Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Having -c- – wherein x is chalcogen – bonded directly to...
Patent
1996-11-22
1999-11-23
Jordan, Kimberly
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Having -c-, wherein x is chalcogen, bonded directly to...
514654, A61K 35445, A61K 35135
Patent
active
059901284
DESCRIPTION:
BRIEF SUMMARY
BACKGROUND OF THE INVENTION
Benign Prostatic Hyperplasia (BPH), also called Benign Prostatic Hypertrophy, is a progressive condition which is characterized by a nodular enlargement of prostatic tissue resulting in obstruction of the urethra. This results in increased frequency of urination, nocturia, a poor urine stream and hesitancy or delay in starting the urine flow. Chronic consequences of BPH can include hypertrophy of bladder smooth muscle, a decompensated bladder and an increased incidence of urinary tract infection. The specific biochemical, histological and pharmacological properties of the prostate adenoma leading to the bladder outlet obstruction are not yet known. However, the development of BPH is considered to be an inescapable phenomenon for the aging male population. BPH is observed in approximately 70% of males over the age of 70. Currently, in the United States, the method of choice for treating BPH is surgery (Lepor, H., Urol. Clinics North Amer., 17, 651 (1990)). Over 400,000 prostatectomies are performed annually (data from 1986). A medicinal alternative to surgery is clearly very desirable. The limitations of surgery for treating BPH include the morbidity rate of an operative procedure in elderly men, persistence or recurrence of obstructive and irritative symptoms, as well as the significant cost of surgery. .alpha.-Adrenergic receptors are specific neuroreceptor proteins located in the peripheral and central nervous systems on tissues throughout the body. These receptors are important switches for controlling many physiological functions and, thus, represent important targets for drug development. In fact, many .alpha.-adrenergic drugs have been developed over the past 40 years. Examples include clonidine, phenoxybenzamine and prazosin (treatment of hypertension), naphazoline (nasal decongestant), and apraclonidine (treating glaucoma). .alpha.-Adrenergic drugs can be broken down into two distinct classes: agonists (clonidine and naphazoline are agonists), which mimic the receptor activation properties of the endogenous neurotransmitter norepinephrine, and antagonists (phenoxybenzamine and prazosin are antagonists), which act to block the effects of norepinephrine. Many of these drugs are effective but also produce unwanted side effects (for example, clonidine produces dry mouth and sedation in addition to its antihypertensive effects).
During the past 15 years a more precise understanding of .alpha.-adrenergic receptors and their drugs has evolved through increased scientific scrutiny. Prior to 1977, only one .alpha.-adrenergic receptor was known to exist. Between 1977 and 1988, it was accepted by the scientific community that at least two .alpha.-adrenergic receptors--.alpha..sub.1 and .alpha..sub.2 --existed in the central and peripheral nervous systems. Since 1988, new techniques in molecular biology have led to the identification of at least six .alpha.-adrenergic receptors which exist throughout the central and peripheral nervous systems: .alpha..sub.1A, .alpha..sub.1B, .alpha..sub.1C, .alpha..sub.2A, .alpha..sub.2B and .alpha..sub.2C (Bylund, D. B., FASEB J., 6, 832 (1992)). It is not known precisely which physiological responses in the body are controlled by each of these receptors. In addition, many .alpha.-adrenergic drugs that were developed before 1992 are not selective for any particular .alpha.-adrenergic receptor. Many of these drugs produce untoward side effects which may be attributed to their poor .alpha.-adrenergic receptor selectivity.
Since the mid 1970's, nonselective .alpha.-antagonists have been prescribed to treat BPH. In 1976, M. Caine, et al. (Brit. J. Urol., 48, 255 (1976)), reported that the nonselective .alpha.-antagonist phenoxybenzamine was useful in relieving the symptoms of BPH. This drug may produce its effects by interacting with .alpha.-receptors located on the prostate. However, this drug also produces significant side effects which severely limit its use in treating patients on a chronic basis. More recently, the .alpha.-adrenergic antagonists
REFERENCES:
patent: 4975440 (1990-12-01), Flockerzi et al.
patent: 4994461 (1991-02-01), Ulrich
patent: 5403842 (1995-04-01), Leonardi et al.
patent: 5403847 (1995-04-01), Gluchowski et al.
patent: 5508306 (1996-04-01), Chiu et al.
patent: 5556753 (1996-09-01), Bard et al.
patent: 5578611 (1996-11-01), Gluchowski et al.
Archibald, et al., "Penzamidopiperidines. 3. Carbocyclic Derivatives Related to Indoramin" J. Med. Chem. (1974) 17(7): 739-744.
