US2020237708A1PendingUtilityA1
9,10-Alpha,Alpha-OH-Taxane Analogs and Methods for Production Thereof
Assignee: TAPESTRY PHARMACEUTICALS INCPriority: Sep 25, 2003Filed: Apr 15, 2020Published: Jul 30, 2020
Est. expirySep 25, 2023(expired)· nominal 20-yr term from priority
Y02P20/55A61P 35/00C07D 409/12A61K 31/357A61P 35/02A61K 31/337C07D 305/14C07D 493/08
71
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Claims
Abstract
The present invention relates to a method for the treatment of cancer in a cancer patient. In particular, the invention provides a method for the treatment comprising administering a taxane compound to a cancer patient, wherein the taxane compound is made by a process comprising treating a first compound represented by either Formula G′ or Formula M′: with a second compound of generalized formula R 8 R 9 C(OCH 3 ) 2 and an acid selected from the group consisting of camphor sulfonic acid (CSA), p-toluene sulfonic acid (PTSA), hydrochloric acid (HCl) and acetic acid (AcOH), wherein R 1 and R 2 are each selected from H, an alkyl group, an olefinic group, an aromatic group, an O-alkyl group, an O-olefinic group, or an O-aromatic group; R 7 is an alkyl group, an olefinic group, or an aromatic group; P 1 is a hydroxyl protecting group; P 5 is H or an acid labile protecting group at the 7-O position; R 8 is H, alkyl group, olefinic or aromatic group; and R 9 is: H, alkyl group, olefinic or aromatic or is as defined in the specification.
Claims
exact text as granted — not AI-modifiedWe claim:
1 . A chemical compound having the formula:
wherein:
R 1 and R 2 are each selected from H, an alkyl group, an olefinic group, an aromatic group, an O-alkyl group, an O-olefinic group, or an O-aromatic group;
R 3 is hydroxyl or OP 1 ;
R 4 and R 5 are each hydroxyl or R 7 COO;
R 6 is hydroxyl, OP 2 , R 7 COO, or an ether functionality;
R 7 is an alkyl group, an olefinic group, or an aromatic group;
P 1 and P 2 are each hydroxyl protecting groups;
and wherein R 1 and R 2 are not both Ph when
R 3 is OP 1 ;
R 4 is a hydroxyl;
R 5 is a hydroxyl; and
R 6 is OP 2 .
2 . A chemical compound according to claim 1 wherein R 1 is an isobutyl group or a tert-butoxyl group.
3 . A chemical compound according to claim 1 wherein R 1 is a tiglyl group.
4 . A chemical compound according to claim 1 wherein R 1 is a phenyl group.
5 . A chemical compound according to claim 1 wherein R 2 is an isobutyl group.
6 . A chemical compound according to claim 1 wherein R 2 is a phenyl group.
7 . A chemical compound according to claim 1 wherein R 6 is an O-methylthiomethyl or other hetero substituted ethers.
8 . A chemical compound according to claim 1 wherein P 1 and P 2 are selected from TBDMS and TES.
9 . A chemical compound according to claim 1 wherein said compound is selected from the formulas:
10 . A chemical compound according to claim 1 wherein said compound has the formula
wherein R 1 is t-BOC; R 2 is an isopropyl group; R 7 is CH 3 ; and P 1 is a hydroxyl protecting group.
11 . A chemical compound having the formula:
wherein:
R 1 and R 2 are each selected from H, an alkyl group, an olefinic group, an aromatic group, an O-alkyl group, an O-olefinic group, or an O-aromatic group;
R 3 is hydroxyl or OP 1 ;
R 4 is hydroxyl or R 7 COO;
R 7 is an alkyl group, an olefinic group, or an aromatic group;
R 8 and R 9 are each selected from H, an alkyl group, an olefinic group, or an aromatic group; and
P 1 is a hydroxyl protecting group.
12 . A chemical compound according to claim 11 wherein R 4 is R 7 COO and wherein R 7 COO is selected from the following structures:
13 . A chemical compound according to claim 11 wherein R 3 is a hydroxyl group, R 8 is either H or CH 3 , and R 9 is selected from:
14 . A chemical compound according to claim 11 wherein said compound is selected from the formulas:
15 . A chemical compound according to claim 11 wherein said compound has the formula
wherein R 4 is hydroxyl or CH 3 COO.
16 . A method for use in producing taxane analogs and derivatives thereof, comprising
(A) providing a starting compound of formula
wherein:
R 1 and R 2 are each selected from H, an alkyl group, an olefinic group, an aromatic group, an O-alkyl group, an O-olefinic group, or an O-aromatic group;
R 7 is an alkyl group, an olefinic group, or an aromatic group; and
P 1 and P 2 are each hydroxyl protecting groups;
(B) converting the starting compound into a first taxane analog of formula
17 . A method according to claim 16 including the step of oxidizing the starting compound to form a first intermediate compound of formula
18 . A method according to claim 16 including the step of acylating the first taxane analog at the C-10 position to form a second taxane analog of formula
19 . A method according to claim 18 including the step of deprotecting the 2′-O position and the 7-O positions of the second taxane analog to form a third taxane analog of formula
20 . A method according to claim 18 including the step of deprotecting the 7-O position of the second taxane analog to form a fourth taxane analog of formula
21 . A method according to claim 16 including the step of deprotecting the 2′-O position and the 7-O position of the first taxane analog to form a fifth taxane analog of formula
22 . A method according to claim 16 including the step of deprotecting the 7-O position of the first taxane analog to form a sixth taxane analog of formula
23 . A method according to claim 22 including the step of acylating the sixth taxane analog at the C-7 position, the C-9 position, or the C10 position to form a seventh taxane analog of formula
24 . A method according to claim 23 including the step of deprotecting the 2′O-position of the seventh taxane analog to form an eighth taxane analog of formula
25 . A method for use in producing taxane analogs and derivatives thereof, comprising:
(A) providing a starting compound of formula
wherein:
R 1 and R 2 are each selected from H, an alkyl group, an olefinic group, an aromatic group, an O-alkyl group, an O-olefinic group, or an O-aromatic group;
R 7 is an alkyl group, an olefinic group, or an aromatic group; and
P 1 and P 2 are each hydroxyl protecting groups;
(B) converting the starting compound into a first taxane analog of the formula
wherein
R 1 and R 2 are each selected from H, an alkyl group, an olefinic group, an aromatic group, an O-alkyl group, an O-olefinic group, and an O-aromatic group;
R 3 is hydroxyl or OP 1 ;
R 7 =an alkyl group, an olefinic group, or an aromatic group;
P 1 is a hydroxyl protecting group.
26 . A method according to claim 25 wherein the first taxane analog has a formula selected from
27 . A method according to claim 25 including the step of protecting the first taxane analog is as a 7,9-acetal linked analog to form a second taxane analog of formula
28 . A method according to claim 27 wherein the second taxane analog is of a formula selected from
29 . A method according to claim 27 including the step of cleaving the sidechain of the second taxane analog at the C-13 position to convert the second taxane analog into a first intermediate compound of formula
30 . A method according to claim 29 including the step of esterifying the first intermediate compound with a second intermediate compound of formula
thereby to form a third taxane analog of formula
wherein:
R 2 is selected from H, an alkyl group, an olefinic group, an aromatic group, an O-alkyl group, an O-olefinic group, and an O-aromatic group;
R 4 is either hydroxyl or R 7 COO;
R 7 is an alkyl group, an olefinic group, or an aromatic group;
R 8 , R 9 , R 11 , and R 12 are each selected from H, an alkyl group, an olefinic group, or an aromatic group; and
P 3 is NH protecting group.
31 . A method according to claim 30 wherein R 9 and R 12 are each selected from
32 . A method according to claim 30 wherein P 3 is carbonbenzyloxy (CBZ).Cited by (0)
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