US4213983A
Expired / Lapsed
US
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Treating gastro-intestinal disorders and emesis with n-(heterocyclic substituted) benzamides
Assignee: Beecham Group PLC
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Filing: 1977-10-25
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Granted: 1980-07-22
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Expires: 1997-10-25
Abstract
Abstract Compounds of the formula (I), and their pharmaceutically acceptable salts: ##STR1## wherein: R 1 is a C 1-6 alkoxy group; R 2 and R 3 are the same or different and are hydrogen, halogen, CF 3 , hydroxy, C 1-6 alkoxy, C 2-7 acyl, amino, amino substituted by one or two C 1-6 alkyl groups, C 2-7 acylamino aminocarbonyl or aminosulphone optionally substituted by one or two C 1-6 alkyl groups, C 1-6 alkylsulphone or nitro groups; X is either a nitrogen atom, in which case m+n is 3 to 5, m is 2 to 4, n is 1 to 3; or X is CH in which case m+n is 2 to 5, m is 1 to 5, and n is 0 to 4; p is 0 to 3; R 4 is hydrogen, C 1-6 alkyl, phenyl or phenyl-C 1-6 alkyl, either of which phenyl moiety may be substituted by C 1-6 alkyl, C 1-6 alkoxy, CF 3 or halogen, and R 5 is hydrogen; or R 4 and R 5 are attached to two adjacent carbon atoms and form together with these two carbon atoms a fused benzene ring, which benzene ring may be substituted by C 1-6 alkyl, C 1-6 alkoxy, CF 3 or halogen; are useful for treating disorders of the gastro-intestional function and for treating emesis.
Inventors
- 👤 Michael S. Hadley
- 👤 Eric A. Watts
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-11-02 11:40
CPC Classifications
C; C07; C07D; C07D471/00; C07D471/02; C07D471/04; A; A61; A61P; A61P1/00; A61P1/04; A61P1/08; A61P1/14; C07D455/00; C07D455/02; C07D455/03; C07D455/04; C07D455/06
Claims Analysis
Total Claims: 119
Claim 1
Independent Claim
265 words
A compound of the formula (I), ##STR42## or a pharmaceutically acceptable salt thereof wherein R 1 is alkoxy of 1 to 6 carbon atoms; R 2 and R 3 are the same or different and are hydrogen, halogen, CF 3 , hydroxy, alkoxy of 1 to 6 carbon atoms, alkanoyl of 2 to 7 carbon atoms, amino, amino substituted by one or two alkyl moieties of 1 to 6 carbon atoms, alkanoylamino of 2 to 7 carbon atoms, aminocarbonyl or aminosulphone unsubstituted or substituted by one or two alkyl moieties of 1 to 6 carbon atoms, alkylsulphone of 1 to 6 carbon atoms or nitro; X is either a nitrogen atom, in which case m+n is 3 to 5, m is 2 to 4, and n is 1 to 3; or X is CH in which case m+n is 2 to 5, m is 1 to 5, and n is 0 to 4; P is 0 to 3; R 4 is hydrogen, alkyl of 1 to 6 carbon atoms, phenyl or phenyl-alkyl of 1 to 6 carbon atoms in the alkyl moiety, said phenyl or phenylalkyl being nuclear-unsubstituted or nuclear-substituted by alkyl of 1 to 6 carbon atoms, alkoxy of 1 to 6 carbon atoms, CF 3 or halogen, and R 5 is hydrogen; or R 4 and R 5 are attached to two adjacent carbon atoms and form together with these two carbon atoms a fused benzene ring, which benzene ring is unsubstituted or substituted by alkyl of 1 to 6 carbon atoms, alkoxy of 1 to 6 carbon atoms, CF 3 or halogen.
Claim 2
Dependent Claim
265 words
A compound of the formula (I), ##STR42## or a pharmaceutically acceptable salt thereof wherein R 1 is alkoxy of 1 to 6 carbon atoms; R 2 and R 3 are the same or different and are hydrogen, halogen, CF 3 , hydroxy, alkoxy of 1 to 6 carbon atoms, alkanoyl of 2 to 7 carbon atoms, amino, amino substituted by one or two alkyl moieties of 1 to 6 carbon atoms, alkanoylamino of 2 to 7 carbon atoms, aminocarbonyl or aminosulphone unsubstituted or substituted by one or two alkyl moieties of 1 to 6 carbon atoms, alkylsulphone of 1 to 6 carbon atoms or nitro; X is either a nitrogen atom, in which case m+n is 3 to 5, m is 2 to 4, and n is 1 to 3; or X is CH in which case m+n is 2 to 5, m is 1 to 5, and n is 0 to 4; P is 0 to 3; R 4 is hydrogen, alkyl of 1 to 6 carbon atoms, phenyl or phenyl-alkyl of 1 to 6 carbon atoms in the alkyl moiety, said phenyl or phenylalkyl being nuclear-unsubstituted or nuclear-substituted by alkyl of 1 to 6 carbon atoms, alkoxy of 1 to 6 carbon atoms, CF 3 or halogen, and R 5 is hydrogen; or R 4 and R 5 are attached to two adjacent carbon atoms and form together with these two carbon atoms a fused benzene ring, which benzene ring is unsubstituted or substituted by alkyl of 1 to 6 carbon atoms, alkoxy of 1 to 6 carbon atoms, CF 3 or halogen.