Chapple, C., "Medical Treatment for Benign Prostatic Hyperplasia" B.M.J. (1992) 304: 1198-1199.
Chow, et al., "Multicentre Controlled Trial of Indoramin in the Symptomatic Relief of Benign Prostatic Hypertrophy" Br. J. Urology (1990) 65(1): 36-38.
Christmas, T.J. and Kirby, R.S., "Alpha-Adrenoceptor Blockers in the Treatment of Bening Prostatic Hyperplasia" World J. Urol. (1991) 9: 36-40.
Heimbach, et al., "Anwendung Von .alpha.-Rezeptorenblockern Bei Urologischen Erkrankungen" Dtsch. Med. Wochenschr. (1992) 117(21): 825-828.
Lepor H., et al., "The Alpha-Adrenoceptor Subtype Mediating the Tension of Human Prostatic Smooth Muscle" The Prostate (1993) 22:301-307.
Lepor, et al., "Laboratory Assessment of Terazosin and Alpha-1 Blockade in Prostatic Hyperplasia" Urology (1988) 32(6): 21-26.
Kaminka, M.E., et al., "Effect of Prazosin on Human Benign Prostatic Hyperplasia Strips" Chemical Abstracts (1998) Abstract No. 563185.
Yamada, et al., "Alpha-1 Adrenoceptors in Human Prostate: Characterization and Alternation in Benign Prostatic Hypertrophy" Chemical Abstracts (1987) Abstract No. 513718.
Marshall, I., et al., "Human .alpha.1C-Adrenoceptor: Functional Characterization In Prostate," Meeting of the British Pharmacological Society (1992), Abst. No. 372P.
Archibald, J.L., et al., "Antihypertensive Ureidopiperidines," Journal of Medicinal Chemistry, 23: 857-861 (1980).
Boer, R., et al., "(+)-Niguldipine binds with very high affinity to Ca.sup.2+ channels and to a subtype of .alpha..sub.1 -adrenoreceptors," European Journal of Pharmacological--Molecular Pharmacology Section, 172: 131-145 (1989); The Netherlands.
Forray, C., et al., "The 60 .sub.1C -Adrenergic Receptor that Meditates Smooth Muscle Contraction in Human Prostate Has the Pharmacological Properties of the Cloned Human .varies.1cSubtype," Molecular Pharmacology, 45: 703-708 (1994); U.S.A..
Forray, C., Chiu, G., et al., "Effects of Novel Alpha-1C Adrenergic Receptor Antagonists on the Contraction of Human Prostate Smmoth Muscle," American Urological Association Eighty-ninth Annual Meeting, May 14-19, 1994 The Journal of Urology, 151(5), Abstract #159 May 1994; U.S.A.
Forray, C., Bard, J.A., et al., "Comparison of the Pharmacological Properties of the Cloned Bovine, Human, and Rat .alpha.1C-Adrenergic Receptors," The FASEB Journal, 8(4), Abstract #2042 (1994); U.S.A.
Gong, E., et al., ".alpha.1C-Adrenergid Antagonists and Orthostatic Hypotension in the Rat," The FASEB Journal, 8(4), Abstract #2043 (1994); U.S.A.
Gup, et al., "Autonomic Receptors in Human Prostate Adenomas," Journal of Urology (1990) 143(1); 179-185.
Hieble, J.P., et al., "In Vitro characterization of the .alpha.1-adrenoreceptors in human prostate," European Jourmal of Pharmacology, 107: 111-117 (1985); The Netherlands.
Lepor, H., et al., "Localization of Alpha .sub.1C Adrenoceptor (.alpha..sub.1C AR) Subtypes in the Human Prostate," American Urological Association Eighty-Ninth Annual Meeting, May 14-19, 1994, The Journal of Urology, 151 (5), Abstract #614 (May 1994); U.S.A.
Lepor and Baumann, et al., Medline Abstracts (1988), Abst. No. 88317113; "The Alpha Adrenergic Binding Properties of Terazosin in the Human Prostate Adenoma and Canine Brain," Journal of Urology (1988), 140(3): 664-667.
Lepor and Knapp-Maloney, et al., "A Dose Titration Study Evaluating Terazosin, A Selective Once-a-Day Alpha-1-Blocker for the Treatment of Symptomatic Benign Prostatic Hyperplasia," Journal of Urology (1990) 144(6); 1393-1398.
Lepor and Shapiro, et al., Medline Abstracts (1988), Abst. No. 88317114; "The Effect o
Branchek Theresa A.
Chiu George
Forray Carlos C.
Gluchowski Charles
Hartig Paul R.
Jordan Kimberly
Synaptic Pharmaceutical Corporation
White John P.
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