Anti-viral compounds
| Title: | Anti-viral compounds |
|---|---|
| Patent Number: | 9,394,279 |
| Publication Date: | July 19, 2016 |
| Appl. No: | 13/328848 |
| Application Filed: | December 16, 2011 |
| Abstract: | Compounds effective in inhibiting replication of Hepatitis C virus (“HCV”) are described. This invention also relates to processes of making such compounds, compositions comprising such compounds, and methods of using such compounds to treat HCV infection. |
| Inventors: | Krueger, Allan C. (Gurnee, IL, US); Kati, Warren M. (Gurnee, IL, US); Carroll, William A. (Evanston, IL, US); Pratt, John K. (Kenosha, WI, US); Hutchinson, Douglas K. (Antioch, IL, US) |
| Assignees: | AbbVie Inc. (North Chicago, IL, US) |
| Claim: | 1. A compound of Formula I, or a pharmaceutically acceptable salt thereof, [chemical expression included] wherein: X is cyclopropyl, and is optionally substituted with one or more R A ; L 1 , L 2 and L 3 are each a bond; A is selected from [chemical expression included] or [chemical expression included] B is selected from [chemical expression included] or [chemical expression included] Z 1 is independently selected at each occurrence from O, S, NH or CH 2 , Z 2 is independently selected at each occurrence from N or CH, and W 1 , W 2 , W 3 , W 4 , W 5 and W 6 are each independently selected at each occurrence from CH or N, wherein A and B are each independently optionally substituted with one or more R A ; D is C 3 -C 12 carbocycle or 3- to 12-membered heterocycle, and is optionally substituted with one or more R A ; or D is C 3 -C 12 carbocycle or 3- to 12-membered heterocycle, and is substituted with J and optionally substituted with one or more R A , wherein J is C 3 -C 12 carbocycle or 3- to 12-membered heterocycle and is optionally substituted with one or more R A ; Y is —C(R 1 R 2)N(R 5)-T-R D , or —C(R 3 R 4)C(R 6 R 7)-T-R D ; Z is —C(R 8 R 9)N(R 12)-T-R D , or —C(R 10 R 11)C(R 13 R 14)-T-R D ; R 1 is R C , and R 2 and R 5 , taken together with the atoms to which they are attached, form a 3- to 12-membered heterocycle which is optionally substituted with one or more R A ; R 3 and R 6 are each independently R C , and R 4 and R 7 , taken together with the atoms to which they are attached, form a 3- to 12-membered carbocycle or heterocycle which is optionally substituted with one or more R A ; R 8 is R C , and R 9 and R 12 , taken together with the atoms to which they are attached, form a 3- to 12-membered heterocycle which is optionally substituted with one or more R A ; R 10 and R 13 are each independently R c , and R 11 and R 14 , taken together with the atoms to which they are attached, form a 3- to 12-membered carbocycle or heterocycle which is optionally substituted with one or more R A ; T is each independently selected at each occurrence from bond, -L S -, -L S -M-L S ′-, or -L S -M-L S ′-M′-L S ″-, wherein M and M′ are each independently selected at each occurrence from bond, —O—, —S—, —N(R B)—, —C(O)—, —S(O) 2 —, —S(O)—, —OS(O)—, —OS(O) 2 —, —S(O) 2 O—, —S(O)O—, —C(O)O—, —OC(O)—, —OC(O)O—, —C(O)N(R B)—, —N(R B)C(O)—, —N(R B)C(O)O—, —OC(O)N(R B)—, —N(R B)S(O)—, —N(R B)S(O) 2 —, —S(O)N(R B)—, —S(O) 2 N(R B)—, —C(O)N(R B)C(O)—, —N(R B)C(O)N(R B ′)—, —N(R B)SO 2 N(R B ′)—, —N(R B)S(O)N(R B ′)—, C 3 -C 12 carbocycle or 3- to 12-membered heterocycle, and