]],4α]]-4-[[2-[[3-(1H-indol-3-yl)-2-methyl-1-oxo-2-[[[(1,7,7-trimethylbicyclo[2.2.1]hept-2-yl)oxy]carbonyl]amino]propyl]amino]-1-phenylethyl]amino]-4-oxo-2-butenoic acid (bicyclo system is 1S-endo).
Claim 32
Dependent Claim
11 words
A ccmpound according to Claim 1 named [R-(R*,R*)]-3-[[2-[[3-(1H-indol-3-yl)-2-methyl-1-oxo-2-[[(tricyclo[3.3.1.1 3,7 ]dec-2-yloxy)carbonyl]amino]propyl]amino]-1-phenylethyl]amino]-3-oxopropanoic acid.
Claim 33
Dependent Claim
14 words
A compound according to Claim 1 named [R-(R*,S*)]-3-(1H-indol-3-ylmethyl)-3-methyl-4,10-dioxo-6-(phenylmethyl)-11-oxo-8-thia-2,5-diazatridecanoic acid, tricyclo[3.3.1.1 3,7 ]dec-2-yl or ester.
Claim 34
Dependent Claim
13 words
A compound according to Claim 1 named [R-(R*,S*)]-β-[[3-(1H-indol-3-yl) 2-methyl-1-oxo-2-[[(tricyclo[3.3.1.1 3,7 ]dec-2-yloxy)carbonyl]- amino]propyl]amino]benzenebutanoic acid.
Claim 35
Dependent Claim
21 words
A compound according to Claim 1 named [R-(R*,S*)]-β-[[3-(1H-indol-3-yl)-2-methyl-1-oxo-2-[[(tricyclo[3.3.1.1 3,7 ]dec-2-yloxy)carbonyl]- amino]propyl]amino]-4-iodo-benzenebutanoic acid, where the iodo group may be I-125 or I-127.
Claim 36
Dependent Claim
10 words
A compound according to Claim 1 named [R-(R*,S*)]-N-[3-[[3-(1H-indol-3-yl)-2-methyl-1-oxo-2-[[(tricyclo[3.3.1.1 3,7 ]dec-2-yloxy)carbonyl]amino]propyl]amino]-4-phenylbutyl]glycine.
Claim 37
Dependent Claim
9 words
A compound according to Claim 1 named [R-[R*,S*-(E)]]-4-[[2-[[3-(1H-indol-3-yl)-2-methyl-2-[[(bicyclo[3.3.1]non-9-yloxy)carbonyl]amino]-1-oxopropyl]amino]-3-phenylpropyl]amino]-4-oxo-2-butenoic acid.
Claim 38
Dependent Claim
26 words
A pharmaceutical composition comprising an amount of a compound according to Claim 1, effective to suppress the appetite in a mammal, and a pharmaceutically acceptable carrier.
Claim 39
Dependent Claim
22 words
A method of suppressing appetite in a mammal, comprising administering an effective appetite suppressing amount of a compound according to Claim 1.
Claim 40
Dependent Claim
27 words
A pharmaceutical composition comprising an amount of a compound according to Claim 1, effective to reduce gastric acid secretion in a mammal, and a pharmaceutically acceptable carrier.
Claim 41
Dependent Claim
26 words
A methcd of reducing gastric acid secretion in a mammal, comprising administering an effective gastric acid secretion reducing amount of a compound according to Claim 1.
Claim 42
Dependent Claim
25 words
A pharmaceutical composition comprising an amount of a compound according to Claim 1, effective to reduce anxiety in a mammal, and a pharmaceutically acceptable carrier.
Claim 43
Dependent Claim
22 words
A method of reducing anxiety in a mammal, comprising administering an effective anxiety reducing amount of a compound according to Claim 1.
Claim 44
Dependent Claim
12 words
A compound of formula: wherein R¹ is as defined in Claim 1.
Claim 45
Dependent Claim
20 words
A compound of formula: wherein R is 1-adamantyl, 2-adamantyl, 4-protoadamantyl, 9-fluorenylmethyl, exo-bornyl, endo-bornyl, exo- norbornyl, endo-norbornyl, 2-chlorocyclohexyl, 2-methylcyclohexyl, or camphoryl.
