Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Having -c- – wherein x is chalcogen – bonded directly to...
Reexamination Certificate
1995-01-05
2002-09-10
Criares, Theodore J. (Department: 1617)
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Having -c-, wherein x is chalcogen, bonded directly to...
C514S382000, C514S214020, C514S213010, C514S314000, C514S337000
Reexamination Certificate
active
06448280
ABSTRACT:
TECHNICAL FIELD
This invention relates to therapeutic agents and in particular to the use of compounds having angiotensin II antagonist activity (hereinafter “AII antagonists”) for the treatment or prevention of disease conditions associated with impaired neuronal conduction velocity in warm-blooded animals including man. The invention also concerns the use of a compound having AII antagonist activity in the production of a medicament for use in the treatment or prevention of disease conditions associated with impaired neuronal conduction velocity. The invention further concerns a method of treating or preventing disease conditions associated with impaired neuronal conduction velocity by administration of an AII antagonist to a warm blooded animal (including man).
BACKGROUND TO INVENTION
Impaired neuronal conduction velocity is a feature of nerve dysfunction commonly found, for example, in diabetic patients, and in disease conditions, such as alcoholic, toxic or compression neuropathy. Consequently an agent which prevents or reverses impairment of nerve conduction velocity may have a beneficial effect in the treatment or prevention of such medical conditions in which nerve conduction velocity is reduced, for example, diabetic neuropathy. We have now surprisingly discovered that impaired neuronal conduction velocity in a diabetic rat is significantly reversed by administration of an AII antagonist.
DISCLOSURE OF INVENTION
According to the invention there is provided a method of treating or preventing the development of disease conditions associated with impaired neuronal conduction velocity in a warm-blooded animal (including a human being) requiring such treatment which comprises administering to said animal a therapeutically effective amount of an AII antagonist, or a pharmaceutically acceptable salt thereof.
Typical AII antagonists useful in the invention include:
(a) 2-butyl-4-chloro-5-hydroxymethyl-1-[(2′-(1H-tetrazol-5-yl)biphenyl-4-yl)methyl]imidazole described in European Patent Application (EPA), Publication No. 253310;
(b) 2-butyl-3-(2′-(1H-1,2,3,4-tetrazol-5-yl)biphenyl-4-yl)-methyl-3H-imidazo[4,5-b]pyridine described in EPA, Publication No. 399731;
(c) 5,7-dimethyl-2-ethyl-3-(2′-(tetrazol-5-yl)biphenyl-4-yl)-methyl-3H-imidazo[4,5-b]pyridine described in EPA, Publication No. 400974;
(d) 1-[[3-bromo-2-[2-(1H-tetrazol-5-yl)phenyl]-5-benzofuranyl]-methyl-2-butyl-4-chloro-1H-imidazole-5-carboxylic acid described in EPA, Publication No. 434249;
(e) 2-ethyl-4-[(2′-(1H-1,2,3,4-tetrazol-5-yl)biphenyl-4-yl)-methoxy]quinoline described in EPA, Publication No. 412848; and
(f) 2-ethyl-5,6,7,8-tetrahydro-4-[(2′-(1H-1,2,3,4-tetrazol-5-yl)biphenyl-4-yl)methoxy]quinoline described in EPA, Publication No. 453210;
(g) 5,7-diethyl-1-[(2′-(1H-tetrazol-5-yl)biphenyl-4-yl)methyl]-1,6-naphthyridin-2(1H)-one described in EPA, Publication No. 516392; and
(h) 5,7-diethyl-1-[(2′-(1H-tetrazol-5-yl)biphenyl-4-yl)methyl]-1,2,3,4-tetrahydro-1,6-naphthyridin-2-one described in EPA, Publication No. 516392;
and the pharmaceutically acceptable salts thereof.