wherein said C 3 -C 12 carbocycle and 3- to 12-membered heterocycle are each independently optionally substituted at each occurrence with one or more R A ; R D is each independently selected at each occurrence from hydrogen or R A ; R A is independently selected at each occurrence from halogen, nitro, oxo, phosphonoxy, phosphono, thioxo, cyano, or -L S -R E ; R B and R B ′ are each independently selected at each occurrence from hydrogen; or C 1 -C 6 alkyl, C 2 -C 6 alkenyl or C 2 -C 6 alkynyl, each of which is independently optionally substituted at each occurrence with one or more substituents selected from halogen, hydroxy, mercapto, amino, carboxy, nitro, oxo, phosphonoxy, phosphono, thioxo, formyl, cyano or 3- to 6-membered carbocycle or heterocycle; or 3- to 6-membered carbocycle or heterocycle; wherein each 3- to 6-membered carbocycle or heterocycle in R B or R B ′ is independently optionally substituted at each occurrence with one or more substituents selected from halogen, hydroxy, mercapto, amino, carboxy, nitro, oxo, phosphonoxy, phosphono, thioxo, formyl, cyano, C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 1 -C 6 haloalkyl, C 2 -C 6 haloalkenyl or C 2 -C 6 haloalkynyl; R C is independently selected at each occurrence from hydrogen, halogen, hydroxy, mercapto, amino, carboxy, nitro, oxo, phosphonoxy, phosphono, thioxo, formyl or cyano; or C 1 -C 6 alkyl, C 2 -C 6 alkenyl or C 2 -C 6 alkynyl, each of which is independently optionally substituted at each occurrence with one or more substituents selected from halogen, hydroxy, mercapto, amino, carboxy, nitro, oxo, phosphonoxy, phosphono, thioxo, formyl, cyano or 3- to 6-membered carbocycle or heterocycle; or 3- to 6-membered carbocycle or heterocycle; wherein each 3- to 6-membered carbocycle or heterocycle in R C is independently optionally substituted at each occurrence with one or more substituents selected from halogen, hydroxy, mercapto, amino, carboxy, nitro, oxo, phosphonoxy, phosphono, thioxo, formyl, cyano, C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 1 -C 6 haloalkyl, C 2 -C 6 haloalkenyl or C 2 -C 6 haloalkynyl; R E is independently selected at each occurrence from —O—R S , —S—R S , —C(O)R S , —OC(O)R S , —C(O)OR S , —N(R S R S ′), —S(O)R S , —SO 2 R S , —C(O)N(R S R S ′), —N(R S)C(O)R S ′, —N(R S)C(O)N(R S ′R S ″), —N(R S)SO 2 R S ′, —SO 2 N(R S R S ′), —N(R S)SO 2 N(R S ′R S ″), —N(R S)S(O)N(R S ′R S ″), —OS(O)—R S , —OS(O) 2 —R S , —S(O) 2 OR S , —S(O)OR S , —OC(O)OR S , —N(R S)C(O)OR S ′, —OC(O)N(R S R S ′), —N(R S)S(O)—R S ′, —S(O)N(R S R S ′), P(O)(OR S) 2 or —C(O)N(R S)C(O)—R S ′; or C 1 -C 6 alkyl, C 2 -C 6 alkenyl or C 2 -C 6 alkynyl, each of which is independently optionally substituted at each occurrence with one or more substituents selected from halogen, hydroxy, mercapto, amino, carboxy, nitro, oxo, phosphonoxy, phosphono, thioxo, formyl or cyano; or C 3 -C 6 carbocycle or 3- to 6-membered heterocycle, each of which is independently optionally substituted at each occurrence with one or more substituents selected from halogen, hydroxy, mercapto, amino, carboxy, nitro, oxo, phosphonoxy, phosphono, thioxo, formyl, cyano, C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 1 -C 6 haloalkyl, C 2 -C 6 haloalkenyl, C 2 -C 6 haloalkynyl, C(O)OR S or —N(R S R S ′); R L is