Claims
- 1. A compound of formula I ##STR13## wherein k is 0, 1, 2 or 3; and R is hydrogen, C.sub.1-6 -alkyl or C.sub.3-6 cycloalkyl; and
- wherein Y is ##STR14## wherein --A--B--C--D-- is selected from .dbd.C(R.sup.1)--O--N.dbd.C(R.sup.2)--, .dbd.C(R.sup.1)--S--N.dbd.C(R.sup.2)--, .dbd.C(R.sup.1)--N.dbd.C(R.sup.2)--O--, .dbd.C(R.sup.1)--C(R.sup.2).dbd.N--O--, .dbd.C(R.sup.1)--N.dbd.C(R.sup.2)--S--, .dbd.C(R.sup.1)--C(R.sup.2).dbd.C(R.sup.3)--S--, .dbd.C(R )--C(R.sup.2).dbd.N--S--, --C(R.sup.1).dbd.C(R.sup.2)--O--C(R.sup.3).dbd., --C(R.sup.1).dbd.C(R.sup.2)--S--C(R.sup.3).dbd., --N(R.sup.4)--N.dbd.C(R.sup.1)--C(R.sup.2).dbd., .dbd.N--N(R.sup.4)--C(R.sup.1).dbd.C(R.sup.2)--, .dbd.N--O--C(R.sup.1).dbd.C(R.sup.2)--, .dbd.N--S--C(R.sup.1).dbd.C(R.sup.2)--, --N(R.sup.1)--C(R.sup.1).dbd.N--C(R.sup.2).dbd., .dbd.C(R.sup.1)--N(R.sup.4)--N.dbd.C(R.sup.2)--, --N.dbd.C(R.sup.1)--O--C(R.sup.2).dbd., --N.dbd.C(R.sup.1)--S--C(R.sup.2).dbd., .dbd.N--C(R.sup.1).dbd.C(R.sup.2)--N(R.sup.4)--, .dbd.N--C(R.sup.1).dbd.C(R.sup.2)--O--, .dbd.N--C(R.sup.1).dbd.C(R.sup.2)--S--, --N(R.sup.4)--N.dbd.N--C(R.sup.1).dbd., .dbd.N--N(R.sup.4)--N.dbd.C(R.sup.1)--, --N.dbd.N--N(R.sup.4)--C(R.sup.1).dbd., --N(R.sup.4)--N.dbd.C(R.sup.1)--N.dbd., .dbd.N--N(R.sup.4)--C(R.sup.1).dbd.N--, .dbd.N--N.dbd.C(R.sup.1)--N(R.sup.4)--, .dbd.N--O--N.dbd.C(R.sup.1)--, .dbd.N--N.dbd.C(R.sup.1)--O--, --N.dbd.C(R.sup.1)--O--N.dbd., .dbd.N--C(R.sup.1).dbd.N--O--, .dbd.N--N.dbd.C(R.sup.1)--S--, .dbd.N--S--N.dbd.C(R.sup.1)--, .dbd.N--C(R.sup.1).dbd.N--S--, --N.dbd.C(R.sup.1)--S--N.dbd., --N(R.sup.4)--N.dbd.N--N.dbd., .dbd.N--N(R.sup.4)--N.dbd.N--; and R.sup.1, R.sup.2 and R.sup.3 independently are hydrogen, halogen, --NO.sub.2, --CN, --NR.sup.5 R.sup.6, --OR.sup.7, --SR.sup.3, --COOR.sup.9, --SOR.sup.1, --SO.sub.2 R.sup.11, --SO.sub.3 R.sup.12, C.sub.1 --alkyl optionally substituted with one, two or three fluorine atoms, C.sub.2-6 -alkenyl, C.sub.2-6 -alkynyl, C.sub.3-6 -cycloalkyl, --R.sup.3 --O--R.sup.14 or --R.sup.15 --S--R.sup.16, and R.sup.4 is C.sub.1-6 -alkyl, C.sub.2-6 -alkenyl, C.sub.2-6 -alkynyl, C.sub.3-6 -cycloalkyl, --R.sup.17 --O--R.sup.18 or --R.sup.19 --S--R.sup.20, wherein R.sup.5 and R.sup.6 independently are hydrogen, C.sub.1-6 -alkyl, C.sub.2-6 --alkenyl or C.sub.2-6 -alkynyl and wherein R.sup.7 R.sup.8, R.sup.9, R.sup.10, R.sup.11, R.sup.12, R.sup.14, R.sup.16, R.sup.18 and R.sup.20 independently are hydrogen, C.sub.1-6 -alkyl, C.sub.2-6 -alkenyl, C.sub.2-6 -alkynyl or C.sub.3-7 -cycloalkyl and wherein R.sup.13, R.sup.15, R.sup.17 and R.sup.19 independently are C.sub.1-6 -alkylene, C.sub.2-6 -alkenylene or C.sub.2-6 -alkynylene; or a pharmaceutically acceptable salt thereof.
- 2. A compound according to claim 1 of formula Ia ##STR15## wherein A--B--C--D is selected from .dbd.C(R.sup.1)--C(R.sup.2).dbd.N--O--, .dbd.C(R.sup.1)--C(R.sup.2).dbd.N--S--, .dbd.N--O--C(R.sup.1).dbd.C(R.sup.2)--, and .dbd.N--S--C(R.sup.1).dbd.C(R.sup.2)--,
- wherein R.sup.1 and R.sup.2 have the meanings defined in claim 1.
- 3. A compound according to claim 1, wherein the compound is selected from the following:
- (Z)--3--(3--Methyl--5--isoxazolyl)methylene--1 --methylpiperidine,
- (E) 3--(3--methyl--5--isoxazolyl)methylene--l--methylpiperidine,
- (E) 3--(3--methyl--5--isoxazolyl)methylene--l--methylpyrrolidine,
- (Z) 3--(3--methyl--5--isoxazolyl)methylene--1--methylpyrrolidine,
- 4--(3--Methyl--5--isoxazolyl)methylene--1 --methylpiperidine,
- (Z)--3--(3--Methyl--5--isoxazolyl)methylenepiperidine,
- (E)--3--(3--Methyl--5--isoxazolyl)methylenepiperidine, and
- 3--(3--methyl--5--isoxazolyl)methyleneazetidine; or a pharmaceutically acceptable salt thereof.
- 4. A method of preparing a compound according to claim 1, comprising
- a) reacting a compound of formula II: ##STR16## wherein k is as defined in claim 1, with a phosphorus ylide of formula III or a phosphonate of formula IV ##STR17## wherein R.sup.21, R.sup.22 and R.sup.23 independently are C.sub.1-6 -alkyl, aryl or aralkyl and --A--B--C--D--has the meaning defined in claim 1, to give a compound of formula I; or
- b) reacting a compound of formula II with a compound of formula V ##STR18## wherein --A--B--C--D--has the meaning defined in claim 1, followed by a dehydration to give a compound of formula I; or
- c) reacting a compound of formula II with a compound of formula VI ##STR19## wherein R.sup.21, R.sup.22 and R.sup.23 have the meanings defined above, to give a compound of formula I; or
- d) reacting a compound of formula II with a compound of formula VII ##STR20## wherein R.sup.1 has the meaning defined in claim 1 and R.sup.21 and R.sup.22 have the meanings defined above, to give a compound of formula VIII ##STR21## followed by reaction with dimethylformamide dimethylacetale and cyclization with hydroxylamine to give a compound of formula IX ##STR22## wherein R and R.sup.1 have the meanings defined in claim 1.
- 5. A pharmaceutical composition comprising as active component a compound according to claim 1 together with a pharmaceutically acceptable carrier or diluent.
- 6. The pharmaceutical composition according to claim 5 in the form of an oral dosage unit or parenteral dosage unit.
- 7. The pharmaceutical composition according to claim 6, wherein said dosage unit comprises from about 1 to about 100 mg of the compound claim 1.
- 8. A method of treating a central nervous system ailment related to malfunctioning of the nicotinic cholinergic system in a subject in need of such treatment comprising administering to said subject an effective amount of a compound according to claim 1.
- 9. A method of treating Alzheimer's disease, Parkinson's disease, Tourette's syndrome, ulcerative colitis, obesity, gastrointestinal disorders or severe pain, preferably obesity, in a subject in need of such treatment comprising administering to said subject an effective amount of a compound according to claim 1.
- 10. A method of treating or preventing withdrawal symptoms caused by cessation of chronic or long term use of tobacco products comprising administering to a subject in need thereof an effective amount of a compound according to claim 1.
Priority Claims (1)
Number |
Date |
Country |
Kind |
0756/95 |
Jun 1995 |
DKX |
|
CROSS-REFERENCE TO RELATED APPLICATIONS
This application is a 35 U.S.C. 371 national application of PCT/DK96/00292 filed Jun. 28, 1996 and claims priority under 35 U.S.C. 119 of Danish application 0756/95 filed Jun. 29, 1995, the contents of which are fully incorporated herein by reference.
PCT Information
Filing Document |
Filing Date |
Country |
Kind |
102e Date |
371c Date |
PCT/DK96/00292 |
6/28/1996 |
|
|
12/19/1997 |
12/19/1997 |
Publishing Document |
Publishing Date |
Country |
Kind |
WO97/01556 |
1/16/1997 |
|
|
Foreign Referenced Citations (3)
Number |
Date |
Country |
0330353 A1 |
Aug 1989 |
EPX |
0414394 A2 |
Feb 1991 |
EPX |
WO 9312108 |
Jun 1993 |
WOX |
Non-Patent Literature Citations (2)
Entry |
Chemical Abstracts, vol. 110, No. 16, The Abstract No. 135678n, p. 761., 1989. |
Helak, B. et al., J. Agric. Food Chem., vol. 37, pp. 405-410 (1989). |