US2007106076A1PendingUtilityA1
Anti-obesity 1,2,3,4,10,10a-hexahydropyrazino [1,2-a] indoles
Individually held — no corporate assignee on recordPriority: Jul 31, 2000Filed: Jan 3, 2007Published: May 10, 2007
Est. expiryJul 31, 2020(expired)· nominal 20-yr term from priority
Inventors:Jonathan BentleyPaul HebeisenPatrizio MatteiMarc MullerHans RichterStephan RoeverSven Taylor
A61P 7/02A61P 9/00A61P 3/04A61P 25/22A61P 25/20A61P 25/24A61P 25/18A61P 25/30A61P 25/06A61P 25/32A61P 25/00A61P 3/10A61P 25/08A61P 25/28A61P 1/00A61P 15/00A61P 13/00A61P 11/00C07D 487/04
60
PatentIndex Score
0
Cited by
0
References
0
Claims
Abstract
The present invention is directed to 1,2,3,4,10,10a,-hexahydropyrazino[1,2-a] indole derivatives as well as pharmaceutically acceptable salts, solvates and esters thereof, wherein R 1 to R 8 have the significance given in claim 1 be used in the form of pharmaceutical preparations for the treatment or prevention of disorders of the central nervous system, damage to the central nervous system, cardiovascular disorders, gastrointestinal disorders, diabetes insipidus, obesity and sleep apnea.
Claims
exact text as granted — not AI-modified1 . A compound of formula (I):
wherein
R 1 , R 2 , R 3 and R 4 are independently hydrogen, halogen, hydroxy, alkyl, cycloalkyl, aralkyl, aryl, alkoxy, alkoxy alkyl, hydroxy alkyl, alkoxy alkoxy alkyl, hydroxyalkoxy alkyl, halo alkyl, halo alkoxy, aryloxy, alkylcarbonyl, arylcarbonyl, alkylthio, arylthio, alkylsulfoxyl, arylsulfoxyl, alkylsulfonyl, arylsulfonyl, amino, nitro, cyano, alkoxycarbonyl, aryloxycarbonyl, alkylaminocarbonyl, dialkylaminocarbonyl, alkylcarbonylamino, carboxy, heterocyclyl or R 3 and R 4 form together with the carbon atoms to which they are attached form a 5- to 7-membered carbocyclic ring which ring is unsubstituted or alkyl substituted;
R 5 is hydrogen, alkyl or cycloalkyl;
R 6 is hydrogen, alkyl, hydroxy alkyl, carbamoyl alkyl, alkoxycarbonyl alkyl, aryloxycarbonyl alkyl or —(CH 2 ) n -A;
R 7 is hydrogen, alkyl, cycloalkyl, hydroxyalkyl or alkoxyalkyl, whereby R 7 is not hydrogen when R 6 is hydrogen, alkyl, cycloalkyl or 1H-pyrrolo(2,3-b)pyridin-3-ylmethyl;
R 8 is hydrogen, alkyl or cycloalkyl;
A is a heterocyclyl or cycloalkyl ring which ring can be unsubstituted or substituted on a ring carbon atom with a hydroxy, carboxy, oxo, alkanoyloxy alkyl, aryloxycarbonyl or alkylcarbamoyl substituent;
n is 0, 1, 2 or 3;
or pharmaceutically acceptable salts, solvates or esters thereof.
2 . The compound of claim 1 wherein all of said alkoxy, alkanoyl, and alkyl are lower alkoxy, lower alkanoyl and lower alkyl groups.
3 . A compound of claim 1 , wherein R 5 and R 6 are as above,
R 1 , R 2 , R 3 and R 4 are independently selected from hydrogen, halogen, hydroxy, alkyl, cycloalkyl, aralkyl, aryl, alkoxy, alkoxy alkyl, halo alkyl, aryloxy, alkylcarbonyl, arylcarbonyl, alkylthio, arylthio, alkylsulfoxyl, arylsulfoxyl, alkylsulfonyl, arylsulfonyl, amino, nitro, cyano, alkanoyloxy alkyl, aryloxycarbonyl, alkylaminocarbonyl, dialkylaminocarbonyl, alkylcarbonylamino, carboxy or heterocyclyl; R 7 is hydrogen, alkyl or cycloalkyl, whereby R 7 is not hydrogen when R 6 is hydrogen, alkyl, cycloalkyl or 1H-pyrrolo(2,3-b)pyridin-3-ylmethyl; and R 8 is hydrogen.