independently selected at each occurrence from halogen, nitro, oxo, phosphonoxy, phosphono, thioxo, cyano, —O—R S , —S—R S , —C(O)R S , —OC(O)R S , —C(O)OR S , —N(R S R S ′), —S(O)R S , —SO 2 R S , —C(O)N(R S R S ′) or —N(R S)C(O)R S ′; or C 3 -C 6 carbocycle 3- to 6-membered heterocycle, each of which is independently optionally substituted at each occurrence with one or more substituents selected from halogen, hydroxy, mercapto, amino, carboxy, nitro, oxo, phosphonoxy, phosphono, thioxo, formyl, cyano, C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 1 -C 6 haloalkyl, C 2 -C 6 haloalkenyl or C 2 -C 6 haloalkynyl; L S , L S ′ and L S ″ are each independently selected at each occurrence from bond; or C 1 -C 6 alkylene, C 2 -C 6 alkenylene or C 2 -C 6 alkynylene, each of which is independently optionally substituted at each occurrence with one or more R L ; and R S , R S ′ and R S ″ are each independently selected at each occurrence from hydrogen; or C 1 -C 6 alkyl, C 2 -C 6 alkenyl or C 2 -C 6 alkynyl, each of which is independently optionally substituted at each occurrence with one or more substituents selected from halogen, hydroxy, mercapto, amino, carboxy, nitro, oxo, phosphonoxy, phosphono, thioxo, formyl, cyano or 3- to 6-membered carbocycle or heterocycle; or —(R G —R H) n —(R G —R H ′), wherein each n is independently 0, 1, 2, 3 or 4; each R G is independently O, S or N(R B); each R H is independently C 1 -C 6 alkylene, C 2 -C 6 alkenylene or C 2 -C 6 alkynylene, each of which is optionally substituted with one or more substituents selected from halogen, hydroxy, mercapto, amino, carboxy, nitro, oxo, phosphonoxy, phosphono, thioxo, formyl, cyano or 3- to 6-membered carbocycle or heterocycle; and each R H ′ is independently C 1 -C 6 alkyl, C 2 -C 6 alkenyl or C 2 -C 6 alkynyl, each of which is optionally substituted with one or more substituents selected from halogen, hydroxy, mercapto, amino, carboxy, nitro, oxo, phosphonoxy, phosphono, thioxo, formyl, cyano or 3- to 6-membered carbocycle or heterocycle; or 3- to 6-membered carbocycle or heterocycle; wherein each 3- to 6-membered carbocycle or heterocycle in R S , R S′ or R S″ is independently optionally substituted at each occurrence with one or more substituents selected from halogen, hydroxy, mercapto, amino, carboxy, nitro, oxo, phosphonoxy, phosphono, thioxo, formyl, cyano, C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 1 -C 6 haloalkyl, C 2 -C 6 haloalkenyl or C 2 -C 6 haloalkynyl. |
| Claim: | 2. The compound or salt of claim 1 , wherein: T is independently selected at each occurrence from —C(O)-L S ′-M′-L S ″- or —N(R B)C(O)-L S ′-M′-L S ″-; and L S ′ is each independently C 1 -C 6 alkylene, and is independently optionally substituted at each occurrence with one or more R L . |
| Claim: | 3. The compound or salt of claim 1 , wherein: Y is —C(R 1 R 2)N(R 5)-T-R D ; Z is —C(R 8 R 9)N(R 12)-T-R D ; T is independently selected at each occurrence from —C(O)-L S ′-M′-L S ″-; and D is C 5 -C 6 carbocycle, 5- to 6-membered heterocycle, or 6- to 10-membered bicycles, and is substituted with one or more R A ; or D is C 5 -C 6 carbocycle or 5- to 6-membered heterocycle, and is substituted with J and optionally substituted with one or more R A , wherein J is C 3 -C 6 carbocycle or 3- to 6-membered heterocycle and is optionally substituted with one or more R A . |
