cas 105763-77-7, 2,4-Dichloro-6-methoxyquinazoline

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Discovery of 2-aryloxy-4-amino-quinazoline derivatives as novel protease-activated receptor 2 (PAR2) antagonists
Protease-activated receptor 2 (PAR2) is a member of G protein-coupled receptor and its activation initiates diverse inflammatory responses. Recent studies suggest that antagonists of PAR2 may provide a novel therapeutic strategy for inflammatory diseases. In this study, we have developed a series of 2-aryloxy-4-amino-quinazoline derivatives as PAR2 antagonists and examined their effects against LPS-induced inflammatory responses in RAW 264.7 macrophages. Among these derivatives, compound 2f displayed the greatest antagonistic activity with the IC50 value of 2.8 μM. Binding modes of the newly identified PAR2 antagonists were analyzed by molecular docking using IFD/MM-GBSA methods in the putative binding site of PAR2 homology model. Moreover, 2f demonstrated significant inhibitory effects on the LPS-activated pro-inflammatory mediators including nitric oxide (NO), prostaglandin E2 (PGE2), interleukin-1β (IL-1β), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) through the regulation of various intracellular signaling pathways involving nuclear factor-κB (NF-κB), activator protein 1 (AP-1) and the mitogen-activated protein kinases (MAPK). Furthermore, administration of 2f significantly reduced the mortality of LPS-induced sepsis in mice. These results provide useful insights into the development of novel PAR2 antagonists with anti-inflammatory activity in vitro and in vivo.
Cho, Nam-Chul,Cha, Ji Hyoun,Kim, Hyojin,Kwak, Jinsook,Kim, Dohee,Seo, Seung-Hwan,Shin, Ji-Sun,Kim, Taehun,Park, Ki Duk,Lee, Jiyoun,No, Kyoung Tai,Kim, Yun Kyung,Lee, Kyung-Tae,Pae, Ae Nim
p. 7717 - 7727
(2015)
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One-pot cascade ring enlargement of isatin-3-oximes to 2,4-dichloroquinazolines mediated by bis(trichloromethyl)carbonate and triarylphosphine oxide
An efficient and convenient one-pot cascade synthesis of 2,4-dichloroquinazolines directly from isatin-3-oximes with the addition of bis(trichloromethyl)carbonate and triarylphosphine oxide was developed, leading to substituted quinazolines in moderate to excellent yields. The efficiency of this transformation was demonstrated by compatibility with a range of functional groups. Thus, the method represents a convenient and practical strategy for the synthesis of substituted 2,4-dichloroquinazolines.
Qin, Jinjing,Li, Zhenhua,Ma, Shengzhe,Ye, Lixian,Jin, Guoqiang,Su, Weike
supporting information
p. 1007 - 1012
(2020/07/10)

INHIBITORS OF CYCLIN-DEPENDENT KINASES
Provided herein are inhibitors of cyclin-dependent kinases (CDKs), pharmaceutical compositions comprising said compounds, and methods for using said compounds for the treatment of diseases.
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Paragraph 00257

(2019/11/19)

