Orally active CCR5 antagonists as anti-HIV-1 agents: Synthesis and biological activity of 1-benzothiepine 1,1-dioxide and 1-benzazepine derivatives containing a tertiary amine moiety

Chemical and Pharmaceutical Bulletin

Volumn 52, Issue 5, 2004, Pages 577-590

  Seto, Masaki ^a   Aramaki, Yoshio ^a   Okawa, Tomohiro ^a   Miyamoto, Naoki ^a   Aikawa, Katsuji ^a   Kanzaki, Naoyuki ^a   Niwa, Shin Ichi ^a   Iizawa, Yuji ^a   Baba, Masanori ^b   Shiraishi, Mitsuru ^a  

^a TAKEDA PHARMACEUTICAL COMPANY LIMITED   (Japan)

^b KAGOSHIMA UNIVERSITY   (Japan)

Author keywords

1 benzazepine; 1 benzothiepine 1,1 dioxide; 2 (alkoxy)ethoxy group; CCR5 antagonist; HIV 1

Indexed keywords

1 ACETYL 7 (4 MORPHOLINOPHENYL) N [4 [[METHYL(TETRAHYDRO 2H PYRAN 4 YL)AMINO]METHYL]PHENYL] 2,3 DIHYDRO 1H 1 BENZAZEPINE 4 CARBOXAMIDE; 1 BENZYL 7 [4 [2 (BUTOXY)ETHOXY]PHENYL] N [4 [[METHYL(TETRAHYDRO 2H PYRAN 4 YL)AMINO]METHYL]PHENYL] 2,3 DIHYDRO 1H 1 BENZAZEPINE 4 CARBOXAMIDE; 1 METHYL N [4 [[METHYL(TETRAHYDRO 2H PYRAN 4 YL)AMINO]METHYL]PHENYL] 7 (4 MORPHOLINOPHENYL) 2,3 DIHYDRO 1H 1 BENZAZEPINE 4 CARBOXAMIDE; 1 METHYL N [4 [[METHYL(TETRAHYDRO 2H PYRAN 4 YL)AMINO]METHYL]PHENYL] 7 [4 [2 (PROPOXY)ETHOXY]PHENYL] 2,3 DIHYDRO 1H 1 BENZAZEPINE 4 CARBOXAMIDE; 7 (4 ETHYLPHENYL) N [4 [[METHYL(TETRAHYDRO 2H PYRAN 4 YL)AMINO]METHYL] PHENYL] 2,3 DIHYDRO 1 BENZOTHIEPINE 4 CARBOXAMIDE 1,1 DIOXIDE; 7 (4 ISOPROPYLPHENYL) N [4 [[METHYL(TETRAHYDRO 2H PYRAN 4 YL)AMINO]METHYL]PHENYL] 2,3 DIHYDRO 1 BENZOTHIEPINE 4 CARBOXAMIDE 1,1 DIOXIDE; 7 [4 [2 (BUTOXY)ETHOXY]PHENYL] 1 [(1 METHYL 1H IMIDAZOL 2 YL)METHYL] N [4 [[METHYL(TETRAHYDRO 2H PYRAN 4 YL)AMINO]METHYL]PHENYL] 2,3 DIHYDRO 1H 1 BENZAZEPINE 4 CARBOXAMIDE; 7 [4 [2 (BUTOXY)ETHOXY]PHENYL] 1 [(1 METHYL 1H PYRAZOL 4 YL)METHYL] N [4 [[METHYL(TETRAHYDRO 2H PYRAN 4 YL)AMINO]METHYL]PHENYL] 2,3 DIHYDRO 1H 1 BENZAZEPINE 4 CARBOXAMIDE; 7 [4 [2 (BUTOXY)ETHOXY]PHENYL] 1 [(1 METHYL 1H PYRAZOL 5 YL)METHYL] N [4 [[METHYL(TETRAHYDRO 2H PYRAN 4 YL)AMINO]METHYL]PHENYL] 2,3 DIHYDRO 1H 1 BENZAZEPINE 4 CARBOXAMIDE; 7 [4 [2 (BUTOXY)ETHOXY]PHENYL] 1 [(THIAZOL 2 YL)METHYL] N [4 [[METHYL(TETRAHYDRO 2H PYRAN 4 YL)AMINO]METHYL]PHENYL] 2,3 DIHYDRO 1H 1 BENZAZEPINE 4 CARBOXAMIDE; 7 [4 [2 (BUTOXY)ETHOXY]PHENYL] 1 CYCLOBUTYLMETHYL N [4 [[METHYL(TETRAHYDRO 2H PYRAN 4 