Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Carbohydrate doai
Reexamination Certificate
2003-05-02
2004-11-09
Wilson, James O. (Department: 1623)
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Carbohydrate doai
C514S406000, C514S407000, C514S866000, C536S004100, C536S017400, C548S373100
Reexamination Certificate
active
06815428
ABSTRACT:
BACKGROUND OF THE INVENTION
The present invention relates to new pyrazole derivatives and diabetic medicine which have those compounds as an active ingredient.
Na
+
-dependent glucose transporter (SGLT) is a membrane protein which transports glucose, and SGLT-1 and SGLT-2 are known. SGLT-2 mainly expresses in renal uriniferous tubules. Glucose that is filtered in glomeruli is reabsorbed at the renal uriferous tubules via SGLT, and the glucose taken is reused in the body through the bloodstream. When SGLT is inhibited, the amount of the glucose reabsorbed at renal uriniferous tubules lowers, and the glucose is discharged through urine. As a result, it is considered that the level of blood sugar decreases. At the present time, no medicine is clinically used such as that inhibiting reabsorption of glucose in the kidney.
DISCLOSURE OF THE INVENTION
The object of the present invention is to provide new pyrazole derivatives.
The object of the present invention is also to provide a pharmaceutical composition containing the new compounds.
The object of the present invention is also to provide a pharmaceutical composition for the treatment of diabetes which comprises the new compound.
The object of the present invention is to find and provide diabetic-medicine which is easy to synthesize, less toxic and has higher curative effect.
The present invention also intends to provide urinary sugar excretion inducers which have the new compounds.
Further, the present invention intends to provide the use of the new compounds for producing a pharmaceutical composition which reduces renal glucose reabsorption at renal uriniferous tubules.
The inventors have synthesized various derivatives (1A) or (1B) wherein glucose (namely, &bgr;-D-glucopyranose) or glucuronic acid (namely, &bgr;-D-glucopyranoside uronic acid) is bonded to pyrazole, and vigorously investigated the action of those derivatives on urinary sugar excretion. As the result of animal tests, they have found that the compounds of general formula (1A) or (1B) have the outstanding action on urinary sugar excretion and completed the present invention. These compounds have not ever been synthesized and, therefore, are completely new pyrazole-O-glycoside derivatives and pyrazole-O-glucuronide derivatives.
Namely, the present invention provides pyrazole derivatives of the following general formula (1A) or (1B) or pharmaceutically acceptable salts thereof:
wherein X represents a &bgr;-D-glucopyranosyl group, of which one or more hydroxyl groups may be acylated or &bgr;-D-glucuronyl group, of which one or more hydroxyl groups may be acylated and carboxyl group may be esterified; Y represents a lower alkyl group or perfluoro lower alkyl group; Z represents a hydrogen atom, lower alkyl group, perfluoro lower alkyl group, aralkyl group or phenyl group; R1 to R5 may be the same or different and represent a hydrogen atom, lower alkyl group, perfluoro lower alkyl group, lower alkoxy group, perfluoro lower alkoxy group, lower alkylthio group, perfluoro lower alkylthio group, lower alkyl amino group, halogeno group, lower alkanoyl group, lower alkenyl group or lower alkynyl group, and n represents an integer from 0 to 3.
The present invention provides a pharmaceutical composition which comprises the above-mentioned pyrazole derivatives or pharmaceutically acceptable salts thereof as an active ingredient.
The present invention also provides a pharmaceutical composition for the treatment of diabetes which comprises the above-mentioned pyrazole derivatives or pharmaceutically acceptable salts thereof as an active ingredient.
The present invention also provides urinary sugar excretion inducers which comprise the above-mentioned pyrazole derivatives or pharmaceutically acceptable salts thereof as an active ingredient.
Further, the present invention provides the use of the above-mentioned pyrazole derivatives or pharmaceutically acceptable salts thereof for producing a pharmaceutical composition which reduces renal glucose reabsorption at renal uriniferons tobules.
REFERENCES:
patent: 5264451 (1993-11-01), Kees
patent: 5274111 (1993-12-01), Kees
patent: 0 850 948 (1998-07-01), None
patent: 1213296 (2002-06-01), None
patent: WO 01/16147 (2001-03-01), None
patent: WO 01/16147 (2001-03-01), None
patent: WO 02/053573 (2002-07-01), None
patent: WO 02/068439 (2002-09-01), None
patent: WO 02/088157 (2002-11-01), None
Basic-abstract of WO 200116147A, Derwent-Acc-No: 2001-265883, Fujikura et al, p. 3 (abstract sent).*
Kenneth L. Kees, et al., “New Potent Antihyperglycemic Agents in db/db Mice: Synthesis and Structure—Activity Relationship Studies of (4-Substituted benzyl)(trifluoromethyl)pryazoles and -pryazolones,”J. Med. Chem., 1996, 39, 3920-3928.
Kenji Tsujihara, et al., “Na+-Glucose Cotransporter (SGLT) Inhibitors as Antidiabetic Agents. 4. Synthesis and Pharmacological Properties of 4′-Dehydroxyphlorizin Derivatives Substituted on the B Ring,”J. Med. Chem., 1999, 42, 5311-5324.
Hatanaka Toshihiro
Kageyama Yoko
Kondo Nobuo
Maezono Katsumi
Matsueda Hiroyuki
Ajinomoto Co. Inc.
Henry Michael C.
Oblon & Spivak, McClelland, Maier & Neustadt P.C.
Wilson James O.
LandOfFree
Pyrazole derivatives and diabetic medicine containing them does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Pyrazole derivatives and diabetic medicine containing them, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Pyrazole derivatives and diabetic medicine containing them will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-3343063