| Claim: | 4. The compound or salt of claim 3 , wherein T is independently selected at each occurrence from —C(O)-L S ′-N(R B)C(O)-L S ″- or —C(O)-L S ′-N(R B)C(O)O-L S ″-; and R 2 and R 5 , taken together with the atoms to which they are attached, form [chemical expression included] which is optionally substituted with one or more R A ; and R 9 and R 12 , taken together with the atoms to which they are attached, form [chemical expression included] which is optionally substituted with one or more R A . |
| Claim: | 5. The compound of claim 4 , wherein A is [chemical expression included] B is [chemical expression included] and A and B are each independently optionally substituted with one or more R A . |
| Claim: | 6. The compound of claim 1 , wherein the compound is selected from the group consisting of: dimethyl (2S,2′S)-1,1′-((2S,2′S)-2,2′-(4,4′-(3-(4-methoxyphenyl)cyclopropane-1,2-diyl)bis(4,1-phenylene))bis(azanediyl)bis(oxomethylene)bis(pyrrolidine-2,1-diyl))bis(3-methyl-1-oxobutane-2,1-diyl)dicarbamate; dimethyl (2S,2′S)-1,1′-((2S,2′S)-2,2′-(4,4′-(3-(4-(benzyloxy)phenyl)cyclopropane-1,2-diyl)bis(4,1-phenylene))bis(azanediyl)bis(oxomethylene)bis(pyrrolidine-2,1-diyl))bis(3-methyl-1-oxobutane-2,1-diyl)dicarbamate; dimethyl (2S,2′S)-1,1′-((2S,2′S)-2,2′-(4,4′-(4,4′-(3-(4-methoxyphenyl)cyclopropane-1,2-diyl)bis(4,1-phenylene))bis(1H-imidazole-4,2-diyl))bis(pyrrolidine-2,1-diyl))bis(3-methyl-1-oxobutane-2,1-diyl)dicarbamate; dimethyl (2S,2′S)-1,1′-((2S,2′S)-2,2′-(4,4′-(4,4′-(3-(4-(benzyloxy)phenyl)cyclopropane-1,2-diyl)bis(4,1-phenylene))bis(1H-imidazole-4,2-diyl))bis(pyrrolidine-2,1-diyl))bis(3-methyl-1-oxobutane-2,1-diyl)dicarbamate; dimethyl (2S,2′S)-1,1′-((2S,2′S)-2,2′-(5,5′-(3-(4-(benzyloxy)phenyl)cyclopropane-1,2-diyl)bis(1H-benzo[d]imidazole-5,2-diyl))bis(pyrrolidine-2,1-diyl))bis(3-methyl-1-oxobutane-2,1-diyl)dicarbamate; dimethyl (2S,2′S)-1,1′-((2S,2′S)-2,2′-(4,4′-(3-(4-cyclohexylphenyl)cyclopropane-1,2-diyl)bis(4,1-phenylene))bis(azanediyl)bis(oxomethylene)bis(pyrrolidine-2,1-diyl))bis(3-methyl-1-oxobutane-2,1-diyl)dicarbamate; dimethyl (2S,2′S)-1,1′-((2S,2′S)-2,2′-(4,4′-(2-(4-tert-butylphenyl)cyclopent-3-ene-1,3-diyl)bis(4,1-phenylene)bis(azanediyl)bis(oxomethylene))bis(pyrrolidine-2,1-diyl))bis(3-methyl-1-oxobutane-2,1-diyl)dicarbamate; and dimethyl (2S,2′S)-1,1′-((2S,2′S)-2,2′-(4,4′-(2-(4-tert-butylphenyl)cyclopentane-1,3-diyl)bis(4,1-phenylene)bis(azanediyl)bis(oxomethylene))bis(pyrrolidine-2,1-diyl))bis(3-methyl-1-oxobutane-2,1-diyl)dicarbamate. |
| Claim: | 7. A pharmaceutical composition comprising a compound or salt according to claim 1 and another anti-HCV agent. |
| Patent References Cited: | 5830867 November 1998 Bhatnagar et al. 5935982 August 1999 Dykstra et al. 6235493 May 2001 Bissell et al. 6369091 April 2002 Sircar et al. 6703403 March 2004 Norbeck et al. 6919366 July 2005 Sircar et al. 7141574 November 2006 Beaulieu et al. 7659270 February 2010 Bachand et al. 7704992 April 2010 Bachand et al. 7728027 June 2010 Pack et al. 7741347 June 2010 Bachand et al. 7745636 June 2010 Bachand et al. 7759495 July 2010 Bachand et al. 7763731 July 2010 Rockway et al. 7906655 March 2011 Belema et al. 8101643 January 2012 Qiu et al. 2003/0004203 January 2003 Sircar et al. 2003/0100582 May 2003 Sircar et al. 2004/0034189 February 