YL)AMINO]METHYL]PHENYL] 2,3 DIHYDRO 1H 1 BENZAZEPINE 4 CARBOXAMIDE; 7 [4 [2 (BUTOXY)ETHOXY]PHENYL] 1 CYCLOHEXYLMETHYL N [4 [[METHYL(TETRAHYDRO 2H PYRAN 4 YL)AMINO]METHYL]PHENYL] 2,3 DIHYDRO 1H 1 BENZAZEPINE 4 CARBOXAMIDE; 7 [4 [2 (BUTOXY)ETHOXY]PHENYL] 1 CYCLOPROPYLMETHYL N [4 [[METHYL(TETRAHYDRO 2H PYRAN 4 YL)AMINO]METHYL]PHENYL] 2,3 DIHYDRO 1H 1 BENZAZEPINE 4 CARBOXAMIDE; 7 [4 [2 (BUTOXY)ETHOXY]PHENYL] 1 ISOBUTYL N [4 [[METHYL(TETRAHYDRO 2H PYRAN 4 YL)AMINO]METHYL]PHENYL] 2,3 DIHYDRO 1H 1 BENZAZEPINE 4 CARBOXAMIDE; 7 [4 [2 (BUTOXY)ETHOXY]PHENYL] 1 METHYL N [4 [[METHYL(TETRAHYDRO 2H PYRAN 4 YL)AMINO]METHYL]PHENYL] 2,3 DIHYDRO 1H 1 BENZAZEPINE 4 CARBOXAMIDE; 7 [4 [2 (BUTOXY)ETHOXY]PHENYL] N [4 [[METHYL(TETRAHYDRO 2H PYRAN 4 YL)AMINO]METHYL]PHENYL] 1 PHENYL 2,3 DIHYDRO 1H 1 BENZAZEPINE 4 CARBOXAMIDE; 7 [4 [2 (BUTOXY)ETHOXY]PHENYL] N [4 [[METHYL(TETRAHYDRO 2H PYRAN 4 YL)AMINO]METHYL]PHENYL] 2,3 DIHYDRO 1 BENZOTHIEPINE 4 CARBOXAMIDE 1,1 DIOXIDE; 7 [4 [2 (ETHOXY)ETHOXY]PHENYL] N [4 [[METHYL(TETRAHYDRO 2H PYRAN 4 YL)AMINO]METHYL]PHENYL] 2,3 DIHYDRO 1 BENZOTHIEPINE 4 CARBOXAMIDE 1,1 DIOXIDE; 7 [4 [2 (METHOXY)ETHOXY]PHENYL] N [4 [[METHYL(TETRAHYDRO 2H PYRAN 4 YL)AMINO]METHYL]PHENYL] 2,3 DIHYDRO 1 BENZOTHIEPINE 4 CARBOXAMIDE 1,1 DIOXIDE; 7 [4 [3 (ETHOXY)PROPOXY]PHENYL] N [4 [[METHYL(TETRAHYDRO 2H PYRAN 4 YL)AMINO]METHYL]PHENYL] 2,3 DIHYDRO 1 BENZOTHIEPINE 4 CARBOXAMIDE 1,1 DIOXIDE; ANTI HUMAN IMMUNODEFICIENCY VIRUS AGENT; BENZAZEPINE DERIVATIVE; BENZOTHIEPIN DERIVATIVE; CHEMOKINE RECEPTOR ANTAGONIST; N [4 [[METHYL(TETRAHYDRO 2H PYRAN 4 YL)AMINO]METHYL]PHENYL] 7 (4 MORPHOLINOPHENYL) 2,3 DIHYDRO 1 BENZOTHIEPINE 4 CARBOXAMIDE 1,1 DIOXIDE; N [4 [[METHYL(TETRAHYDRO 2H PYRAN 4 YL)AMINO]METHYL]PHENYL] 7 (4 PROPOXYPHENYL) 2,3 DIHYDRO 1 BENZOTHIEPINE 4 CARBOXAMIDE 1,1 DIOXIDE; N [4 [[METHYL(TETRAHYDRO 2H PYRAN 4 YL)AMINO]METHYL]PHENYL] 7 (4 PROPYLPHENYL) 2,3 DIHYDRO 1 BENZOTHIEPINE 4 CARBOXAMIDE 1,1 DIOXIDE; N [4 [[METHYL(TETRAHYDRO 2H PYRAN 4 YL)AMINO]METHYL]PHENYL] 7 [4 [2 (PENTYLOXY)ETHOXY]PHENYL] 2,3 DIHYDRO 1 BENZOTHIEPINE 4 CARBOXAMIDE 1,1 DIOXIDE; N [4 [[METHYL(TETRAHYDRO 2H PYRAN 4 YL)AMINO]METHYL]PHENYL] 7 [4 [2 (PROPOXY)ETHOXY]PHENYL] 2,3 DIHYDRO 1 BENZOTHIEPINE 4 CARBOXAMIDE 1,1 DIOXIDE; UNCLASSIFIED DRUG; UNINDEXED DRUG; AMINE; CHEMOKINE RECEPTOR CCR5;

ANALYTIC METHOD; ANIMAL CELL; ANIMAL EXPERIMENT; ARTICLE; CHEMICAL MODIFICATION; CONTROLLED STUDY; DRUG ACTIVITY; DRUG POTENCY; DRUG SYNTHESIS; IC 50; MEMBRANE FUSION; NONHUMAN; RAT; STRUCTURE ACTIVITY RELATION; ANIMAL; CELL STRAIN COS1; CERCOPITHECUS; CHO CELL; DRUG ANTAGONISM; DRUG EFFECT; HAMSTER; HUMAN; HUMAN IMMUNODEFICIENCY VIRUS 1; MALE; METABOLISM; ORAL DRUG ADMINISTRATION; SPRAGUE DAWLEY RAT; SYNTHESIS;

ADMINISTRATION, ORAL; AMINES; ANIMALS; ANTI-HIV AGENTS; BENZAZEPINES; BENZOTHIEPINS; CERCOPITHECUS AETHIOPS; CHO CELLS; COS CELLS; CRICETINAE; HIV-1; HUMANS; MALE; RATS; RATS, SPRAGUE-DAWLEY; RECEPTORS, CCR5;

EID: 8844238461     PISSN: 00092363     EISSN: 13475223     Source Type: Journal    
DOI: 10.1248/cpb.52.577     Document Type: Article

References (23)

1. Deng H., Liu R., Ellmeier W., Choe S., Unutmaz D., Burkhart M., Di Marzio P., Marmon S., Sutton R. E., Hill C. M., Davis C. B., Peiper S. C., Schall T. J., Littman D. R., Landau N. R., Nature (London), 381, 661-666 (1996).
2. Dragic T., Litwin V., Allaway G. P., Martin S. R., Huang Y., Nagashima K. A., Cayanan C., Maddon P. J., Koup R. A., Moore J. P., Paxton W. A., Nature (London), 381, 667-673 (1996).
3. Alkhatib G., Combadiere C., Broder C. C., Feng Y., Kennedy P. E., Murphy P. M., Berger E. A., Science, 272, 1955-1958 (1996).
4. Choe H., Farzan M., Sun Y., Sullivan N., Rollins B., Ponath P. D., Wu L., Mackay C. R., LaRosa G., Newman W., Gerard N., Gerard C., Sodroski J., Cell, 85, 1135-1148 (1996).
5. Doranz B. J., Rucker J., Yi Y., Smyth R. J., Samson M., Peiper S. C., Parmentier M., Collman R. G., Doms R. W., Cell, 85, 1149-1159 (1996).
6. Cocchi F., DeVico A. L., Garzino-Demo A., Arya S. K., Gallo R. C., Lusso P., Science, 270, 1811-1815 (1995).
7. Liu R., Paxton W. A., Choe S., Ceradini D., Martin S. R., Horuk R., MacDonald M. E., Stuhlmann H., Koup R. A., Landau N. R., Cell, 86, 367-377 (1996).
8. Samson M., Libert F., Doranz B. J., Rucker J., Liesnard C., Farber C. M., Saragosti S., Lapoumeroulie C., Cognaux J., Forceille C., Muyldermans G., Verhofstede C., Burtonboy G., Georges M., Imai T., Rana S., Yi Y., Smyth R. J., Collman R. G., Doms R. W., Vassart G., Parmentier M., Nature (London), 382, 722-725 (1996).
9. Dean M., Carrington M., Winkler C., Huttley G. A., Smith M. W., Allikmets R., Goedert J. J., Buchbinder S. P., Vittinghoff E., Gomperts E., Donfield S., Vlahov D., Kaslow R., Saah A., Rinaldo C., Detels R., O'Brien S. J., Science, 273, 1856-1862 (1996).
10. Carpenter C. C., Fischl M. A., Hammer S. M., Hirsch M. S., Jacobsen D. M., Katzenstein D. A., Montaner J. S., Richman D. D., Saag M. S., Schooley R. T., Thompson M. A., Vella S., Yeni P. G., Volberding P. A., J. Am. Med. Assoc., 280, 78-86 (1998).
11. Finzi D., Blankson J., Siliciano J. D., Margolick J. B., Chadwick K., Pierson T., Smith K., Lisziewicz J., Lori F., Flexner C., Quinn T. C., Chaisson R. E., Rosenberg E., Walker B., Gange S., Gallant J., Siliciano R. F., Nat. Med., 5, 512-517 (1999).
12. Pomerantz R. J., J. Am. Med. Assoc., 282, 1177-1178 (1999).
13. Deeks S. G., Smith M., Holodniy M., Kahn J. O., J. Am. Med. Assoc., 277, 145-153 (1997).
14. Saunders J., Tarby C. M., Drug Discov. Today, 4, 80-92 (1999).
15. Schwarz M. K., Wells T. N., Nat. Rev. Drug. Disc., 1, 347-358 (2002).
16. Baba M., Nishimura O., Kanzaki N., Okamoto M., Sawada H., Iizawa Y., Shiraishi M., Aramaki Y., Okonogi K., Ogawa Y., Meguro K., Fujino M., Proc. Natl. Acad. Sci. U.S.A., 96, 5698-6703 (1999).
17. Shiraishi M., Aramaki Y., Seto M., Imoto H., Nishikawa Y., Kanzaki N., Okamoto M., Sawada H., Nishimura O., Baba M., Fujino M., J. Med. Chem., 43, 2049-2063 (2000).
18. Aramaki Y., Seto M., Okawa T., Oda T., Kanzaki N., Shiraishi M., Chem. Pharm. Bull., 52, 254-258 (2004).
19. Takeda K., Akiyama A., Nakamura H., Takizawa S., Mizuno Y., Takayanagi H., Harigaya Y., Synthesis., 1994, 1063 (1994).
20. Hewson A. T., Hughes K, Richardson S. K., Sharpe D. A., Wadsworth A. H., J. Chem. Soc. Perkin Trans. 1, 1991, 1565-1569 (1991).
21. Booker-Milburn K. I., Dunkin I. R., Kelly F. C., Khalaf A. I., Learmonth D. A., Proctor G. R., Scopes D. I., J. Chem. Soc. Perkin Trans. 1, 1997, 3261-3274 (1997).
22. Abdel-Mggid A. F., Carson K. G., Harris B. D., Maryanoff C. A., Shah R. D., J. Org. Chem., 61, 3849-4862 (1996).
23. Arnauld T., Barton D. H. R., Doris E., Tetrahedron, 53, 4137-4144 (1997).