Category: pyrimidines

On February 5, 1998, Murugesan, Natesan; Barrish, Joel C.; Stein, Philip D. published a patent.Computed Properties of 160377-42-4 The title of the patent was Preparation of heterocyclyl-substituted biphenylsulfonamide as endothelin antagonists. And the patent contained the following:

Compounds of formula (I; R1 and R2 are directly bonded to a ring carbon and are each independently hydrogen, alkyl or alkoxy, hydroxyl, halo, or amino; one of X and Y is N and the other is O: R3 and R4 are each directly bonded to a ring carbon and are each independently hydrogen, alkyl, alkenyl, alkynyl, alkoxy, cycloalkyl, cycloalkylalkyl, cycloalkenyl, cycloalkenylalkyl, aryl, aryloxy, aralkyl or aralkoxy, any of which may be substituted or R3 and R4 together may also be alkylene or alkenylene, either of which may be substituted, completing a 4- to 8-membered saturated, unsaturated or aromatic ring together with the carbon atoms to which they are attached; R11 – R14 are each independently are hydrogen alkyl, alkenyl, alkynyl, alkoxy, cycloalkyl, cycloalkylalkyl, cycloalkenyl, cycloalkenylalkyl, aryl, aryloxy, aralkyl, aralkoxy, or heterocyclyl, any of which may be substituted, halo, OH, cyano, NO2, CHO, CO2H, etc.; J, K, L, T, and U are each independently N or C, provided that at least one is N, and at most two are N; and when only one of J, K, L, T, and U is N, the N may be substituted with O- so that N-oxide is formed), which inhibit the activity of endothelin (no data), are prepared Also claimed is a method for treating endothelin-related disorders in a mammal, such as (1) hypertension, (2) pulmonary hypertension, (3) renal, glomerular, or mesangial cell disorders, (4) endotoxemia, (5) ischemia, (6) atherosclerosis, (7) restenosis, (8) subarachnoid hemorrhage, (9) prostatic hypertrophy, and (10) congestive heart failure, and a method for inhibiting cell growth. Said compound I is used in combination with at least one angiotensin II receptor antagonist, renin inhibitor, angiotensin converting enzyme (ACE) inhibitor, or a dual neutral endopeptidase-ACE inhibitor for treating the endothelin-related disorder. A pharmaceutical composition for the treating the endothelin-related disorders comprises said compound optionally in combination with at least one angiotensin II receptor antagonist, renin inhibitor, angiotensin converting enzyme (ACE) inhibitor, or a dual neutral endopeptidase-ACE inhibitor. Thus, 2-(4-bromophenyl)pyrimidine is coupled with 2-borono-N-(3,4-dimethyl-5-isoxazolyl)-N-[(2-methoxyethoxy)methyl]benzenesulfonamide in the presence of (Ph3P)4Pd in a mixture of toluene, 2 M aqueous Na2CO3, and 95% ethanol under reflux for 1.5 h to give the title compound, N-isoxazolylpyrimidinylbiphenylsulfonamide (II). The experimental process involved the reaction of 5-(4-Bromophenyl)pyrimidine(cas: 160377-42-4).Computed Properties of 160377-42-4

The Article related to angiotensin ii receptor antagonists, antiatherosclerotics, antihypertensives, benign prostatic hyperplasia, cell (renal, glomerular, or mesangial cell disorders), endotoxemia, growth inhibitors, animal role: spn (synthetic preparation), thu (therapeutic use), prep (preparation), biol (biological study), uses (uses), heart failure, ischemia, mesangium (disorders), subarachnoid hemorrhage and other aspects.Computed Properties of 160377-42-4

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

COA of Formula: C13H12N2O4On November 12, 2009 ,《Coordination Chemistry Based Approach to Lipophilic Inhibitors of 1-Deoxy-D-xylulose-5-phosphate Reductoisomerase》 appeared in Journal of Medicinal Chemistry. The author of the article were Deng, Lisheng; Sundriyal, Sandeep; Rubio, Valentina; Shi, Zheng-zheng; Song, Yongcheng. The article conveys some information:

1-Deoxy-D-xylulose-5-phosphate reductoisomerase (DXR) in the non-mevalonate pathway found in most bacteria is a validated anti-infective drug target. Fosmidomycin, a potent DXR inhibitor, is active against Gram-neg. bacteria. A coordination chem. and structure based approach was used to discover a novel, lipophilic DXR inhibitor with an IC50 of 1.4 μM. It exhibited a broad spectrum of activity against Gram-neg. and -pos. bacteria with minimal inhibition concentrations of 20-100 μM (or 3.7-19 μg/mL). In the part of experimental materials, we found many familiar compounds, such as Methyl 2-benzyl-5,6-dihydroxypyrimidine-4-carboxylate(cas: 519032-07-6COA of Formula: C13H12N2O4)

