Methanol derivatives for treatment of retroviral infections especially HIV infections
AssigneePharmacia & Upjohn Company
InventorHerman W. Smith
Life of this patent
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Abstract
The present invention relates to compounds of formula (I) which are imidazo[2,1-b]benzothiazole-3-methanol and imidazo[2,1-b]thiazole-5-methanol derivatives useful for inhibiting a retrovirus in a mammalian cell infected with said retrovirus, wherein R1 is —H or —CH3; wherein R2 is —H or —CH3; or wherein R1 and R2 taken together are (a) formula (II), or (b) formula (III).
Claims15
A compound of the formula I
- wherein R1 is —H or —CH3;
- wherein R2 is —H or —CH3;
- or
- wherein R1 and R2 taken together are
- wherein p is 1 to 4 inclusive;
- or
- wherein R6 is
- a) —H,
- b) —CH3,
- c) —F, or
- d) —OCH3;
- wherein R3 is
- a) —CH2C6H5,
- b) —CH2CH2C6H5,
- c) —CH2CH2CH2C6H5,
- d) —CH2CH2CH2CH2C6H5,
- e) —CH2CH(CH3)C6H5,
- f) —CH2CH2C6H4X,
- wherein X may occupy either the ortho, meta or para-positions and is
- i) F
- ii) Cl,
- iii) Br,
- iv) OCH2R1,
- v) N(CH3)2,
- vi) NHSO2CH2R1,
- vii) SCH3
- viii) NHCOCH2R1, or
- ix) NHSO2C6H4X1,
- wherein X1 is
- a. H,
- b. CH3,
- c. F, or
- d. CN;
- g) —CH═CH—C6H5, (cis or trans);
- h) —CH≡C—C6H5);
- i) CH═CH—C6H3X2
- wherein X2 is
- a. F,
- b. Cl,
- c. OCH3, or
- d. OCH2O;
- wherein CH2CH2 is appended to the 1- or 2-positions;
- or
- wherein
- i) —CH2CH2— appended to the 2- or 3-positions,
- ii) X3 is
- a. O,
- b. S,
- c. NH,
- d. NCH3, and
- iii) R7 is
- a. CH3, or
- b. CH3CH2;
- wherein R4 is —H or —CH3;
- and
- wherein R5 is —H or —CH3;
- provided that when R1 is —CH3 and R2 is —H or —CH3, R4 is not —H.
A method for treatment of mammals infected with a retrovirus, said method comprising administering to a mammal infected with said retrovirus a therapeutically effective amount of a compound of the formula I
- wherein R1 is —H or —CH3;
- wherein R2 is —H or —CH3;
- or
- wherein R1 and R2 taken together are
- wherein p is 1 to 4 inclusive;
- or
- wherein R6 is
- a) —H
- b) —CH3,
- c) —F, or
- d) —OCH3;
- wherein R3 is
- a) —CH2C6H5,
- b) —CH2CH2C6H5,
- c) —CH2CH2CH2C6H5,
- d) —CH2CH2CH2CH2C6H5,
- e) —CH2CH(CH3)C6H5,
- f) —CH2CH2C6H4X,
- wherein X may occupy either the ortho, meta or para-positions and is
- i) F,
- ii) Cl,
- iii) Br,
- iv) OCH2R1,
- v) N(CH3)2,
- vi) NHSO2CH2R1,
- vii) SCH3
- viii) NHCOCH2R1, or
- ix) NHSO2C6H4X1,
- wherein X1is
- a. H,
- b. CH3,
- c. F, or
- d. CN;
- g) —CH═CH—C6H5, (cis or trans);
- h) —CH≡C—C6H5);
- i) —CH═CH—C6H3X2
- wherein X2 is
- a. F,
- b. Cl,
- c. OCH3, or
- d. —O—CH2O;
- wherein CH2CH2 is appended to the 1- or 2-positions;
- or
- wherein
- i) —CH2CH2— appended to the 2- or 3- positions,
- ii) X3 is
- a. O,
- b. S,
- c. NH, and
- d. —NCH3;
- iii) R7 is
- a. CH3, or
- b. CH3CH2;
- wherein R4 is —H or —CH3;
- and
- wherein R5 is —H or —CH3;
- provided that when R1 is —CH3 and R2 is —H or —CH3, R4 is not —H.
A pharmaceutical composition for use in treatment of a mammal infected with a retrovirus, said composition comprising a pharmaceutically acceptable solvent, diluent, adjuvant or carrier and, as the active ingredient, from about 0.1 mg to 100 mg per kg of body weight per day of a compound of the formula I
- wherein R1 is —H or —CH3;
- wherein R2 is —H or —CH3;
- or
- wherein R1 and R2 taken together are
- wherein p is 1 to 4 inclusive;
- or
- wherein R6 is
- a) —H
- b) —CH3,
- c) —F, or
- d) —OCH3;
- wherein R3 is
- a) —CH2C6H5,
- b) —CH2CH2C6H5,
- c) —CH2CH2CH2C6H5,
- d) —CH2CH2CH2CH2C6H5,
- e) —CH2CH(CH3)C6H5,
- f) —CH2CH2C6H4X,
- wherein X may occupy either the ortho, meta or para positions and is
- i) F,
- ii) Cl,
- iii) Br,
- iv) OCH2R1,
- v) N(CH3)2,
- vi) NHSO2CH2R1,
- vii) SCH3
- viii) NHCOCH2R1, or
- ix) NHSO2C6H4X1,
- wherein X1 is
- a. H,
- b. CH3,
- c. F, or
- d. CN;
- g) —CH═CH—C6H5, (cis or trans);
- h) —CH≡C—C6H5);
- i) CH═CH—C6H3X2
- wherein X2 is
- a. F,
- b. Cl,
- c. OCH3, or
- d. —O—CH2O;
- wherein CH2CH2 is appended to the 1- or 2-positions;
- or
- wherein
- i) —CH2CH2— appended to the 2- or 3-positions,
- ii) X3 is
- a. O,
- b. S,
- c. NH,
- d. —NCH3, and
- iii) R7 is
- a. CH3, or
- b. CH3CH2;
- wherein R4 is —H or —CH3;
- and
- wherein R5 is —H or —CH3;
- provided that when R1 is —CH3 and R2 is —H or —CH3, R4 is not —H.