2004 Cho et al. 2005/0075343 April 2005 Sircar et al. 2005/0197375 September 2005 Sircar et al. 2006/0003942 January 2006 Tung et al. 2006/0058317 March 2006 Gravestock et al. 2006/0105997 May 2006 Arrington et al. 2007/0004741 January 2007 Apodaca et al. 2007/0015757 January 2007 Madsen et al. 2007/0142434 June 2007 Sandanayaka et al. 2007/0197558 August 2007 Betebenner et al. 2007/0232627 October 2007 Betebenner et al. 2007/0299068 December 2007 Karp et al. 2008/0044379 February 2008 Bachand et al. 2008/0044380 February 2008 Bachand et al. 2008/0050336 February 2008 Bachand et al. 2008/0075696 March 2008 Parsons et al. 2008/0221107 September 2008 Giordanetto et al. 2008/0299075 December 2008 Bachand et al. 2008/0311075 December 2008 Bachand et al. 2009/0004111 January 2009 Rice et al. 2009/0041716 February 2009 Kim et al. 2009/0043107 February 2009 Pack et al. 2009/0068140 March 2009 Bachand et al. 2009/0093456 April 2009 Arnold et al. 2009/0104151 April 2009 Hanson et al. 2009/0202478 August 2009 Bachand et al. 2009/0202483 August 2009 Bachand et al. 2010/0055071 March 2010 Leivers et al. 2010/0068176 March 2010 Belema et al. 2010/0080772 April 2010 Belema et al. 2010/0143499 June 2010 Condon 2010/0158862 June 2010 Kim et al. 2010/0160355 June 2010 DeGoey et al. 2010/0168138 July 2010 Degoey et al. 2010/0215616 August 2010 Romine et al. 2010/0215618 August 2010 Carter et al. 2010/0221214 September 2010 Or et al. 2010/0221215 September 2010 Qiu et al. 2010/0221216 September 2010 Or et al. 2010/0226882 September 2010 Or et al. 2010/0226883 September 2010 Qiu et al. 2010/0233120 September 2010 Bachand et al. 2010/0233122 September 2010 Qiu et al. 2010/0249190 September 2010 Lopez et al. 2010/0260708 October 2010 Belema et al. 2010/0260715 October 2010 Or et al. 2010/0266543 October 2010 Qiu et al. 2010/0267634 October 2010 Donner et al. 2010/0303755 December 2010 Lopez et al. 2010/0310512 December 2010 Guo et al. 2010/0316607 December 2010 Or et al. 2011/0008288 January 2011 Or et al. 2011/0064695 March 2011 Qiu et al. 2011/0064696 March 2011 Or et al. 2011/0064697 March 2011 Qiu et al. 2011/0064698 March 2011 Or et al. 2011/0070196 March 2011 Qiu et al. 2011/0070197 March 2011 Or et al. 2011/0077280 March 2011 Bender et al. 2011/0092415 April 2011 Degoey et al. 2011/0112100 May 2011 Milbank et al. 2011/0136799 June 2011 Chern et al. 2011/0142798 June 2011 Qiu et al. 2011/0150827 June 2011 Dousson et al. 2011/0152246 June 2011 Buckman et al. 2011/0189129 August 2011 Qiu et al. 2011/0195044 August 2011 Romine 2011/0207699 August 2011 Degoey et al. 2011/0217261 September 2011 Or et al. 2011/0218175 September 2011 Or et al. 2011/0223134 September 2011 Nair et al. 2011/0237579 September 2011 Li et al. 2011/0237636 September 2011 Belema et al. 2011/0274648 November 2011 Lavoie et al. 2011/0281910 November 2011 Lavoie et al. 2011/0286961 November 2011 Belema et al. 2011/0294819 December 2011 Lopez et al. 2011/0300104 December 2011 Qiu et al. 2012/0004196 January 2012 Degoey et al. 2012/0028978 February 2012 Zhong et al. 2012/0040977 February 2012 Li et al. PI0401908 January 2006 75755 June 1984 2242751 October 2010 2003282270 October 2003 2010126571 June 2010 WO9427627 December 1994 WO9961020 December 1999 WO0012521 March 2000 WO03082186 October 2003 WO2004005283 January 2004 WO2004014313 