Claim 3
Dependent Claim
227 words
A compound according to claim 26, wherein R 1 is alkoxy of 1 to 6 carbon atoms; R 2 and R 3 are the same or different and are hydrogen, halogen, CF 3 , hydroxy, alkoxy of 1 to 6 carbon atoms, alkanoyl of 2 to 7 carbon atoms, amino, amino substituted by one or two alkyl moieties of 1 to 6 carbon atoms, alkanoylamino of 2 to 7 carbon atoms, aminosulphone, aminosulphone substituted by one or two alkyl moieties of 1 to 6 carbon atoms, alkylsulphone of 1 to 6 carbon atoms or nitro; m+n is 2 or 3, and m is 1, 2 or 3 and n is 0, 1 or 2; P is 0 or 1; R 4 is hydrogen, alkyl of 1 to 6 carbon atoms, phenyl or phenyl-alkyl of 1 to 6 carbon atoms in the alkyl moiety, said phenyl or said phenyl-alkyl being nuclear-unsubstituted or nuclear-substituted by alkyl of 1 to 6 carbon atoms, alkoxy of 1 to 6 carbon atoms, CF 3 or halogen, and R 5 is hydrogen; or R 4 and R 5 are attached to two adjacent carbon atoms and form together with these two carbon atoms a fused benzene ring, which benzene ring is unsubstituted or substituted by alkyl of 1 to 6 carbon atoms, alkoxy of 1 to 6 carbon atoms, CF 3 or halogen.
Claim 4
Dependent Claim
17 words
A compound according to claim 1 wherein R 2 is 4-amino and R3 is hydrogen or 5-halo.
Claim 5
Dependent Claim
11 words
A compound according to claim 3, wherein R 3 is 5-chloro.
Claim 6
Dependent Claim
11 words
A compound according to claim 3 wherein R 1 is methoxy.
Claim 7
Dependent Claim
25 words
A compound according to claim 1, wherein the moiety of the formula (IV): ##STR43## in the compound of formula (I) has the structure (V): ##STR44##
Claim 8
Dependent Claim
89 words
A compound according to claim 6, wherein the moiety of the formula (VI): ##STR45## in the compound of formula (I) has the structure (XI): ##STR46## wherein q is 0 to 3, p is 0 to 3, and R 7 is hydrogen, alkyl of 1 to 6 carbon atoms, phenyl or phenyl-alkyl of 1 to 6 carbon atoms in the alkyl moiety, said phenyl or said phenyl-alkyl being nuclear-unsubstituted or nuclear-substituted by alkyl of 1 to 6 carbon atoms, alkoxy of 1 to 6 carbon atoms, CF 3 or halogen.
Claim 9
Dependent Claim
18 words
A compound according to claim 7, wherein q is 0 or 1 and p is 0 or 1.
Claim 10
Dependent Claim
14 words
A compound according to claim 8, wherein q is 1 and p is 1.
Claim 11
Dependent Claim
22 words
A compound according to claim 9, wherein the moiety of formula (XI) is 4-substituted by the moiety of the formula (V) ##STR47##
Claim 12
Dependent Claim
11 words
A compound according to claim 8 wherein R 7 is hydrogen.
Claim 13
Dependent Claim
56 words
A compound according to claim 7, wherein the moiety of the formula (VI) is of the formula (XII), (XIII), or (XIV): ##STR48## wherein q' is 0 or 1, p' is 0 or 1 and R 8 is hydrogen, alkyl of 1 to 6 carbon atoms, alkoxy of 1 to 6 carbon atoms, CF 3 or halogen.
Claim 14
Dependent Claim
13 words
A compound according to claim 12, wherein p' and q' are both 1.
Claim 15
Dependent Claim
11 words
A compound according to claim 13, wherein R 8 is hydrogen.
Claim 16
Dependent Claim
74 words
A compound according to claim 7, wherein the moiety of the formula (VI) is of the formula (VII): ##STR49## wherein p' is 0 or 1, and R 7 is hydrogen, alkyl of 1 to 6 carbon atoms, phenyl or phenyl-alkyl of 1 to 6 carbon atoms, said phenyl or said phenyl-alkyl being nuclear-unsubstituted or nuclear-substituted by alkyl of 1 to 6 carbon atoms, alkoxy of 1 to 6 carbon atoms, CF 3 or halogen.
Claim 17
Dependent Claim
11 words
A compound according to claim 15, wherein R 7 is hydrogen.
Claim 18
Dependent Claim
10 words
A compound according to claim 16, wherein p' is 1.
Claim 19
Dependent Claim
50 words
A compound according to claim 7, wherein the moiety of the formula (VI) is of the formula (VIII), (IX), or (X): ##STR50## wherein p' is 0 or 1, R 8 is hydrogen, alkyl of 1 to 6 carbon atoms alkoxy of 1 to 6 carbon atoms CF 3 or halogen.
Claim 20
Dependent Claim
11 words
A compound according to claim 18, wherein R 8 is hydrogen.
Claim 21
Dependent Claim
10 words
A compound according to claim 18 wherein p' is 1.
Claim 22
Dependent Claim
27 words
A compound according to claim 1 wherein X is CH wherein m+n is 2 to 5, m is 1 to 5 and n is 0 to 4.
Claim 23
Dependent Claim
27 words
A compound according to claim 1 wherein X is CH wherein m+n is 2 to 4, m is 1 to 4 and n is 0 to 3.
Claim 24
Dependent Claim
9 words
The compound according to claim 1 which is 4-Acetylamino-0-chloro-2-methoxy-N-(2-quinolizidinyl)-benzamide.
Claim 25
Dependent Claim
9 words
The compound according to claim 1 which is 4-Amino-5-chloro-2-methoxy-N-(2-quinolizidinyl)-benzamide.
Claim 26
Dependent Claim
9 words
The compound according to claim 1 which is 4-Acetylamino-5-chloro-2-methoxy-N-(7-octahydro-indolizinyl)-benzamide.
Claim 27
Dependent Claim
9 words
The compound according to claim 1 which is 4-Amino-5-chloro-2-methoxy-N-(7-octahydro-indolizinyl)-benzamide.
Claim 28
Dependent Claim
9 words
The compound according to claim 1 which is 4-Acetylamino-5-chloro-2-methoxy-N-(3-quinolizidinyl)-benzamide.
Claim 29
Dependent Claim
9 words
The compound according to claim 1 which is 4-Amino-5-chloro-2-methoxy-N-(3-quinolizidinyl)-benzamide.
Claim 30
Dependent Claim
9 words
The compound according to claim 1 which is 4-Acetylamino-5-chloro-2-methoxy-N-(1-quinolizidinyl)-benzamide.
Claim 31
Dependent Claim
9 words
The compound according to claim 1 which is 4-Amino-5-chloro-2-methoxy-N-(1-quinolizidinyl)-benzamide.
Claim 32
Dependent Claim
9 words
The compound according to claim 1 which is 4-Acetylamino-5-chloro-N-[2-(2H-benzo[a]-quinolizine-1,3,4,6,7,11b-hexahydro)]-2-methoxy-benzamide.
Claim 33
Dependent Claim
9 words
The compound according to claim 1 which is 4-Amino-5-chloro-N-[2-(2H-benzo[a]-quinolizine-1,3,4,6,7,11b-hexahydro)]-2-methoxy-benzamide.
Claim 34
Dependent Claim
9 words
The compound according to claim 1 which is 4-Acetylamino-5-chloro-2-methoxy-N-(pyrido-[1,2a]-pyrazinyl)-benzamide.
Claim 35
Dependent Claim
9 words
The compound according to claim 1 which is 4-Amino-5-chloro-2-methoxy-N-(2-pyrido-[1,2-a]-pyrazinyl)-benzamide.
Claim 36
Dependent Claim
9 words
The compound according to claim 1 which is 4-Acetylamino-5-chloro-2-methoxy-N-(2-octahydroindolizinyl)-benzamide.
Claim 37
Dependent Claim
9 words
The compound according to claim 1 which is 4-Amino-5-chloro-2-methoxy-N-(2-octahydroinodolizinyl)-benzamide.
Claim 38
Dependent Claim
9 words
The compound according to claim 1 which is 4-Acetylamino-5-chloro-2-methoxy-N-(6-methyl-2-quinolizidinyl)-benzamide.
Claim 39
Dependent Claim
9 words
The compound according to claim 1 which is 4-Amino-5-chloro-2-methoxy-N-(6-methyl-2-quinolizidinyl)-benzamide.
Claim 40
Dependent Claim
12 words
The compound according to claim 1 which is a diastereomer of 4-Amino-5-chloro-2-methoxy-N-(6-methyl-2-quinolizidinyl)-benzamide.
Claim 41
Dependent Claim
17 words
The diastereomer of 4-Amino-5-chloro-2-methoxy-N-(6-methyl-2-quinolizidinyl)-benzamide of claim 39 having a melting point of 242° C. to 243° C.
Claim 42
Dependent Claim
14 words
The diastereomer of 4-Amino-5-chloro-2-methoxy-N-(6-methyl-2-quinolizidinyl)-benzamide of claim 39 having a melting point of 204° C.
Claim 43
Dependent Claim
12 words
The compound according to claim 24 which is a diastereomer of 4-Amino-5-chloro-2-methoxy-N-(2-quinolizidinyl)-benzamide.
Claim 44
Dependent Claim
41 words
The diastereomer of 4-Amino-5-chloro-2-methoxy-N-(2-quinolizidinyl)-benzamide according to claim 42 having a 1H n.m.r. spectrum in deuterocloroform, containing the following resonances in γ units: 1.93 (1H, s), 2.43 (1H, d, J=7Hz), 3.68 (1H, s), 6.16 (3H, s), 6.0 (1H, m), 7.0-9.0 (15H, m).
Claim 45
Dependent Claim
296 words
A pharmaceutical composition useful for the treatment of disorders of the gastro-intestional function and emesis which comprises a therapeutically effective amount of a compound of the formula (I) ##STR51## or a pharmaceutically acceptable salt thereof wherein R 1 is alkoxy of 1 to 6 carbon atoms; R 2 and R 3 are the same or different and are hydrogen, halogen, CF 3 , hydroxy, alkoxy of 1 to 6 carbon atoms, alkanoyl of 2 to 7 carbon atoms, amino, amino substituted by one or two alkyl moieties of 1 to 6 carbon atoms, alkanoylamino of 2 to 7 carbon atoms, aminocarbonyl or aminosulphone unsubstituted or substituted by one or two alkyl moieties of 1 to 6 carbon atoms, alkylsulphone of 1 to 6 carbon atoms or nitro; X is either a nitrogen atom, in which case m+n is 3 to 5, m is 2 to 4 and n is 1 to 3; or X is CH in which case m+n is 2 to 5, m is 1 to 5, and n is 0 to 4; p is 0 to 3; R 4 is hydrogen, alkyl of 1 to 6 carbon atoms, phenyl or phenyl-alkyl of 1 to 6 carbon atoms in the alkyl moiety, said phenyl or phenyl-alkyl being nuclear-unsubstituted or nuclear substituted by alkyl of 1 to 6 carbon atoms, alkoxy of 1 to 6 carbon atoms, CF 3 or halogen, and R 5 is hydrogen; or R 4 and R 5 are attached to two adjacent carbon atoms and form together with these two adjacent carbon atoms, a fused benzene ring, which benzene ring is unsubstituted or substituted by alkyl of 1 to 6 carbon atoms, alkoxy of 1 to 6 carbon atoms, CF 3 or halogen, in combination with a pharmaceutically acceptable carrier.
Claim 46
Dependent Claim
296 words
A pharmaceutical composition useful for the treatment of disorders of the gastro-intestional function and emesis which comprises a therapeutically effective amount of a compound of the formula (I) ##STR51## or a pharmaceutically acceptable salt thereof wherein R 1 is alkoxy of 1 to 6 carbon atoms; R 2 and R 3 are the same or different and are hydrogen, halogen, CF 3 , hydroxy, alkoxy of 1 to 6 carbon atoms, alkanoyl of 2 to 7 carbon atoms, amino, amino substituted by one or two alkyl moieties of 1 to 6 carbon atoms, alkanoylamino of 2 to 7 carbon atoms, aminocarbonyl or aminosulphone unsubstituted or substituted by one or two alkyl moieties of 1 to 6 carbon atoms, alkylsulphone of 1 to 6 carbon atoms or nitro; X is either a nitrogen atom, in which case m+n is 3 to 5, m is 2 to 4 and n is 1 to 3; or X is CH in which case m+n is 2 to 5, m is 1 to 5, and n is 0 to 4; p is 0 to 3; R 4 is hydrogen, alkyl of 1 to 6 carbon atoms, phenyl or phenyl-alkyl of 1 to 6 carbon atoms in the alkyl moiety, said phenyl or phenyl-alkyl being nuclear-unsubstituted or nuclear substituted by alkyl of 1 to 6 carbon atoms, alkoxy of 1 to 6 carbon atoms, CF 3 or halogen, and R 5 is hydrogen; or R 4 and R 5 are attached to two adjacent carbon atoms and form together with these two adjacent carbon atoms, a fused benzene ring, which benzene ring is unsubstituted or substituted by alkyl of 1 to 6 carbon atoms, alkoxy of 1 to 6 carbon atoms, CF 3 or halogen, in combination with a pharmaceutically acceptable carrier.
Claim 47
Dependent Claim
227 words
A composition according to claim 44 wherein R 1 is alkoxy of 1 to 6 carbon atoms; R 2 and R 3 are the same or different and are hydrogen, halogen, CF 3 , hydroxy, alkoxy of 1 to 6 carbon atoms, alkanoyl of 2 to 7 carbon atoms, amino, amino substituted by one or two alkyl moieties of 1 to 6 carbon atoms, alkanoylamino or 2 to 7 carbon atoms, aminosulphone, aminosulphone substituted by one or two alkyl moieties of 1 to 6 carbon atoms, alkylsulphone of 1 to 6 carbon atoms or nitro, m+n is 2 or 3, and m is 1, 2 or 3 and n is 0, 1 or 2; p is 0 or 1; R 4 is hydrogen, alkyl of 1 to 6 carbon atoms, phenyl or phenyl-alkyl of 1 to 6 carbon atoms in the alkyl moiety, said phenyl or said phenyl-alkyl being nuclear-unsubstituted or nuclear-substituted by alkyl of 1 to 6 carbon atoms, alkoxy of 1 to 6 carbon atoms, CF 3 or halogen, and R 5 is hydrogen; or R 4 and R 5 are attached to two adjacent carbon atoms and form together with these two carbon atoms a fused benzene ring, which benzene ring is unsubstituted or substituted by alkyl of 1 to 6 carbon atoms, alkoxy of 1 to 6 carbon atoms, CF 3 or halogen.
Claim 48
Dependent Claim
18 words
A composition according to claim 44 wherein R 2 is 4-amino and R 3 is hydrogen or 5-halo.
Claim 49
Dependent Claim
11 words
A composition according to claim 46 wherein R 3 is 5-chloro.
Claim 50
Dependent Claim
11 words
A composition according to claim 46 wherein R 1 is methoxy.
Claim 51
Dependent Claim
25 words
A composition according to claim 44 wherein the moiety of the formula (IV): ##STR52## in the compound of formula (I) has the structure (V): ##STR53##
Claim 52
Dependent Claim
88 words
A composition according to claim 49 wherein the moiety of formula (VI): ##STR54## in the compound of formula (I) has the structure (XI): ##STR55## wherein q is 0 to 3, p is 0 to 3, and R 7 is hydrogen, alkyl of 1 to 6 carbon atoms, phenyl or phenyl-alkyl of 1 to 6 carbon atoms in the alkyl moiety, said phenyl or said phenyl-alkyl being nuclear-unsubstituted or nuclear-substituted by alkyl of 1 to 6 carbon atoms, alkoxy of 1 to 6 carbon atoms, CF 3 or halogen.
Claim 53
Dependent Claim
18 words
A composition according to claim 50, wherein q is 0 to 1 and p is 0 or 1.
Claim 54
Dependent Claim
14 words
A composition according to claim 51 wherein q is 1 and p is 1.
Claim 55
Dependent Claim
22 words
A composition according to claim 52 wherein the moiety of formula (XI) is 4-substituted by the moiety of the formula (V) ##STR56##
Claim 56
Dependent Claim
11 words
A composition according to claim 51 wherein R 7 is hydrogen.
Claim 57
Dependent Claim
56 words
A composition according to claim 50 wherein the moiety of the formula (VI) is of the formula (XII), (XIII), or (XIV): ##STR57## wherein q' is 0 or 1, p' is 0 or 1 and R 8 is hydrogen, alkyl of 1 to 6 carbon atoms, alkoxy of 1 to 6 carbon atoms, CF 3 or halogen.
Claim 58
Dependent Claim
13 words
A composition according to claim 55 wherein p' and q' are both 1.
Claim 59
Dependent Claim
11 words
A composition according to claim 56 wherein R 8 is hydrogen.
Claim 60
Dependent Claim
27 words
A composition according to claim 44 wherein X is CH wherein m+n is 2 to 5, m is 1 to 5 and n is 0 to 4.
Claim 61
Dependent Claim
26 words
A composition according to claim 44 wherein X is CH wherein m+n is 2 to 4, m is 1 to4 and n is 0 to 3.
Claim 62
Dependent Claim
11 words
A composition according to claim 44 wherein the compound is 4-Acetylamino-5-chloro-2-methoxy-N-(2-quinolizidinyl)-benzamide.
Claim 63
Dependent Claim
11 words
A composition according to claim 44 wherein the compound is 4-Amino-5-chloro-2-methoxy-N-(2-quinolizidinyl)-benzamide.
Claim 64
Dependent Claim
11 words
A composition according to claim 44 wherein the compound is 4-Acetylamino-5-chloro-2-methoxy-N-(7-octahydro-indolizinyl)-benzamide.
Claim 65
Dependent Claim
11 words
A composition according to claim 44 wherein the compound is 4-Amino-5-chloro-2-methoxy-N-(7-octahydro-indolizinyl)-benzamide.
Claim 66
Dependent Claim
11 words
A composition according to claim 44 wherein the compound is 4-Acetylamino-5-chloro-2-methoxy-N-(3-quinolizidinyl)-benzamide.
Claim 67
Dependent Claim
11 words
A composition according to claim 44 wherein the compound is 4-Amino-5-chloro-2-methoxy-N-(3-quinolizidinyl)-benzamide.
Claim 68
Dependent Claim
11 words
A composition according to claim 44 wherein the compound is 4-Acetylamino-5-chloro-2-methoxy-N-(1-quinolizidinyl)-benzamide.
Claim 69
Dependent Claim
11 words
A composition according to claim 28 wherein the compound is 4-Amino-5-chloro-2-methoxy-N-(1-quinolizidinyl)-benzamide.
Claim 70
Dependent Claim
11 words
A composition according to claim 44 wherein the compound is 4-Acetylamino-5-chloro-N-[2-(2H-benzo[a]-quinolizine-1,3,4,6,7,11b-hexahydro)]2-methoxy-benzamide.
Claim 71
Dependent Claim
11 words
A composition according to claim 44 wherein the compound is 4-Amino-5-chloro-N-[2-(2H-benzo[a]-quinolizine-1,3,4,6,7,11b-hexahydro)]-2-methoxy-benzamide.
Claim 72
Dependent Claim
11 words
A composition according to claim 44 wherein the compound is 4-Acetylamino-5-chloro-2-methoxy-N-(pyrido-[1,2-a]-pyrazinyl)-benzamide.
Claim 73
Dependent Claim
11 words
A composition according to claim 44 wherein the compound is 4-Amino-5-chloro-2-methoxy-N-(2-pyrido-[1,2-a]-pyrazinyl)-benzamide.
Claim 74
Dependent Claim
11 words
A composition according to claim 44 wherein the compound is 4-Acetylamino-5-chloro-2-methoxy-N-(2-octahydroindolizinyl)-benzamide.
Claim 75
Dependent Claim
11 words
A composition according to claim 44 wherein the compound is 4-Amino-5-chloro-2-methoxy-N-(2-octahydroinodolizinyl)-benzamide.
Claim 76
Dependent Claim
10 words
A composition according to claim 28 wherein the compound 4-Acetylamino-5-chloro-2-methoxy-N-(6-methyl-2-quinolizinyl)-benzamide.
Claim 77
Dependent Claim
11 words
A composition according to claim 44 wherein the compound is 4-Amino-5-chloro-2-methoxy-N-(6-methyl-2-quinolizidinyl)-benzamide.
Claim 78
Dependent Claim
14 words
The compound according to claim 44 wherein the compound is a diastereomer of 4-Amino-5-chloro-2-methoxy-N-(6-methyl-2-quinolizidinyl)-benzamide.
Claim 79
Dependent Claim
24 words
A composition according to claim 76 wherein the compound is the diastereomer of 4-Amino-5-chloro-2-methoxy-N-(6-methyl-2-quinolizidinyl)-benzamide, having a melting point of 242° C. to 243° C.
Claim 80
Dependent Claim
21 words
A composition according to claim 76 wherein the compound is the diastereomer of 4-Amino-5-chloro-2-methoxy-N-(6-methyl-2-quinolizidinyl)-benzamide, having a melting point of 204° C.
Claim 81
Dependent Claim
14 words
A composition according to claim 61 wherein the compound is a diastereomer of 4-Amino-5-chloro-2-methoxy-N-(2-quinolizidinyl)-benzamide.
Claim 82
Dependent Claim
52 words
A composition according to claim 79 wherein the compound is the diastereomer of 4-Amino-5-chloro-2-methoxy-N-(2-quinolizidinyl)-benzamide according to claim 42 having a 1H n.m.r. spectrum in deuterocloroform, containing the following resonances in γ units: 1.93 (1H, s), 2.43 (1H, d, J=7 Hz), 3.68 (1H, s), 6.16 (3H, s), 6.0 (1H, m), 7.0-9.0 (15H, m).
Claim 83
Independent Claim
305 words
A method of treating disorders of the gastro-intestinal function and emesis in humans and animals which comprises administering to a human or animal in need thereof a therapeutically effective amount of a compound of the formula (I) ##STR58## or a pharmaceutically acceptable salt thereof wherein R 1 is alkoxy of 1 to 6 carbon atoms; R 2 and R 3 are the same or different and are hydrogen, halogen, CF 3 , hydroxy, alkoxy of 1 to 6 carbon atoms, alkanoyl of 2 to 7 carbon atoms, amino, amino substituted by one or two alkyl moieties of 1 to 6 carbon atoms, alkanoylamino of 2 to 7 carbon atoms, aminocarbonyl or aminosulphone unsubstituted or substituted by one or two alkyl moieties of 1 to 6 carbon atoms, alkylsulphone of 1 to 6 carbon atoms or nitro; X is either a nitrogen atom, in which case m+n is 3 to 5, m is 2 to 4 and n is 1 to 3; or X is CH in which case m+n is 2 to 5, m is 1 to 5, and n is 0 to 4; p is 0 to 3; R 4 is hydrogen, alkyl of 1 to 6 carbon atoms, phenyl or phenyl-alkyl of 1 to 6 carbon atoms in the alkyl moiety, said phenyl or phenyl-alkyl being nuclear-unsubstituted or nuclear substituted by alkyl of 1 to 6 carbon atoms, alkoxy of 1 to 6 carbon atoms, CF 3 or halogen, and R 5 is hydrogen; or R 4 and R 5 are attached to two adjacent carbon atoms and form together with these two adjacent carbon atoms, a fused benzene ring, which benzene ring is unsubstituted or substituted by alkyl of 1 to 6 carbon atoms, alkoxy of 1 to 6 carbon atoms, CF 3 or halogen, in combination with a pharmaceutically acceptable carrier.
Claim 84
Independent Claim
305 words
A method of treating disorders of the gastro-intestinal function and emesis in humans and animals which comprises administering to a human or animal in need thereof a therapeutically effective amount of a compound of the formula (I) ##STR58## or a pharmaceutically acceptable salt thereof wherein R 1 is alkoxy of 1 to 6 carbon atoms; R 2 and R 3 are the same or different and are hydrogen, halogen, CF 3 , hydroxy, alkoxy of 1 to 6 carbon atoms, alkanoyl of 2 to 7 carbon atoms, amino, amino substituted by one or two alkyl moieties of 1 to 6 carbon atoms, alkanoylamino of 2 to 7 carbon atoms, aminocarbonyl or aminosulphone unsubstituted or substituted by one or two alkyl moieties of 1 to 6 carbon atoms, alkylsulphone of 1 to 6 carbon atoms or nitro; X is either a nitrogen atom, in which case m+n is 3 to 5, m is 2 to 4 and n is 1 to 3; or X is CH in which case m+n is 2 to 5, m is 1 to 5, and n is 0 to 4; p is 0 to 3; R 4 is hydrogen, alkyl of 1 to 6 carbon atoms, phenyl or phenyl-alkyl of 1 to 6 carbon atoms in the alkyl moiety, said phenyl or phenyl-alkyl being nuclear-unsubstituted or nuclear substituted by alkyl of 1 to 6 carbon atoms, alkoxy of 1 to 6 carbon atoms, CF 3 or halogen, and R 5 is hydrogen; or R 4 and R 5 are attached to two adjacent carbon atoms and form together with these two adjacent carbon atoms, a fused benzene ring, which benzene ring is unsubstituted or substituted by alkyl of 1 to 6 carbon atoms, alkoxy of 1 to 6 carbon atoms, CF 3 or halogen, in combination with a pharmaceutically acceptable carrier.
Claim 85
Dependent Claim
227 words
A method according to claim 81 wherein R 1 is alkoxy of 1 to 6 carbon atoms; R 2 and R 3 are the same or different and are hydrogen, halogen, CF 3 , hydroxy, alkoxy of 1 to 6 carbon atoms, alkanoyl of 2 to 7 carbon atoms, amino, amino substituted by one or two alkyl moieties of 1 to 6 carbon atoms, alkanoylamino or 2 to 7 carbon atoms, aminosulphone, aminosulphone substituted by one or two alkyl moieties of 1 to 6 carbon atoms, alkysulphone of 1 to 6 carbon atoms or nitro, m+n is 2 or 3, and m is 1, 2 or 3 and n is 0, 1 or 2; p is 0 or 1; R 4 is hydrogen, alkyl of 1 to 6 carbon atoms, phenyl or phenyl-alkyl of 1 to 6 carbon atoms in the alkyl moiety, said phenyl or said phenyl-alkyl being nuclear-unsubstituted or nuclear-substituted by alkyl of 1 to 6 carbon atoms, alkoxy of 1 to 6 carbon atoms, CF 3 or halogen, and R 5 is hydrogen; or R 4 and R 5 are attached to two adjacent carbon atoms and form together with these two carbon atoms a fused benzene ring, which benzene ring is unsubstituted or substituted by alkyl of 1 to 6 carbon atoms, alkoxy of 1 to 6 carbon atoms, CF 3 or halogen.
Claim 86
Dependent Claim
18 words
A method according to claim 81 wherein R 2 is 4-amino and R 3 is hydrogen or 5-halo.
Claim 87
Dependent Claim
11 words
A method according to claim 83 wherein R 3 is 5-chloro.
Claim 88
Dependent Claim
11 words
A method according to claim 83 wherein R 1 is methoxy.
Claim 89
Dependent Claim
25 words
A method according to claim 81 wherein the moiety of the formula (IV): ##STR59## in the compound of formula (I) has the structure (V): ##STR60##
Claim 90
Dependent Claim
88 words
A method according to claim 85 wherein the moiety of formula (VI): ##STR61## in the compound of formula (I) has the structure (XI): ##STR62## wherein q is 0 to 3, p is 0 to 3, and R 7 is hydrogen alkyl of 1 to 6 carbon atoms, phenyl or phenyl-alkyl of 1 to 6 carbon atoms in the phenyl moiety, said phenyl or said phenyl-alkyl being nuclear-unsubstituted or nuclear-substituted by alkyl of 1 to 6 carbon atoms, alkoxy of 1 to 6 carbon atoms, CF 3 or halogen.
Claim 91
Dependent Claim
18 words
A method according to claim 87 wherein q is 0 to 1 and p is 0 or 1.
Claim 92
Dependent Claim
14 words
A method according to claim 88 wherein q is 1 and p is 1.
Claim 93
Dependent Claim
22 words
A method according to claim 89 wherein the moiety of formula (XI) is 4-substituted by the moiety of the formula (V) ##STR63##
Claim 94
Dependent Claim
56 words
A method according to claim 87 wherein the moiety of the formula (VI) is of the formula (XII), (XIII), or (XIV): ##STR64## wherein q' is 0 or 1, p' is 0 or 1 and R 8 is hydrogen, alkyl of 1 to 6 carbon atoms, alkoxy of 1 to 6 carbon atoms, CF 3 or halogen.
Claim 95
Dependent Claim
13 words
A method according to claim 90 wherein p' and q' are both 1.
Claim 96
Dependent Claim
11 words
A method according to claim 90 wherein R 8 is hydrogen.
Claim 97
Dependent Claim
27 words
A method according to claim 81 wherein X is CH wherein m+n is 2 to 5, m is 1 to 5 and n is 0 to 4.
Claim 98
Dependent Claim
27 words
A method according to claim 81 wherein X is CH wherein m+n is 2 to 4, m is 1 to 4 and n is 0 to 3.
