And 2Azol1yl1propen3ols

Compounds 3.82 respresent the first group of the title compounds, which have also been named azole-1-ylvinylcarbinols or P-(azol-1-yl)substituted allylalcohols. (The allyloxy group is also a structural fragment of enilconazole, see section 3.3.1). A large number of disclosures attest to the fungicidal and plant growth-regulator (PGA) activities of this series. 3.654, 3.655. 3.656, 3.657, 3.658, 3.659, 3.660, 3.661, 3.662, 3.663, 3.664, 3.665, 3.666, 3.667 The preferred stereoisomers have often...

Contents

1 Introduction Scope, chronology and statistics, beneficial side effects, acknowledgements 2 l-(Hydrogen-, alkyl-, aryl-, heterocyclyl-, arylalkyl-, heterocyclylalkyl-, diphenylalkyl- and trityl)l-H-azoles 7 2.1 1-Hydrogen- and 1-alkyl-azoles 2.1.1 Pyrroles and 2.1.2 Imidazoles 2.1.3 Azoles 2.2 1-Aryl-lH-azoles 2.2.1 Pyrazoles 2.2.2 Imidazoles 2.3 1-Heteroaryl-lH-azoles 2.3.1 Pyrazoles 2.3.2 Imidazoles 2.3.3 Azoles and triazoles 2.4 1-Benzyl-lH-azoles 2.4.1 Pyrazoles 2.4.2 Imidazoles 2.4.3...

Aryloxyalkyloxy1alkenyl1Hazoles

Title compounds, which might also be regarded as 2-(1H-azol-1-yl)vinyl-ethers, have been discovered by first extending the -OCH2- substructure of econazole 3.48A to -X(CH2)n X'- with X, X' O, S and n 1 to 4, hoping to increase solubility in water. The first series of products culminated in a substance 3.79 with higher i.v. antimycotic activity than the standard, much lower toxicity in mice, and better curative action in the treatment of vaginal candidiasis in rats. 3.636 It has same potency as...

Diphenylmethyl1Himidazoles

phenyl)methylimidazoles Title compounds form part of a large claim for agricultural microbicides. 2.301 For example, substance 2.46 inhibits Phaseolus vulgaris on kidney beans, Pythium aphan-idermatum, Fusarium oxysporum and Rhizoctonia solani. 2.47 has been claimed as a medical fungi-cide. 2.302 Compound 2.48 which is not only related to bifonazole, but also to naftifine, shows high activity against Candida strains. 2.303 The most successful drug in this series however is bifonazole 2.49A...

Azol1ylalkylnitriles

Title compounds 4.51 have been claimed as antimycotics and fungicides. 4.217, 4.218, 4.219, 4.220, 4.221, 4.222, 4.223, 4.224, 4.225, 4.226, 4.227 Some nitriles are part of the claims for the corresponding carboxylic acid derivatives in section 4.11.1. Trimellitic acid salts of the title compounds have been prepared. 4.220, 4.228 These nitriles, after p.o. doses, protect mice infected with Candida albicans. They also control Puccinia recondita and Erysiphe graminis on wheat seeds, Pyri- cularia...

Azolyl1hydroxyalkan2one ethers 4511 11HImidazolylphenoxyalkan2ones

Climbazole 4.24, 38083-17-9 presents the most prominent of the title com-pounds. 4.112, 4.113 In contrast to triadimefon (see section 4.5.1.2), climbazole is not reduced by fungi, e.g. Cladosporium cucumerinum to the carbinol, suggesting that the unme-tabolized drug is the fungitoxic agent. 4.114 Indeed, the reduced climbazole (Bay-L 9139 55362-18-0 (see section 3.8.1) is less fungitoxic. Thus, it appears that climbazole acts as a fungicidal agent through its enolic form. 4.114 Climbazole...

Azol1yl1hydroxyalkan4ones

From these series, compound 4.33, PP969 69141-50-0 has been selected for further investigation. 4.163, 4.164, 4.165 The main activity of this systemic agent against foliar fungal diseases, either by foliar or by stem application, rests in the (R*,R*)-(+)-enantiomer. The high water solubility of 3.6 g L is 28 times larger than that of fluotriafol (see section 3.2.2.5). Due to its mobility in woody plants, PP969 shows excellent activity against Ery-siphe graminis hordei, E. gr. tritici, Puccinia...

Alkenyl and alkinyl1Hazoles and their halogen derivatives

Title compounds 2.35 can be prepared a) by dehydration of 1-(2-hydroxyalkyl)azoles, 2.225, 2.226, 2.227, 2.228, 2.229 b) by vinylation with alkines, 2.230, 2.231 c) by reaction of ketones with with N',N'-sulfinylimidazole, 2.232, 2.233 or with diethyl (1H-1,2,4-triazol-1-yl)methyl phos-phonate, 2.234 d) by dehydrohalogenation of 1,1-dihalogenalkanes followed by condensation with an azole, 2.235 or e) by chlorination dehydrochlorination of carbinols. 2.236 1-Halovinyl-1-azoles are formed from...