Claim 46
Dependent Claim
20 words
A compound of formula: wherein R is 1-adamantyl, 2-adamantyl, 4-protoadamantyl, 9-fluorenylmethyl, exo-bornyl, endo-bornyl, exo- norbornyl, endo-norbornyl, 2-chlorocyclohexyl, 2-methylcyclohexyl, or camphoryl.
Claim 47
Dependent Claim
48 words
A process for preparing a compound according to Claim 44, comprising reacting a compound of formula ROH (III) with a phosgene or phosgene substitute to produce a compound of formula ROCOCl (IV) and reacting a compound of formula IV with [D]-α-methyltryptophan to produce a compound of Claim 44.
Claim 48
Dependent Claim
51 words
A process for preparing a compound of formula wherein R is 1-adamantyl, 2-adamantyl, 4-protoadamantyl, 9-fluorenylmethyl, exo-bornyl, endo-bornyl, exo-norbornyl, endo-norbornyl, 2-chlcrocyclohexyl, 2-methylcyclohexyl, or camphoryl, comprising reacting a free amine of with a substituted acetylchloride RCH₂COCl to form a compound of formula I and converting it, if desired, to a pharmaceutically acceptable salt.
Claim 49
Dependent Claim
51 words
A process for preparing a compound of formula wherein R is 1-adamantyl, 2-adamantyl, 4-protoadamantyl, 9-fluorenylmethyl, exo-bornyl, endo-bornyl, exo-norbornyl, endo-norbornyl, 2-chlcrocyclohexyl, 2-methylcyclohexyl, or camphoryl, comprising reacting a free amine of with a substituted acetylchloride RCH₂COCl to form a compound of formula I and converting it, if desired, to a pharmaceutically acceptable salt.
Claim 50
Dependent Claim
48 words
A process for preparing a sulphonamide wherein R is 1-adamantyl, 2-adamantyl, 4-protoadamantyl, 9-fluorenylmethyl, exo-bornyl, endo-bornyl, exo-norbornyl, endo-norbornyl, 2-chlorocyclohexyl, 2-methylcyclohexyl, or camphoryl, comprising reacting a free amine with a substituted sulphonylchloride RSO₂Cl to form a compound of formula I and converting it, if desired, to a pharmaceutically acceptable salt.
Claim 51
Dependent Claim
48 words
A process for preparing a sulphonamide wherein R is 1-adamantyl, 2-adamantyl, 4-protoadamantyl, 9-fluorenylmethyl, exo-bornyl, endo-bornyl, exo-norbornyl, endo-norbornyl, 2-chlorocyclohexyl, 2-methylcyclohexyl, or camphoryl, comprising reacting a free amine with a substituted sulphonylchloride RSO₂Cl to form a compound of formula I and converting it, if desired, to a pharmaceutically acceptable salt.
Claim 52
Dependent Claim
51 words
A process for preparing a compound of formula wherein R is 1-adamantyl, 2-adamantyl, 4-protoadamantyl, 9-fluorenylmethyl, exo-bornyl, endo-bornyl, exo- norbornyl, endo-norbornyl, 2-chlorocyclohexyl, 2-methylcyclohexyl, or camphoryl, comprising reacting a free amine with a substituted isocyanate R-N=C=O to form a compound of formula I and converting it, if desired, to a pharmaceutically acceptable salt.
Claim 53
Dependent Claim
51 words
A process for preparing a compound of formula wherein R is 1-adamantyl, 2-adamantyl, 4-protoadamantyl, 9-fluorenylmethyl, exo-bornyl, endo-bornyl, exo- norbornyl, endo-norbornyl, 2-chlorocyclohexyl, 2-methylcyclohexyl, or camphoryl, comprising reacting a free amine with a substituted isocyanate R-N=C=O to form a compound of formula I and converting it, if desired, to a pharmaceutically acceptable salt.
Claim 54
Dependent Claim
26 words
A pharmaceutical composition comprising an amount of a compound according to Claim 1 effective to treat gastrointestinal ulcers in a mammal, and a pharmaceutically acceptable carrier.
