Details for Patent: 7,241,755

Title:	Epothilone derivatives
Abstract:	The present invention relates to compounds of the formula ##STR00001## in which the variables G, W, Q, X, Y, B.sub.1, B.sub.2, Z.sub.1, Z.sub.2, and R.sub.1 R.sub.7 are as defined herein, methods for the preparation of the derivatives and intermediates thereof.
Inventor(s):	Vite; Gregory D. (Titusville, NJ), Kim; Soong-Hoon (Lawrenceville, NJ), Borzilleri; Robert M. (Lawrenceville, NJ), Johnson; James A. (Lawrenceville, NJ)
Assignee:	Bristol-Myers Squibb Company (Princeton, NJ)
Filing Date:	Aug 30, 2006
Application Number:	11/512,623
Claims:	1. A compound of the formula ##STR00052## wherein: ##STR00053## G is selected from the group consisting of alkyl; substituted alkyl; substituted aryl; a 4 to 7 membered monocyclic, 7 to 11 membered bicyclic, or 10 to 15 membered tricyclic saturated or unsaturated ring system having between 1 and 3 heteroatoms selected from nitrogen, oxygen, and sulfur; ##STR00054## W is O or NR.sub.15; X is O or H, H; Y is selected from the group consisting of O; H, OR.sub.16; OR.sub.17, OR.sub.17; NOR.sub.18; H, NHOR.sub.19; H, NR.sub.20R.sub.21; H, H; and CHR.sub.22; wherein OR.sub.17, OR.sub.17 can be a cyclic ketal; Z.sub.1 and Z.sub.2 are independently CH.sub.2; B.sub.1 and B.sub.2 are independently selected from the group consisting of OR.sub.24, OCOR.sub.25, and O--C(.dbd.O)--NR.sub.26R.sub.27, and when B.sub.1 is OH and Y is OH, H they can form a six-membered ring ketal or acetal; R.sub.1, R.sub.2, R.sub.3, R.sub.4, R.sub.5, R.sub.7, R.sub.13, R.sub.14, R.sub.18, R.sub.19, R.sub.20, R.sub.21, R.sub.22, R.sub.26, and selected from the group consisting of H, alkyl, substituted alkyl, and aryl, and when R.sub.1 and R.sub.2 are alky, they can be joined to form a cycloalkyl; and when R.sub.3 and R.sub.4 are alkyl they can be joined to form a cycloalkyl; R.sub.6 is methyl; R.sub.16, R.sub.17, R.sub.24, and R.sub.25 are selected from the group consisting of H, alkyl, and substituted alkyl; R.sub.11, R.sub.12, R.sub.32, and R.sub.33 are selected from the group consisting of H; alkyl; substituted alkyl; aryl; substituted aryl; cycloalkyl containing 1 to 3 rings and 3 to 7 carbons per ring which may be further fused with an unsaturated C.sub.3 C.sub.7 carbocyclic ring; and a 4 to 7 membered monocyclic, 7 to 11 membered bicyclic, or 10 to 15 membered tricyclic saturated or unsaturated ring system having between 1 and 3 heteroatoms selected from nitrogen, oxygen, and sulfur; R.sub.8 is hydrogen or methyl; R.sub.15 is selected from the group consisting of H; alkyl; substituted alkyl; aryl; substituted aryl; cycloalkyl containing 1 to 3 rings and 3 to 7 carbons per ring which may be further fused with an unsaturated C.sub.3 C.sub.7 carbocyclic ring; a 4 to 7 membered monocyclic, 7 to 11 membered bicyclic, or 10 to 15 membered tricyclic saturated or unsaturated ring system having between 1 and 3 heteroatoms selected from nitrogen, oxygen, and sulfur; R.sub.32C.dbd.O, R.sub.33SO2, hydroxy, O-alkyl or O-substituted alkyl; or a pharmaceutically acceptable salt thereof; with the proviso that compounds wherein W and X are both O; and R.sub.1, R.sub.2 and R.sub.7 are H; and R.sub.3 and R.sub.4 are methyl; and G is 1-methyl-2-(substituted)-4-thiazolyl-ethenyl; are excluded. 2. The compound of claim 1, wherein: X is O and Y is O; or a pharmaceutically acceptable salt thereof. 3. The compound of claim 2, wherein: B.sub.1 is OH and B.sub.2 is OH; or a pharmaceutically acceptable salt thereof. 4. The compound of claim 3, wherein W is O; or a pharmaceutically acceptable salt thereof. 5. The compound of claim 4, wherein: R.sub.1, R.sub.2, and R.sub.7 are H; and R.sub.3, R.sub.4, and R.sub.5 are methyl; or a pharmaceutically acceptable salt thereof. 6. The compound of claim 5, wherein G is: ##STR00055## or a pharmaceutically acceptable salt thereof. 7. The compound of claim 6, wherein R.sub.11 is a 4 to 7 membered monocyclic saturated or unsaturated ring system having from 1 and 3 heteroatoms selected from nitrogen, oxygen, and sulfur; or a pharmaceutically acceptable salt thereof. 8. The compound of claim 3, wherein W is NR.sub.15; or a pharmaceutically acceptable salt thereof. 9. The compound of claim 8, wherein: R.sub.1, R.sub.2, and R.sub.7 are H; and R.sub.3, R.sub.4, and R.sub.5 are methyl; or a pharmaceutically acceptable salt thereof. 10. The compound of claim 9, wherein G is: ##STR00056## or a pharmaceutically acceptable salt thereof. 11. The compound of claim 10, wherein R.sub.11 is a 4 to 7 membered monocyclic saturated or unsaturated ring system having from 1 and 3 heteroatoms selected from nitrogen, oxygen, and sulfur; or a pharmaceutically acceptable salt thereof. 12. The compound of claim 11, wherein R.sub.15 is H; or a pharmaceutically acceptable salt thereof. 13. A pharmaceutical composition comprising the compound of claim 1 or a pharmaceutically acceptable salt thereof; and a pharmaceutically acceptable vehicle or diluent.