4 . The compound of claim 3 , wherein R 1 , R 2 , R 3 and R 4 are independently selected from hydrogen, halogen, alkyl, alkoxy, haloalkyl, halo alkoxy and cyano.
5 . The compound of claim 4 , wherein one or two of R 1 , R 2 , R 3 and R 4 are independently selected from chloro, bromo, methyl, trifluoromethyl and cyano and the others are hydrogen.
6 . The compound of claim 5 , wherein R 5 is hydrogen.
7 . The compound of claim 6 , wherein R 6 is hydrogen, hydroxyalkyl, carbamoylalkyl, alkyloxycarbonylalkyl or —(CH 2 ) n -A.
8 . The compound of claim 7 , wherein R 6 is hydrogen.
9 . The compound of claim 8 , wherein A is oxazolidinone, cyclobutanonyl, [1,2,4]triazol-3-yl, [1,2,4]oxadiazol-3-yl, [1,2,4]triazol-3-one-5-yl, tetrazolyl, [1,3,4]oxadiazol-2-yl, [1,3,4]thiadiazol-2-yl, 1H-imidazol-2-yl or 1H-imidazol-4-yl.
10 . The compound of claim 9 , wherein A is 2-oxazolidin-2-one or cyclobutanon-2-yl.
11 . The compound of claim 10 , wherein n is 0 or 1.
12 . The compound of claim 11 , wherein R 7 is hydrogen or alkyl.
13 . The compound to claim 12 , wherein R 7 is methyl or ethyl.
14 . The compound to claim 13 , wherein R 8 is hydrogen.
15 . The compound of claim 1 wherein said compound has the formula:
wherein
R 12 , R 13 and R 14 are independently hydrogen, halogen, trifluoromethyl, lower alkyl, lower alkoxy lower alkyl, lower alkoxy-lower alkoxy lower alkyl, halo lower alkoxy, lower alkyl-aminocarbonyl, di-lower alkyl aminocarbonyl or cyano and R 17 is lower alkyl or hydroxy-lower alkyl.
16 . The compound of claim 15 wherein R 12 and R 13 are halo and R 14 is hydrogen and R 17 is lower alkyl.
17 . The compound of claim 16 wherein said compound is (4R,10aR)-7-chloro-8-fluoro-4-methyl-1,2,3,4,10,10a-hexahydro-pyrazino[1,2-a]indole hydrochloride.
18 . The compound of claim 16 wherein said compound is (4R,10aR)-9-chloro-6-fluoro-4-methyl-1,2,3,4,10,10a-hexahydro-pyrazino[1,2-a]indole hydrochloride.
19 . The compound of claim 16 wherein said compound is (4R,10aR)-6,7-difluoro-4-methyl-1,2,3,4,10,10a-hexahydro-pyrazino[1,2-a]indole hydrochloride.
20 . The compound of claim 16 wherein said compound is (4R,10aS)-6,7-difluoro-4-methyl-1,2,3,4,10,10a-hexahydro-pyrazino[1,2-a]indole hydrochloride.
21 . The compound of claim 16 wherein said compound is (4R,10aR)-7-chloro-6-fluoro-4-methyl-1,2,3,4,10,10a-hexahydro-pyrazino[1,2-a]indole hydrochloride.
22 . The compound of claim 16 wherein said compound is (4RS,10aSR)-7,8-dibromo-4-ethyl-1,2,3,4,10,10a-hexahydro-pyrazino[1,2-a]indole.
