Claims
- 1. A method for preventing or treating HIV-1 infection which comprises administering, to a human exposed to or infected by HIV-1, a prophylactically or therapeutically effective amount of a compound of the formula I ##STR20## wherein, A is a fused ring of the formula ##STR21## Z is oxygen, sulfur, .dbd.NCN or a group of the formula .dbd.NOR.sup.14 wherein R.sup.14 is alkyl of 1 to 3 carbon atoms;
- R.sup.1 is hydrogen, alkyl or fluoroalkyl of 1 to 4 carbon atoms, cyclopropyl, alkenyl or alkynyl of 3 to 4 carbon atoms, 2-halo-propen-1-yl, arylmethyl (wherein the aryl moiety is phenyl or thienyl, which is either unsubstituted or substituted by methyl, methoxy or halogen), acetyl, or alkoxyalkyl or alkylthioalkyl of 2 to 3 carbon atoms;
- R.sup.2 is alkyl or fluoroalkyl of 1 to 4 carbon atoms, cycloalkyl of 3 to 5 carbon atoms, alkenyl or alkynyl of 2 to 4 carbon atoms, alkoxyalkyl or alkylthioalkyl of 2 to 3 carbon atoms, alkanoyl of 2 to 3 carbon atoms, hydroxyalkyl of 2 to 4 carbon atoms, arylmethyl (wherein the aryl moiety is phenyl, thienyl or furanyl, which is either unsubstituted or substituted by alkyl or alkoxy of 1 to 3 carbon atoms, hydroxyl or halogen), phenyl (which is either unsubstituted or substituted by alkyl or alkoxy of 1 to 3 carbon atoms, halogen or hydroxyl) or alkoxycarbonylmethyl wherein the alkoxy moiety contains 1 to 5 carbon atoms;
- R.sup.3, R.sup.4 and R.sup.5 are each independently hydrogen, alkyl of 1 to 3 carbon atoms or chloro, with the proviso that at least one of these substituents is hydrogen or methyl; or,
- one of R.sup.3, R.sup.4 and R.sup.5 is butyl, alkanoyl of 2 to 4 carbon atoms, alkoxycarbonyl or 2 to 4 carbon atoms, hydroxyalkyl of 1 to 4 carbon atoms, alkoxycarbonylalkyl wherein the alkoxy and alkyl moieties each contain 1 to 2 carbon atoms, halogen, trihalomethyl, hydroxyl, alkoxy of 1 to 3 carbon atoms, alkylthio of 1 to 3 carbon atoms, aryl or arylalkyl (wherein the alkyl moiety contains 1 to 3 carbon atoms, and the aryl moiety is phenyl, thienyl, furanyl, pyridyl, or imidazolyl, which is either unsubstituted or substituted by alkyl or alkoxy of 1 to 3 carbon atoms, hydroxyl or halogen), alkanoyloxy of 2 to 3 carbon atoms, alkanoylamino of 1 to 3 carbon atoms, aminoalkyl of 1 to 3 carbon atoms, mono- or di-alkylamino wherein each alkyl moiety contains 1 to 3 carbon atoms, N-pyrrolidino, N-piperidino, N-morpholino, carboxyalkyl of 2 to 3 carbon atoms, cyano, nitro, carboxyl, carbamyl, amino, azido, mono- or di-alkylaminoalkyl wherein each alkyl moiety contains 1 to 2 carbon atoms, with the proviso that the remaining two substituents are hydrogen or methyl; or,
- when Z is oxygen, one of R.sup.3, R.sup.4 and R.sup.5 is alkylsulfinyl or alkylsulfonyl of 1 to 3 carbon atoms, with the proviso that the remaining two substituents are hydrogen or methyl;
- R.sup.6, R.sup.7, R.sup.8 and R.sup.9 are each hydrogen; or
- one of R.sup.6, R.sup.7, R.sup.8 and R.sup.9 is alkyl of 1 to 4 carbon atoms, alkanoyl of 2 to 4 carbon atoms, alkoxycarbonyl of 2 to 4 carbon atoms, hydroxyalkyl of 1 to 4 carbon atoms, alkoxycarbonylalkyl wherein the alkoxy and alkyl moieties each contain 1 to 2 carbon atoms, halogen, trihalomethyl, hydroxyl, alkoxy of 1 to 3 carbon atoms, alkylthio of 1 to 3 carbon atoms, alkanoyloxy of 2 to 3 carbon atoms, alkanoylamino of 1 to 3 carbon atoms, aminoalkyl of 1 to 3 carbon atoms, mono- or di-alkylamino wherein each alkyl moiety contains 1 to 2 carbon atoms, carboxyalkyl of 2 to 3 carbon atoms, cyano, nitro, carboxyl, carbamyl, amino, azido, mono- or di-alkylaminoalkyl wherein each alkyl moiety contains 1 to 2 carbon atoms, and the remaining three substituents are hydrogen or two of the remaining three substituents are hydrogen and one is methyl, ethyl or halogen;
- R.sup.10 and R.sup.11 are each independently hydrogen, alkyl of 1 to 3 carbon atoms or halogen; and,
- R.sup.12 and R.sup.13 are each independently hydrogen, methyl, ethyl or halogen,
- or a pharmaceutically acceptable acid addition salt thereof.