Further AII antagonists include those described in EPA, Publication Nos. 253310, 323841, 324377, 399731, 400974, 401030, 403158, 403159, 407102, 407342, 409332, 411507, 411766, 412594, 412848, 415886, 419048, 420237, 424317, 425921, 425211, 426021, 427463, 429257, 430709, 430300, 434249, 432737, 434038, 435827, 437103, 438869, 442473, 443983, 443568, 445811, 446062, 449699, 450566, 453210, 454511, 454831, 456442, 459136, 456442, 456510, 461039, 461040, 465323, 465368, 467207, 467715, 468372, 468470, 470543, 475206, 475898, 479479, 480204, 480659, 481448, 481614, 483683, 485929, 487252, 487745, 488532, 490587, 490820, 492105, 497121, 497150, 497516, 498721, 498722, 498723, 499414, 499415, 499416, 500297, 500409, 501269, 501892, 502314, 502575, 502725, 503162, 503785, 503838, 504888, 505098, 505111, 505893, 505954, 507594, 508393, 508445, 508723, 510812, 510813, 511767, 511791, 512675, 512676, 512870, 513533, 513979, 514192, 514193, 514197, 514198, 514216; 514217, 515265, 515357, 515535, 515546, 515548, 516392, 517357, 517812, 518033, 518931, 520423, 520723, 520724, 521768, 522038, 523141, 526001, 527534, and 528762. Other AII antagonists include those disclosed in International Patent Application, Publication Nos. WO 91/00277, WO 91/00281, WO 91/11909, WO 91/11999, WO 91/12001, WO 91/12002, WO 91/13063, 91/15209, WO 91/15479, WO 91/16313, WO 91/17148, WO 91/18888, WO 91/19697, WO 91/19715, WO 92/00067, WO 92/00068, WO 92/00977, WO 92/02510, WO 92/04335, WO 92/04343, WO 92/05161, WO 92/06081, WO 92/07834, WO 92/07852, WO 92/09278, WO 92/09600, WO 92/10189, WO 92/11255, WO 92/14714, WO 92/16523, WO 92/16552, WO 92/17469, WO 92/18092, WO 92/19211, WO 92/20651, WO 92/20660, WO 92/20687, WO 92/21666, WO 92/22533, WO 93/00341, WO 93/01177, WO 93/03018, WO 93/03033 and WO 93/03040. The contents of the aforesaid European and International Patent Applications are hereby incorporated by reference thereto.
Prior to the present invention, AII antagonists have been described as having use in, for example, the treatment of hypertension and congestive heart failure. However there has been no suggestion that a compound possessing AII antagonist activity might be useful in treating or preventing impaired nerve conduction velocity.
According to a further aspect of the invention there is provided the use of an AII antagonist, or a pharmaceutically acceptable salt thereof, for the manufacture of a medicament for use in the treatment or prevention of the development of disease conditions associated with impaired neuronal conduction velocity.
According to a further aspect of the invention there is provided a method of reversing impaired neuronal conduction velocity in a warm-blooded animal (including a human being) requiring such treatment which comprises administering to said animal a therapeutically effective amount of a compound having AII antagonist activity, or a pharmaceutically acceptable salt thereof.
According to a further aspect of the invention there is provided the use of a compound having AII antagonist activity, or a pharmaceutically acceptable salt thereof, for the manufacture of a medicament for use in the reversal of impaired neuronal conduction velocity.
According to a further aspect of the invention there is provided a method of treating or preventing diabetic neuropathy in a warm-blooded animal (including a human being) requiring such treatment which comprises administering to said animal a therapeutically effective amount of a compound having AII antagonist activity, or a pharmaceutically acceptable salt thereof.
According to a further aspect of the invention there is provided the use of a compound having AII antagonist activity, or a pharmaceutically acceptable salt thereof, for the manufacture of a medicament for use in the treatment or prevention of diabetic neuropathy.
Preferred AII antagonists for use in the invention include:
(i) 2-butyl-4-chloro-5-hydroxymethyl-1-[(2′-(1H-tetrazol-5-yl)-biphenyl-4-yl)methyl]imidazole;
(ii) 2-ethyl-4-[(2′-(1H-1,2,3,4-tetrazol-5-yl)biphenyl-4-yl)methoxy]-quinoline;
(iii) 2-ethyl-5,6,7,8-tetrahydro-4-[(2′-(1H-1,2,3,4-tetrazol-5-yl)-biphenyl-4-yl)methoxy]quinoline;
(iv) 5,7-diethyl-1-[(2′-(1H-tetrazol-5-yl)biphenyl-4-yl)methyl]-1,6-naphthyridin-2(1H)-one; and
(v) 5,7-diethyl-1-[(2′-(1H-tetrazol-5-yl)biphenyl-4-yl)methyl]-1,2,3,4-tetrahydro-1,6-naphthyridin-2-one;
and the pharmaceutically acceptable salts thereof.
A particularly preferred AII antagonist is compound (ii).
A preferred pharmaceutically acceptable salt of compound (i) is, for example, an alkali metal salt, especially the potassium salt.
A preferred pharmaceutically acceptable salt of compound (ii), (iii), (iv) or (v) is, for example, an acid addition salt, especially the hydrochloride salt.
The AII antagonists and their pharmaceutically
Cameron Norman Eugene
Carey Frank
Cotter Mary Anne
Oldham Alexander Anthony
Criares Theodore J.
Morgan & Lewis & Bockius, LLP
Zeneca Limited
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