23 . The compound of claim 16 wherein said compound is (4R,10aR)-7-bromo-9-fluoro-4-methyl-1,2,3,4,10,10a-hexahydro-pyrazino[1,2-a]indole hydrochloride.
24 . The compound of claim 16 wherein said compound is (4R,10aR)-7,9-dichloro-4-methyl-1,2,3,4,10,10a-hexahydro-pyrazino[1,2-a]indole hydrochloride.
25 . The compound of claim 16 wherein said compound is (4R,10aS)-7,9-dichloro-4-methyl-1,2,3,4,10,10a-hexahydro-pyrazino[1,2-a]indole hydrochloride.
26 . The compound of claim 16 wherein said compound is (4R,10aR)-6,7-dichloro-4-methyl-1,2,3,4,10,10a-hexahydro-pyrazino[1,2-a]indole.
27 . The compound of claim 16 wherein said compound is (4R,10aR)-6,9-difluoro-4-methyl-1,2,3,4,10,10a-hexahydro-pyrazino[1,2-a]indole; hydrochloride.
28 . The compound of claim 16 wherein said compound is (4R,10aR)-8-bromo-7-fluoro-4-methyl-1,2,3,4,10,10a-hexahydro-pyrazino[1,2-a]indole.
29 . The compound of claim 16 wherein said compound is (4R,10aS)-8-bromo-7-fluoro-4-methyl-1,2,3,4,10,10a-hexahydro-pyrazino[1,2-a]indole.
30 . The compound of claim 15 wherein R 12 is halogen and R 13 and R 14 are hydrogen.
31 . The compound of claim 30 wherein R 17 is methyl.
32 . The compound of claim 31 wherein said compound is (4R,10aR)-7-chloro-4-methyl-1,2,3,4,10,10a-hexahydro-pyrazino[1,2-a]indole.
33 . The compound of claim 31 wherein said compound is(4R,10aS)-7-chloro-4-methyl-1,2,3,4,10,10a-hexahydro-pyrazino[1,2-a]indole.
34 . The compound of claim 31 wherein said compound is (4S,10aS)-7-chloro-4-methyl-1,2,3,4,10,10a-hexahydro-pyrazino[1,2-a]indole.
35 . The compound of claim 31 wherein said compound is (4S,10aR)-7-chloro-4-methyl-1,2,3,4,10,10a-hexahydro-pyrazino[1,2-a]indole.
36 . The compound of claim 31 wherein said compound is (4R,10aR)-7-bromo-4-methyl-1,2,3,4,10,10a-hexahydro-pyrazino[1,2-a]indole hydrochloride.
37 . The compound of claim 31 wherein said compound is (4R,10aR)-9-chloro-4-methyl-1,2,3,4,10,10a-hexahydro-pyrazino[1,2-a]indole hydrochloride.
38 . The compound of claim 31 wherein said compound is (4R,10aR)-8-fluoro-4-methyl-1,2,3,4,10,10a-hexahydro-pyrazino[1,2-a]indole hydrochloride.
39 . The compound of claim 31 wherein said compound is (4R,10aR)-6-fluoro-4-methyl-1,2,3,4,10,10a-hexahydro-pyrazino[1,2-a]indole.
40 . The compound of claim 31 wherein said compound is (4R,10aS)-6-bromo-4-methyl-1,2,3,4,10,10a-hexahydro-pyrazino[1,2-a]indole hydrochloride.
41 . The compound of claim 30 wherein R 17 is ethyl.
42 . The compound of claim 41 wherein said compound is (4RS,10aRS)-7-bromo-4-ethyl-1,2,3,4,10,10a-hexahydro-pyrazino[1,2-a]indole.
43 . The compound of claim 41 wherein said compound is (4RS,10aSR)-7-bromo-4-ethyl-1,2,3,4,10,10a-hexahydro-pyrazino[1,2-a]indole.
44 . The compound of claim 41 wherein said compound is (4R,10aR)-7-bromo-4-ethyl-1,2,3,4,10,10a-hexahydro-pyrazino[1,2-a]indole.
