Claims
- 1. A compound of Formula I
- or pharmaceutically acceptable salt thereof,
- wherein:
- X is hydrogen, C.sub.1 -C.sub.5 alkyl, or a halogen atom;
- Y is selected from the group consisting of
- --(CH.sub.2).sub.n NR.sub.9 R.sub.10 wherein R.sub.9 and R.sub.10, are independently selected from the group consisting of
- (a) hydrogen;
- (b) C.sub.1 -C.sub.12 alkyl;
- (c) phenyl optionally substituted with one, 2 or 3 C.sub.1 -C.sub.4 alkyl, C.sub.1 -C.sub.4 alkoxy, halo, OH, trifluoromethyl or --CO.sub.2 (C.sub.1 -C.sub.4 alkyl);
- (d)--(CH.sub.2).sub.q phenyl wherein phenyl is optionally substituted with one, 2 or 3 C.sub.1 -C.sub.4 alkyl, C.sub.1 -C.sub.4 alkoxy, halo, OH, trifluoromethyl or --CO.sub.2 (C.sub.1 -C.sub.4 alkyl);
- (e) --(CH.sub.2).sub.n pyridinyl; or
- (f) wherein R.sub.9 and R.sub.10, taken together with N, form a saturated or unsaturated heterocyclic amine ring selected from the group consisting of
- (aa) 4-morpholine optionally substituted with one or two members selected from the group consisting of C.sub.1 -C.sub.4 alkyl, C.sub.1 -C.sub.4 alkoxy, halo or trifluoromethyl,
- (bb) 4-thiomorpholine optionally substituted with one or two members selected from the group consisting of C.sub.1 -C.sub.4 alkyl, C.sub.1 -C.sub.4 alkoxy, halo or trifluoromethyl,
- (cc) 3-amino-1-pyrrolidine,
- (dd) 1-pyrrolidine optionally substituted with one or two members selected from the group consisting of C.sub.1 -C.sub.4 alkyl, C.sub.1 -C.sub.4 alkyl, halo, OH, --CH.sub.2 OH, or trifluoromethyl,
- (ee) 1-piperidine optionally substituted with one or two members selected from the group consisting of C.sub.1 -C.sub.4 alkyl, C.sub.1 -C.sub.4 alkoxy, halo, trifluoromethyl, --(CH.sub.2)qOH, --CO.sub.2 H, --CO.sub.2 CH.sub.3, --CO.sub.2 CH.sub.2 CH.sub.3 or phenyl (wherein phenyl is optionally substituted with one, 2 or 3 C.sub.1 -C.sub.4 alkyl, C.sub.1 -C.sub.4 alkoxy, halo or trifluoromethyl),
- (ff) 1-piperazine, 4-methyl-1-piperazine, 4-(cycloC.sub.3 -C.sub.6 alkyl)-1-piperazine, 4-phenyl-1-piperazine (wherein phenyl is optionally substituted with one, 2 or 3 C.sub.1 -C.sub.4 alkyl, C.sub.1 -C.sub.4 alkoxy, halo or trifluoromethyl) or 4-pyridinyl-1-piperazine optionally substituted with one or two members selected from the group consisting of C.sub.1 -C.sub.4 alkyl, C.sub.1 -C.sub.4 alkoxy, halo, OH, trifluoromethyl, --CH.sub.2 OH, --CO.sub.2 H, --CO.sub.2 CH.sub.3 or --CO.sub.2 CH.sub.2 CH.sub.3, and
- (gg) thiazolidine, thiazolidine-4-carboxylic acid, pipecolinic acid, p-piperazinacetophenone, 1-piperazine, 1-methylpiperazine, 4-phenyl-1,2,-3,6-tetrahydropyridine, proline, tetrahydrofurylamine, 1-(3-hydroxy)pyrrolidine, nipecotamide, 1,2,3,4-tetrahydroisoquinoline or imidazole;