Molecular Hybridization-Inspired Optimization of Diarylbenzopyrimidines as HIV-1 Nonnucleoside Reverse Transcriptase Inhibitors with Improved Activity against K103N and E138K Mutants and Pharmacokinetic Profiles
Molecular hybridization is a powerful strategy in drug discovery. A series of novel diarylbenzopyrimidine (DABP) analogues were developed by the hybridization of FDA-approved drugs etravirine (ETR) and efavirenz (EFV) as potential HIV-1 nonnucleoside reverse transcriptase inhibitors (NNRTIs). Substituent modifications resulted in the identification of new DABPs with the combination of the strengths of the two drugs, especially compound 12d, which showed promising activity toward the EFV-resistant K103N mutant. 12d also had a favorable pharmacokinetic (PK) profile with liver microsome clearances of 14.4 μL/min/mg (human) and 33.2 μL/min/mg (rat) and an oral bioavailability of 15.5% in rat. However, its activity against the E138K mutant was still unsatisfactory; E138K is the most prevalent NNRTI resistance-associated mutant in ETR treatment. Further optimizations resulted in a highly potent compound (12z) with no substituents on the phenyl ring and a 2-methyl-6-nitro substitution pattern on the 4-cyanovinyl-2,6-disubstitued phenyl motif. The antiviral activity of this compound was much higher than those of ETR and EFV against the WT, E138K, and K103N variants (EC50 = 3.4, 4.3, and 3.6 nM, respectively), and the cytotoxicity was decreased while the selectivity index (SI) was increased. In particular, this compound exhibited acceptable intrinsic liver microsome stability (human, 34.5 μL/min/mg; rat, 33.2 μL/min/mg) and maintained the good PK profile of its parent compound EFV and showed an oral bioavailability of 16.5% in rat. Molecular docking and structure-activity relationship (SAR) analysis provided further insights into the binding of the DABPs with HIV-1 reverse transcriptase and provided a deeper understanding of the key structural features responsible for their interactions.
Han, Sheng,Sang, Yali,Wu, Yan,Tao, Yuan,Pannecouque, Christophe,De Clercq, Erik,Zhuang, Chunlin,Chen, Fen-Er
(2019/11/11)

HEPARANASE INHIBITORS AND USE THEREOF
The invention relates to functionalized quinazoline compounds, pharmaceutical compositions comprising such compounds, and the use of such compounds as heparanase inhibitors for the treatment of diseases or conditions related to heparanse activity.
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Paragraph 0143; 0149

(2018/07/05)

Pyrimidine derivatives, preparation method therefor and application of pyrimidine derivatives
The invention belongs to the field of drug synthesis and relates to novel pyrimidine derivatives, pharmaceutically acceptable salts, hydrates, solvates or prodrugs thereof, preparation methods of thenovel pyrimidine derivatives and the pharmaceutically acceptable salts, hydrates, solvates or prodrugs thereof and use of the novel pyrimidine derivatives and the pharmaceutically acceptable salts, hydrates, solvates or prodrugs thereof in preparation of therapeutic agents, particularly PAK inhibitors. The derivatives disclosed by the invention are represented by a general formula (I) or (II), wherein each substituent is as defined in claims.
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Paragraph 0135; 0136; 0140; 0141; 0146; 0147

(2018/03/26)

The therapeutic compound, use and related method (by machine translation)
PROBLEM TO BE SOLVED: To provide a pharmaceutical composition containing a compound or its salt which prevents or treats a central nervous system disease in which integration dysfunction syndrome and agnosia are enumerated as exemplary disorders.SOLUTION: The pharmaceutical composition includes the compound or its salt represented by chemical formula (A) which modulates striatal-enriched protein tyrosine phosphatase (STEP).
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Paragraph 1096; 1099

(2017/06/29)

Synthesis and Antibacterial Activity of Sulfur-linked Bis and Tris Heterocycles
The bis and tris heterocycles-benzoxazolyl/benzothiazolyl/benzimidazolyl quinazolines linked by sulfur and/or nitrogen were prepared from 2,4-dichloroquinazoline and benzazolyl-2-thiol/benzazolyl-2-amine and studied their antibacterial activity. The nitro-substituted sulfur-linked bisbenzothiazolylquinazoline (12f), bisbenzimidazolylquinazoline (13f), and nitro-substituted sulfur and nitrogen-linked bisbenzothiazolylquinazoline (15f) were found to be potential antibacterial agents against Staphylococcus aureus.
Mallikarjuna Reddy,Lavanya,Lakshmi Teja,Padmaja,Padmavathi
p. 2755 - 2766
(2017/09/26)