45 . The compound of claim 41 wherein said compound is (4S,10aS)-7-bromo-4-ethyl-1,2,3,4,10,10a-hexahydro-pyrazino[1,2-a]indole.
46 . The compound of claim 41 wherein said compound is 7-chloro-4-ethyl-1,2,3,4,10,10a-hexahydro-pyrazino[1,2-a]indole.
47 . The compound of claim 46 wherein said compound is (4R,10aR)-7-chloro-4-ethyl-1,2,3,4,10,10a-hexahydro-pyrazino[1,2-a]indole.
48 . The compound of claim 46 wherein said compound is (4R,10aS)-7-chloro-4-ethyl-1,2,3,4,10,10a-hexahydro-pyrazino[1,2-a]indole.
49 . The compound of claim 46 wherein said compound is (4S,10aS)-7-chloro-4-ethyl-1,2,3,4,10,10a-hexahydro-pyrazino[1,2-a]indole.
50 . The compound of claim 46 wherein said compound is (4S,10aR)-7-chloro-4-ethyl-1,2,3,4,10,10a-hexahydro-pyrazino[1,2-a]indole.
51 . The compound of claim 15 wherein R 12 , R 13 and R 14 are halo and R 17 is lower alkyl.
52 . The compound of claim 51 wherein said compound is (4RS,10aRS)-6,7,8-tribromo-4-ethyl-1,2,3,4,10,10a-hexahydro-pyrazino[1,2-a]indole.
53 . The compound of claim 15 wherein R 12 is hydrogen and R 13 and R 14 are independently hydrogen or lower alkyl; and R 17 is lower alkyl.
54 . The compound of claim 53 wherein said compound is (4R,10aS)-6-ethyl-4-methyl-1,2,3,4,10,10a-hexahydro-pyrazino[1,2-a]indole.
55 . The compound of claim 53 wherein said compound is (4R,10aR)-6-ethyl-4-methyl-1,2,3,4,10,10a-hexahydro-pyrazino[1,2-a]indole.
56 . The compound of claim 53 wherein said compound is (4R,10aR)-4,6,7-trimethyl-1,2,3,4,10,10a-hexahydro-pyrazino[1,2-a]indole hydrochloride.
57 . The compound of claim 53 wherein said compound is (4RS,10aSR)-4-ethyl-1,2,3,4,10,10a-hexahydro-pyrazino[1,2-a]indole.
58 . The compound of claim 53 wherein said compound is (4RS,10aRS)-4-ethyl-1,2,3,4,10,10a-hexahydro-pyrazino[1,2-a]indole.
59 . The compound of claim 53 wherein said compound is (4R,10S,10aR)-4,6,10-trimethyl-1,2,3,4,10,10a-hexahydro-pyrazino[1,2-a]indole.
60 . The compound of claim 53 wherein said compound is (4R,10R,10aR)-4,6,10-trimethyl-1,2,3,4,10,10a-hexahydro-pyrazino[1,2-a]indole.
61 . The compound of claim 53 wherein said compound is (4R,10aR)-4,6-dimethyl-1,2,3,4,10,10a-hexahydro-pyrazino[1,2-a]indole hydrochloride.
62 . The compound of claim 53 wherein said compound is (4R,10aS)-4,6-dimethyl-1,2,3,4,10,10a-hexahydro-pyrazino[1,2-a]indole hydrochloride.
63 . The compound of claim 53 wherein said compound is (4R,10aR)-4,7,9-trimethyl-1,2,3,4,10,10a-hexahydro-pyrazino[1,2-a]indole.
64 . The compound of claim 53 wherein said compound is (4R,10aR)-4,6,9-trimethyl-1,2,3,4,10,10a-hexahydro-pyrazino[1,2-a]indole.
65 . The compound of claim 53 wherein said compound is (4R,10aS)-4,6,7-trimethyl-1,2,3,4,10,10a-hexahydro-pyrazino[1,2-a]indol.
66 . The compound of claim 53 wherein said compound is (4R,10aS)-4,6,9-trimethyl-1,2,3,4,10,10a-hexahydro-pyrazino[1,2-a]indole.