- R.sub.1, R.sub.2, R.sub.3, R.sub.4 and R.sub.5 are independently selected from the group consisting of: hydrogen,
- C.sub.1 -C.sub.8 alkyl,
- --(CH.sub.2).sub.n phenyl (wherein phenyl is optionally substituted with one, 2 or 3 C.sub.1 -C.sub.4 alkyl, C.sub.1 -C.sub.4 alkoxy, halo, OH, trifluoromethyl or --CO.sub.2 (C.sub.1 -C.sub.4 alkyl)),
- --(CH.sub.2).sub.n naphthyl,
- --(CH.sub.2).sub.n pyridinyl,
- --(CH.sub.2).sub.q NR.sub.9 R.sub.10,
- --CH.dbd.CH-phenyl (wherein phenyl is optionally substituted with one, 2 or 3 C.sub.1 -C.sub.4 alkyl, C.sub.1 -C.sub.4 alkoxy, halo, OH, trifluoromethyl or --CO.sub.2 (C.sub.1 -C.sub.4 alkyl)),
- --CH.sub.2 --CH.dbd.CH.sub.2,
- --CH.dbd.CH--CH.sub.3,
- --O--CH.sub.2 --CH.dbd.CH.sub.2,
- --C.tbd.C-phenyl (wherein phenyl is optionally substituted with one, 2 or 3 C.sub.1 -C.sub.4 alkyl, C.sub.1 -C.sub.4 alkoxy, halo, OH, trifluoromethyl or --CO.sub.2 (C.sub.1 -C.sub.4 alkyl)),
- --O(CH.sub.2)p(N-methylpiperdin-3-yl),
- --O--(CH.sub.2)pNR.sub.9 R.sub.10,
- --O--CH.sub.2 CH(0CH.sub.3).sub.2,
- --O--(CH.sub.2)pOR.sub.15 (wherein R.sub.15 is selected from C.sub.1 -C.sub.5 alkyl, --(CH.sub.2).sub.n phenyl (phenyl optionally substituted with one, 2 or 3 C.sub.1 -C.sub.4 alkyl, C.sub.1 -C.sub.4 alkoxy, halo, OH, trifluoromethyl or --CO.sub.2 (C.sub.1 -C.sub.4 alkyl)),
- --(CH.sub.2).sub.n pyridin-yl or --(CH.sub.2).sub.p piperidin-1-yl,
- --(CH.sub.2).sub.n C(O)--(CH.sub.2).sub.n R.sub.9,
- --(CH.sub.2).sub.n C(O)O--(CH.sub.2).sub.n R.sub.9,
- --(CH).sub.n C(O)O--(CH.sub.2).sub.p NR.sub.9 R.sub.10,
- --(CH.sub.2).sub.n C(O)(CH.sub.2).sub.n NR.sub.9 R.sub.10,
- NO.sub.2,
- --O--(CH.sub.2).sub.n C(O)--(CH.sub.2).sub.n R.sub.9,
- --O--(CH.sub.2).sub.n C(O)O--(CH.sub.2).sub.n R.sub.9,
- --O--(CH.sub.2).sub.n C(O)--(CH.sub.2).sub.n NR.sub.9 R.sub.10,
- --NR.sub.9 R.sub.10,
- --N(R.sub.9)(CH.sub.2).sub.n C(O)--(CH.sub.2).sub.n R.sub.10,
- --N(R.sub.9)--(CH.sub.2).sub.n C(O)O--(CH.sub.2).sub.n R.sub.10,
- N(R.sub.9)(CH.sub.2).sub.n C(O)--(CH.sub.2).sub.n NR.sub.9 R.sub.10,
- --OCH(C.sub.4 H.sub.9)phenyl,
- --O--(CH.sub.2).sub.n phenyl (wherein phenyl is optionally substituted with one, 2 or 3 C.sub.1 -C.sub.4 alkyl, C.sub.1 -C.sub.4 alkoxy, halo, OH, trifluoromethyl or --CO.sub.2 (C.sub.1 -C.sub.4 alkyl)),
- --O--(CH.sub.2).sub.n pyridine,
- --O(CH.sub.2).sub.n C(O)--(CH.sub.2).sub.n pyridine,
- --O--(CH.sub.2).sub.n C(O)O--(CH.sub.2).sub.n pyridine,
- --O(CH.sub.2).sub.n C(O)--N(R.sub.9)(CH.sub.2).sub.n pyridine,
- --O--(CH.sub.2).sub.n quinoxalinyl,
- --O--(CH.sub.2).sub.n quinolinyl,
- --O--(CH.sub.2).sub.n pyrazinyl,
- --O--(CH.sub.2).sub.n naphthyl,
- --O--(CH.sub.2).sub.n C(O)--(CH.sub.2).sub.n naphthyl,
- --O--(CH.sub.2).sub.n C(O)O--(CH.sub.2).sub.n naphthyl,
- --O--(CH.sub.2).sub.n C(O)NR.sub.9 --(CH.sub.2).sub.n naphthyl,
- halo,
- OH,
- --(CH.sub.2).sub.q --OH,
- (CH.sub.2).sub.q OC(O)R.sub.9,
- --(CH.sub.2).sub.q OC(O)--NR.sub.9 R.sub.10,
- -(1-cyclohexyl-1H-tetrazol-5-yl)C.sub.1 -C.sub.4 alkoxy,
- -(1-(C.sub.1 -C.sub.5 alkyl)-1H-tetrazol-5-yl)C.sub.1 -C.sub.4 alkoxy,
- -(1-(phenyl)-1H-tetrazol-5-yl) C.sub.1 -C.sub.4 alkoxy (wherein phenyl is optionally substituted with one, 2 or 3 C.sub.1 -C.sub.4 alkyl, C.sub.1 -C.sub.4 alkoxy, halo, OH, trifluoromethyl or --CO.sub.2 (C.sub.1 -C.sub.4 alkyl)),
- -(1-(pyridinyl)-1H-tetrazol-5-yl)C.sub.1 -C.sub.4 alkoxy,
- -(1-(1-phenylethyl)-1H-tetrazol-5-yl)C.sub.1 -C.sub.4 alkoxy,
- -C.sub.1 -C.sub.4 alkoxyl;
- n is 0-5;
- p is 2-5; and
- q is 1-5.
- 2. The compound of claim 1 wherein X is hydrogen.
- 3. The compound of claim 1 wherein Y is (CH.sub.2).sub.n -4-morpholine where n is 0 or 1.
- 4. The compound of claim 3 wherein R.sub.1, R.sub.2, R.sub.4 and R.sub.5 are hydrogen.
- 5. The compound of claim 4 which is
- a) 2-(4-hydroxyphenyl)-6-(4-morpholinyl)-4H-pyran-4-one;
- b) 2-(4-morpholinyl)-6-(4-(phenylmethoxy)phenyl)-4H-pyran-4-one;
- c) 2-(4-morpholinyl)-6-phenyl-4H-pyran-4-one;
- d) 2-(4-(3,3-dimethyl-2-oxobutoxy)phenyl)-6-(4-morpholinyl)-4H-pyran-4-one;
- e) 2-(4-morpholinyl)-6-(4-(3-pyridinylmethoxy)phenyl)-4H-pyran-4-one;
- f) 2-(4-Morpholinyl)-6-(4-(2-pyridinylmethoxy)phenyl)-4H-pyran-4-one;
- g) 2-(4-Morpholinyl)-6-((4-(2-(1-piperidinyl)ethyl)oxy)phenyl)-4H-pyran-4-one
- h) 2-(4-Morpholinyl)-6-(4-(2-quinolinylmethoxy)phenyl)-4H-pyran-4-one;
- i) 2-(4-Morpholinyl)-6-(2-(phenylmethoxy)phenyl)-4H-pyran-4-one;
- j) 2-(2-Hydroxyphenyl)-6-(4-morpholinyl)-4H-pyran-4-one;
- k) 2-(4-Morpholinyl)-6-(4-((1-phenylpentyl)oxy)phenyl)-4H-pyran-4-one;
- l) 2-(4-morpholinylmethyl)-6-(4-(phenylmethoxy)phenyl)-4H-pyran-4-one;
- m) 2-(4-(phenylmethoxy)phenyl)-6-(1-piperidinylmethyl)-4H-pyran-4-one;
- n) 2-(4-hydroxyphenyl)-6-(4-morpholinylmethyl)-4H-pyran-4-one;
- o) 2-(4-morpholinyl)-6-(3-(phenylmethoxy)phenyl)-4H-pyran-4-one;
- p) 2-(3-hydroxyphenyl)-6-(4-morpholinyl)-4H-pyran-4-one;
- q) 2-(4-(hydroxymethyl)phenyl)-6-(4-morpholinyl)-4H-pyran-4-one;
- r) 2-(4-morpholinyl)-6-(4-(1-piperidinylmethyl)phenyl)-4H-pyran-4-one;
- s) 2-(4-morpholinyl)-6-(4-(1-pyrrolidinylmethyl)phenyl)-4H-pyran-4-one;
- t) 2-(4-((4-methyl-1-piperazinyl)methyl)phenyl)-6-(4-morpholinyl)-4H-pyran-4-one;
- u) 2-(4-((2-(hydroxymethyl)-1-piperidinyl)methyl)phenyl)-6-(4-morpholinyl)-4H-pyran-4-one;
- v) 2-(4-fluorophenyl)-6-(4-morpholinyl)-4H-pyran-4-one;
- w) 2-(4-Morpholinyl)-6-4-(1-pyrrolidinyl)phenyl-4H-pyran-4-one;
- x) 2-(4-Morpholinyl)-6-4-(1-piperidinyl)phenyl-4H-pyran-4-one; or
- y) 2-(4-Aminophenyl)-6-(4-morpholinyl)-4H-pyran-4-one.
- 6. A compound of Formula II ##STR45## or pharmaceutically acceptable salt thereof, wherein:
- X is hydrogen, C.sub.1 -C.sub.5 alkyl, or a halogen atom;
- R.sub.1, R.sub.2, R.sub.3, R.sub.4 and R.sub.5 are independently selected from the group consisting of:
- hydrogen,
- C.sub.1 -C.sub.8 alkyl,
- --(CH.sub.2).sub.n phenyl (wherein phenyl is optionally substituted with one, 2 or 3 C.sub.1 -C.sub.4 alkyl, C.sub.1 -C.sub.4 alkoxy, halo, OH, trifluoromethyl or --CO.sub.2 (C.sub.1 -C.sub.4 alkyl)),
- --(CH.sub.2).sub.n naphthyl,
- --(CH.sub.2).sub.n pyridinyl,
- --(CH.sub.2).sub.q NR.sub.9 R.sub.10,
- --CH.dbd.CH-phenyl (wherein phenyl is optionally substituted with one, 2 or 3 C.sub.1 -C.sub.4 alkyl, C.sub.1 -C.sub.4 alkoxy, halo, OH, trifluoromethyl or --CO.sub.2 (C.sub.1 -C.sub.4 alkyl)),
- --CH.sub.2 --CH.dbd.CH.sub.2,
- --CH.dbd.CH--CH.sub.3,
- --O--CH.sub.2 --CH.dbd.CH.sub.2,
- --C.tbd.C-phenyl (wherein phenyl is optionally substituted with one, 2 or 3 C.sub.1 -C.sub.4 alkyl, C.sub.1 -C.sub.4 alkoxy, halo, OH, trifluoromethyl or --CO.sub.2 (C.sub.1 -C.sub.4 alkyl)),
- --O(CH.sub.2)p(N-methylpiperdin-3-yl),
- --O--(CH.sub.2)pNR.sub.9 R.sub.10,
- --O--CH.sub.2 CH(OCH.sub.3).sub.2,
- --O--(CH.sub.2)pOR.sub.15 (wherein R.sub.15 is selected from C.sub.1 -C.sub.5 alkyl, --(CH.sub.2).sub.n phenyl (phenyl optionally substituted with one, 2 or 3 C.sub.1 -C.sub.4 alkyl, C.sub.1 -C.sub.4 alkoxy, halo, OH, trifluoromethyl or --CO.sub.2 (C.sub.1 -C.sub.4 alkyl)),
- --(CH.sub.2).sub.n pyridin-yl or --(CH.sub.2).sub.p piperidin-1-yl),
- --(CH.sub.2).sub.n C(O)--(CH.sub.2).sub.n R.sub.9,
- --(CH.sub.2).sub.n C(O)O--(CH.sub.2).sub.n R.sub.9,
- --(CH).sub.n C(O)O--(CH.sub.2).sub.p NR.sub.9 R.sub.10,
- --(CH.sub.2).sub.n C(O)(CH.sub.2).sub.n NR.sub.9 R.sub.10,
- NO.sub.2,
- --O--(CH.sub.2).sub.n C(O)--(CH.sub.2).sub.n R.sub.9,
- --O--(CH.sub.2).sub.n C(O)O--(CH.sub.2).sub.n R.sub.9,
- --O--(CH.sub.2).sub.n C(O)--(CH.sub.2).sub.n NR.sub.9 R.sub.10,
- --NR.sub.9 R.sub.10,
- --N(R.sub.9)(CH.sub.2).sub.n C(O)--(CH.sub.2).sub.n R.sub.10,
- --N(R.sub.9)--(CH.sub.2).sub.n C(O)O--(CH.sub.2).sub.n R.sub.10,
- N(R.sub.9)(CH.sub.2).sub.n C(O)--(CH.sub.2).sub.n NR.sub.9 R.sub.10,
- --OCH(C.sub.4 H.sub.9)phenyl,
- --O--(CH.sub.2).sub.n phenyl (wherein phenyl is optionally substituted with one, 2 or 3 C.sub.1 -C.sub.4 alkyl, C.sub.1 -C.sub.4 alkoxy, halo, OH, trifluoromethyl or --CO.sub.2 (C.sub.1 -C.sub.4 alkyl)),
- --O--(CH.sub.2).sub.n pyridine,
- --O(CH.sub.2).sub.n C(O)--(CH.sub.2).sub.n pyridine,
- --O--(CH.sub.2).sub.n C(O)O--(CH.sub.2).sub.n pyridine,
- --O(CH.sub.2).sub.n C(O)--N(R.sub.9)(CH.sub.2).sub.n pyridine,
- --O--(CH.sub.2).sub.n quinoxalinyl,
- --O--(CH.sub.2).sub.n quinolinyl,
- --O--(CH.sub.2).sub.n pyrazinyl,
- --O--(CH.sub.2).sub.n naphthyl,
- --O--(CH.sub.2).sub.n C(O)--(CH.sub.2).sub.n naphthyl,
- --O--(CH.sub.2).sub.n C(O)O--(CH.sub.2).sub.n naphthyl,
- --O--(CH.sub.2).sub.n C(O)NR.sub.9 --(CH.sub.2).sub.n naphthyl,
- halo,
- --OH,
- --(CH.sub.2).sub.q --OH,
- (CH.sub.2).sub.q OC(O)R.sub.9,
- --(CH.sub.2).sub.q OC(O)--NR.sub.9 R.sub.10,
- -(1-cyclohexyl-1H-tetrazol-5-yl)C.sub.1 -C.sub.4 alkoxy,
- -(1-(C.sub.1 -C.sub.5 alkyl)-1H-tetrazol-5-yl)C.sub.1 -C.sub.4 alkoxy,
- -(1-(phenyl)-1H-tetrazol-5-yl) C.sub.1 -C.sub.4 alkoxy (wherein phenyl is optionally substituted with one, 2 or 3 C.sub.1 -C.sub.4 alkyl, C.sub.1 -C.sub.4 alkoxy, halo, OH, trifluoromethyl or --CO.sub.2 (C.sub.1 -C.sub.4 alkyl)),
- -(1-(pyridinyl)-1H-tetrazol-5-yl)C.sub.1 -C.sub.4 alkoxy,
- -(1-(1-phenylethyl)-1H-tetrazol-5-yl)C.sub.1 -C.sub.4 alkoxy,
- --C.sub.1 -C.sub.4 alkoxyl;
- n is 0-5;
- p is 2-5; and
- q is 1-5.
- 7. The compound of claim 6 wherein X is hydrogen.
CROSS-REFERENCE TO RELATED APPLICATIONS
This application is the continuation of PCT/US91/03659 abandoned which was a continuation-in-part of U.S. Ser. No. 07/545,935 filed Jun. 29, 1990, abandoned.
US Referenced Citations (3)
Foreign Referenced Citations (2)
Number |
Date |
Country |
3528601 |
Feb 1987 |
DEX |
WO9006921 |
Jun 1990 |
WOX |
Non-Patent Literature Citations (1)
Entry |
Capuano, L. et al., "Reactions of 2-Diazo-1,3-diketones with Enamines and Ketene-N,O-Acetals, II," Chem. Ber. 109:3497-3504 (1976). |
Continuation in Parts (1)
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Number |
Date |
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Parent |
545935 |
Jun 1990 |
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