Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Having -c- – wherein x is chalcogen – bonded directly to...
Reexamination Certificate
1998-08-28
2001-01-16
Krass, Frederick (Department: 1618)
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Having -c-, wherein x is chalcogen, bonded directly to...
C514S299000, C514S300000, C514S311000, C514S314000, C514S337000, C514S338000, C514S339000, C514S340000, C514S341000, C514S342000, C514S382000, C514S386000, C514S387000, C514S390000, C514S392000, C514S393000, C514S394000, C514S395000, C514S396000, C514S397000, C514S398000, C514S399000, C514S400000
Reexamination Certificate
active
06174910
ABSTRACT:
This is a 371 of international application PCT/EP 97/00757 filed Feb. 18, 1997.
The enzyme cascade of the renin-angiotensin system (RAS) comprises a series of biochemical events and, as is well known, there are a variety of approaches for using regulatory intervention to open up treatment possibilities, for example treatment of hypertension.
Angiotensinogen, an &agr;2-macroglycoprotein, is cleaved by the enzyme renin into the decapeptide angiotensin I, which is itself only very slightly active biologically. In the next step of the cascade, two further amino acids are cleaved off by the action of the enzyme angiotensin converting enzyme (ACE), which is mainly bound in the endothelium, with the formation of angiotensin II. The latter is regarded as being one of the most powerful natural vasconstrictors.
The vasoconstrictive effects of angiotensin II are brought about by its action on the smooth muscle cells, and by stimulating formation of the adrenergic hormones adrenaline and noradrenaline and by increasing the activity of the sympathetic nervous system due to the formation of noradrenaline. In addition angiotensin II affects the electrolyte balance, generating, for example, antinatriuretic and antiuretic effects in the kidney, and consequently promotes release of the peptide vasopressin from the pituitary, on the one hand, and of aldosterone from the adrenal glomerulosa, on the other. All these effects play an important role in blood pressure regulation.
Angiotensin II interacts with specific receptors on the surface of the target cell. Success has by now been achieved in identifying receptor subtypes which are, for example, designated AT
1
receptors and AT
2
receptors. Recently, considerable efforts have been made to identify the substances which bind to the AT
1
receptor, with active compounds of this nature frequently being termed angiotensin II antagonists. As a consequence of the inhibition of the AT
1
receptor, these antagonists can, for example, be employed as antihypertensives or for treating congestive heart failure.
Angiotensin II antagonists are understood to mean those active compounds which bind to the AT
1
receptor subtype. This category includes compounds having differing structural features. For example, mention may be made of the compounds which are listed in the European Patent Application having the publication No. 443983 (EP 443983), in particular in the substance claims, the subject-matter of which claims is hereby incorporated into the present application by reference to this publication.
Preference is given to (S)-N-(1-carboxy-2-methylprop-1-yl)-N-pentanoyl-N-[2′(1H-tetrazol-5-yl)biphenyl-4-ylmethyl]amine [Valsartan] of the formula:
and its pharmaceutically utilizable salts.
Furthermore, the compounds which are listed in European Patent Application having the publication No. 253310 (EP 253310), in particular in the substance claims, are hereby incorporated into the present application by reference to this publication.
Preference is given to the compound [Losartan] of the following formula:
and its pharmaceutically utilizable salts.
Furthermore, the compounds listed in the European Patent Application having the publication No. 403159 (EP 403159), in particular in the substance claims, are hereby incorporated into the present application by reference to this publication.
Preference is given to the compound [Eprosartan] of the following formula:
and its pharmaceutically utilizable salts.
Furthermore, the compounds listed in the PCT Patent Application having the publication No. WO 91/14679, in particular in the substance claims, are hereby incorporated into the present application by reference to this publication.
Preference is given to the compound [Irbesartan] of the following formula:
and its pharmaceutically utilizable salts.
Furthermore, the compounds listed in the European Patent Application having the publication No. EP 420237 (EP 420237), in particular in the substance claims, are hereby incorporated into the present application by reference to this publication.
Preference is given to the compound [E-1477] of the following formula:
and its pharmaceutically utilizable salts.
Furthermore, the compounds listed in the European Patent Application having the publication No. 502314 (EP 502314), in particular in the substance claims, are hereby incorporated into the present application by reference to this publication.
Preference is given to the compound [Telmisartan] of the following formula:
and its pharmaceutically utilizable salts.
Furthermore, the compounds listed in the European Patent Application having the publication No. 459136 (EP 459136), in particular in the substance claims, are hereby incorporated into the present application by reference to this publication.
Preference is given to the compound [Candesartan] of the following formula:
and its pharmaceutically utilizable salts.
Furthermore, the compounds listed in European Patent Application having the publication No. 504888 (EP 504888), in particular in the substance claims, are hereby incorporated into the present application by reference to this publication.
Preference is given to the compound [SC-52458] of the following formula:
and its pharmaceutically utilizable salts.
Furthermore, the compounds listed in the European Patent Application having the publication No. 514198 (EP 514198), in particular in the substance claims, are hereby incorporated into the present application by reference to this publication.
Preference is given to the compound [Saprisartan] of the following formula:
and its pharmaceutically utilizable salts.
Furthermore, the compounds listed in the European Patent Application having the publication No. 475206 (EP 475206), in particular in the substance claims, are hereby incorporated into the present application by reference to this publication.
Preference is given to the compound of the following formula:
and its pharmaceutically utilizable salts.
Furthermore, the compounds listed in the PCT Patent Application having the publication No. WO 93/20816, in particular in the substance claims, are hereby incorporated into the present application by reference to this publication.
Preference is given to the compound [ZD-8731] of the following formula:
and its pharmaceutically utilizable salts.
AT
1
receptor antagonists which, for example, possess at least one basic centre can form acid addition salts. These are formed, for example, using strong inorganic acids, such as mineral acids, e.g. sulfuric acid, a phosphoric acid or a hydrohalic acid, using strong organic carboxylic acids, such as C
1
-C
4
alkanecarboxylic acids which are unsubstituted or substituted, for example, by halogen, e.g. acetic acid, such as saturated or unsaturated dicarboxylic acids, e.g. oxalic, malonic, succinic, maleic, fumaric, phthalic or terephthalic acid, such as hydroxycarboxylic acids, e.g. ascorbic, glycolic, lactic, malic, tartaric or citric acid, such as amino acids, e.g. aspartic or glutamic acid, or such as benzoic acid, or using organic sulfonic acids, such as C
1
-C
4
alkanesulfonic acids or arylsulfonic acids which are unsubstituted or substituted, for example, by halogen, e.g. methanesulfonic acid or p-toluenesulfonic acid. Examples of suitable salts with bases are metal salts, such as alkali metal or alkaline earth metal salts, e.g. sodium, potassium or magnesium salts, or salts with ammonia or an organic amine, such as morpholine, thiomorpholine, piperidine, pyrrolidine, a mono-, di- or tri-lower alkyl amine, e.g. ethyl-, tert-butyl-, diethyl-, diisopropyl-, triethyl-, tributyl- or dimethylpropyl-amines, or a mono-, di- or tri-hydroxy lower alkyl amine, e.g. mono-, di- or tri-ethanolamine. Furthermore, corresponding internal salts can be formed.
It has now been found, surprisingly, that AT
1
receptor antagonists stimulate the process of apoptosis.
Apoptosis plays an important role in morphogenesis, in dealing with hormonal and immunological responses and in th
Bullock Gillian Rosemary
Criscione Leoluca
de Gasparo Marc
Ferraro Gregory D.
Krass Frederick
Novartis AG
LandOfFree
AT1 receptor antagonist for the stimulation of apoptosis does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with AT1 receptor antagonist for the stimulation of apoptosis, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and AT1 receptor antagonist for the stimulation of apoptosis will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-2557353