67 . The compound of claim 53 wherein said compound is (4R,10aR)-4,8-dimethyl-1,2,3,4,10,10a-hexahydro-pyrazino[1,2-a]indole trifluoroacetate.
68 . The compound of claim 53 wherein said compound is (4R,10aS)4,7-dimethyl-1,2,3,4,10,10a-hexahydro-pyrazino[1,2-a]indole.
69 . The compound of claim 53 wherein said compound is (4R,10aR)4,7-dimethyl-1,2,3,4,10,10a-hexahydro-pyrazino[1,2-a]indole.
70 . The compound of claim 53 wherein said compound is (4R,10aR)-4,7,8-trimethyl-1,2,3,4,10,10a-hexahydro-pyrazino[1,2-a]indole.
71 . The compound of claim 53 wherein said compound is (4R,10aS)4,7,8-trimethyl-1,2,3,4,10,10a-hexahydro-pyrazino[1,2-a]indole.
72 . The compound of claim 15 wherein R 12 is hydrogen, one of R 13 and R 14 is halo and the other is lower alkyl and R 17 is lower alkyl.
73 . The compound of claim 72 wherein said compound is (4R,10aR)-8-fluoro-4,7-dimethyl-1,2,3,4,10,10a-hexahydro-pyrazino[1,2-a]indole hydrochloride.
74 . The compound of claim 72 wherein said compound is (4R,10aS)-8-fluoro-4,7-dimethyl-1,2,3,4,10,10a-hexahydro-pyrazino[1,2-a]indole hydrochloride.
75 . The compound of claim 72 wherein said compound is (4R,10aR)-6-fluoro-4,7-dimethyl-1,2,3,4,10,10a-hexahydro-pyrazino[1,2-a] indole; hydrochloride.
76 . The compound of claim 72 wherein said compound is (4R,10aS)-6-fluoro-4,7-dimethyl-1,2,3,4,10,10a-hexahydro-pyrazino[1,2-a]indole; hydrochloride.
77 . The compound of claim 72 wherein said compound is (4R,10aS)-7-chloro-4,8-dimethyl-1,2,3,4,10,10a-hexahydro-pyrazino[1,2-a]indole.
78 . The compound of claim 72 wherein said compound is (4R,10aR)-7-chloro-4,8-dimethyl-1,2,3,4,10,10a-hexahydro-pyrazino[1,2-a]indole.
79 . The compound of claim 72 wherein said compound is 4R,10aR)-6-fluoro-4,9-dimethyl-1,2,3,4,10,10a-hexahydro-pyrazino[1,2-a]indole hydrochloride.
80 . The compound of claim 72 wherein said compound is (4R,10aS)-6-fluoro-4,9-dimethyl-1,2,3,4,10,10a-hexahydro-pyrazino[1,2-a]indole hydrochloride.
81 . The compound of claim 72 wherein said compound is (4R,10aR)-6-chloro-4,8-dimethyl-1,2,3,4,10,10a-hexahydro-pyrazino[1,2-a]indole hydrochloride.
82 . The compound of claim 72 wherein said compound is (4R,10aS)-6-chloro-4,8-dimethyl-1,2,3,4,10,10a-hexahydro-pyrazino[1,2-a]indole hydrochloride.
83 . The compound of claim 72 wherein said compound is (4R,10aR)-7-chloro-4,6-dimethyl-1,2,3,4,10,10a-hexahydro-pyrazino[1,2-a]indole.
84 . The compound of claim 72 wherein said compound is (4R,10aS)-7-chloro-4,6-dimethyl-1,2,3,4,10,10a-hexahydro-pyrazino[1,2-a]indole.
85 . The compound of claim 72 wherein said compound is 4R,10aS)-6-chloro-4,7-dimethyl-1,2,3,4,10,10a-hexahydro-pyrazino[1,2-a]indole.
86 . The compound of claim 72 wherein said compound is (4R,10aR)-6-chloro-4,7-dimethyl-1,2,3,4,10,10a-hexahydro-pyrazino[1,2-a]indole.
