2002-16-6

Usage

Uses

Used in Pharmaceutical Industry:
1-Phenylguanidine is used as a chemical intermediate for the synthesis of various pharmaceutical compounds. It plays a crucial role in the preparation of (4-Aminomethyl)phenylguanidine derivatives, which are nonpeptidic, highly selective inhibitors of human urokinase. These derivatives have significant potential in the development of therapeutic agents targeting urokinase, an enzyme involved in various physiological processes, including tissue remodeling and cancer progression.
Additionally, a series of substituted phenylguanidine compounds have been identified as selective inhibitors of urokinase. These compounds can be further optimized and developed into effective drugs for the treatment of diseases where urokinase plays a critical role, such as cancer and inflammatory disorders. The use of 1-phenylguanidine in the development of these inhibitors highlights its importance in the pharmaceutical industry and its potential to contribute to the discovery of novel therapeutic agents.

InChI:InChI=1/C7H9N3.ClH/c8-7(9)10-6-4-2-1-3-5-6;/h1-5H,(H4,8,9,10);1H

Upstream product

• 64-17-5 ethanol 
• 674-81-7 nitrosoguanidine 
• 142-04-1 aniline hydrochloride 
• 420-04-2 CYANAMID 
• 14527-26-5 2-methylisothiourea sulphate 
• 62-53-3 aniline 
• 6522-91-4 N-phenyl-guanidine hydrochloride 
• 17356-08-0 thiourea 
• 556-88-7 nitroguanidine 
• 7732-18-5 water 
• 102-02-3 1-phenylbiguanide 
• 1071-37-0 2-ethylisothiourea hydrobromide 
• 56140-50-2 N-[anilino(imino)methyl]benzamide 
• 7647-01-0 hydrogenchloride 

Downstream Products

• 57356-49-7 phenyl-pyrimidin-2-yl-amine 
• 101269-02-7 5-ethyl-2-anilino-5-butyl-1H-pyrimidine-4,6-dione 
• 102660-99-1 phenylcarbamimidoyl-amidophosphoric acid dibenzyl ester 
• 102319-15-3 phenylcarbamimidoyl-amidophosphoric acid bis-(4-nitro-benzyl ester) 
• 90563-33-0 N-methyl-N'-phenylcarbamimidoyl-thiourea 
• 101599-91-1 5-ethyl-2-anilino-5-isopentyl-1H-pyrimidine-4,6-dione 
• 109813-20-9 phenylcarbamimidoyl-amidophosphoric acid diphenyl ester 
• 66940-97-4 5,5-diethyl-2-anilino-1H-pyrimidine-4,6-dione 
• 101260-15-5 phenylcarbamimidoyl-amidophosphoric acid diisobutyl ester 
• 149-30-4 2-thioxo-3H-1,3-benzothiazole 
• 77407-40-0 N-4,5-triphenyl-1H-imidazol-2-amine 
• 136437-05-3 C₁₅H₂₁N₃O₄ 
• 136465-66-2 C₂₃H₂₁N₃O₄ 
• 100185-43-1 2-Amino-1-phenyl-5,6-dihydro-4(1H)-pyrimidinon 

Relevant academic research and scientific papers

Iron-promoted sulfur sequestration for the substituent-dependent regioselective synthesis of tetrazoles and guanidines

We have established a facile and versatile synthetic methodology for the construction of tetrazoles and guanidines in the presence of an eco-friendly, inexpensive, easily available iron reagent. Aromatic thioureas with electron-donating substituents produced their respective target products in quantitative yield. In contrast, when electron-withdrawing substituted aromatic thioureas were used, the expected products were obtained in reduced yield. However, the desired products were obtained in good yield at moderate temperature. In addition, mechanistic studies revealed that the synthetic route involved iron-based subsequent reactions of addition and removal of sulfur.

The utilization of ball milling in synthesis of aryl guanidines through guanidinylation and N-Boc-deprotection sequence

Solid state ball milling was used in guanidinylation reactions of aromatic amines with N,N′-Di-Boc-1H-pyrazole-1-carboxamidine reagent. Reaction conditions are advantageous, and in general reactions proceed in significantly shorter reaction times and in higher yields than under the conventional solution conditions. Mechanochemical conditions were also successfully applied to the cleavage of N-Boc protecting group.

One-Pot Evolution of Ageladine A through a Bio-Inspired Cascade towards Selective Modulators of Neuronal Differentiation

A bio-inspired cascade reaction has been developed for the construction of the marine natural product ageladine A and a de novo array of its N1-substituted derivatives. This cascade features a 2-aminoimidazole formation that is modeled after an arginine post-translational modification and an aza-electrocyclization. It can be effectively carried out in a one-pot procedure from simple anilines or guanidines, leading to structural analogues of ageladine A that had been otherwise synthetically inaccessible. We found that some compounds out of this structurally novel library show a significant activity in modulating the neural differentiation. Namely, these compounds selectively activate or inhibit the differentiation of neural stem cells to neurons, while being negligible in the differentiation to astrocytes. This study represents a successful case in which the native biofunction of a natural product could be altered by structural modifications.

