Detail of "13889-98-0"

Reference

Preparation of 5-(arylalkynyl)pyrimidines having neurotrophic activity for the treatment of neurodegerative and other neurological disorders

Preparation of 5-(arylalkynyl)pyrimidines having neurotrophic activity for the treatment of neurodegerative and other neurological disorders. Beauchamp, Lilia; Krenitsky, Thomas A.; Kelley, James L. (Krenitsky Pharmaceuticals, Inc., USA). PCT Int. Appl. WO 2002008205 A1 31 Jan 2002, 60 pp. DESIGNATED STATES: W: AE, AG, AL, AM, AT, AU, AZ, BA, BB, BG, BR, BY, BZ, CA, CH, CN, CO, CR, CU, CZ, DE, DK, DM, DZ, EC, EE, ES, FI, GB, GD, GE, GH, GM, HR, HU, ID, IL, IN, IS, JP, KE, KG, KP, KR, KZ, LC, LK, LR, LS, LT, LU, LV, MA, MD, MG, MK, MN, MW, MX, MZ, NO, NZ, PL, PT, RO, RU, SD, SE, SG, SI, SK, SL, TJ, TM, TR, TT, TZ, UA, UG, US, UZ, VN, YU, ZA, ZW, AM, AZ, BY, KG, KZ, MD, RU, TJ, TM; RW: AT, BE, BF, BJ, CF, CG, CH, CI, CM, CY, DE, DK, ES, FI, FR, GA, GB, GR, IE, IT, LU, MC, ML, MR, NE, NL, PT, SE, SN, TD, TG, TR. (English). (World Intellectual Property Organization). CODEN: PIXXD2. CLASS: ICM: C07D239-34. ICS: C07D239-38; C07D239-42; C07D239-48; C07D239-46; A61K031-505; A61P025-00; A61P025-28; A61P003-10. APPLICATION: WO 2001-US23088 20 Jul 2001. PRIORITY: US 2000-PV220348 24 Jul 2000. DOCUMENT TYPE: Patent CA Section: 28 (Heterocyclic Compounds (More Than One Hetero Atom)) Section cross-reference(s): 1 Title compds. I [wherein Z = O, NH, or S; m = 0-1; R1 = (un)substituted (alkyl)a((hetero)cycloalkyl or (hetero)aryl)b(alkyl)c; a, b, and c = independently 0-1 and a + b + c 3 1, with provisos; R2 = H, NH2, or NHCOR3; R3 = H or alkyl; X = (un)substituted aryl; and pharmaceutically acceptable esters, amides, salts, or solvates thereof] were prepd. Pharmaceutical compns. which contain I, methods for their prepn., and their use in therapy, particularly in the treatment of neurodegenerative or other neurol. disorders of the central and peripheral nervous systems, including age related cognitive disorders such as senility and Alzheimer's disease, nerve injuries, peripheral neuropathies, and seizure disorders such as epilepsy, are disclosed. For example, 4-chloro-5-(4-chlorophenylethynyl)pyrimidine (prepn. given) was coupled with (trans)-4-aminocyclohexanol·HCl using TEA and MeCN in CH2Cl2 to afford II. The latter increased the choline acetyltransferase (ChAT) activity relative to nerve growth factor (NGF) alone with EC2x of 0.2 mM. Keywords arylalkynyl pyrimidine prepn neurotrophic activity phenylethynylpyrimidine prepn nervous system agents Index Entries Nervous system degeneration, treatment; prepn. of (arylalkynyl)pyrimidines having neurotrophic activity for the treatment of neurodegenerative and other neurol. disorders Nerve, disease peripheral neuropathy, treatment; prepn. of (arylalkynyl)pyrimidines having neurotrophic activity for the treatment of neurodegenerative and other neurol. disorders Nervous system peripheral, disease, treatment; prepn. of (arylalkynyl)pyrimidines having neurotrophic activity for the treatment of neurodegenerative and other neurol. disorders Anti-Alzheimer's agents Anticonvulsants Antidiabetic agents Cognition enhancers Human Nervous system agents prepn. of (arylalkynyl)pyrimidines having neurotrophic activity for the treatment of neurodegenerative and other neurol. disorders Mental disorder senile psychosis, treatment; prepn. of (arylalkynyl)pyrimidines having neurotrophic activity for the treatment of neurodegenerative and other neurol. disorders Aging, animal senility, treatment; prepn. of (arylalkynyl)pyrimidines having neurotrophic activity for the treatment of neurodegenerative and other neurol. disorders 393856-66-1 393856-71-8 393856-87-6 393857-07-3 393857-16-4 393855-70-4 393855-73-7 393855-76-0 393855-79-3 393855-81-7 393855-83-9 393855-87-3 393855-89-5 393855-91-9 393855-93-1 393855-96-4 393855-99-7 393856-02-5 393856-04-7 393856-07-0 393856-10-5 393856-13-8 393856-17-2 393856-21-8 393856-24-1 393856-26-3 393856-29-6 393856-31-0 393856-34-3 393856-36-5 393856-39-8 393856-42-3 393856-45-6 393856-48-9 393856-51-4 393856-54-7 393856-57-0 393856-60-5 393856-63-8 393856-69-4 393856-73-0 393856-76-3 393856-79-6 393856-82-1 393856-85-4 393856-89-8 393856-91-2 393856-95-6 393857-11-9 393857-13-1 393857-18-6 393857-31-3 393857-34-6 393857-35-7 393857-41-5 393857-43-7 393857-47-1 393857-50-6 CNS agent; prepn. of (arylalkynyl)pyrimidines having neurotrophic activity for the treatment of neurodegenerative and other neurol. disorders 3993-79-1 35447-83-7 40307-11-7 62452-73-7 81631-65-4 393856-98-9 393857-01-7 393857-03-9 393857-05-1 393857-09-5 393857-14-2 393857-20-0 393857-23-3 393857-27-7 393857-29-9 393857-33-5 393857-36-8 393857-37-9 393857-39-1 intermediate; prepn. of (arylalkynyl)pyrimidines having neurotrophic activity for the treatment of neurodegenerative and other neurol. disorders 9012-78-6 9061-61-4 prepn. of (arylalkynyl)pyrimidines having neurotrophic activity for the treatment of neurodegenerative and other neurol. disorders 108-53-2 123-30-8 123-31-9, reactions 536-74-3 588-93-2 637-89-8 766-96-1 873-73-4 929-06-6 1066-54-2 6850-65-3 13889-98-0 14235-81-5 22428-87-1 25309-64-2 26912-67-4 27489-62-9 50910-54-8 63558-65-6 76445-65-3 reactant; prepn. of (arylalkynyl)pyrimidines having neurotrophic activity for the treatment of neurodegenerative and other neurol. disorders

Towards new methodologies for the synthesis of biologically interesting 6-substituted pyrimidines and 4(3H)-pyrimidinones

All Rights Reserved.Some chemicals with cas registry numbers like 13889-98-0 and 823220-85-5 are also used. Towards new methodologies for the synthesis of biologically interesting 6-substituted pyrimidines and 4(3H)-pyrimidinones. Petricci, Elena; Mugnaini, Claudia; Radi, Marco; Togninelli, Andrea; Bernardini, Cesare; Manetti, Fabrizio; Parlato, Maria Cristina; Renzulli, Michela Lucia; Alongi, Maddalena; Falciani, Chiara; Corelli, Federico; Botta, Maurizio (Dipartimento Farmaco Chimico Tecnologico, Universita degli Studi di Siena, Siena 53100, Italy). ARKIVOC (Gainesville, FL, United States), (7), 452-478 (English) 2006 Arkat USA Inc. URL: http://www.arkat-usa.org/ark/journal/2006/I07_ICHC-20/1848/HL-1848 GR%20as%20published%20mainmanuscript.pdf. CODEN: AGFUAR. DOCUMENT TYPE: Journal; General Review; (online computer file) CA Section: 28 (Heterocyclic Compounds (More Than One Hetero Atom)) Section cross-reference(s): 1 A review. The present paper describes the application of modern combinatorial and microwave assisted techniques for the lead discovery and optimization of novel non-nucleoside HIV-1 reverse transcriptase (HIV-1RT) inhibitors. Starting from the parallel solid phase synthesis of highly substituted pyrimidinone derivs., compd. (I; R = benzyl, R1 = 4-hydroxybenzylthio) (S-DABO) was identified as interesting lead compd. for further structure optimizations. The generation and screening of a small virtual combinatorial library led to the optimization of the lead structure I to give highly active derivs. I (R = methoxybenzylsulfonyl, 4-methoxybenzylthio, 4-nitrobenzylthio; R1 = 2,6-dichlorobenzyl) (S-DABO analogs) (against HIV1-RT wild-type and mutant strains) in the nanomolar range. Moreover, a straightforward three-step parallel soln. phase approach was developed for the generation of a small library of novel 4-dialkylamino-2-methylsulfonyl-6-vinylpyrimidines [II; R1 = R2 = Me, Et, n-Pr, n-Bu, allyl; R1 = benzyl, R2 = Me; R1R2N = 4-acetylpiperazin-1-yl, 4-oxo-4-phenylpiperazin-1-yl, 4-(4-fluorophenyl)-4-oxopiperazin-1-yl, 4-(3-trifluoromethylphenyl)-4-oxopiperazin-1-yl, 4-(2-methoxyphenyl)-4-oxopiperazin-1-yl] which were obtained in high yield after a simple Et acetate extn. with no need of further purifn. Surprisingly, some of these derivs. showed a new competitive inhibition of HIV1-RT never reported in the literature for this class of compds. Mol. modeling calcns. were also performed to investigate the binding mode of all synthesized compds. onto the non-nucleoside reverse transcriptase inhibitor binding site and to rationalize the relationships between their chem. structure and activity. .