SUBSTITUTED QUINAZOLINE COMPOUNDS AND PREPARATION AND USES THEREOF
The present invention relates quinazolinone compounds of Formula (I), as well as their preparation and uses, and further relates pharmaceutical compositions comprising these compounds and their uses； wherein the compounds or pharmaceutical compositions disclosed herein can be used for antagonizing the orexin receptor. The present invention also relates to uses of the compounds or pharmaceutical compositions in treating or preventing neurological and psychiatric disorders and diseases of the central nervous system in mammals, especially in humans.
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Page/Page column 52; 68

(2017/03/08)

OCTAHYDROPYRROLO [3, 4-c] PYRROLE DERIVATIVES AND USES THEREOF
The invention relates to octahydropyrrolo [3, 4-c] pyrrole derivatives and uses thereof. Compounds and pharmaceutical compositions comprising the compounds provided herein are used for antagonizing orexin receptors. The invention also relates to processes for preparing the compounds and pharmaceutical compositions, and uses thereof in treating or preventing a disease related to orexin receptors.
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Paragraph 00214; 00226

(2017/07/04)

BICYCLIC DERIVATIVE CONTAINING PYRIMIDINE RING, AND PREPARATION METHOD THEREFOR
The present invention provides: a bicyclic derivative comprising a pyrimidine ring, or a pharmaceutically acceptable salt thereof; a preparation method therefor, a pharmaceutical composition comprising the same; and a use therefor. According to the present invention, the bicyclic compound derivative comprising a pyrimidine ring, or a pharmaceutically acceptable salt thereof acts as a 5-HT4 receptor agonist, and thus can be usefully applied to the prevention or treatment of dysfunction in gastrointestinal motility, for example, gastrointestinal diseases such as gastroesophageal reflux disease (GERD), constipation, irritable bowel syndrome (IBS), dyspepsia, post-operative ileus, delayed gastric emptying, gastroparesis, intestinal pseudo-obstruction, drug-induced delayed transit, diabetic gastric atony and the like.
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Paragraph 0122

(2016/04/26)

Octahydropyrrole[3, 4-c]pyrrole derivative and using method and application thereof
The invention relates to an ctahydropyrrole[3, 4-c]pyrrole derivative and a using method and application thereof. A compound and a drug composition containing the same are used for resisting orexin receptors. The invention further relates to methods of pr
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Paragraph 0186; 0309; 0315; 0316

(2018/02/04)

THERAPEUTIC COMPOUNDS AND RELATED METHODS OF USE
Methods of treating disorders using compounds that modulate striatal-enriched tyrosine phosphatase (STEP) are described herein. Exemplary disorders include schizophrenia and cognitive deficit.
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Paragraph 1497

(2015/11/16)

PYRROLO[2,3-C]PYRIDINES AS IMAGING AGENTS FOR NEUROFIBRILARY TANGLES
Pyrrolopyridine compounds of formula (I) or their pharmaceutically acceptable salts are disclosed, which may be suitable for imaging tau aggregates, b-sheet aggregates, beta-amyloid aggregates or alpha- synuclein aggregates, and hence are useful in binding and imaging tau aggregates in Alzheimer's patients. More specifically, the compounds are used as tracers in positron emission tomography (PET) imaging to study tau deposits in brain in vivo to allow diagnosis of Alzheimer's disease and other neurodegenerative diseases characterized by tau pathology. Futher, the compounds are useful for measuring clinical efficacy of therapeutic agents for Alzheimer's disease and other neurodegenerative diseases characterized by tau pathology.
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Page/Page column 89

(2016/01/01)

Synthesis and antimicrobial activity of amino linked heterocycles
Amino-linked benzoxazolyl/benzothiazolyl/benzimidazolyl quinazolines were prepared and their antimicrobial activity studied. The nitro-substituted benzothiazolyl quinazoline (8f) may be a potential antibacterial agent against Staphylococcus aureus and nitro-substituted benzimidazolyl quinazoline (9f) may be a potential antifungal agent against Aspergillus niger.
Mallikarjuna Reddy, Lingaladinne,Dinneswara Reddy, Guda,Padmaja, Adivireddy,Padmavathi, Venkatapuram
p. 75 - 80
(2015/03/04)

