Brotizolam

Chemical Name 8-Bromo-6-(o-chlorophenyl)-1-methyl-4H-s-triazolo-[3,4c] -thieno-[2,3e] 1,4-diazepine 

7-8romo-5-(o-chlorophenyl)-3H-[2,3e] thleno-1,4-diazepin-2-one Phosphorus Pentesulfide Hydrazine Hydrate 

Danneberg, P. and Kunn, F.J. U.S. Patent 4,094,984 June 13, 1978 assigned to 8oehringer Ingelheim GmbH 

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H4N2 302-01-2) see Acetazolaraide Allopurinol Brotizolam Carbidopa Cibenzoline Desmopressin Estazolam Etizolam Guanadrel Isoniazid Itraconazole Mitopodozide Niftiroxazide Nifurtimox Nitrofurantoin Phenelzine Primaquine Ziprasidone hydrochloride hydrazine-1,2-bis(thiocarbaxamide)... 

Sonogashira reactions of both a-halothiophenes [117] and P-halothiophenes [118] proceed smoothly even for fairly complicated molecules as illustrated by the transformation of brotizolam (134) to alkyne 135 [119]. Interestingly, 3,4-bis(trimethylsilyl)thiophene (137), derived from the intermolecular cyclization of 4-phenylthiazole (136) and bis(trimethylsilyl)acetylene, underwent consecutive iodination and Sonogashira reaction to make 3,4-bisalkynylthiophenes [120], Therefore, a regiospecific mono-i/wo-iodination of 137 gave iodothiophene 138, which was coupled with phenylacetylene to afford alkynylthiophene 139. A second iodination and a Sonogashira reaction then provided the unsymmetrically substituted 3,4-bisalkynylthiophene 140. 

Broom corn fiber, 11 298 Broom root fiber, 11 298 Broperamole, 4 359t Bropirimine, 4 360t Brotizolam, 4 360t Brovincamine, 4 360t Brown asbestos, world production in 2000, 3 289t... 

Fusion of an additional heterocyclic ring onto a benzodiazepine is well known to considerably increase potency. This increase in potency is apparently maintained when the benzene ring is replaced by thiophene. Thiophene aminoketone 161 is converted to the benzodiazepine analogue 164 via chloroacetamide 162 and then glycine derivative 163 by the same sequence as that used in the benzene series. Treatment of the product 164 with phosphorus pentasulfide gives the thio-amide 165 reaction of that intermediate with hydrazine leads to the amino amidine 166. Condensation of this with ethyl orthoacetate gives the anxiolytic agent brotizolam (167) [31]. 

Biological response modifier, 95 Bipenamol, 45 Bisantrene, 62 Bisoprolol, 28 Brocrinat, 130 Bromadoline, 6 Bromfenac, 46 Bronchodilator, 168, 213 Bropirimine, 116 Brotizolam, 219 Buspirone, 119 Butaprost, 13 Butoprozine, 156... 

Nevertheless, the GABAergic properties of benzodiazepines remain their most important clinical application. Over the past 30 years, the most widely used benzodiazepine drug has been diazepam (1.6). It is an anxiolytic, sedative, and muscle relaxant the anxious, depressed person becomes more outgoing and relaxed. There have been many diazepam analogs. Oxazepam (4.177) and lorazepam (4.178) have similar effects. Temazepam (4.179), flunitrazepam (4.180), and flurazepam (4.181) are useful sedative-hypnotics. Clonazepam (4.182) is a clinically useful anticonvulsant. Brotizolam (4.183), a novel benzodiazepine analog, seems to be an effective sedative-hypnotic. Midazolam (4.184) is an imidazolo-benzodiazepine that is water soluble and thus easily injectable. It is a hypnotic sedative with marked amnestic (i.e., memory loss) properties and is used in dentistry, endoscopic procedures, and induction to anesthetics in the elderly and in... 

The principal disadvantages of barbiturates as hypnotics include the development of physical dependence, a relatively low therapeutic index (and the potential of poisoning, as in suicide), suppression of REM sleep, and possible hangover effects. As mentioned above, benzodiazepines (e.g., flurazepam or brotizolam) are hypnotics as effective as barbiturates and are much safer in terms of their therapeutic index, addiction potential, and REM sleep-deprivation effects. Thus benzodiazepines have displaced barbiturates as sedative hypnotics. 

In addition, another group of diazepines features replacement of the fused benzene ring with other heteroaromatic systems such as thieno or pyrazolo. Most compounds of this type are under investigation (e.g., brotizolam, a thienodiazepine). Because pharmacological effects are comparable with the BZDs, both groups of diazepines are considered BZDs from a clinical standpoint. 

Some short-acting BZDs (e.g., midazolam and triazolam) are ultrarapidly eliminated and their effect on sleep duration may be so short that patients may awaken earlier then they desire. Brotizolam, in contrast, has a half-life of around 5 hours that places it in the middle of the range of activity of the rapidly eliminated hypnotics. Thus, brotizolam may not only induce sleep quickly but also sustain sleep without residual effects the next day and without accumulation on repeated ingestion. 

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