87 . The compound of claim 72 wherein said compound is (4R,10aR)-8-bromo-4,7-dimethyl-1,2,3,4,10,10a-hexahydro-pyrazino[1,2-a]indole.
88 . The compound of claim 72 wherein said compound is (4R,10aS)-8-bromo-4,7-dimethyl-1,2,3,4,10,10a-hexahydro-pyrazino[1,2-a]indole.
89 . The compound of claim 72 wherein said compound is (4R,10aS)-8-fluoro-4,6-dimethyl-1,2,3,4,10,10a-hexahydro-pyrazino[1,2-a]indole hydrochloride.
90 . The compound of claim 72 wherein said compound is (4R,10aR)-8-fluoro-4,6-dimethyl-1,2,3,4,10,10a-hexahydro-pyrazino[1,2-a]indole; hydrochloride.
91 . The compound of claim 72 wherein said compound is (4R,10aR)-6-bromo-4,7-dimethyl-1,2,3,4,10,10a-hexahydro-pyrazino[1,2-a]indole hydrochloride.
92 . The compound of claim 72 wherein said compound is (4R,10aR)-8-bromo-6-ethyl-4-methyl-1,2,3,4,10,10a-hexahydro-pyrazino[1,2-a]indole.
93 . The compound of claim 72 wherein said compound is (4R,10aR)-7-fluoro-4,6-dimethyl-1,2,3,4,10,10a-hexahydro-pyrazino[1,2-a]indole hydrochloride.
94 . The compound of claim 15 wherein R 12 is hydrogen, one of R 13 and R 14 is trifluoromethyl, trifluoromethoxy or cyano and the other is hydrogen, halo or lower alkyl.
95 . The compound of claim 94 wherein R 17 is methyl.
96 . The compound of claim 95 wherein R 13 is trifluoromethyl.
97 . The compound of claim 96 wherein said compound is (4R,10aR)-4-methyl-7-trifluoromethyl-1,2,3,4,10,10a-hexahydro-pyrazino[1,2-a]indole hydrochloride.
98 . The compound of claim 96 wherein said compound is (4R,10aS)-4-methyl-7-trifluoromethyl-1,2,3,4,10,10a-hexahydro-pyrazino[1,2-a]indole hydrochloride.
99 . The compound of claim 96 wherein said compound is (4R,10aR)-4,8-dimethyl-7-trifluoromethyl-1,2,3,4,10,10a-hexahydro-pyrazino[1,2-a]indole hydrochloride.
100 . The compound of claim 96 wherein said compound is (4R,10aS)-4,8-dimethyl-7-trifluoromethyl-1,2,3,4,10,10a-hexahydro-pyrazino[1,2-a]indole hydrochloride.
101 . The compound of claim 96 wherein said compound is (4R,10aS)-8-bromo-4-methyl-7-trifluoromethyl-1,2,3,4,10,10a-hexahydro-pyrazino[1,2-a]indole hydrochloride.
102 . The compound of claim 96 wherein said compound is (4R,10aR)-8-bromo-4-methyl-7-trifluoromethyl-1,2,3,4,10,10a-hexahydro-pyrazino[1,2-a]indole hydrochloride.
103 . The compound of claim 95 wherein R 13 is cyano.
104 . The compound of claim 103 wherein said compound is (4R,10aR)-4-methyl-1,2,3,4,10,10a-hexahydro-pyrazino[1,2-a]indole-7-carbonitrile hydrochloric acid.
105 . The compound of claim 104 wherein said compound is (4R,10aR)-4-methyl-1,2,3,4,10,10a-hexahydro-pyrazino[1,2-a]indole-6-carbonitrile hydrochloride.
106 . The compound of claim 95 wherein R 13 is trifluoromethoxy.
107 . The compound of claim 106 wherein said compound is (4R,10aR)-4-methyl-6-trifluoromethoxy-1,2,3,4,10,10a-hexahydro-pyrazino[1,2-a]indole.