Hydroxyalkyl1Hazoles and their ethers

Fungicidal title compounds like 3.66 (n 0, R H) have been claimed as agricultural fungicides. 3.598 A related substance, with n 2, R CH3 in the form of the 1,2,4-triazole oxide, displays fungicidal and plant growth-regulating activity. 3.599 Some 1-(3-subst. phenoxypropyl)-1H-pyrazoles have been claimed as pesticides for the control of Aphis gossypii larvae on cucumber seedlings. 3.600 Ethers of the title compounds 3.66 display good activity against Candida albi-cans. 3.601 From this series,...

Azol1ylalkylketon hydrazones and semicarbazones

Title compounds 5.42 with Az pyrrol-1-yl, have been disclosed as antimycotics with in vitro inhibition of a large group of Candida spp. 5.192 1-Pyrazole derivatives of the title compounds 5.42 with R CONHPhs and (Z)-stereochemistry give complete control of Spodoptera litura. 5.198 Their imidazole derivatives show antifungal activity superior to that of clotri-mazole. 5.193 A thienyl analog zinoconazole 5.43, base, 84697-21-2 hydrochloride, 80168-44-1 has been selected as an antimycotic. 5.194...

Trityl1Himidazoles

2.12.1 Clotrimazole Chemical and pharmaceutical aspects Clotrimazole 2.61 23593-75-1 , one of the first azolyl antimycotic drugs, is still much prescribed and one of the standards against which new developments are compa-red. 2.366 It combines good skin penetration with broad-spectrum activity against dermatophytes, yeasts, 2.367 Aspergillus, Malassezia furfur, and inhibits Corynebacte-rium minutissimum, Staphylococci, Streptococci which all may accompany myco-tic infections. In the treatment...

Azol1yl1alken3ones

Title compounds of the general structure 4.17 have been claimed often as antimycotics and fungicides. 4.074, 4.075, 4.076, 4.077, 4.078, 4.079, 4.080, 4.081, 4.082, 4.083, 4.084, 4.085, 4.086, 4.087, 4.088, 4.089, 4.090, 4.091, 4.092 They are also the subject of several papers. 4.093, 4.094, 4.095, 4.096 R alkyl, haloalkyl C CHR' R1 - aryl, aralkyl, amino Some sulfonyl ketone bromides have been claimed as intermediates. 4.097 (E)-isomer content, which generally includes the main microbiocidal...

Hydroxy3thioalkyl1Hazole derivatives

In a great number of disclosures, title compounds 3.113 have been claimed as antimy-cotics, fungicides and plant growth regulators. 3.891, 3.892, 3.893, 3.894, 3.895, 3.896, 3.897, 3.898, 3.899, 3,900, 3.901, 3.902, 3.903, 3.903a, 3.904, 3.905 From these, substances SM-4470 and genaconazole have been investigated further. For compound 3.114, SM-4470 as (R)-enantiomer 89433-57-8 synthesis, 3.906, 3.907 and chiral preparations have been described. 3.908, 3.909 SM-4470 is endowed with very high...

Heteroarylmethyl and heteroarylmethylenazoles

1-Imidazol-1-yl-methyl-furans show only minor antifungal activity. 2.129 3-(1H-Imidazolylmethyl)-indoles 2.24 inhibit Cryptococcus neoformans (the cause of fatal meningitis in humans) and Candida pseudotropicalis. 2.130, 2.131 inhibit C. albicans, C. tropicalis and C. stellastoida, and vaginal yeast infection of hamsters. 2.132, 2.133, 2.135, 2.161 Optimal compounds 2.25 with Az Im W, Y, Z H X Cl have been compared with rotamer forms of miconazole. 2.134 These substances also include one in...

Saperconazole and terconazole

Saperconazole 6.44, 110588-57-3 was developed as a successor for ketocona-zole. 6.447 In vitro activity against 234 species of fungi with a total of 2775 strains demonstrated > 95 inhibition in the range of 0.1 to 1.0 mg mL with most species, except Furarium and Zygomycetes. 6.448, 6.449 In vivo, the drug is highly effective in the treatment of microsporosis, tricho-phytosis, skin dermatoses, vaginal candidiasis, pityrosporosis, keratomycosis (caused by C. albicans, F. moniliforme, A....

Benzyl1Hazoles

1,1'-Methylenedipyrazoles inhibit anaerobic protozoa such as Trichomonas and Ent-amoeba. 2.098, 2.099 1-Benzylimidazoles 2.14 can be prepared from benzyl halides and imidazole under alkaline conditions, 2.099, 2.100 or from 3-acetyl or 3-benzoyl-imidazoles and benzyl halides followed by deprotection of the acyl group in water or alcohol. 2.101 Chiral a-alkyl-1-benzylimidazoles may be prepared from the corresponding 4,5-dicyanoimidazoles. 2.021, 2.022 While 1-benzylimidazole is devoid of...

Hydroxyalkyl1Hazoles with a andor bcarbon as part of a cycloalkane

All three possible products 3.38A, 3.38B and 3.38C have been described. z Az R - R' H, alkyl, Phs 3.38A 3.38B A large number of claims for 1-azolylmethyl-2-benzylcyclopentanols 3.38A (R R1 H, n 4) have been applied as inhibitors of Erysiphe graminis tritici, Puccinia recondita and P. striiformis on apple seedlings, Cochlibolus miyabeanus, Giberella fujikuroi and Pseudomonas glumae and other pathogens on rice, and Pyricularia oryzae. 3.352, 3.353, 3.354, 3.355, 3.356, 3.357, 3.358, 3.359, 3.360,...

Azoles

2.11.1 Replacing one or two phenyls of bifonazole 2.49A by heterocyclic rings to arrive at structures 2.52 has been a favored strategy in the work originating from the university La Sapienza Rome, Italy. Such antifungal compounds, with Ar1 pyrrol-3-yl, 2.53 have been found to be as potent as ketoconazole, and half as potent as bifonazole against Candida albi-cans. 2.337 Introduction of trans-CH CH-COOEt or n-propyl at the 1-position of pyrrol does not influence the level of activity. 2.338...

Azol1yliminocarbonic and carboxylic acid esters and their thio analogs

Title compounds 5.16 have been claimed as fungicides which control Spaerotheca fuli-ginea and Pseudoperonospora cubensis on cucumber, Puccinia recondita, Helminthos-porium oryzae, Erysiphe graminis on barley, and Fusarium moniliforme. 5.066, 5.067, 5.068, 5.069, 5.070, 5.071, 5.072, 5.073, 5.074, 5.075 R alkyl, alkenyl, Phs R' CH3, CI, CF3, N02 R - CH3, F n 0, 1,2 X O, S From these series, triflumizole 5.17, (E)-isomer, 99387-89-0 unstated stereochemistry, 68694-11-1 has been developed. 5.065,...

Scope chronology and statistics beneficial side effects acknowledgements

0 -1 I I i I I i I I i I I i I I i I I i I I i I I i I I i I I i I I i I I i I I i I I i I I ----- 1980 81 82 83 84 85 86 87 88 89 90 91 92 93 94 95 Fig. 1.1 Chronology of 1309 patent applications of antifungal azoles, chapters 2 to 7, up to 30 June 1996 see also appendix. Almost 15 years ago a forerunner of this book presented the first 15 years of research on antifungal azoles, first discovered in 1965. 1.01 The results of 575 patent applications and 225 papers had been presented based...

Hazoles

Only a few of all conceivable ways of connecting the numbered atoms of skeleton 3.110 by alkylen groups to arrive at non-spiro cycloalkanes, oxacycloalkanes or dioxa-cycloalkanes have been reported. 100 3 1-(Mono- and dihydroxyalkyl- and alkenyl)-1H-azoles Az Connecting formally 2C with 3C by -(CH2)n- with n 3 yields cyclopentandiols 3.111, 3.888 or with n 4 cyclohexandiols. 3.889 Connecting 2C- with 3C-3O- by alkylen, n 2 produces tetrahydrofuran-3-ols These substances inhibit Pyricularia...

Azol1ylalkanealdehyde orketon oximes with further substituents on the alkyl

4-Arylthio-2-oximino-1-(1H-azole) ethers have been claimed as fungicides. 5.173 5-Phenoxy-2-oximino-1-(1H-azole) ethers 5.37 control Cochliobolus sativus on bar-ley. 5.174 show superior activity against Puccinia recondita on wheat. 5.175 5.38 have been disclosed as antimycotics, with high activity against C. albicans, and as fungicides. 5.176, 5.177, 5.178, 5.179 A methoxymethyl-oxim ether 5.40B is superior to fluconazole after p.o. administration to infected mice by a factor of ca. 12 against...

And 41HAzol1ylmethyl13dioxolanes

6.1.4.1 2- 1H-Azol-1-yl methyl-4-H-, or 4-alkyl-or 4-heterocyclyl-1,3-dioxolanes Title substances 6.09 which can be regarded as cyclic ketals, have been disclosed as antimycotics and fungicides, 6.059, 6.060, 6.061, 6.062, 6.063, 6.064 and described in papers compare also section 6.1.7.1 . 6.065, 6.066, 6.067 2-Bromomethyl-1,3-dioxolanes have been claimed as precursors. 6.068 R H, alkyl, alkoxy, Phs, acyl R. R' H, alkyl X H. O, S Title compounds inhibit Staphylococcus aureus and Epidermophyton...

AaDisubstituted 12hydroxyalkyl1Hazoles

Synthetic strategy and synthetic procedures have been reviewed recently. 3.048ff 3.2.2.1 a,a-Di halogenalkyl 1- 2-hydroxyalkyl -1H-azoles Title compounds with additional halogen on the alkyl have been claimed as agroche-mical fungicides. 3.049, 3.050, 3.051 A typical substance 3.12 shows superior activity against Botrytis cinerea on beans. 3.2.2.2 a-Alkyl, cycloalkyl, alkenyl and halogenoalkyl-, a-aryl or A large number of patent applications have been filed, and some original papers appeared,...