Direct guanylation of amino groups by cyanamide in water: Catalytic generation and activation of unsubstituted carbodiimide by scandium(iii) triflate

Guanylation proceeded efficiently upon treatment of the various amines with cyanamide in the presence of catalytic amounts of scandium(III) triflate under mild conditions. The method did not require the guanylation reagents to be preactivated, and the reaction proceeded efficiently in water. The method, therefore, has practical utility for substrates that dissolve only in aqueous solutions, for example, peptides or pharmacologically important compounds. Georg Thieme Verlag Stuttgart New York.

Reaction of quinones and guanidine derivatives: Simple access to bis-2-aminobenzimidazole moiety of benzosceptrin and other benzazole motifs

A new strategy for the synthesis of 2-aminobenzimidazol-6-ols via a reaction of quinones with guanidine derivatives is reported. Sequential application of this methodology provided a simple access to the first benzosceptrin analogue bearing a bis-2-aminoimidazole moiety. A concomitant addition of two guanidines to the naphtho[1′,2′:4,5]imidazo[1,2-a] pyrimidine-5,6-dione, which includes the redox neutral debenzylation and guanidine-assisted cleavage of the 2-aminopyrimidine part resulted in the synthesis of the free challenging contiguous bis-2-aminoimidazole moiety of benzosceprins in one step.

Discovery of 5-(2-(phenylamino)pyrimidin-4-yl)thiazol-2(3H)-one derivatives as potent Mnk2 inhibitors: Synthesis, SAR analysis and biological evaluation

Phosphorylation of eIF4E by human mitogen-activated protein kinase (MAPK)-interacting kinases (Mnks) is crucial for human tumourigenesis and development. Targeting Mnks may provide a novel anticancer therapeutic strategy. However, the lack of selective Mnk inhibitors has so far hampered pharmacological target validation and clinical drug development. Herein, we report, for the first time, the discovery of a series of 5-(2-(phenylamino) pyrimidin-4-yl)thiazole-2(3H)-one derivatives as Mnk inhibitors. Several derivatives demonstrate very potent Mnk2 inhibitory activity. The most active and selective compounds were tested against a panel of cancer cell lines, and the results confirm the cell-type-specific effect of these Mnk inhibitors. Detailed cellular mechanistic studies reveal that Mnk inhibitors are capable of reducing the expression level of anti-apoptotic protein Mcl-1, and of promoting apoptosis in MV4-11 acute myeloid leukaemia cells. Highly active Mnk2 inhibitors: Mnk-related cancer biology is an area of intensive research, but its inhibitor discovery has lagged behind due to a lack of understanding of the protein structure. Herein we report the discovery of Mnk2 inhibitors (e.g. 8 e). These potent and selective inhibitors are extremely valuable for target validation and drug discovery.

Synthesis of a 2,4,6-trisubstituted 5-cyano-pyrimidine library and evaluation of its immunosuppressive activity in a Mixed Lymphocyte Reaction assay

A series of novel pyrimidine analogues were synthesized and evaluated for immunosuppressive activity in the Mixed Lymphocyte Reaction assay, which is well-known as the in vitro model for in vivo rejection after organ transplantation. Systematic variation of the substituents at positions 2, 4 and 6 of the pyrimidine scaffold led to the discovery of 2-benzylthio-5-cyano-6-(4- methoxyphenyl)-4-morpholinopyrimidine with an IC50 value of 1.6 μM in the MLR assay.

Identification of pyrimidine derivatives as hSMG-1 inhibitors

hSMG-1 kinase plays a dual role in a highly conserved RNA surveillance pathway termed nonsense-mediated RNA decay (NMD) and in cellular genotoxic stress response. Since deregulation of cellular responses to stress contributes to tumor growth and resistance to chemotherapy, hSMG-1 is a potential target for cancer treatment. From our screening efforts, we have identified pyrimidine derivatives as hSMG-1 kinase inhibitors. We report structure-based optimization of this pan-kinase scaffold to improve its biochemical profile and overall kinome selectivity, including mTOR and CDK, to generate the first reported selective hSMG-1 tool compound.

Palladium-catalyzed C-H functionalization using guanidine as a directing group: Ortho arylation and olefination of arylguanidines

Palladium-catalyzed C-H functionalization using guanidine as the directing group was achieved under mild reaction conditions. Various guanidine derivatives were produced in moderate to good yields by using simple unactivated arenes or ethyl acrylate as the source of arylation or olefination, respectively.

CURABLE COMPOSITION

The present invention has its object to provide a curable composition which comprises a guanidine compound as a non-organotin type catalyst, is less discolored, has good surface curability, depth curability, strength rise and adhesiveness, and can retain the curability even after storage; the above object can be achieved by a curable composition which comprises: (A) an organic polymer containing a silyl group capable of crosslinking under siloxane bond formation, the silyl group being a group represented by the general formula (1): -SiX 3 (1) (wherein X represents a hydroxyl group or a hydrolyzable group and the three X groups may be mutually the same or different), (B) a guanidine compound (B-1) as a silanol condensation catalyst, and (C) a plasticizer, wherein the content of the component (B-1) is not lower than 0.1 part by weight but lower than 8 parts by weight per 100 parts by weight of the component (A), and a non-phthalate ester plasticizer accounts for 80 to 100% by weight of the (C) component plasticizer.