1. A compound of Formula I
wherein:
R1 is
R2 and R3 are independently hydrogen or C1-6alkyl;
R4 and R5 are independently hydrogen, halo, cyano, C1-6alkoxy, CO2R2, CON(R2)(R2), or Ar5;
R6 is hydrogen, amino, C1-6alkylamino, C1-6dialkylamino, or pyrrolyl;
Ar1 is
Ar2 is phenyl, furanyl, thienyl, or pyrrolyl and is substituted with 0\u20132 substituents selected from the group consisting of C1-6alkoxy, halo, trifluoromethyl, cyano, amino, and hydroxy; and
Ar5 is pyridinyl, pyrimidinyl, pyrazolyl, triazolyl, or tetraolyl, and is substituted with 0\u20131 C1-6alkyl;
or a pharmaceutically acceptable salt thereof.
2. A compound of claim 1 where Ar1 is
3. A compound of claim 2 where Ar1 is
4. A compound of claim 1 where Ar1 is
5. A compound of claim 4 where R6 is hydrogen, amino, or pyrrolyl.
6. A compound of claim 1 where R2 and R3 are hydrogen.
7. A compound of claim 1 where R2 is methyl and R3 is hydrogen.
8. A compound of claim 1 where R2 is hydrogen and R3 is methyl.
9. A compound of claim 1 where Ar2 is phenyl and is substituted with 0\u20132 substituents selected from the group consisting of C1-6alkoxy, halo, trifluoromethyl, cyano, amino, and hydroxy.
10. A compound of claim 9 where Ar2 is phenyl.
11. A compound of claim 1 selected from the group consisting of
(2R)-1-2-(2-benzothiazolyl)-1,2-dioxoethyl-4-benzoyl-2-methyl-piperazine;
(2R)-4-benzoyl-1-2-(6-methoxy-2-benzothiazolyl)- 1,2-dioxoethyl-2-methyl-piperazine;
(2R)-1-2-(5-benzothiazolyl)-1,2-dioxoethyl-4-benzoyl-2-methyl-piperazine;
(2R)-4-benzoyl- 1-1,2-dioxo-2-2-(1H-pyrrol-1-yl)-5-benzothiazolylethyl-2-methyl-piperazine; and
(2R)- 1 -2-(2-amino-5 -bezothiazolyl)- 1,2-dioxoethyl-4-benzoyl-2-methyl-piperazine;
or a pharmaceutically acceptable salt thereof.
12. A compound of Formula IIa or IIb
wherein:
Ar1 is
Ar2 is phenyl, furanyl, thienyl, or pyrrolyl and is substituted with 0\u20132 substituents selected from the group consisting of C6-4alkoxy, halo, trifluoromethyl, cyano, amino, and hydroxy;
R2 and R3 are independently hydrogen or C1-6alkyl;
R4 and R5 are independently hydrogen, halo, or C1-6alkoxy; and
R6 is hydrogen, amino, C1-6alkylamino, C1-6dialkylamino, or pyrrolyl;
or a pharmaceutically acceptable salt thereof.
13. A pharmaceutical composition comprising a therapeutically effective amount of a compound of claim 1 and a pharmaceutically acceptable carrier.
14. A pharmaceutical composition comprising a therapeutically effective amount of a compound of claim 12 and a pharmaceutically acceptable carrier.
15. A method of treating HIV infection in a patient comprising administering a therapeutically effective amount of a compound of claim 1.
16. The method of claim 15 further comprising administering a therapeutically effective amount of at least one other agent for treating HIV selected from the group consisting of HIV reverse transcriptase inhibitors, non-nucleoside HIV reverse transcriptase inhibitors, HIV protease inhibitors, HIV fusion inhibitors, HIV attachment inhibitors, CCR5 inhibitors, CXCR4 inhibitors, HIV budding or maturation inhibitors, and HIV integrase inhibitors.
17. A method of treating HIV infection in a patient comprising administering a therapeutically effective amount of a compound of claim 12.
18. The method of claim 17 further comprising administering a therapeutically effective amount of at least one other agent for treating HIV selected from the group consisting of HIV reverse transcriptase inhibitors, non-nucleoside HIV reverse transcriptase inhibitors, HIV protease inhibitors, HIV fusion inhibitors, HIV attachment inhibitors, CCR5 inhibitors, CXCR4 inhibitors, HIV budding or maturation inhibitors, and HIV integrase inhibitors.
The claims below are in addition to those above.
All refrences to claim(s) which appear below refer to the numbering after this setence.
1-5. (canceled)
6. An in vitro culture comprising a replenishable population of primate trophoblast cells derived from undifferentiated primate stem cells exposed to a trophoblast inducing factor, wherein the factor is selected from the group consisting of bone morphogenic protein 4 (BMP4), bone morphogenic protein 2(BMP2), bone morphogenic protein 7(BMP7) and growth and differentiation factor 5(GDF5), and wherein the stem-cell derived trophoblast cells express chorionic gonadotropin and are derived directly from undifferentiated cells without passing through an embryoid body stage.
7. (canceled)
8. The culture of claim 6 wherein the trophoblast cells are human cells.
9. The culture of claim 6 wherein the trophoblast cells are non-human primate cells.
10. A method of testing the effect of an agent on cells of the primate trophoblast lineage comprising:
(a) culturing undifferentiated primate stem cells in a culture medium comprising a protein trophoblast inducing factor selected from the group consisting of bone morphogenic protein 4 (BMP4), bone morphogenic protein 2(BMP2), bone morphogenic protein 7(BMP7) and growth and differentiation factor 5 (GDF5);
(b) exposing the cells of step (a) to the agent; and
(c) observing the effects of the agent on the trophoblast cells.
11. (canceled)
12. The method of claim 10 wherein the trophoblast-inducing factor is applied to the stem cells at a concentration of between 1 and 100 nanograms per milliliter of culture medium.
13. The method of claim 10 wherein the undifferentiated stem cells are human embryonic stem cells.
14. (canceled)
15. the method of claim 10 wherein the agent is a contraceptive or a birth control agent.
16. the method of claim 10 wherein the agent is a therapeutic for preventing placenta-related birth defects.
17. An in vitro culture comprising a replenishable population of primate trophoblast cells derived from undifferentiated primate stem cells exposed to a trophoblast inducing factor, wherein the factor is selected from the group consisting of bone morphogenic protein 4 (BMP4), bone morphogenic protein 2(BMP2), bone morphogenic protein 7(BMP7) and growth and differentiation factor 5(GDF5), and wherein the stem-cell derived trophoblast cells are mononuclear, express chorionic gonadotropin and are derived directly from undifferentiated cells without passing through an embryoid body stage.