- 2. The method of claim 1, utilizing a compound of the formula Ia, ##STR22## wherein, Z is oxygen or sulfur;
- R.sup.1 is hydrogen, alkyl of 1 to 3 carbon atoms, allyl, propargyl, 2-halo-propen-1-yl, methoxymethyl or methylthiomethyl;
- R.sup.2 is alkyl 1 to 4 carbon atoms, cycloalkyl of 3 to 4 carbon atoms, alkenyl or alkynyl of 2 to 4 carbon atoms, alkoxyalkyl or alkylthioalkyl of 2 to 3 carbon atoms, alkanoyl of 2 to 3 carbon atoms, hydroxyalkyl of 2 to 4 carbon atoms, arylmethyl (wherein the aryl moiety is phenyl or thienyl, which is either unsubstituted or substituted by methyl, methoxy or halogen) or alkoxycarbonylmethyl wherein the alkoxy moiety contains 1 to 4 carbon atoms;
- R.sup.3, R.sup.4, and R.sup.5 are each independently hydrogen, methyl, chloro, mono- or di-alkylamino wherein each alkyl moiety contains 1 to 3 carbon atoms, N-pyrrolidino, N-piperidino or N-morpholino, with the proviso that at least one of these substituents is hydrogen or methyl, or R.sup.5 is ethyl, propyl or butyl with the remaining two substituents being hydrogen;
- R.sup.6 is hydrogen, or methyl or ethyl with the proviso that R.sup.7 is hydrogen or methyl;
- R.sup.7 is alkyl of 1 to 2 carbon atoms, acetyl, hydroxyalkyl of 1 to 2 carbon atoms, alkoxycarbonyl of 2 to 3 carbon atoms, alkoxycarbonylalkyl wherein the alkoxy and alkyl moieties each contain 1 to 2 carbon atoms, halogen, trifluoromethyl, hydroxyl, alkoxy of 1 to 2 carbon atoms, alkylthio of 1 to 2 carbon atoms, acetyloxy, alkanoylamino of 1 to 2 carbon atoms or cyano, with the proviso that R.sup.8 is hydrogen;
- R.sup.8 is alkyl of 1 to 2 carbon atoms, acetyl, hydroxyalkyl of 1 to 2 carbon atoms, alkoxycarbonyl of 2 to 3 carbon atoms, alkoxycarbonylalkyl wherein the alkoxy and alkyl moieties each contain 1 to 2 carbon atoms, halogen, trifluoromethyl, hydroxyl, alkoxy of 1 to 2 carbon atoms, alkylthio of 1 to 2 carbon atoms, acetyl, alkanoylamino of 1 to 2 carbon atoms or cyano, with the proviso that R.sup.7 is hydrogen; or,
- R.sup.7 and R.sup.8 are both hydrogen, methyl or halogen; and,
- R.sup.9 is hydrogen, or methyl with the proviso that R.sup.8 is hydrogen or methyl;
- or a pharmaceutically acceptable acid addition salt thereof.
- 3. The method of claim 2, wherein, in the compound of formula Ia:
- Z is oxygen or sulfur;
- R.sup.1 is hydrogen, 2-halo-2-propen-1-yl, or alkyl of 1 to 3 carbon atoms;
- R.sup.2 is alkyl of 1 to 4 carbon atoms or cycloalkyl of 3 to 4 carbon atoms;
- R.sup.3 is hydrogen, methyl, chloro, methoxy, mono- or di-alkylamino wherein each alkyl moiety contains 1 to 3 carbon atoms, or N-pyrrolidino;
- R.sup.4 and R.sup.5 are each independently hydrogen or methyl; and,
- R.sup.6 through R.sup.9 are each hydrogen.
RELATED APPLICATIONS
This is a continuation-in-part of application Ser. No. 600,554, filed Oct. 19, 1990, which is a continuation-in-part of application Ser. No. 438,922, filed Nov. 17, 1989, now abandoned, which is a continuation-in-part of application Ser. No. 372,728, filed June 28, 1989, now abandoned, which is a continuation-in-part of application Ser. No. 340,937, filed Apr. 20, 1989, now abandoned.
US Referenced Citations (1)
Number |
Name |
Date |
Kind |
3539554 |
Schmidt |
Nov 1970 |
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Continuation in Parts (4)
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Number |
Date |
Country |
Parent |
600554 |
Oct 1990 |
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Parent |
438922 |
Nov 1989 |
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Parent |
372728 |
Jun 1989 |
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Parent |
340937 |
Apr 1989 |
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