Methyl 2-benzyl-5,6-dihydroxypyrimidine-4-carboxylate(cas: 519032-07-6) belongs to pyrimidine. Pyrimidine derivatives also play an important role in drug development, either in concert with other compounds or on their own. COA of Formula: C13H12N2O4They have been used in a wide variety of pharmaceuticals including general anesthetics, anti-epilepsy medication, anti-malaria medication, drugs for treating high blood pressure, and HIV medication.

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Application of 29458-38-6On October 31, 1978 ,《O-Methylation of barbituric acids》 appeared in Farmaco, Edizione Scientifica. The author of the article were Stankiewicz, K.; Bobranski, B.. The article conveys some information:

Treating barbituric and N-phenylbarbituric acid with dry HCl in MeOH at room temperature gave 77.4% I (R = H) and 85% I (R = Ph), resp. In the part of experimental materials, we found many familiar compounds, such as 6-Methoxypyrimidine-2,4(1H,3H)-dione(cas: 29458-38-6Application of 29458-38-6)

6-Methoxypyrimidine-2,4(1H,3H)-dione(cas: 29458-38-6) belongs to pyrimidine. Pyrimidine nucleotide derivatives have a wide range of biological applications. For example, pyrimidine derivatives are useful in DNA repair studies involving cancer and epigenetics.Application of 29458-38-6

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Electric Literature of C23H22N4OOn September 1, 2015 ,《Discovery of thieno[3,2-c]pyridin-4-amines as novel Bruton’s tyrosine kinase (BTK) inhibitors》 was published in Bioorganic & Medicinal Chemistry. The article was written by Zhao, Xinge; Xin, Minhang; Wang, Yazhou; Huang, Wei; Jin, Qiu; Tang, Feng; Wu, Gang; Zhao, Yong; Xiang, Hua. The article contains the following contents:

A novel series of BTK inhibitors bearing thieno[3,2-c]pyridin-4-amine framework as the core scaffold were designed, synthesized and well characterized. In this paper, twenty one compounds displayed variant inhibitory activities against BTK in vitro, and compound 14g showed the most potent inhibitory activity against BTK enzyme, with the IC50 value of 12.8 nM. Moreover, compounds 14g displayed relatively good kinase selectivity and was subsequently evaluated in vivo for profiling its PK properties. This work identified the thieno[3,2-c]pyridin-4-amine derivatives as novel BTK inhibitors and verified the value of thieno[3,2-c]pyridin-4-amine scaffold in drug design. After reading the article, we found that the author used 7-Cyclopentyl-5-(4-phenoxyphenyl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine(cas: 213743-31-8Electric Literature of C23H22N4O)

7-Cyclopentyl-5-(4-phenoxyphenyl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine(cas: 213743-31-8) belongs to pyrimidine. The pyrimidine ring system has wide occurrence in nature as substituted and ring fused compounds and derivatives, including the nucleotides cytosine, thymine and uracil, thiamine (vitamin B1) and alloxan. Electric Literature of C23H22N4O

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

《Tyrosine kinase inhibitor prodrug-loaded liposomes for controlled release at tumor microenvironment》 was written by Salmaso, Stefano; Mastrotto, Francesca; Roverso, Marco; Gandin, Valentina; De Martin, Sara; Gabbia, Daniela; De Franco, Michele; Vaccarin, Christian; Verona, Marco; Chilin, Adriana; Caliceti, Paolo; Bogialli, Sara; Marzaro, Giovanni. HPLC of Formula: 1193-21-1This research focused ontyrosine kinase inhibitor prodrug liposomes controlled release tumor microenvironment; Drug release; Kinase inhibitors; Liposomes; Microsomes; pH-dependent hydrolysis. The article conveys some information:

Tyrosine kinase inhibitors (TKIs) represent one of the most advanced class of therapeutics for cancer treatment. Most of them are also cytochrome P 450 (CYP) inhibitors and/or substrates thereof. Accordingly, their efficacy and/or toxicity can be affected by CYP-mediated metabolism and by metabolism-derived drug-drug interactions. In order to enhance the therapeutic performance of these drugs, we developed a prodrug (Pro962) of our TKI TK962 specifically designed for liposome loading and pH-controlled release in the tumor. A cholesterol moiety was linked to TK962 through pH-sensitive hydrazone bond for anchoring to the liposome phospholipid bilayer to prevent leakage of the prodrug from the nanocarrier. Bioactivity studies performed on isolated target kinases showed that the prodrug maintains only partial activity against them and the release of TK962 is required. Biopharmaceutical studies carried out with prodrug loaded liposomes showed that the prodrug was firmly associated with the vesicles and the drug release was prevented under blood-mimicking conditions. Conversely, conventional liposome loaded with TK962 readily released the drug. Flow cytometric studies showed that liposomes efficiently provided for intracellular prodrug delivery. The use of the hydrazone linker yielded a pH-controlled drug release, which resulted in about 50% drug release at pH 4 and 5 in 2 h. Prodrug, prodrug loaded liposomes and active lead compound have been tested against cancer cell lines in either 2D or 3D models. The liposome formulation showed higher cytotoxicity than the unformulated lead TK962 in both 2D and 3D models. The stability of prodrug, prodrug loaded liposomes and active lead compound in human serum and against human, mouse, and rat microsomes was also assessed, demonstrating that liposome formulations impair the metabolic reactions and protect the loaded compounds from catabolism. The results suggest that the liposomal formulation of pH releasable TKI prodrugs is a promising strategy to improve the metabolic stability, intracellular cancer cell delivery and release, and in turn the efficacy of this class of anticancer drugs. In the experiment, the researchers used 4,6-Dichloropyrimidine(cas: 1193-21-1HPLC of Formula: 1193-21-1)

4,6-Dichloropyrimidine(cas: 1193-21-1) is a member of organic chlorides. Organic chlorides are compounds containing a carbon-chlorine bond, which are widely used in the oil field as a wax dissolver. They are generally not present in crude oils and are typically the result of additives, cleaning solutions or chemicals used for oil recovery.HPLC of Formula: 1193-21-1

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

《A pyrrolo-pyrimidine derivative targets human primary AML stem cells in vivo》 was written by Saito, Yoriko; Yuki, Hitomi; Kuratani, Mitsuo; Hashizume, Yoshinobu; Takagi, Shinsuke; Honma, Teruki; Tanaka, Akiko; Shirouzu, Mikako; Mikuni, Junko; Handa, Noriko; Ogahara, Ikuko; Sone, Akiko; Najima, Yuho; Tomabechi, Yuri; Wakiyama, Motoaki; Uchida, Naoyuki; Tomizawa-Murasawa, Mariko; Kaneko, Akiko; Tanaka, Satoshi; Suzuki, Nahoko; Kajita, Hiroshi; Aoki, Yuki; Ohara, Osamu; Shultz, Leonard D.; Fukami, Takehiro; Goto, Toshio; Taniguchi, Shuichi; Yokoyama, Shigeyuki; Ishikawa, Fumihiko. Computed Properties of C23H22N4O And the article was included in Science Translational Medicine on April 17 ,2013. The article conveys some information:

Leukemia stem cells (LSCs) that survive conventional chemotherapy are thought to contribute to disease relapse, leading to poor long-term outcomes for patients with acute myeloid leukemia (AML). We previously identified a Src-family kinase (SFK) member, hematopoietic cell kinase (HCK), as a mol. target that is highly differentially expressed in human primary LSCs compared with human normal hematopoietic stem cells (HSCs). We performed a large-scale chem. library screen that integrated a high-throughput enzyme inhibition assay, in silico binding prediction, and crystal structure determination and found a candidate HCK inhibitor, RK-20449, a pyrrolo-pyrimidine derivative with an enzymic IC50 (half maximal inhibitory concentration) in the subnanomolar range. A crystal structure revealed that RK-20449 bound the activation pocket of HCK. In vivo administration of RK-20449 to nonobese diabetic (NOD)/severe combined immunodeficient (SCID)/IL2rgnull mice engrafted with highly aggressive therapy-resistant AML significantly reduced human LSC and non-stem AML burden. By eliminating chemotherapy-resistant LSCs, RK-20449 may help to prevent relapse and lead to improved patient outcomes in AML.7-Cyclopentyl-5-(4-phenoxyphenyl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine(cas: 213743-31-8Computed Properties of C23H22N4O) was used in this study.

7-Cyclopentyl-5-(4-phenoxyphenyl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine(cas: 213743-31-8) belongs to pyrimidine. Pyrimidine derivatives also play an important role in drug development, either in concert with other compounds or on their own. Computed Properties of C23H22N4OThey have been used in a wide variety of pharmaceuticals including general anesthetics, anti-epilepsy medication, anti-malaria medication, drugs for treating high blood pressure, and HIV medication.

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia