Synthesis and Antiallergy Activity of (1,3,4)Thiadiazolo(3,2-a)-1,2,3-triazolo(4,5-d)pyrimidin-9(3H)-one Derivatives. II. 6-Alkyl- and 6-Cycloalkylalkyl Derivatives.

Yokohama, Shuichi; Miwa, Tamotsu; Aibara, Shigeo; Fujiwara, Hiroyuki; Matsumoto, Hiromichi; Nakayama, Kiyoshi; Iwamoto, Teiji; Mori, Mikiko; Moroi, Reimei; Tsukada, Wataru; Isoda, Sumiro

doi:10.1248/cpb.40.2391

Cited by 11 publications

(6 citation statements)

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“…Traditionally, small molecules have been a reliable source for discovering novel biologically active compounds. [6][7][8][9][10][11][12][13][14] . Through utilization of combinatorial chemistry large libraries of small molecules have been generated and screened for specific biological activities.…”

Section: Introductionmentioning

confidence: 99%

Synthesis andin Vitro Antifungal and Cytotoxicity Evaluation of Thiazolo-4H-1,2,4-triazoles and 1,2,3-Thiadiazolo-4H-1,2,4-triazoles

Jalilian

Sattari

Bineshmarvasti

et al. 2000

Arch. Pharm. Pharm. Med. Chem.

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The increasing clinical importance of drug‐resistant fungal pathogens has lent additional urgency to microbiological and antifungal research. Various thiazolo(or 1,2,3‐thiadiazolo)thiosemicarbazides (2a—2e), 3‐thiono‐1,4‐dihydrotriazolothiazoles‐(or 1,2,3‐thiadiazoles) (3a—3e), their related substituted thio‐4H‐1,2,4‐triazoles (4a—4p) and sulfones (5a—5o) were synthesized. Most of the compounds tested for antifungal activity exhibited significant effects against Cryptococcus neoofrmans and Sacchromyces cerevisiae at MIC ranges of 0.53 to 12.5μg/mL, whereas their activities were moderate against Candida albicans and weak against Aspergillus fumigatus. At 10 ppm concentration, all compounds showed low toxicity on brine shrimps (higher than 80% survival), except compounds 4c and 2c. At 100 ppm concentration most of the compounds showed toxicity except compounds 2b, 2e, 3c, 3d, 3e, and 4e. Compounds 4b, 4c, and 4h showed in vitro cytotoxicity against Kbalb cell lines and compounds 4c and 4g against 143B cell lines at 0.1 mM concentration.

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Section: Introductionmentioning

confidence: 99%

Synthesis andin Vitro Antifungal and Cytotoxicity Evaluation of Thiazolo-4H-1,2,4-triazoles and 1,2,3-Thiadiazolo-4H-1,2,4-triazoles

Jalilian

Sattari

Bineshmarvasti

et al. 2000

Arch. Pharm. Pharm. Med. Chem.

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“…Synthetic Utility. Most of the presently considered nitriles 3 have been previously employed in the synthesis of thiadiazole derivatives known for their antiallergic activity as well as in the synthesis of 9-deazaguanine derivatives used as inhibitors of purine nucleoside phosphorylase . Furthermore, compound 3bj can be easily transformed in other important building blocks used in the synthesis of molecule of biological interest, e.g., in the corresponding amine, acid, or their homologues …”

Section: Discussionmentioning

confidence: 99%

Hydrocarbon Activation. Synthesis of β-Cycloalkyl (Di)nitriles through Photosensitized Conjugate Radical Addition

et al. 2001

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Photoinduced hydrogen abstraction from aliphatic cyclic hydrocarbons (C(5) to C(7), C(12), as well as adamantane) by triplet aromatic ketones in the presence of alpha,beta-unsaturated (di)nitriles offers a straightforward entry to the corresponding alkylated (di)nitriles via the alkyl radicals. Yields are moderate to good depending on the olefins structure (substitution in beta slows down the addition to mononitriles, but with alpha,alpha-dinitriles electronic activation allows efficient alkylation also of beta,beta-disubstituted substrates). A tandem alkylation-cyclization process has been obtained with (1-methylpent-4-enylidene)malononitrile.

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“…3-Adamantan-1-ylpropionic acid was prepared from 1-bromoadamantane, and cycloheptylacetic acid was obtained from cycloheptanone . The aniline derivatives 9a and 9b were prepared from the relevant nitrobenzoic acids, while 9c was synthesized from 5-nitro- m -xylene-α, α ‘ -diol.…”

Section: Methodsmentioning

confidence: 99%

Scaffold Hopping with Molecular Field Points: Identification of a Cholecystokinin-2 (CCK₂) Receptor Pharmacophore and Its Use in the Design of a Prototypical Series of Pyrrole- and Imidazole-Based CCK₂ Antagonists

et al. 2005

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A new molecular modeling approach has been used to derive a pharmacophore of the potent and selective cholecystokinin-2 (CCK(2)) receptor antagonist 5 (JB93182), based on features shared with two related series. The technique uses "field points" as simple and effective descriptions of the electrostatic and van der Waals maxima and minima surrounding a molecule equipped with XED (extended electron distribution) charges. Problems associated with the high levels of biliary elimination of 5 in vivo required us to design a compound with significantly lower molecular weight without sacrificing its nanomolar levels of in vitro activity. Two new series of compounds were designed to mimic the arrangement of field points present in the pharmacophore rather than its structural elements. In a formal sense, two of the three amides in 5 were replaced with either a simple pyrrole or imidazole, while some features thought to be essential for the high levels of in vitro activity of the parent compounds were retained and others deleted. These compounds maintained activity and selectivity for this receptor over CCK(1). In addition, the reduction in molecular weight coupled with lower polarities greatly reduced levels of biliary elimination associated with 5. This makes them good lead compounds for development of drug candidates whose structures are not obviously related to those of the parents and represents the first example of scaffold hopping using molecular field points.

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Synthesis and Antiallergy Activity of (1,3,4)Thiadiazolo(3,2-a)-1,2,3-triazolo(4,5-d)pyrimidin-9(3H)-one Derivatives. II. 6-Alkyl- and 6-Cycloalkylalkyl Derivatives.

Cited by 11 publications

References 1 publication

Synthesis andin Vitro Antifungal and Cytotoxicity Evaluation of Thiazolo-4H-1,2,4-triazoles and 1,2,3-Thiadiazolo-4H-1,2,4-triazoles

Synthesis andin Vitro Antifungal and Cytotoxicity Evaluation of Thiazolo-4H-1,2,4-triazoles and 1,2,3-Thiadiazolo-4H-1,2,4-triazoles

Hydrocarbon Activation. Synthesis of β-Cycloalkyl (Di)nitriles through Photosensitized Conjugate Radical Addition

Scaffold Hopping with Molecular Field Points: Identification of a Cholecystokinin-2 (CCK₂) Receptor Pharmacophore and Its Use in the Design of a Prototypical Series of Pyrrole- and Imidazole-Based CCK₂ Antagonists

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Synthesis and Antiallergy Activity of (1,3,4)Thiadiazolo(3,2-a)-1,2,3-triazolo(4,5-d)pyrimidin-9(3H)-one Derivatives. II. 6-Alkyl- and 6-Cycloalkylalkyl Derivatives.

Cited by 11 publications

References 1 publication

Synthesis andin Vitro Antifungal and Cytotoxicity Evaluation of Thiazolo-4H-1,2,4-triazoles and 1,2,3-Thiadiazolo-4H-1,2,4-triazoles

Synthesis andin Vitro Antifungal and Cytotoxicity Evaluation of Thiazolo-4H-1,2,4-triazoles and 1,2,3-Thiadiazolo-4H-1,2,4-triazoles

Hydrocarbon Activation. Synthesis of β-Cycloalkyl (Di)nitriles through Photosensitized Conjugate Radical Addition

Scaffold Hopping with Molecular Field Points: Identification of a Cholecystokinin-2 (CCK2) Receptor Pharmacophore and Its Use in the Design of a Prototypical Series of Pyrrole- and Imidazole-Based CCK2 Antagonists

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Scaffold Hopping with Molecular Field Points: Identification of a Cholecystokinin-2 (CCK₂) Receptor Pharmacophore and Its Use in the Design of a Prototypical Series of Pyrrole- and Imidazole-Based CCK₂ Antagonists