Claim 99
Dependent Claim
11 words
A method according to claim 81 wherein the compound is 4-Acetylamino-5-chloro-2-methoxy-N-(2-quinolizidinyl)-benzamide.
Claim 100
Dependent Claim
11 words
A method according to claim 81 wherein the compound is 4-Amino-5-chloro-2-methoxy-N-(2-quinolizidinyl)-benzamide.
Claim 101
Dependent Claim
11 words
A method according to claim 81 wherein the compound is 4-Acetylamino-5-chloro-2-methoxy-N-(7-octahydro-indolizinyl)-benzamide.
Claim 102
Dependent Claim
11 words
A method according to claim 81 wherein the compound is 4-Amino-5-chloro-2-methoxy-N-(7-octahydro-indolizinyl)-benzamide.
Claim 103
Dependent Claim
11 words
A method according to claim 81 wherein the compound is 4-Acetylamino-5-chloro-2-methoxy-N-(3-quinolizidinyl)-benzamide.
Claim 104
Dependent Claim
11 words
A method according to claim 81 wherein the compound is 4-Amino-5-chloro-2-methoxy-N-(3-quinolizidinyl)-benzamide.
Claim 105
Dependent Claim
11 words
A method according to claim 81 wherein the compound is 4-Acetylamino-5-chloro-2-methoxy-N-(1-quinolizidinyl)-benzamide.
Claim 106
Dependent Claim
11 words
A method according to claim 81 wherein the compound is 4-Amino-5-chloro-2-methoxy-N-(1-quinolizidinyl)-benzamide.
Claim 107
Dependent Claim
11 words
A method according to claim 81 wherein the compound is 4-Acetylamino-5-chloro-N-[2-(2H-benzo[a]-quinolizine-1,3,4,6,7,11b-hexahydro)]-2-methoxy-benzamide.
Claim 108
Dependent Claim
11 words
A method according to claim 81 wherein the compound is 4-Amino-5-chloro-N-[2-(2H-benzo[a]-quinolizine-1,3,4,6,7,11b-hexahydro)]-2-methoxy-benzamide.
Claim 109
Dependent Claim
11 words
A method according to claim 81 wherein the compound is 4-Acetylamino-5-chloro-2-methoxy-N-(pyrido-[1,2-a]-pyrazinyl)-benzamide.
Claim 110
Dependent Claim
11 words
A method according to claim 81 wherein the compound is 4-Amino-5-chloro-2-methoxy-N-(2-pyrido-[1,2-a]-pyrazinyl)-benzamide.
Claim 111
Dependent Claim
11 words
A method according to claim 81 wherein the compound is 4-Acetylamino-5-chloro-2-methoxy-N-(2-octahydroindolizinyl)-benzamide.
Claim 112
Dependent Claim
11 words
A method according to claim 81 wherein the compound is 4-Amino-5-chloro-2-methoxy-N-(2-octahydroinodolizinyl)-benzamide.
Claim 113
Dependent Claim
11 words
A method according to claim 81 wherein the compound is 4-Acetylamino-5-chloro-2-methoxy-N-(6-methyl-2-quinolizinyl)-benzamide.
Claim 114
Dependent Claim
11 words
A method according to claim 81 wherein the compound is 4-Amino-5-chloro-2-methoxy-N-(6-methyl-2-quinolizidinyl)-benzamide.
Claim 115
Dependent Claim
14 words
A method according to claim 81 wherein the compound is a diastereomer of 4-Amino-5-chloro-2-methoxy-N-(6-methyl-2-quinolizidinyl)-benzamide.
Claim 116
Dependent Claim
24 words
A method according to claim 112 wherein the compound is the diastereomer of 4-Amino-5-chloro-2-methoxy-N-(6-methyl-2-quinolizidinyl)-benzamide, having a melting point of 242° C. to 243° C.
Claim 117
Dependent Claim
21 words
A method according to claim 112 wherein the compound is the diastereomer of 4-Amino-5-chloro-2-methoxy-N-(6-methyl-2-quinolizidinyl)-benzamide, having a melting point of 204° C.
Claim 118
Dependent Claim
14 words
A method according to claim 97 wherein the compound is a diastereomer of 4-Amino-5-chloro-2-methoxy-N-(2-quinolizidinyl)-benzamide.
Claim 119
Dependent Claim
48 words
A method according to claim 115 wherein the compound is the diastereomer of 4-Amino-5-chloro-2-methoxy-N-(2-quinolizidinyl)-benzamide having a 1H n.m.r. spectrum in deuterocloroform, containing the following resonances in γ units: 1.93 (1H, s), 2.43 (1H, d, J=7 Hz), 3.68 (1H, s), 6.16 (3H, s), 6.0 (1H, m), 7.0-9.0 (15H, m).
References Cited (Backward Citations)
USPTO Annuity & Maintenance Windows
| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
|---|---|---|---|---|---|
| 3.5 Years (Year 4) | 1983-07-22 | 1984-01-21 | 1984-07-22 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 1987-07-22 | 1988-01-21 | 1988-07-22 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 1991-07-22 | 1992-01-21 | 1992-07-22 | $7700.00 | Window Closed / Lapsed |