Betulinol derivatives as anti-HIV agents

A method of treating HIV-1 infection in a subject, said method comprising:

• administering to a subject with HIV-1 infection a therapeutically effective amount of a compound having the formula
• wherein
• R1 is selected from the group consisting of —CH3, ═O, —OH, —OCH3, —OC(O)CH3, —NNH-2,4-DNP, and ═S and
• n is an integer from 1 to 12;
• and
• Z is H or a protective group,
• or a pharmaceutically acceptable salt or derivative thereof, under conditions effective to treat the subject for HIV-1 infection.

A method of treating HIV-1 infection in a subject, said method comprising:

• administering to a subject with HIV-1 infection a therapeutically effective amount of a compound having the formula
• wherein
• Y1 and Y2 are independently selected from the group consisting of —CH3, ═O, —OH, —OCH3, —OC(O)CH3, —NNH-2,4-DNP, and ═S;
• R3 is selected from the group consisting of H and C1-C5 alkyl;
• Z is H or a protective group;
• and
• n is an integer from 1 to 12,
• or a pharmaceutically acceptable salt or derivative thereof, under conditions effective to treat the subject for HIV-1 infection.

A method of treating HIV-1 infection in a subject, said method comprising:

• administering to a subject with HIV-1 infection a therapeutically effective amount of a compound having the formula
• wherein
• Y1 and Y2 are independently selected from the group consisting of —CH3, ═O, —OH, —OCH3, —OC(O)CH3, —NNH-2,4-DNP, and ═S;
• Z is H or a protective group;
• and
• n is an integer from 1 to 12,
• or a pharmaceutically acceptable salt or derivative thereof, under conditions effective to treat the subject for HIV-1 infection.

A method of treating HIV-1 infection in a subject, said method comprising:

• administering to a subject with HIV-1 infection a therapeutically effective amount of a compound having the formula
• wherein
• Y1, Y2, Y3, and Y4 are independently selected from the group consisting of —CH3, ═O, —OH, —OCH3, —OC(O)CH3, —NNH-2,4-DNP, and ═S;
• R3 is selected from the group consisting of H and C1-C5 alkyl;
• n is an integer from 1 to 12;
• and
• Z is H or a protective group,
• or a pharmaceutically acceptable salt or derivative thereof, under conditions effective to treat the subject for HIV-1 infection.

A method of treating HIV-1 infection in a subject, said method comprising:

• administering to a subject with HIV-1 infection a therapeutically effective amount of a compound having the formula
• wherein
• Y1, Y2, Y3, and Y4 are independently selected from the group consisting of —CH3, ═O, —OH, —OCH3, —OC(O)CH3, —NNH-2,4-DNP, and ═S;
• n is an integer from 1 to 12;
• and
• Z is H or a protective group,
• or a pharmaceutically acceptable salt or derivative thereof, under conditions effective to treat the subject for HIV-1 infection.

A method of treating HIV-1 infection in a subject, said method comprising:

• administering to a subject with HIV-1 infection a therapeutically effective amount of a compound having the formula
• wherein
• BA is a compound having the formula:
• wherein
• Y is selected from the group consisting of —CH3, ═O, —OH, —OCH3, —OC(O)CH3, —NNH-2,4-DNP, and ═S;
• * is a binding site;
• Q is BA, a leaving group, or H;
• R3 is H or C1-C5 alkyl;
• n is an integer from 1 to 12;
• and
• m is an integer from 1 to 6,
• or a pharmaceutically acceptable salt or derivative thereof, under conditions effective to treat the subject for HIV-1 infection.

A method of treating HIV-1 infection in a subject, said method comprising:

• administering to a subject with HIV-1 infection a therapeutically effective amount of a compound having the formula
• wherein
• BA is a compound having the formula:
• wherein
• Y is selected from the group consisting of —CH3, ═O, —OH, —OCH3, —OC(O)CH3, —NNH-2,4-DNP, and ═S;
• * is a binding site;
• Q is BA, a leaving group, or H;
• n is an integer from 1 to 12;
• and
• m is an integer from 1 to 6,
• or a pharmaceutically acceptable salt or derivative thereof, under conditions effective to treat the subject for HIV-1 infection.

A method of inhibiting HIV-1 activity in a cell, said method comprising:

• providing a cell infected with HIV-1 and
• contacting the cell with a compound having the formula
• wherein
• R1 is selected from the group consisting of —CH3, ═O, —OH, —OCH3, —OC(O)CH3, —NNH-2,4-DNP, and ═S and
• R3 is selected from the group consisting of H and C1-C5 alkyl,
• n is an integer from 1 to 12;
• and
• Z is H or a protective group,
• or a pharmaceutically acceptable salt or derivative thereof, under conditions effective to inhibit HIV-1 activity in the cell.

