Claims
- 1. A compound of formula ##STR62## or a pharmaceutically acceptable salt thereof wherein: R.sup.1 is a ##STR63## where W, X, Y, and Z are each independently hydrogen, a straight or branched alkyl of from one to six carbon atoms CF.sub.3, NR.sup.5 R.sup.6, --(CH.sub.2).sub.n CO.sub.2 R*, or CN, F, Cl, Br, OR*, SR*, wherein R* is hydrogen or a straight or branched alkyl of from one to six carbon atoms and wherein R.sup.5 and R.sup.6 are each independently hydrogen or alkyl of from one to six carbon atoms and n is an integer of from one to three;
- A is --(CH.sub.2).sub.n CO--, --SO.sub.2 --, --SO--, --NHCO--, ##STR64## --SCO--, --O--(CH.sub.2).sub.n CO-- or --HC.dbd.CHCO-- wherein n is an integer from zero to six;
- R.sup.2 is a straight or branched alkyl of from one to six carbon atoms, --HC.dbd.CH.sub.2, --C.tbd.CH, --(CH.sub.2).sub.n --CH.tbd.CH.sub.2, --(CH.sub.2).sub.n C.tbd.CH, --(CH.sub.2).sub.n OR*, --(CH.sub.2)--(CH.sub.2).sub.n CO.sub.2 R*, --(CH.sub.2).sub.n NR.sup.5 R.sup.6 wherein n, R*, R.sup.5, and R.sup.6 are as defined above;
- R.sup.9 is H, or a straight or branched alkyl of from one to six carbon atoms, --(CH.sub.2).sub.n CO.sub.2 R*, (CH.sub.2).sub.n NR.sup.5 R.sup.6, wherein n, R*, R.sup.5, and R.sup.6 are as defined above and w is 1;
- Ar.sup.2 is ##STR65##
- 2. A compound according to claim 1 wherein R.sup.1 is ##STR66## where W, X, Y, and Z are each independently hydrogen, a straight or branched alkyl of from one to six carbon atoms CF.sub.3, NR.sup.5 R.sup.6, --(CH.sub.2).sub.n CO.sub.2 R*, or CN, F, Cl, Br, OR*, SR*, wherein R* is hydrogen or a straight or branched alkyl of from one to six carbon atoms and wherein R.sup.5 and R.sup.6 are each independently hydrogen or alkyl of from one to six carbon atoms and n is an integer of from 1 to 3;
- A is --NHCO--,
- --OCO--,
- --SO.sub.2 --,
- --S(.dbd.O)--,
- --CH.sub.2 CO--,
- R.sup.2 is --CH.sub.3,
- --CH.sub.2 CO.sub.2 CH.sub.3,
- --CH.sub.2 C.tbd.CH,
- R.sup.9 is hydrogen,
- when w is 1, Ar.sup.2 is unsubstituted or substituted in the manner indicated above, and Ar.sup.2 can also be: ##STR67##
- 3. A compound according to claim 2 wherein:
- R.sup.1 is 2-adamantyl or 1-(S)-2-endobornyl,
- A is ##STR68## R.sup.2 is --CH.sub.3, Ar.sup.2 is unsubstituted or substituted by one to three substitutents each independently selected from hydrogen, --CH.sub.2 OH, --CH.sub.2 OCOCH.sub.2 CH.sub.2 COOH, --CH.sub.2 OCOCH.dbd.CHCO.sub.2 H, --CH.sub.2 NHCOCH.sub.2 CH.sub.2 COOH, --CH.sub.2 NHCOCH.dbd.CHCO.sub.2 H, --NHCOCH.sub.2 CH.sub.2 CO.sub.2 H, --NHCOCH.dbd.CHCO.sub.2 H, --NHCOCH2CH2CO.sub.2 H, --NHCOCH.alpha.CHCO.sub.2 H, oxo, hydroxy, phenyl, CO.sub.2 Me, CONHCH2CH.sub.2 CO.sub.2 Bz, --CO.sub.2 Bz, --CONHCH.sub.2 CO.sub.2 H, --CONHCH.sub.2 CH2CO.sub.2 H, --SCH.sub.2 CO.sub.2 H, --SCH2CH.sub.2 CO.sub.2 H.
- 4. A compound according to claim 1 selected from
- carbamic acid, [2-[(2,3-dihydro-2-hydroxy-1H-inden-1-yl)amino]-1-(1H-indol-3-ylmethyl)-1-methyl-2-oxoethyl]-, 1,7,7-trimethylbicyclo-[2.2.1]hept-2-yl ester (bicyclo ring is 1S-endo (+-isomer), trp center is D, indene ring centers are unknown),
- carbamic acid, [2-[(2,3-dihydro-1-hydroxy-1H-inden-2-yl)amino]-1-1H-indol-3 ylmethyl)-2-methyl-2-oxoethyl]-, 1,7,7-trimethylbicyclo-[2.2.1]hept-2-yl ester, [1S*[1.alpha.,2.beta.[S-(trans)],4.beta.]]- (Bicyclo system is 1S-endo), and
- carbamic acid, [2-[(2,3-dihydro-1 hydroxy-1H-inden-2-yl)amino]-1-(1H-indol-3-ylmethyl)-1-methyl-2-oxoethyl]-, 1,7,7-trimethylbicyclo-[2.2.1]hept-2-yl ester, [1S-[1.alpha.,2.beta.[S*(1S*,2S*)],4.alpha.]]- [Bicyclo system is 1S-endo, all other centers are R].
- 5. A compound according to claim 1 selected from
- carbamic acid, [1-(1H-indol-3-ylmethyl)-1-methyl-2-oxo-2-[(1,2,3,4-tetrahydro-1-oxo-2-naphthalenyl)amino]ethyl]-, 1,7,7-trimethyl-bicyclo[2.2.1]hept-2-yl ester (Bicyclo system 1S-endo; TRO center R; naphthyl center (-) or (+)), (Isomer II) and
- carbamic acid, [1-(1H-indol-3-ylmethyl)-1-methyl-2-oxo-2-[(1-2,3,4-tetrahydro-1-oxo-2-naphthalenyl)amino]ethyl]-, 1,7,7-trimethylbicyclo[2.2.1.1]hept-2-yl ester (Bicyclo system 1S-endo; TRP center R; naphthyl center (+) or (-)), (Isomer I).
- 6. A compound according to claim 1 selected from
- carbamic acid, [1-(1H-indol-3-ylmethyl)-1-methyl-2-oxo-2-[(1,2,3,4-tetrahydro-1-naphthalenyl)amino]ethyl]-, tricyclo[3.3..1.1.sup.3,7 ]-dec-2-yl ester, (.+-.)- and
- carbamic acid, [1-1H-indol-3-ylmethyl)-1-methyl-2-oxo-2-[(1,2,3,4-tetrahydro-2-naphthalenyl)amino]ethyl]-, tricyclo[3.3.1.1.sup.3,7 ]-dec-2-yl ester, (.+-.)-.
- 7. A compound according to claim 1 named 4-[[1,2,3,4-tetrahydro-2-[[3-(1H-indol-3-yl)-2-methyl-1-oxo-2-[[(tricyclo[3.3.1.1.sup.3,7 ]dec-2-yloxy)carbonyl]amino]propyl]amino]-1-naphthalenyl]amino]-4-oxobutanoate.
- 8. A compound according to claim 1 named tricyclo[3.3.1.1.sup.3,7 ]dec-2-yl-[2-[(1-azido-1,2,3,4-tetrahydro-2-naphthalenyl)amino]-1(1H-indol-3-ylmethyl)-1-methyl 2-oxoethyl]carbamate.
- 9. A compound according to claim- 1 named methyl 3-[[2-[[3 (1H-indol-3-yl)-2 methyl-1-oxo-2-[[(tricyclo[3.3.1.1.sup.3,7 ]dec 2-yloxy)carbonyl]amino]propyl]amino]-1,2,3,4-tetrahydro-1-naphthalenyl]amino]-3-oxopropanoate.
- 10. A compound according to claim 1 named methyl 3-[[2-[[3-(1H-indol-3-yl)-2-methyl-1-oxo-2-[[(tricyclo[3,3,1,1.sup.3.7 ]dec-2-yloxy)carbonyl]amino]propyl]amino]-1,2,3,4-tetrahydro-1-naphthalenyl]amino]-3-oxopropanoate.
- 11. A compound according to claim 1 named methyl 1-[[1,2,3,4-tetrahydro-2-[[3-(1H-indol-3-yl)-2-methyl-1-oxo-2-[[(tricyclo[3.3.1.1.sup.3,7 ]dec-2-yloxy)carbonyl]amino]propyl]amino]-1-naphthalenyl]amino]-4-oxo-2-butanoate.
- 12. 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.
CROSS-REFERENCE TO RELATED APPLICATION
This application is a continuation-in-part of U.S. Ser. No. 07/576,296 filed Aug. 31, 1990 now abandoned.
US Referenced Citations (4)
Continuation in Parts (1)
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Number |
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576296 |
Aug 1990 |
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