Function-oriented development of CXCR4 antagonists as selective human immunodeficiency virus (HIV)-1 entry inhibitors
Motivated by the pivotal role of CXCR4 as an HIV entry co-receptor, we herein report a de novo hit-to-lead effort on the identification of subnanomolar purine-based CXCR4 antagonists against HIV-1 infection. Compound 24, with an EC50 of 0.5 nM against HIV-1 entry into host cells and an IC50 of 16.4 nM for inhibition of radioligand stromal-derived factor-1α (SDF-1α) binding to CXCR4, was also found to be highly selective against closely related chemokine receptors. We rationalized that compound 24 complementarily interacted with the critical CXCR4 residues that are essential for binding to HIV-1 gp120 V3 loop and subsequent viral entry. Compound 24 showed a 130-fold increase in anti-HIV activity compared to that of the marketed CXCR4 antagonist, AMD3100 (Plerixafor), whereas both compounds exhibited similar potency in mobilization of CXCR4+/CD34+ stem cells at a high dose. Our study offers insight into the design of anti-HIV therapeutics devoid of major interference with SDF-1α function.
Wu, Chien-Huang,Wang, Chuan-Jen,Chang, Chun-Ping,Cheng, Yung-Chi,Song, Jen-Shin,Jan, Jiing-Jyh,Chou, Ming-Chen,Ke, Yi-Yu,Ma, Jing,Wong, Ying-Chieh,Hsieh, Tsung-Chih,Tien, Yun-Chen,Gullen, Elizabeth A.,Lo, Chen-Fu,Cheng, Chia-Yi,Liu, Yu-Wei,Sadani, Amit A.,Tsai, Chia-Hua,Hsieh, Hsin-Pang,Tsou, Lun K.,Shia, Kak-Shan
supporting information
p. 1452 - 1465
(2015/03/04)

Antileishmanial activity of a series of N2, N 4-disubstituted quinazoline-2,4-diamines
A series of N2,N4-disubstituted quinazoline-2,4- diamines has been synthesized and tested against Leishmania donovani and L. amazonensis intracellular amastigotes. A structure-activity and structure-property relationship study was conducted in part using the Topliss operational scheme to identify new lead compounds. This study led to the identification of quinazolines with EC50 values in the single digit micromolar or high nanomolar range in addition to favorable physicochemical properties. Quinazoline 23 also displayed efficacy in a murine model of visceral leishmaniasis, reducing liver parasitemia by 37% when given by the intraperitoneal route at 15 mg kg-1 day-1 for 5 consecutive days. Their antileishmanial efficacy, ease of synthesis, and favorable physicochemical properties make the N2,N 4-disubstituted quinazoline-2,4-diamine compound series a suitable platform for future development of antileishmanial agents.
Van Horn, Kurt S.,Zhu, Xiaohua,Pandharkar, Trupti,Yang, Sihyung,Vesely, Brian,Vanaerschot, Manu,Dujardin, Jean-Claude,Rijal, Suman,Kyle, Dennis E.,Wang, Michael Zhuo,Werbovetz, Karl A.,Manetsch, Roman
p. 5141 - 5156
(2014/07/08)

