Category: piperazines

[(S)-γ-(4-Aryl-1-piperazinyl)-L-prolyl]thiazolidines as a novel series of highly potent and long-lasting DPP-IV inhibitors was written by Yoshida, Tomohiro;Sakashita, Hiroshi;Akahoshi, Fumihiko;Hayashi, Yoshiharu. And the article was included in Bioorganic & Medicinal Chemistry Letters in 2007.COA of Formula: C10H12N4 This article mentions the following:

In the search for an inhibitor of dipeptidyl peptidase IV (DPP-IV) highly potent both in vitro and in vivo, a series of L-prolylthiazolidine-based DPP-IV inhibitors, e.g., I, having 4-arylpiperazine or 4-arylpiperidine at the γ-position of the proline structure was synthesized. Of these compounds, the 4-(5-nitro-2-pyridyl)piperazine analog I showed a sub-nanomolar (IC₅₀ = 0.92 nmol/L) DPP-IV inhibitory activity and a long-lasting in vivo DPP-IV inhibition profile. In the experiment, the researchers used many compounds, for example, 6-(Piperazin-1-yl)nicotinonitrile (cas: 149554-29-0COA of Formula: C10H12N4).

6-(Piperazin-1-yl)nicotinonitrile (cas: 149554-29-0) belongs to piperazine derivatives. Simple N-substituted piperazines have been found in many drug molecules. Piperazine is formed as a co-product in the ammoniation of 1,2-dichloroethane or ethanolamine. These are the only routes to the chemical used commercially.COA of Formula: C10H12N4

Referemce:
Piperazine – Wikipedia,
Piperazines – an overview | ScienceDirect Topics

Syntheses of Mannich basic compounds of tetrahydronaphthol containing piperazine side chains was written by Gao, Shouhai;Li, Fulin. And the article was included in Zhongguo Yaowu Huaxue Zazhi in 1993.Application of 21867-64-1 This article mentions the following:

Title compounds I (R = Me, Et, Pr, Me₂CH, Bu, iso-Bu, EtCHMe, pentyl, isopentyl) were prepared starting from 1-naphthol. I (R = Bu, EtCHMe, isopentyl) showed antimalarial activity comparable to that of chloroquine. In the experiment, the researchers used many compounds, for example, 1-Propylpiperazine (cas: 21867-64-1Application of 21867-64-1).

1-Propylpiperazine (cas: 21867-64-1) belongs to piperazine derivatives. The piperazine scaffold is often found in biologically active compounds in different therapeutic areas. These therapeutic areas include antifungals, antidepressants, antivirals, and serotonin receptor (5-HT) antagonists/agonists. Piperazine is an anthelminthic especially useful in the treatment of partial intestinal obstruction caused by Ascaris worms, which is a condition primarily seen in children. Piperazine hydrate and piperazine citrate are the main anthelminthic piperazines.Application of 21867-64-1

Referemce:
Piperazine – Wikipedia,
Piperazines – an overview | ScienceDirect Topics

Synthesis and screening of 3-substituted thioxanthen-9-one-10,10-dioxides was written by Lory, Pedro M. J.;Estrella-Jimenez, Maria E.;Shashack, Matthew J.;Lokesh, Ganesh L.;Natarajan, Amarnath;Gilbertson, Scott R.. And the article was included in Bioorganic & Medicinal Chemistry Letters in 2007.Quality Control of 6-(Piperazin-1-yl)nicotinonitrile This article mentions the following:

Methods appropriate for the parallel synthesis of libraries based on the thioxanthen-9-one 10,10-dioxide scaffold are reported. The novel compounds were synthesized from previously reported 3-chlorothioxanthen-9-one-10,10-dioxide and com. available 3-carboxythioxanthen-9-one 10,10-dioxide. The library members were screened for activity in a fluorescence polarization assay for inhibitors of BRCT domains of breast cancer gene 1 and in cell-based secreted alk. phosphatase reported replicon system for activity against hepatitis C virus. In the experiment, the researchers used many compounds, for example, 6-(Piperazin-1-yl)nicotinonitrile (cas: 149554-29-0Quality Control of 6-(Piperazin-1-yl)nicotinonitrile).

6-(Piperazin-1-yl)nicotinonitrile (cas: 149554-29-0) belongs to piperazine derivatives. The piperazine scaffold is often found in biologically active compounds in different therapeutic areas. These therapeutic areas include antifungals, antidepressants, antivirals, and serotonin receptor (5-HT) antagonists/agonists. Outside the body, piperazine has a remarkable power to dissolve uric acid and producing a soluble urate, but in clinical experience it has not proved equally successful. Quality Control of 6-(Piperazin-1-yl)nicotinonitrile

Referemce:
Piperazine – Wikipedia,
Piperazines – an overview | ScienceDirect Topics

Substituted (ω-aminoalkoxy)stilbene derivatives as a new class of anticonvulsants was written by Kikumoto, Ryoji;Tobe, Akihiro;Fukami, Harukazu;Ninomiya, Kunihiro;Egawa, Mitsuo. And the article was included in Journal of Medicinal Chemistry in 1984.Synthetic Route of C7H16N2 This article mentions the following:

(ω-Aminoalkoxy)stilbenes I [R¹ = H, Cl, F, 2-MeO, 2-Me, 3,4-Cl₂; R² = H, 3-MeO, 5-Cl; R³ = NMe₂, NEt₂, NHMe, NPr₂, 1-pyrrolidinyl, 1-piperidinyl, morpholino, 4-alkyl-1-piperazinyl, 3-R⁴-substituted-1-piperidinyl (R⁴ = OH, alkoxy, OAc, CH₂OH, CONH₂, CO₂Me, Me, CO₂H); n = 2-5] and II (butoxy at 2, 3, 4) were prepared by successive Grignard reaction of benzyl chlorides III with salicylaldehydes IV, dehydration of (1-hydroxyphenethyl)phenols, ω-bromoalkylation of hydroxy-trans-stilbenes, and amination of the product bromoalkyl ethers with amines. The effect of structural modification of these mols. on the activities was examined Potent anticonvulsant activity was displayed by 2-[4-(4-methyl-1-piperazinyl)butoxy]stilbene and piperidinobutoxystilbene derivatives V (R⁴ = OH, OMe, OEt, and OAc) as determined by maximal electroshock seizure (MES) and pentylenetetrazol-induced convulsion tests in mice. V (R⁴ = OH) exhibited more potent anti-MES activity than diphenylhydantoin and carbamazepine in further pharmacol. tests in rats, and its therapeutic index was superior to those of two antiepileptic drugs. In the experiment, the researchers used many compounds, for example, 1-Propylpiperazine (cas: 21867-64-1Synthetic Route of C7H16N2).

1-Propylpiperazine (cas: 21867-64-1) belongs to piperazine derivatives. Piperazine was first introduced as an anthelmintic in 1953. Piperazine compounds mediate their anthelmintic action by generally paralyzing parasites, allowing the host body to easily remove or expel the invading organism. Although many piperazine derivatives occur naturally, piperazine itself can be synthesized by reacting alcoholic ammonia with 1,2-dichloroethane, by the action of sodium and ethylene glycol on ethylene diamine hydrochloride, or by reduction of pyrazine with sodium in ethanol.Synthetic Route of C7H16N2

Referemce:
Piperazine – Wikipedia,
Piperazines – an overview | ScienceDirect Topics

Site-Selective C-H Alkylation of Piperazine Substrates via Organic Photoredox Catalysis was written by McManus, Joshua B.;Onuska, Nicholas P. R.;Jeffreys, Matthew S.;Goodwin, Nicole C.;Nicewicz, David A.. And the article was included in Organic Letters in 2020.Formula: C13H20N4O2 This article mentions the following:

Substituted piperazines such as I were prepared by C-H alkylation of piperazines such as tert-Bu 4-benzoyl-1-piperazinecarboxylate with electron-deficient alkenes such as PhCH:C(CN)₂ under blue LED irradiation in the presence of a diarylacridinium salt as a photoredox catalyst. The regioselectivity of the photoredox alkylation reactions was correlated to the difference between the calculated electron populations at the nitrogen atoms of the neutral compounds and the calculated electron populations at the nitrogen atoms of the radical cations. In the experiment, the researchers used many compounds, for example, tert-Butyl 4-(pyrimidin-2-yl)piperazine-1-carboxylate (cas: 780705-64-8Formula: C13H20N4O2).

tert-Butyl 4-(pyrimidin-2-yl)piperazine-1-carboxylate (cas: 780705-64-8) belongs to piperazine derivatives. Piperazine is a fairly basic compound and is an amine solvent. Intermediate for a wide range of pharmaceuticals, polymers, dyes, corrosion inhibitors, rubber accelerators and surfactants.Formula: C13H20N4O2

Referemce:
Piperazine – Wikipedia,
Piperazines – an overview | ScienceDirect Topics

Discovery of A031 as effective proteolysis targeting chimera (PROTAC) androgen receptor (AR) degrader for the treatment of prostate cancer was written by Chen, Linrong;Han, Liuquan;Mao, Shujun;Xu, Ping;Xu, Xinxin;Zhao, Ruibo;Wu, Zhihua;Zhong, Kai;Yu, Guangliang;Wang, Xiaolei. And the article was included in European Journal of Medicinal Chemistry in 2021.Formula: C16H22N2O4 This article mentions the following:

Herein the design, synthesis, and biol. evaluation of highly effective proteolysis targeting chimeras (PROTAC) androgen receptor (AR) degraders, such as compound I was reported. It could induce the degradation of AR protein in VCaP cell lines in a time-dependent manner, achieving the IC₅₀ value of less than 0.25μM. The I was 5 times less toxic than EZLA and works with an appropriate half-life (t 1/2) or clearance rate (Cl). Also, it had a significant inhibitory effect on tumor growth in zebrafish transplanted with human prostate cancer (VCaP). Therefore, I provided a further idea of developing novel drugs for prostate cancer. In the experiment, the researchers used many compounds, for example, 4-(4-(tert-Butoxycarbonyl)piperazin-1-yl)benzoic acid (cas: 162046-66-4Formula: C16H22N2O4).

4-(4-(tert-Butoxycarbonyl)piperazin-1-yl)benzoic acid (cas: 162046-66-4) belongs to piperazine derivatives. A form in which piperazine is commonly available industrially is as the hexahydrate, C4H10N2. 6H2O, which melts at 44 °C and boils at 125–130 °C. Piperazine is formed as a co-product in the ammoniation of 1,2-dichloroethane or ethanolamine. These are the only routes to the chemical used commercially.Formula: C16H22N2O4

Referemce:
Piperazine – Wikipedia,
Piperazines – an overview | ScienceDirect Topics

Bis(β-haloethyl)amines. VII. A new synthesis of N-monoalkylpiperazines was written by Prelog, V.;Stepan, V.. And the article was included in Collection of Czechoslovak Chemical Communications in 1935.Electric Literature of C7H16N2 This article mentions the following:

The N- and N,N’ -substituted piperazines are readily obtained by interaction of primary amines with (XCH₂CH₂)₂NR (X = Cl or, better, Br). (HOCH₂CH₂)₂NMe (I) (60 g.) in 100 g. 48% HBr, evaporated to a sirup and heated 6 hrs. at 160-80°, yields 66% (BrCH₂CH₂)₂NMe (II), m. 151-2° (picrate, m. 121-2°). In 170 g. CHCl₃, 20 g. I and 87 g. SOCl₂, refluxed 1 hr. give 56% (ClCH₂CH₂)₂NMe (III), m. 116-17°. Refluxed 15 hrs. in 100 cc. MeOH, 48 g. II and 28 g. PhNH₂ give, after fractional distillation, 58% N-methyl-N’-phenylpiperazine (IV), b₃ 140-2°; similarly, III gives the HCl salt, m. 233.5°, in 26% yield. With MeI. IV gives an impure methiodide, m. 238-9°, which with AgCl yields a methochloride, decomposing at 215°. Treated with NaNO₂ followed by SO₂ (cf. Friedländer, III, 957), IV is decomposed to N-methyl-piperazine (V), b. 134-6° (dihydrochloride monohydrate, m. 242-3°; dichloroplatinate; dipicrate, decomposing at 272°; addition compound with CS₂, subliming without decomposition about 180°). With BzCl, V gives C₁₂H₁₇ON₂Cl, m. 240°. Prepared like II, in 58% yield, (BrCH₂CH₂)₂NEt m. 170° (picrate, m. 120.5°) and yields 63.5% N-ethyl-N’-phenylpiperazine,m. 50-1°. This, with NaNO₂, gives the unstable di-HCl salt of N-ethyl-N’-p-nitrosophenylpiperazine, decomposing near 210°, which with SO₂ yields N-ethylpiperazine (di-HCl salt, m. 210-11°; dipicrate,decomposes at 257°). Similarly obtained are (BrCH₂CH₂)₂N-Pr, m. 157° (picrate, m. 101-2°); N-propyl-N’-phenylpiperazine, b<0.1 102-3° (HBr salt, m. 231-2°) and N-propylpiperazine (di-HCl salt, decomposes at 256°; dipicrate, m. 241-2° (decomposition)). In the experiment, the researchers used many compounds, for example, 1-Propylpiperazine (cas: 21867-64-1Electric Literature of C7H16N2).

1-Propylpiperazine (cas: 21867-64-1) belongs to piperazine derivatives. Simple N-substituted piperazines have been found in many drug molecules. Piperazines are very broad chemical group, covering a wide range of drugs from antidepressants to antihistamines. The connecting property of all these chemicals is the presence of a piperazine functional group.Electric Literature of C7H16N2

Referemce:
Piperazine – Wikipedia,
Piperazines – an overview | ScienceDirect Topics

Photocatalyzed Dehydrogenation of Aliphatic N-Heterocycles Releasing Dihydrogen was written by Ritu;Das, Saikat;Tian, Ya-Ming;Karl, Tobias;Jain, Nidhi;Konig, Burkhard. And the article was included in ACS Catalysis in 2022.Application of 780705-64-8 This article mentions the following:

Author’s report the iridium-nickel dual photocatalytic acceptorless and redox neutral dehydrogenation of aliphatic heterocycles yielding cyclic alkenes without overoxidn. at room temperature Excitation of the iridium photocatalyst initiates the formation of a nickel hydride intermediate that yields alkenes and H₂ via β-hydride elimination. The reaction proceeds regioselectively and the scope was demonstrated by the synthesis of 12 biol. relevant mols. and drugs. In addition, com. and easily available N-heterocyclic alkane starting materials were converted into functionalized alkenes of high synthetic and com. value using the method. In the experiment, the researchers used many compounds, for example, tert-Butyl 4-(pyrimidin-2-yl)piperazine-1-carboxylate (cas: 780705-64-8Application of 780705-64-8).

tert-Butyl 4-(pyrimidin-2-yl)piperazine-1-carboxylate (cas: 780705-64-8) belongs to piperazine derivatives. Piperazine causes primary dermal irritation and skin burns at high concentrations. Piperazine also causes eye irritation in humans. Piperazines are very broad chemical group, covering a wide range of drugs from antidepressants to antihistamines. The connecting property of all these chemicals is the presence of a piperazine functional group.Application of 780705-64-8

Referemce:
Piperazine – Wikipedia,
Piperazines – an overview | ScienceDirect Topics

Benzamide capped peptidomimetics as non-ATP competitive inhibitors of CDK2 using the REPLACE strategy was written by Premnath, Padmavathy Nandha;Craig, Sandra N.;Liu, Shu;McInnes, Campbell. And the article was included in Bioorganic & Medicinal Chemistry Letters in 2016.Category: piperazines This article mentions the following:

Inhibition of cyclin dependent kinase 2 (CDK2) in complex with cyclin A in G1/S phase of the cell cycle has been shown to promote selective apoptosis of cancer cells through the E2F1 pathway. An alternative approach to catalytic inhibition is to target the substrate recruitment site also known as the cyclin binding groove (CBG) to generate selective non-ATP competitive inhibitors. The REPLACE strategy has been applied to identify fragment alternatives and substituted benzoic acid derivatives were evaluated as a promising scaffold to present appropriate functionality to mimic key peptide determinants. Fragment Ligated Inhibitory Peptides (FLIPs) are described which potently inhibit both CDK2/cyclin A and CDK4/cyclin D1 and have preliminary antitumor activity. A structural rationale for binding was obtained through mol. modeling further demonstrating their potential for further development as next generation non ATP competitive CDK inhibitors. In the experiment, the researchers used many compounds, for example, 4-(4-(tert-Butoxycarbonyl)piperazin-1-yl)benzoic acid (cas: 162046-66-4Category: piperazines).

4-(4-(tert-Butoxycarbonyl)piperazin-1-yl)benzoic acid (cas: 162046-66-4) belongs to piperazine derivatives. Simple N-substituted piperazines have been found in many drug molecules. Piperazines are very broad chemical group, covering a wide range of drugs from antidepressants to antihistamines. The connecting property of all these chemicals is the presence of a piperazine functional group.Category: piperazines

Referemce:
Piperazine – Wikipedia,
Piperazines – an overview | ScienceDirect Topics

Non-imidazole histamine H₃ ligands. Part III. New 4-n-propylpiperazines as non-imidazole histamine H₃-antagonists was written by Walczynski, Krzysztof;Zuiderveld, Obbe P.;Timmerman, Henk. And the article was included in European Journal of Medicinal Chemistry in 2005.Safety of 1-Propylpiperazine This article mentions the following:

Propylpiperazinyl benzoxazoles, benzothiazoles, oxazolopyridines, and thiazolopyridines I [X = O, S; Y, Z, A, B = CH, N (either none or one of the variable groups is N)] and their hydrobromide salts are prepared as selective histamine H₃ receptor antagonists; their histamine H₃ antagonist activities and the relationship between their structures and activities are discussed. Propylpiperazinyl-substituted thiazolopyridines and a propylpiperazinyl-substituted benzothiazole are better histamine H₃ antagonists than propylpiperazinyl-substituted oxazolopyridines and a propylpiperazinyl-substituted benzooxazole. I (X = S; Y = A = B = CH; Z = N) is the most potent histamine H₃ antagonist of the series, with a pA₂ value of 7.25, while the corresponding oxazolopyridine I (X = O; Y = A = B = CH; Z = N) has a pA₂ value of 6.9. In the experiment, the researchers used many compounds, for example, 1-Propylpiperazine (cas: 21867-64-1Safety of 1-Propylpiperazine).

1-Propylpiperazine (cas: 21867-64-1) belongs to piperazine derivatives. Simple N-substituted piperazines have been found in many drug molecules. Intermediate for a wide range of pharmaceuticals, polymers, dyes, corrosion inhibitors, rubber accelerators and surfactants.Safety of 1-Propylpiperazine

Referemce:
Piperazine – Wikipedia,
Piperazines – an overview | ScienceDirect Topics