Organic compounds -- part of the class 532-570 series – Organic compounds – Heterocyclic carbon compounds containing a hetero ring...
Patent
1994-06-17
1996-12-17
Gerstl, Robert
Organic compounds -- part of the class 532-570 series
Organic compounds
Heterocyclic carbon compounds containing a hetero ring...
C07D27734
Patent
active
055854958
DESCRIPTION:
BRIEF SUMMARY
The present invention provides a new method of making organic compounds. In particular, the present invention provides a new reduction method for making certain pharmaceutically active compounds, such as thiazolidinedione derivatives, including pioglitazone, ciglitazone, englitazone and CS-045. These compounds are known for the treatment of diabetes and as insulin sensitizing agents.
BACKGROUND
Pioglitazone hydrochloride ((.+-.)-5-[4-[2-(5-ethyl-2-pyridyl)ethoxy]benzyl]-2,4-thiazolidinedione monohydrochloride), a thiazolidinedione derivative, is currently under clinical evaluation and is expected to effectively ameliorate the abnormal glucose and lipid metabolism associated with NIDDM or obesity (cf. Y. Momose et al., Chem. Pharm. Bull., 39:1440 (1991)).
T. Sohda, et al., J. Med. Chem. 35:2617-2626 (1992), discloses additional thiazolidinedione derivatives as potent hypoglycemic and hypolipidemic agents. including 5-[4-[2-(5-methyl-2-phenyl-4-oxazolyl)ethoxy]benzyl]-2,4-thiazolidinedione , which had the most potent activity, more than 100 times that of pioglitazone.
Another thiazolidine derivative under-going clinical studies as a hypoglycemic agent is englitazone sodium, 5-([3,4-dihydro-2-(phenylmethyl)-2H- 1-benzopyran-6-yl[methyl]-2,4-thiazolidinedione sodium salt) (cf. D. A. Clark et al., J. Med. Chem., 34:319-325 (1991)).
Ciglitazone ((.+-.)-5- [4- [(1-methylcyclohexyl)methoxy]benzyl]-2,4-thiazolidinedione) is characteristic of a new class of thiazolidine antidiabetic agents which lower blood glucose in animal models of noninsulin diabetes mellitus (NIDDM), while actually reducing circulating concentrations of insulin. This is believed to be accomplished by improving the responsiveness of the peripheral tissues to insulin. See, e.g., Chang, et al, Diabetes 32:830-838 (September 1983).
CS-045 is an antidiabetic, thiazolidinedione derivative. Its activity and preparation are described in Drugs Fut. 1991, 16(9).
Also, thiazolidine derivatives useful for the treatment of diabetes are described in U.S. Pat. Nos. 4,287,200; 4,687,777; and 4,572,9 12. Their effect on insulin resistance are described, e.g. in, Chang, et al, Diabetes 32:839-845 (1983) and Chang, et al. Diabetes 32:830-838 (1983).
The preparation of these thiazolidinedione derivatives, especially pioglitazone hydrochloride, includes the reduction of an intermediate previously performed by a troublesome high pressure hydrogenation on a palladium on carbon catalyst. What is needed in the art is an easier, more efficient method for perfoming this reduction.
INFORMATION DISCLOSURE
Y. Momose et at., Chem. Pharm. Bull., 39:1440 (1991); K. Meguro et al., Japan. Patent 139182 (1988); Chem. Abstr., 109:6504h (1988); disclose the process for making thiazolidinedione-derivatives, including pioglitazone, using hydrogen on a palladium on carbon catalyst.
D. A. Clark et at., J. Med. Chem., 34:319-325 (1991) discloses the process for making substituted dihydrobenzopyran and dihydrobenzofuran thiazolidine-2,4-diones, including englitazone, using hydrogen on a palladium on carbon catalyst.
Drugs Fut. 1991, 16(9) discloses the multistep process, via carbon alkylation, for the preparation of the thiazolidinedione CS-045.
The following references disclose cobalt catalyzed reductions: U. Leutenegger et al., Angew. Chem. Int. Ed., 28:60 (1989) discloses the enantioselective reduction of .alpha.,.beta.-unsaturated carboxylates with sodium borohydride and catalytic amounts of chiral cobalt semicorrin complexes; and M. N. Ricroch and A. Gaudemer, J. Organometal. Chem., 67:119 (1974) discloses (pyridinato) cobaloxime, chloro (pyridinato) cobaloxime and vitamin B .sub.12 catalyzing the hydrogenation of .alpha.,.beta.-unsaturated esters by hydrogen or sodium borohydride.
J. O. Oshy, et al., J.A.C.S. 108:67-72 (1986), discloses cobalt (II)-mediated sodium borohydride and lithium aluminum hydride reductions, which do not involve the use of ligands.
SUMMARY OF THE INVENTION
The present invention particularly provides: below)
wherein X.sub.1 is an organic residue; wh
REFERENCES:
Y. Momose, K. Meguro, et. al., "Studies on Antidiabetic Agents X. Synthesis and Biological Activities of Pioglitazone and Realted Compounds" Chem. Pharm. Bull., 39:1440-1445 (1991).
Chemical Abstract, 109:6504h (1988).
D. A. Clark, et. al., "Substituted Dihydrobenzopyran Thiazolidine-2,4-diones as Hypoglycemic Agents", J. Med. Chem. 1991, 34, 319-325.
Drugs Fat., 1991 16(9) CS-045, EN: 105806.
Urs Leutenegger, et. al., "Enatioselective Reduction of .alpha.,.beta.-Unsaturated Carboxylates with NaBH.sub.4 and Catalytic Amounts of Chiral Cobalt Semicorrin Complexes" Angew. Chem. Int. Ed. Engl. 28 (1989) No. 1.
M. N. Ricroch, et. al., "Etude Du Mecanisme De L'Hydrogenation Des Esters Insatures Catalysee Par La Vitamine B.sub.12 Ou Les Cobaloximes" J. Organometallic Chemistry, 67 (1974)119-129.
Gammill Martha A.
Gerstl Robert
The Upjohn Company
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