108 . The compound of claim 94 wherein R 17 is hydroxylower alkyl.
109 . The compound of claim 108 wherein R 13 is trifluoromethyl.
110 . The compound of claim 109 wherein said compound is (4S,10aS)-(7-trifluoromethyl-1,2,3,4,10,10a-hexahydro-pyrazino[1,2-a]indol-4-yl)-methanol.
111 . the compound of claim 108 wherein said compound is (4S,10aR)-(7-trifluoromethyl-1,2,3,4,10,10a-hexahydro-pyrazino[1,2-a]indol-4-yl)-methanol.
112 . The compound of claim 1 wherein said compound has the formula
wherein one of R 22 and R 23 is hydrogen and the other is hydroxy lower alkyl, lower-alkylaminocarbonyl, di-lower alkylaminocarbonyl, alkoxy lower alkyl, lower alkylcarbonylamino or lower alkoxy-lower alkoxy lower alkyl; or
R 22 and R 23 taken together with the carbon atoms to which they are added to form a 4- to 6-membered saturated carbocyclic ring which ring is unsubstituted or lower alkyl substituted and R 27 is lower alkyl.
113 . The compound of claim 112 wherein R 22 and R 23 form with their attached carbon atoms said carbocyclic ring.
114 . The compound of claim 113 wherein said compound is (10R,6aS)-10-methyl-2,3,6,6a,7,8,9,10-octahydro-1H-8,10a-diaza-cyclopenta[c]fluorene hydrochloride.
115 . The compound of claim 112 wherein one of R 22 and R 23 is hydrogen and the other is hydroxy lower alkyl, lower alkylaminocarbonyl, di-lower alkylaminocarbonyl, lower alkoxy-lower alkyl, lower alkyl carbonylamino or lower alkoxy lower alkoxy lower alkyl.
116 . The compound of claim 115 wherein said compound is (4R,10aR)—N-(4-methyl-1,2,3,4,10,10a-hexahydro-pyrazino[1,2-a]indol-7-yl)-acetamide; hydrochloride.
117 . The compound of claim 115 wherein said compound is (4R,10aR)-(4-methyl-1,2,3,4,10,10a-hexahydro-pyrazino[1,2-a]indol-7-yl)-methanol; hydrochloride.
118 . The compound of claim 115 wherein said compound is (4R,10aR)-4-methyl-1,2,3,4,10,10a-hexahydro-pyrazino[1,2-a]indole-7-carboxylic acid butylamide; hydrochloride.
119 . The compound of claim 115 wherein said compound is (4R,10aR)-4-methyl-1,2,3,4,10,10a-hexahydro-pyrazino[1,2-a]indole-7-carboxylic acid diethylamide hydrochloride.
120 . The compound of claim 115 wherein said compound is (4R,10aR)-7-methoxymethyl-4-methyl-1,2,3,4,10,10a-hexahydro-pyrazino[1,2-a]indole.
121 . The compound of claim 115 wherein said compound is (4R,10aR)-7-(2-methoxy-ethoxymethyl)-4-methyl-1,2,3,4,10,10a-hexahydro-pyrazino[1,2-a]indole.
122 . A method of treatment of obesity or Type II diabetes in a human in need of such treatment which comprises administration to the human a therapeutically effective amount of the compound of claim 1 in conjunction with a therapeutically effective amount of a lipase inhibitor.
123 . The method of claim 122 wherein the lipase inhibitor is orlistat.
124 . The method of claim 123 wherein the orlistat and the compound of formula I are simultaneously, separately or sequentially administered.
125 . A pharmaceutical composition comprising a compound of claim 1 in combination with a pharmaceutically acceptable carrier or excipient.
126 . The pharmaceutical composition of claim 125 wherein the composition contains a therapeutically effective amount of a lipase inhibitor.
127 . The pharmaceutical composition of claim 126 wherein the lipase inhibitor is orlistat.Join the waitlist — get patent alerts
Track US2007106076A1 — get alerts on status changes and closely related new filings.
We store only your email — no account needed. See our privacy policy.