Claim 55
Dependent Claim
24 words
A method for treating gastrointestinal ulcers in a mammal comprising administering an effective gastrointestinal ulcer treating amount of a compound according to Claim 1.
Claim 56
Dependent Claim
26 words
An pharmaceutical composition comprising an amount of a compound according to Claim 1 effective to treat psychotic behavior in a mammal, and a pharmaceutically acceptable carrier.
Claim 57
Dependent Claim
22 words
A method of treating psychosis in a mammal, comprising administering an effective psychosis treating amount of a compound according to Claim 1.
Claim 58
Dependent Claim
34 words
A pharmaceutical composition comprising an amount of a compound according to Claim 1 effective to block the reaction caused by withdrawal from drug or alcohol use in a mammal, and a pharmaceutically acceptable carrier.
Claim 59
Dependent Claim
27 words
A method of blocking drug or alcohol withdrawal reaction in a mammal comprising administering an effective withdrawal reaction blocking amount of a compound according to Claim 1.
Claim 60
Independent Claim
19 words
A method of treating reaction from alcohol withdrawal in a mammal, comprising administering an effective amount of compound (20).
Claim 61
Independent Claim
19 words
A method of treating reaction from alcohol withdrawal in a mammal, comprising administering an effective amount of compound (20).
Claim 62
Independent Claim
19 words
A method of treating reaction from cocaine withdrawal in a mammal, comprising administering an effective amount of compound (20).
Claim 63
Independent Claim
19 words
A method of treating reaction from cocaine withdrawal in a mammal, comprising administering an effective amount of compound (20).
Claim 64
Independent Claim
19 words
A method of treating reaction from benzodiazepine withdrawal in a mammal, comprising administering an effective amount of compound (20).
Claim 65
Independent Claim
19 words
A method of treating reaction from benzodiazepine withdrawal in a mammal, comprising administering an effective amount of compound (20).
Claim 66
Independent Claim
19 words
A method of treating reaction from diazepam withdrawal in a mammal, comprising administering an effective amount of compound (20).
Claim 67
Independent Claim
19 words
A method of treating reaction from diazepam withdrawal in a mammal, comprising administering an effective amount of compound (20).
Claim 68
Independent Claim
19 words
A method of treating reaction from nicotine withdrawal in a mammal, comprising administering an effective amount of compound (20).
Claim 69
Independent Claim
19 words
A method of treating reaction from nicotine withdrawal in a mammal, comprising administering an effective amount of compound (20).
Claim 70
Dependent Claim
26 words
A pharmaceutical composition comprising an amount of a compound according to Claim 1 effective to potentiate the effects of morphine and other opioids in treating pain.
Claim 71
Dependent Claim
20 words
A method of trating pain in a mammal, comprising administering an effective amount of a compound according to claim 1.
Claim 72
Dependent Claim
43 words
A process for the preparation of a compound of formula I which comprises condensing a compound of formula with an appropriate amine of formula using a suitable condensing agent and a suitable solvent at a temperature of from about 20°C to about 80°C.
Claim 73
Dependent Claim
43 words
A process for the preparation of a compound of formula I which comprises condensing a compound of formula with an appropriate amine of formula using a suitable condensing agent and a suitable solvent at a temperature of from about 20°C to about 80°C.
Claim 74
Dependent Claim
58 words
Method of use of a compound of general formula I according to Claim 1, for the manufacturing of pharmaceuticals for suppressing the appetite, reducing gastric acid secretion, reducing anxiety, treating gastrointestinal ulcers, treating psychotic behavior, blocking the reaction caused by withdrawal from drug, alcohol, cocaine, benzodiazepine, diazepam, or nicotine, or potentiating the effects of morphine for treating pain.
Claim 75
Dependent Claim
27 words
Method of use of a radioactive iodo compound of formula I to prepare a pharmaceutical or diagnostic composition for the treatment or diagnosis of gastrin dependent tumors.
Claim 76
Dependent Claim
27 words
Method of use of a radioactive iodo compound of formula I to prepare a pharmaceutical or diagnostic composition for the treatment or diagnosis of gastrin dependent tumors.
References Cited (Backward Citations)
USPTO Annuity & Maintenance Windows
Maintenance schedule is calculated for granted US utility patents.