A method of inhibiting HIV-1 activity in a cell, said method comprising:

• providing a cell infected with HIV-1 and
• contacting the cell with a compound having the formula
• wherein
• R1 is selected from the group consisting of —CH3, ═O, —OH, OCH3, —OC(O)CH3, —NNH-2,4-DNP, and ═S and
• n is an integer from 1 to 12;
• and
• Z is H or a protective group,
• or a pharmaceutically acceptable salt or derivative thereof, under conditions effective to inhibit HIV-1 activity in the cell.

A method of inhibiting HIV-1 activity in a cell, said method comprising:

• providing a cell infected with HIV-1 and
• contacting the cell with a compound having the formula
• wherein
• Y1 and Y2 are independently selected from the group consisting of —CH3, ═O, —OH, —OCH3, —OC(O)CH3, —NNH-2,4-DNP, and ═S;
• R3 is selected from the group consisting of H and C1-C5 alkyl;
• Z is H or a protective group;
• and
• n is an integer from 1 to 12,
• or a pharmaceutically acceptable salt or derivative thereof, under conditions effective to inhibit HIV-1 activity in the cell.

A method of inhibiting HIV-1 activity in a cell, said method comprising:

• providing a cell infected with HIV-1 and
• contacting the cell with a compound having the formula
• wherein
• Y1 and Y2 are independently selected from the group consisting of —CH3, ═O, —OH, —OCH3, —OC(O)CH3, —NNH-2,4-DNP, and ═S;
• Z is H or a protective group;
• and
• n is an integer from 1 to 12,
• or a pharmaceutically acceptable salt or derivative thereof, under conditions effective to inhibit HIV-1 activity in the cell.

A method of inhibiting HIV-1 activity in a cell, said method comprising:

• providing a cell infected with HIV-1 and
• contacting the cell with a compound having the formula
• wherein
• Y1, Y2, Y3, and Y4 are independently selected from the group consisting of —CH3, ═O, —OH, —OCH3, —OC(O)CH3, —NNH-2,4-DNP, and ═S;
• R3 is selected from the group consisting of H and C1-C5 alkyl;
• n is an integer from 1 to 12;
• and
• Z is H or a protective group,
• or a pharmaceutically acceptable salt or derivative thereof, under conditions effective to inhibit HIV-1 activity in the cell.

A method of inhibiting HIV-1 activity in a cell, said method comprising:

• providing a cell infected with HIV-1 and
• contacting the cell with a compound having the formula
• wherein
• Y1, Y2, Y3, and Y4 are independently selected from the group consisting of —CH3, ═O, —OH, —OCH3, —OC(O)CH3, —NNH-2,4-DNP, and ═S;
• n is an integer from 1 to 12;
• and
• Z is H or a protective group,
• or a pharmaceutically acceptable salt or derivative thereof, under conditions effective to inhibit HIV-1 activity in the cell.

A method of inhibiting HIV-1 activity in a cell, said method comprising:

• providing a cell infected with HIV-1 and
• contacting the cell with a compound having the formula
• wherein
• BA is a compound having the formula:
• wherein
• Y is selected from the group consisting of —CH3, ═O, —OH, —OCH3, —OC(O)CH3, —NNH-2,4-DNP, and ═S;
• * is a binding site;
• Q is BA, a leaving group, or H;
• R3 is H or C1-C5 alkyl;
• n is an integer from 1 to 12;
• and
• m is an integer from 1 to 6,
• or a pharmaceutically acceptable salt or derivative thereof, under conditions effective to inhibit HIV-1 activity in the cell.

A method of inhibiting HIV-1 activity in a cell, said method comprising:

• providing a cell infected with HIV-1 and
• contacting the cell with a compound having the formula
• wherein
• BA is a compound having the formula:
• wherein
• Y is selected from the group consisting of —CH3, ═O, —OH, —OCH3, —OC(O)CH3, —NNH-2,4-DNP, and ═S;
• * is a binding site;
• Q is BA, a leaving group, or H;
• n is an integer from 1 to 12;
• and
• m is an integer from 1 to 6,
• or a pharmaceutically acceptable salt or derivative thereof, under conditions effective to inhibit HIV-1 activity in the cell.

A method of treating and/or inhibiting HIV-1 infection in a human, which comprises:

• administering to a human infected with HIV-1 a therapeutically effective amount of a compound having the formula
• wherein
• n is an integer from 1 to 12 and
• Z is H or a protective group,
• or a pharmaceutically acceptable salt or derivative thereof, under conditions effective to treat and/or inhibit the human for HIV-1 infection.