A compound selected from the group consisting of:
- α-[2-(4-Fluorophenyl)ethenyl]-6,7,8,9-tetrahydro-5H-cyclohept[d]imidazo[2,1-b]thiazol-3-methanol,
- α-[2-(3,5-Difluorophenyl)ethyl]-1-6,7,8,9-tetrahydro-5H-cyclohept[d]-imidazothiazol-3-methanol,
- α-[2-(2,3-Difluorophenyl)ethyl]-6,7,8,9-tetrahydro-5H-cyclohept[d]imidazothiazol-3-methanol,
- α-[2-(4-methoxyphenyl)ethenyl]-6,7,8,9-tetrahydro-5H-cyclohept-[d]imidazo[2, 1-b]thiazol-3-methanol,
- α-[2-(2-Furanyl)ethenyl]-6,7,8,9-tetrahydro-5H-cyclohept[d]imidazo[2,1-b]thiazol-3-methanol,
- α-[2-(2-Furanyl)ethyl]-6,7,8,9-tetrahydro-5H-cyclohept[d]imidazo[2,1-b]thiazol-3-methanol,
- α-[2-(3-Furanyl)ethyl]-6,7,8,9-tetrahydro-5H-cyclohept[d]imidazo[2,1-b]thiazol-3-methanol,
- α-[2-(2-Furanyl)ethenyl]2,3-dimethylimidazo[2,1-b]thiazol-3-methanol, and
- α-[2-(2-Furanyl)ethyl]2,3-dimethylimidazo[2,1-b]thiazol-3-methanol.
A method for treatment of mammals infected with a retrovirus, said method comprising administering to a mammal infected with said retrovirus a therapeutically effective amount of a compound selected from the group consisting of:
- α-[2-(4-Fluorophenyl)ethenyl]-6,7,8,9-tetrahydro-5H-cyclohept[d]imidazo[2,1-b]thiazol-3-methanol,
- α-[2-(3,5-Difluorophenyl)ethyl]-1-6,7,8,9-tetrahydro-5H-cyclohept[d]-imidazothiazol-3-methanol,
- α-[2-(2,3-Difluorophenyl)ethyl]-6,7,8,9-tetrahydro-5H-cyclohept[d]imidazothiazol-3-methanol,
- α-[2-(4-methoxyphenyl)ethenyl]-6,7,8,9-tetrahydro-5H-cyclohept-[d]imidazo[2, 1-b]thiazol-3-methanol,
- α-[2-(2-Furanyl)ethenyl]-6,7,8,9-tetrahydro-5H-cyclohept[d]imidazo[2,1-b]thiazol-3-methanol,
- α-[2-(2-Furanyl)ethyl]-6,7,8,9-tetrahydro-5H-cyclohept[d]imidazo[2,1-b]thiazol-3-methanol,
- α-[2-(3-Furanyl)ethyl]-6,7,8,9-tetrahydro-5H-cyclohept[d]imidazo[2,1-b]thiazol-3-methanol,
- α-[2-(2-Furanyl)ethenyl]2,3-dimethylimidazo[2,1-b]thiazol-3-methanol, and
- α-[2-(2-Furanyl)ethyl]2,3-dimethylimidazo[2,1-b]thiazol-3-methanol.
A pharmaceutical composition for use in treatment of a mammal infected with a retrovirus, said composition comprising a pharmaceutically acceptable solvent, diluent, adjuvant or carrier and, as the active ingredient, from about 0.1 mg to 100 mg per kg of body weight per day of a compound selected from the group consisting of:
- α[2-(4-Fluorophenyl)ethenyl]-6,7,8,9-tetrahydro-5H-cyclohept[d]imidazo[2,1-b]thiazol-3-methanol,
- α[2-(3,5-Difluorophenyl)ethyl]-6,7,8,9-tetrahydro-5H-cyclohept[d]-imidazothiazol-3-methanol,
- α[2-(2,3-Difluorophenyl)ethyl]-6,7,8,9-tetrahydro-5H-cyclohept[d]-imidazothiazol-3-methanol,
- α[2-(4-methoxyphenyl)ethenyl]-6,7,8,9-tetrahydro-5H-cyclohept-[d]imidazo[2, 1-b]thiazol-3-methanol,
- α[2-(2-Furanyl)ethenyl]-6,7,8,9-tetrahydro-5H-cyclohept[d]imidazo[2,1-b]thiazol-3-methanol,
- α[2-(2-Furanyl)ethyl]-6,7,8,9-tetrahydro-5H-cyclohept[d]imidazo[2,1-b]thiazol-3-methanol,
- α[2-(3-Furanyl)ethyl]-6,7,8,9-tetrahydro-5H-cyclohept[d]imidazo[2,1-b]thiazol-3-methanol,
- α[2-(2-Furanyl)ethenyl]2,3-dimethylimidazo[2,1-b]thiazol-3-methanol, and
- α[2-(2-Furanyl)ethyl]2,3-dimethylimidazo[2,1-b]thiazol-3-methanol.
Dependencies are inferred from the claim text.