Claims
- 1. A chroman of the formula ##STR8## wherein R.sup.1 is A,
- R.sup.2 is H or A,
- R.sup.1 and R.sup.2 together are also alkylene having 3-6 C atoms,
- R.sup.3 is, OH, or OAc,
- R.sup.4 is H,
- R.sup.3 and R.sup.4 together are also a bond,
- R.sup.5 is 1H-6-pyridazinon-1-yl, which is unsubstituted or monosubstituted or disubstituted by A, F, Cl, Br, I, OA, OAc, NO.sub.2, NH.sub.2, AcNH, HOOC and/or AOOC,
- R.sup.6 and R.sup.7 are each H, A, HO, AO, CHO, ACO, ACS, HOOC, AOOC, AO--CS, ACOO, A--CS--O, hydroxyalkyl having 1-6 C atoms, mercaptoalkyl having 1-6 C atoms, NO.sub.2, NH.sub.2, NHA, NA.sub.2, CN, F, Cl, Br, I, CF.sub.3, ASO, ASO.sub.2, AO--SO, AO--SO.sub.2, AcNH, AO--CO--NH, H.sub.2 NSO, HANSO, A.sub.2 NSO, H.sub.2 NSO.sub.2, HANSO.sub.2, A.sub.2 NSO.sub.2, H.sub.2 NCO, HANCO, A.sub.2 NCO, H.sub.2 NCS, HANCS, A.sub.2 NCS, ASONH, ASO.sub.2 NH, AOSONH, AOSO.sub.2 NH, ACO-alkyl, nitroalkyl, cyanoalkyl, A--C(.dbd.NOH) or A--C(.dbd.NNH.sub.2),
- R.sup.8 is H
- A is alkyl having 1-6 C atoms;
- alkyl is of 1-6 C atoms; and
- Ac is alkanoyl having 1-8 C atoms or aroyl having 7-11 C atoms, or a physiologically acceptable salt thereof.
- 2. A chroman according to claim 1, wherein R.sup.1 and R.sup.2 are each CH.sub.3.
- 3. A chroman according to claim 1, wherein R.sup.3 is OH, OCHO or OCOCH.sub.3 and R.sup.4 is H.
- 4. A chroman according to claim 1, wherein R.sup.3 and R.sup.4 together are a bond.
- 5. A pharmaceutical composition comprising a compound of claim 1 and a pharmaceutically acceptable carrier.
- 6. A method of relaxing smooth muscle organs comprising administering a compound of claim 1.
- 7. A pharmaceutical composition comprising about 0.1 to 50 mg of a compound of claim 1 and a pharmaceutically acceptable carrier.
- 8. A pharmaceutical composition comprising about 0.2 to 5 mg of a compound of claim 1 and a pharmaceutically acceptable carrier.
- 9. A method according to claim 6, comprising administering daily dosages of about 0.001 to 1 mg/kg of body weight.
- 10. A compound of claim 1 wherein R.sup.6 is in the 6-position of the ring and R.sup.7 is in the 7-position of the ring.
- 11. A compound of claim 10 wherein one of R.sup.6 and R.sup.7 is H and the other one is not H.
- 12. A chroman of the formula ##STR9## wherein R.sup.1 and R.sup.8 are in each case independently A,
- R.sup.2 is H or A, or
- R.sup.1 and R.sup.2 together are alkylene having 3-6 C atoms,
- R.sup.3 is OH or OAc,
- R.sup.4 is H, or
- R.sup.3 and R.sup.4 together are a bond,
- R.sup.5 is pyridazinyl-oxy, or oxo-dihydro-pyridazinyl-oxy, which is unsubstituted or monosubstituted or disubstituted by A, F, Cl, Br, I, OH, OA, OAc, NO.sub.2, NH.sub.2, AcNH, HOOC and/or AOOC
- R.sup.6 and R.sup.7 are the same or different and are H, A, HO AO, CHO, ACO, ACS, HOOC, AOOC, AO--CS, ACOO, A--CS--O, hydroxyalkyl having 1-6 atoms, mercaptoalkyl having 1-6 C atoms, NO.sub.2, NH.sub.2 NHA, NA.sub.2, CN, F, Cl, Br, I, CF.sub.3, ASO, ASO.sub.2 AO--SO, AO--SO.sub.2, AcNH, AO--CO--NH, H.sub.2 NSO, HANSO, A.sub.2 NSO.sub.2, H.sub.2 NSO.sub.2, A.sub.2 NSO, HANSO.sub.2 H.sub.2 NCO, HANCO, A.sub.2 NCO, H.sub.2 NCS, HANCS, A.sub.2 NCS, ASONH, ASO.sub.2 NH, AOSONH, AOSO.sub.2 NH, ACO-alkyl, nitroalkyl, cyanoalkyl, A--C(.dbd.NOH) or A--(.dbd.NNH.sub.2),
- A is alkyl having 1-6 C atoms,
- alkyl is alkylene having 1-6 C atoms and
- Ac is alkanoyl having 1-8 C atoms or aroyl having 7-11 C atoms;
- wherein each A group is chosen independently from all others;
- or a pharmaceutically acceptable salt thereof.