A method of treating and/or inhibiting HIV-1 infection in a human, said method comprising:

• administering to a human infected with HIV-1 a therapeutically effective amount of a compound having the formula
• wherein
• Z is H or a protective group,
• or a pharmaceutically acceptable salt or derivative thereof, under conditions effective to treat and/or inhibit the human for HIV-1 infection.

A method of treating and/or inhibiting HIV-1 infection in a subject, which comprises:

• administering to a subject infected with HIV- I a therapeutically effective amount of a compound having the formula:
• wherein
• BA is a compound having the formula:
• wherein
• Y is selected from the group consisting of —CH3, ═O, —OH, —OCH3, —OC(O)CH3, —NNH-2,4-dinitrophenyl hydrazine, and ═S;
• * is a binding site;
• X is selected from the group consisting of
• each R4 is independently selected from the group consisting of H, CH3, CH2—CH3, NH2 and OH;
• Z is H, a protective group, or BA;
• n is an integer from 1 to 8;
• m is an integer from 1 to 6;
• and
• q is 0 or 1,
• or a pharmaceutically acceptable salt thereof.

A method of treating HIV-1 infection in a subject, which comprises:

• administering to a subject infected with HIV-1 a therapeutically effective amount of a compound having the formula:
• wherein
• W is H, OX, or CH2—OX;
• and
• each X is independently H, a sugar, or BA, and wherein at least 1 X is BA;
• and
• BA is a compound having the formula:
• wherein
• Y is selected from the group consisting of —CH3, ═O, —OH, —OCH3, —OC(O)CH3, —NNH-2,4-dinitrophenyl hydrazine, and ═S;
• and
• * is a binding site,
• or a pharmaceutically acceptable salt thereof.

A method of treating HIV-1 infection in a human, which comprises:

• administering to a human infected with HIV-1 a therapeutically effective amount of a compound having the formula:
• wherein
• W is H, OX, or CH2—OX;
• and
• each X is independently H, a sugar, or BA, and wherein at least 1 X is BA;
• and
• BA is a compound having the formula:
• wherein
• Y is selected from the group consisting of —CH3, ═O, —OH, —OCH3, —OC(O)CH3, —NNH-2,4-dinitrophenyl hydrazine, and ═S;
• and
• * is a binding site,
• or a pharmaceutically acceptable salt thereof under conditions effective to treat the human for HIV-1 infection.

A method of treating HIV-1 infection in a subject, which comprises:

• administering to a subject infected with HIV-1 a therapeutically effective amount of a compound having the formula:
• wherein
• each X is H or a compound of the formula:
• wherein
• Y is selected from the group consisting of —CH3, ═O, —H, —OCH3, —OC(O)CH3, —NNH-2,4-dinitrophenyl hydrazine, and ═S;
• * is a binding site,
• n is an integer from 1 to 8;
• p is 0 or 1;
• and
• m is an integer from 1 to 8;
• wherein at least one X is not H, or a pharmaceutically acceptable salt thereof.

A method of treating HIV-1 infection in a human, which comprises:

• administering to a human infected with HIV-1 a therapeutically effective amount of a compound having the formula:
• wherein
• each X is H or a compound of the formula:
• wherein
• Y is selected from the group consisting of —CH3, ═O, —OH, —OCH3, —OC(O)CH3, —NNH-2,4-dinitrophenyl hydrazine, and ═S;
• * is a binding site,
• n is an integer from 1 to 8;
• p is 0 or 1;
• and
• m is an integer from 1 to 8;
• wherein at least one X is not H, or a pharmaceutically acceptable salt thereof under conditions effective to treat the human for HIV-1 infection.

A method of treating HIV-1 infection in a subject, which comprises:

• administering to a subject infected with HIV-1 a therapeutically effective amount of a compound having the formula:
• wherein
• R is a C1 to C5 alkyl;
• n is an integer between 5 and 1000;
• and
• BA is a compound having the formula:
• wherein
• Y is selected from the group consisting of —CH3, ═O, —OH, —OCH3, —OC(O)CH3, —NNH-2,4-dinitrophenyl hydrazine, and ═S;
• and
• * is a binding site,
• or a pharmaceutically acceptable salt thereof.

A method of treating HIV-1 infection in a human, which comprises:

• administering to a human infected with HIV-1 a therapeutically effective amount of a compound having the formula:
• wherein
• R is a C1 to C5 alkyl;
• n is an integer between 5 and 1000;
• and
• BA is a compound having the formula:
• wherein
• Y is selected from the group consisting of CH3, ═O, —OH, —OCH3, —OC(O)CH3, —NNH-2,4-dinitrophenyl hydrazine, and ═S;
• and
• * is a binding site,
• or a pharmaceutically acceptable salt thereof under conditions effective to treat the human for HIV-1 infection.