Discovery of 1-methyl-1 H-imidazole derivatives as potent Jak2 inhibitors
Structure based design, synthesis, and biological evaluation of a novel series of 1-methyl-1H-imidazole, as potent Jak2 inhibitors to modulate the Jak/STAT pathway, are described. Using the C-ring fragment from our first clinical candidate AZD1480 (24), optimization of the series led to the discovery of compound 19a, a potent, orally bioavailable Jak2 inhibitor. Compound 19a displayed a high level of cellular activity in hematopoietic cell lines harboring the V617F mutation and in murine BaF3 TEL-Jak2 cells. Compound 19a demonstrated significant tumor growth inhibition in a UKE-1 xenograft model within a well-tolerated dose range.
Su, Qibin,Ioannidis, Stephanos,Chuaqui, Claudio,Almeida, Lynsie,Alimzhanov, Marat,Bebernitz, Geraldine,Bell, Kirsten,Block, Michael,Howard, Tina,Huang, Shan,Huszar, Dennis,Read, Jon A.,Rivard Costa, Caroline,Shi, Jie,Su, Mei,Ye, Minwei,Zinda, Michael
p. 144 - 158
(2014/02/14)

NOVEL SUBSTITUTED BICYCLIC AROMATIC COMPOUNDS AS S-NITROSOGLUTATHIONE REDUCTASE INHIBITORS
The present invention is directed to novel substituted bicyclic aromatic compounds useful as S-nitrosoglutathione reductase (GSNOR) inhibitors, pharmaceutical compositions comprising such compounds, and methods of making and using the same.
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Page/Page column 96

(2012/06/30)

Facile and efficient cyclization of anthranilonitrile to 2,4-dichloroquinazoline by bis(trichloromethyl) carbonate and catalytic amount triphenylphosphine oxide
2,4-Dichloroquinazolines were synthesized by the cyclization of anthranilonitrile using bis(trichloromethyl) carbonate (BTC) with the aid of catalytic amount of triphenylphosphine oxide (Ph3PO) at 120 °C. This method was also applied to the syn
Li, Zhenhua,Wu, Danli,Zhong, Weihui
experimental part
p. 1417 - 1426
(2012/08/28)

PHARMACEUTICAL COMPOUNDS AS INHIBITORS OF CELL PROLIFERATION AND THE USE THEREOF
Disclosed are compounds of Formula I effective as cytotoxic agents. The compounds of this invention are useful in the treatment of a variety of clinical conditions in which uncontrolled growth and spread of abnormal cells occurs.
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Page/Page column 17

(2010/04/23)

HETEROCYCLIC JAK KINASE INHIBITORS
The present invention relates to compounds of Formula (I) and to their salts, pharmaceutical compositions, methods of use, and methods for their preparation. These compounds provide a treatment for myeloproliferative disorders and cancer
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Page/Page column 92-94

(2010/04/27)

Discovery of potent CCR4 antagonists: Synthesis and structure-activity relationship study of 2,4-diaminoquinazolines
A new series of quinazolines that function as CCR4 antagonists were discovered during the screening of our corporate compound libraries. Subsequent compound optimization elucidated the structure-activity relationships and led the identification of 2-(1,4′-bipiperidine-1′-yl)-N-cycloheptyl-6,7-dimethoxyquinazolin-4-amine 14a, which showed potent inhibition in the [35S]GTPγS-binding assay (IC50 = 18 nM). This compound also inhibited the chemotaxis of human and mouse CCR4-expressing cells (IC50 = 140 nM, 39 nM).
Yokoyama, Kazuhiro,Ishikawa, Noriko,Igarashi, Susumu,Kawano, Noriyuki,Hattori, Kazuyuki,Miyazaki, Takahiro,Ogino, Shin-ichi,Matsumoto, Yuzo,Takeuchi, Makoto,Ohta, Mitsuaki
p. 7021 - 7032
(2008/12/22)

ADENOSINE A2A RECEPTOR ANTAGONISTS
Compounds having the structural formula I or a pharmaceutically acceptable salt thereof, wherein: X1 and X2 are 1-3 substituents independently selected from the group consisting of H, alkyl, halo, —CF3, —OCF3, alkoxy, —OH and —CN;n is 0, 1 or 2; andR and R1 are H or alkyl; also disclosed is the use of the compounds in the treatment of CNS diseases such as Parkinson's disease, alone or in combination with other agents for treating CNS diseases, pharmaceutical compositions comprising them and kits comprising the components of the combinations.
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Page/Page column 11

(2008/12/04)

AMINOPYRROLIDINE COMPOUND
Disclosed is an aminopyrrolidine compound represented by the formula [I] or a pharmaceutically acceptable salt thereof. The compound or the salt is useful as a prophylactic/therapeutic agent for mode disorder such as depression, anxiety disorder, anorexia, cachexia, pain and drug dependence, whose action relies on the MC4 receptor antagonistic effect.
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Page/Page column 57-58

(2009/01/24)

Discovery of alogliptin: A potent, selective, bioavailable, and efficacious inhibitor of dipeptidyl peptidase IV
Alogliptin is a potent, selective inhibitor of the serine protease dipeptidyl peptidase IV (DPP-4). Herein, we describe the structure-based design and optimization of alogliptin and related quinazolinone-based DPP-4 inhibitors. Following an oral dose, these noncovalent inhibitors provide sustained reduction of plasma DPP-4 activity and a lowering of blood glucose in animal models of diabetes. Alogliptin is currently undergoing phase 111 trials in patients with type 2 diabetes.
Feng, Jun,Zhang, Zhiyuan,Wallace, Michael B.,Stafford, Jeffrey A.,Kaldor, Stephen W.,Kassel, Daniel B.,Navre, Marc,Shi, Lihong,Skene, Robert J.,Asakawa, Tomoko,Takeuchi, Koji,Xu, Rongda,Webb, David R.,Gwaltney II, Stephen L.
p. 2297 - 2300
(2008/02/05)

PYRAZOLE DERIVATIVES AS INHIBITORS OF RECEPTOR TYROSYNE KINASES
Compounds of formula (I): and their use in the inhibition of Trk activity are described.
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Page/Page column 110-111

(2008/06/13)

Synthesis and antihyperglycemic activity of suitably functionalized 3H-quinazolin-4-ones
A series of 2-sec-amino-3H-quinazolin-4-ones (4a-p) and 4-sec-amino-2-chloroquinazolines (5a-b) have been synthesized by nucleophilic substitution reaction of 2-chloro-4(3H)-quinazolones (3) and 2,4-dichloroquinazolines (2) with amines, respectively. Most of the synthesized compounds were evaluated for antihyperglycemic activity but only 4a,b,d,j,o displayed significant reduction in blood glucose level in streptozotocin and sucrose loaded rat models.
Ram, Vishnu Ji,Farhanullah,Tripathi, Brajendra K.,Srivastava, Arvind K.
p. 2439 - 2444
(2007/10/03)

Tricyclic dicarbonyl derivatives
Compounds of general formula (Ia), (Ib) and (II), wherein R1 and R2 each independently signify hydrogen, lower alkyl, lower alkoxy, nitro, trifluoromethyl, amino, halogen, cyano or R3 R4 NS(O)2 -- and R3 and R4 signify lower alkyl, and R2 can additionally signify morpholino or thiomorpholino, a 5- or 6-membered heterocycle with 1-3N atoms optionally substituted by lower alkyl, hydroxy, amino or the group --CH2 NHCH3, a bicyclic heterocycle with 1-3N atoms or a group --NR5 R6 or --OR5 in which R5 and R6 can be the same or different and signify hydrogen, lower alkyl, hydroxy-lower alkyl, lower alkoxy-lower alkyl, amino-lower alkyl or lower alkylamino-lower alkyl, and X in formula (II) signifies --CH=CH--, --CH=N--, --NH--, --CO-- or --O--, as well as pharmaceutically usable salts of compounds of general formula (Ia), (Ib) and (II). They can be used for the treatment or prevention of illnesses, especially for the treatment or prevention of ischemia, hypoglycaemia, hypoxia, cerebral vascular spasms, spasticity, trauma, hemorrhagia, infection (viral, bacterial, amoebic, prional), epileptic seizures, autoimmune diseases, withdrawal symptoms, Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, Huntington's disease, intoxications, olivoponto-cerebellar atrophy, spinal cord injuries, schizophrenia, depressions, anxiety states, dependence, pains,autism and mental retardation.
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(2008/06/13)

Discovery of potent cyclic GMP phosphodiesterase inhibitors. 2-Pyridyl- and 2-imidazolylquinazolines possessing cyclic GMP phosphodiesterase and thromboxane synthesis inhibitory activities
Moderate cyclic GMP phosphodiesterase (cGMP-PDE, PDE V) inhibitor 2- phenyl-4-anilino-quinazoline (1) was identified utilizing MultiCASE assisted drug design (MCADD) technology. Modification of compound 1 was conducted at the 2-, 4-, and 6-positions of the quinazoline ring for enhancement of cGMP- PDE inhibitory activity. The 6-substituted 2-(imidazol-1-yl)-quinazolines are 1000 times more potent in in vitro PDE V enzyme assay than the well-known inhibitor zaprinast. The 6-substituted derivatives of 2-(3- pyridyl)quinazoline 84 and 2-(imidazol-1-yl)quinazoline 86 exhibited more than 1000-fold selectivity for PDE V over the other four PDE isozymes. In addition, cGMP-PDE inhibitors 64, 65, and 73 were found to have an additional property of thromboxane synthesis inhibitory activity.
Lee,Konishi,Yu,Miskowski,Riviello,Macina,Frierson,Kondo,Sugitani,Sircar,Blazejewski
p. 3547 - 3557
(2007/10/03)

Reversible Inhibitors of the Gastric (H+/K+)-ATPase. 5. Substituted 2,4-Diaminoquinazolines and Thienopyrimidines
Quinazolines bearing a secondary 4-(arylamino) substituent demonstrate an SAR for inhibition of the gastric (H+/K+)-ATPase different from the previously described 3-acylquinolines, suggesting that, although these compounds are also K+-competitive, they probably bind to the enzyme in a different orientation.Compounds bearing a tertiary 4-(arylamino)substituent, however, in particular 4-(N-methylarylamino), appear to possess an SAR quite similar to the 3-acylquinolines.We show that this arises from the effect of the N-methylation, which is to orientate the 4-(arylamino) substituent syn to C5, analogous to the 3-acylquinolines.Compounds possessing both a 4-(N-methylarylamino) substituent and a 2-(arylamino) substituent proved to be very potent, K+-competitive inhibitors of K+-stimulated ATPase activity with Ki values down to 12 nM.Some compounds also proved to be effective inhibitors of stimulated acid secretion in both the rat and dog when dosed intravenously.However, although a number of these demonstrated activity after oral administration in the dog, the level and variability precluded further evaluation.
Ife, Robert J.,Brown, Thomas H.,Blurton, Peter,Keeling, David J.,Leach, Colin A.,et al.
p. 2763 - 2773
(2007/10/03)

SUBSTITUTED QUINAZOLINE DERIVATIVES FOR USE IN GASTROINTESTINAL DISEASES
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(2008/06/13)

Quinazoline derivatives
Compounds of structure (I): in which, , R1 to R4 are the same or different and are each hydrogen, C1 4alkyl, C1 4alkoxy, phenyl, C1 4alkylthio, C1 4alkanoyl
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(2008/06/13)

Process for preparing 2,4-dihaloquinazolines
A one-step process for the preparation of 2,4-dihaloquinazolines is disclosed beginning with methoxycarbonyl- or phenoxycarbonyl-derivatives of substituted phenylureas which are cyclized and concomitantly halogenated with a cyclizing-halogenating reagent such as N,N-dimethylaniline in phosphorus oxychloride. The 2,4-dihaloquinazolines of the instant process are particularly valuable as intermediates in the preparation of 4-amino-2-(4-substituted-piperazin-1-yl) quinazolines useful in the treatment of cardiovascular disorders such as hypertension.
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(2008/06/13)