Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Having -c- – wherein x is chalcogen – bonded directly to...
Patent
1997-03-13
1999-01-12
McKane, Joseph K.
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Having -c-, wherein x is chalcogen, bonded directly to...
514414, 514422, 514423, 514448, 5483415, 548465, 548518, 548525, 548527, 548539, 548540, 549 70, A61K 31415, A61K 3140, C07D23358, C07D207323
Patent
active
058590420
DESCRIPTION:
BRIEF SUMMARY
This application is a 371 of PCT/US95/1962 filed Sep. 27, 1995.
SUMMARY
This invention is related to five membered heterocyclic compounds. More particularly, this invention is related to: membered heterocyclic compound of the formula (Ia): ##STR1## wherein all the symbols are the same meaning as hereafter defined, and non-toxic salts thereof as active ingredient, ##STR2## wherein all the symbols are the same meaning as hereafter defined, and non-toxic salts thereof, compound of the formula (Ib) and non-toxic salts thereof.
BACKGROUND
So far as the origin of androgenic alopecia, many theories are exposited such as (1) imbalance of hormones, (2) genetics, (3) circulatory failure, (4) nutrition. And it has been suggested that testosterone (androgenic hormone) played an important role on the generation of hairs. The relation between testosterone and androgenic alopecia is as follows: dihydrotestosterone(DHT) by 5.alpha.-reductase existed in hair follicle, sebaceous gland etc. at the head, 41,884(1970)!.
Large quantities of metabolites by 5.alpha.-reductase such as DHT etc. in hair follicles of androgenic alopecia-patient exist more than that in
It was reported that DHT converted from testosterone by 5.alpha.-reductase also plays an important physiological role in the generation of acnes 123(1974); J. Invest. Dermatol., 56, 366(1971)!.
It has been clear that DHT also plays an important role in the generation 609(1979); J. Clinical Endocrinol and Metabolism, 56, 139(1983)!.
And, it is thought that DHT is also related to prostatic cancer.
Recently, it was confirmed that the existence of at least two 5.alpha.-reductase isozymes (I type and II type) in human. There are differences between these isozymes about gene formation, of course, biochemical properties, expression styles, hereditary properties and 89,293-300(1992)!. Among two type isozymes, it is considered that II type one exists more than I type one in human testis.
Therefore, it was confirmed that inhibition of a change from testosterone to DHT by 5.alpha.-reductase inhibitor is useful for above diseases.
Now, research and development of 5.alpha.-reductase inhibitors are carried out energetically. Many kinds of compounds are synthesized and tested. 5.alpha.-Reductase inhibitors are largely divided into compounds having steroidal structure and compounds having non-steroidal structure.
A representation of steroidal compound is finasteride, shown by below formula, and the compound is available in the market. ##STR3##
As a non-steroidal compound, ONO-3805 shown below formula is known. ##STR4##
RELATED ARTS
Non-steroidal compounds possessing 5.alpha.-reductase inhibitory activity, for example, are the following: disclosed. WO9303012, WO 9305019 and WO9316996, indole derivatives are disclosed. indolizine derivatives are disclosed. disclosed. R.sup.2A is optionally substituted aralkyl, or amino-protective group, and dihydrobenzimidazole, each of which may be substituted by one or more suitable substituent(s).
(5) On the 24th National Medicinal Chemistry Symposium (Jun. 21-24, 1994), it was discussed that benzoic acid derivatives and indole derivatives having 5.alpha.-reductase inhibitory activity.
Meanwhile, (6) in the specification of GB1195628, the compound of the formula (B): ##STR5## wherein Ar.sup.B is phenyl, phenyl substituted by one or more halogen, lower alkyl, lower alkoxy, NO.sub.2, NH.sub.2, CN or SCH.sub.3 ; R.sup.B is hydrogen, lower alkyl; R.sup.1B is hydrogen, lower alkyl, benzyl; R.sup.2B is CN, COOH, COO(lower alkyl), CONH2, CONH(lower alkyl), CON(lower alkyl).sub.2, the formula: ##STR6## which is available in the market as an antiinflammatory agent (Tolmetin), is disclosed.
(7) In the specification of GB1327308, the compound of the formula (C): ##STR7## wherein Ar.sub.2.sup.C is thienyl, 5-methylthienyl or substituted phenyl; R.sup.3C is COOH, COO(lower alkyl) etc.; R.sup.4C is lower alkyl; R.sup.5C is lower alkyl; R.sup.6C is hydrogen, lower alkyl, the formula: ##STR8## which is available in the market as an analgesic, antiinflammator
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Cao Charles Xian
Frierson Manton Rodgers
Lee Sung Jai
Seko Takuya
Sircar Jagadish Chandra
McKane Joseph K.
Ono Pharmaceutical Co. Ltd.
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