- 13. A chroman compound of the formula ##STR10## wherein R.sup.1 is A,
- R.sup.2 and R.sup.8 are each independently H or A, or
- R.sup.1 and R.sup.2 together are C.sub.3-6 -alkylene,
- R.sup.3 is H, OH, OA, or OAC,
- R.sup.4 is H, or
- R.sup.3 and R.sup.4 together are a bond,
- R.sup.5 is pyridazinyl-, or oxo-dihydro-pyridazinyl-, which is unsubstituted or monosubstituted or disubstituted by A, F, Cl, Br, I, OH, OA, OAc, SH, NO.sub.2, AcNH, HOOC and/or AOOC,
- R.sup.6 and R.sup.7 are each H, A, HO, AO, CHO, ACO, ACS, HOOC, AOOC, AO--CS, ACOO, A--CS--O, hydroxyalkyl having 1-6 C atoms, mercaptoalkyl having 1-6 C atoms, NO.sub.2, NH.sub.2, NHA, NA.sub.2, CN, F, Cl, Br, I, CF.sub.3, ASO, ASO.sub.2, AO--SO, AO--SO.sub.2, AcNH, AO--CO--NH, H.sub.2 NSO, HANSO, A.sub.2 NSO, H.sub.2 NSO.sub.2, HANSO.sub.2, A.sub.2 NSO.sub.2, H.sub.2 NCO, HANCO, A.sub.2 NCO, H.sub.2 NCS, HANCS, A.sub.2 NCS, ASONH, ASO.sub.2 NH, AOSONH, AOSO.sub.2 NH, ACO--C.sub.1-6 -alkyl, nitro-C.sub.1-6 -alkyl, cyano-C.sub.1-6 -alkyl, A--C(.dbd.NOH), or A--C(.dbd.NNH.sub.2),
- Z is O,
- A is alkyl having 1-6 C atoms,
- Ac is alkanoyl having 1-8 C atoms or aroyl having 7-11 C atoms, or a physiologically acceptable salt thereof.
- 14. 2,2-dimethyl-4-(1,6-dihydro-1-methyl-6-oxo-3-pyridazinyl-oxy)-6-cyano-3-chromanol.
- 15. (-)-(3S,4R)-2,2-dimethyl-4-(1,6-dihydro-1-methyl-6-oxo-3-pyridazinyl-oxy)-6-cyano-3-chromanol.
- 16. A chroman according to claim 13, wherein R.sup.1 and R.sup.2 are each CH.sub.3.
- 17. 2,2-dimethyl-4-(6-hydroxy-3-pyridazinyloxy)-6-cyano-3-chromanol, isolated from the medium in which it is prepared.
Priority Claims (5)
Number |
Date |
Country |
Kind |
36 44 094 |
Dec 1986 |
DEX |
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37 26 261 |
Aug 1987 |
DEX |
|
38 15 504 |
May 1988 |
DEX |
|
38 20 506 |
Jun 1988 |
DEX |
|
38 35 011 |
Oct 1988 |
DEX |
|
Parent Case Info
This application is a divisional of application U.S. Ser. No. 07/766,725, filed on Sep. 27, 1991, now U.S. Pat. No. 5,387,587, which is a continuation-in-part of U.S. Ser. No. 07/766,362, filed on Sep. 26, 1991, now abandoned, whose disclosure is entirely incorporated by reference herein, and which is a continuation-in-part of U.S. Ser. No. 07/655,190, filed on Feb. 13, 1991, now abandoned, which is a continuation of U.S. Ser. No. 07/137,201, filed on Dec. 23, 1987, now abandoned; U.S. Ser. No. 07/660,080, filed on Feb. 25, 1991, now abandoned, which is a divisional of U.S. Ser. No. 07/347,710, filed on May 5, 1989, now U.S. Pat. No. 5,013,853; U.S. Ser. No. 07/664,441, filed on Feb. 21, 1991, now abandoned, which is a continuation of U.S. Ser. No. 07/367,281, filed on Jun. 15, 1989, now abandoned; U.S. Ser. No. 07/420,978, filed Oct. 13, 1989, now abandoned, whose entire disclosures are hereby incorporated by reference herein. This application is related to the following disclosures: Bergmann et al., J. Med. Chem. 33 (1990) 492-504; Bergmann et al., J. Med. Chem. 33 (1990) 2760-2767; U.S. Pat. No. 4,952,696; and FRG P 38 35 011.4 of Oct. 14, 1988, the entireties of all of which are hereby incorporated by reference.
US Referenced Citations (19)
Foreign Referenced Citations (4)
Number |
Date |
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0 273 262 |
Jul 1988 |
EPX |
0 296 975 |
Dec 1988 |
EPX |
0 312 432 |
Apr 1989 |
EPX |
38 15 504 |
Nov 1989 |
DEX |
Non-Patent Literature Citations (2)
Entry |
Bergmann et al.I "Synthesis and Antihypertensive Activity of 4-(1,2-Di-hydro-2-oxo-1-pyridyl)-2H-1-benzopyrans and Related Compounds, New Potassium Channel Activators," Journal of Medical Chemistry, vol. 33, No. 2, 1990, pp. 492-504. |
Bergmann et al.II "4-Heterocyclyloxy-2H-1-benzopyran Potassium Channel Activators," Journal of Medical Chemistry, vol. 33, No. 10, 1990, pp. 2759-2767. |
Divisions (2)
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Number |
Date |
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Parent |
766725 |
Sep 1991 |
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Parent |
347710 |
May 1989 |
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Continuations (2)
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Date |
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Parent |
137201 |
Dec 1987 |
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Parent |
367281 |
Jun 1989 |
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Continuation in Parts (2)
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Date |
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Parent |
766362 |
Sep 1991 |
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Parent |
655190 |
Feb 1991 |
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