February 2004 WO2004014852 February 2004 WO2004014852 April 2004 WO2004014313 December 2005 WO2006020951 February 2006 WO2006033703 March 2006 WO2006133326 December 2006 WO2007070556 June 2007 WO2007070600 June 2007 WO2007076034 July 2007 WO2007076035 July 2007 WO2007082554 July 2007 WO2007070556 August 2007 WO2007081517 September 2007 WO2007070600 November 2007 WO2007131366 November 2007 WO2007136921 November 2007 WO2007144174 December 2007 WO2008014236 January 2008 WO2008014238 January 2008 WO2008021927 February 2008 WO2008021928 February 2008 WO2008021936 February 2008 WO2008021928 March 2008 WO2008021936 April 2008 WO2008021927 May 2008 WO2008064218 May 2008 WO2008070447 June 2008 WO2008074450 June 2008 WO2008064218 October 2008 WO2008128121 October 2008 WO2008133753 November 2008 WO2008144380 November 2008 WO2009003009 December 2008 WO2009020534 February 2009 WO2009020825 February 2009 WO2009020828 February 2009 WO2008070447 March 2009 WO2009093082 July 2009 WO2009094224 July 2009 WO2009102318 August 2009 WO2009102325 August 2009 WO2009102568 August 2009 WO2009102633 August 2009 WO2009102694 August 2009 WO2009136290 November 2009 WO2009143361 November 2009 WO2009155709 December 2009 WO2010015090 February 2010 WO2010017401 February 2010 WO2010039793 April 2010 WO2010059858 May 2010 WO2010062821 June 2010 WO2010065668 June 2010 WO2010065674 June 2010 WO2010065681 June 2010 WO2010075376 July 2010 WO2010091413 August 2010 WO2010096302 August 2010 WO2010096462 August 2010 WO2010096777 August 2010 WO2010099527 September 2010 WO2010111483 September 2010 WO2010111534 September 2010 WO2010111673 September 2010 WO2010115767 October 2010 WO2010117635 October 2010 WO2010117704 October 2010 WO2010117977 October 2010 WO2010120621 October 2010 WO2010120935 October 2010 WO2010122162 October 2010 WO2010132538 November 2010 WO2010132601 November 2010 WO2010138368 December 2010 WO2010138488 December 2010 WO2010138790 December 2010 WO2010138791 December 2010 WO2010144646 December 2010 WO2010148006 December 2010 WO2011004276 January 2011 WO2011009084 January 2011 WO2011015658 February 2011 WO2011026920 March 2011 WO2011028596 March 2011 WO2011031904 March 2011 WO2011031934 March 2011 WO2011050146 April 2011 WO2011054834 May 2011 WO2011059850 May 2011 WO2011059887 May 2011 WO2011060000 May 2011 WO2011066241 June 2011 WO2011068941 June 2011 WO2011075439 June 2011 WO2011075607 June 2011 WO2011075615 June 2011 WO2011079327 June 2011 WO2011081918 July 2011 WO2011082077 July 2011 WO2011087740 July 2011 WO2011091417 July 2011 WO2011091446 July 2011 WO2011091532 August 2011 WO2011112429 September 2011 WO2011119853 September 2011 WO2011119858 September 2011 WO2011119860 September 2011 WO2011119870 September 2011 WO2011127350 October 2011 WO2011146401 November 2011 WO2011150243 December 2011 WO2011156543 December 2011 |
| Other References: | Adjabeng G., et al., “Novel Class of Tertiary Phosphine Ligands Based on a Phospha-adamantane Framework and use in the Suzuki cross-Coupling Reactions of Aryl Halides Under Mild Conditions,” Organic Letters, 2003, vol. 5 (6), pp. 953-955. cited by applicant Adjabeng G., et al., “Palladium Complexes of 1,3,5,7-tetramethy1-2,4,8-trioxa-6-phenyl-6-phosphaadamantane: Synthesis, Crystal Structure and Use in the Suzuki and Sonogashira Reactions and the Alpha-arylation of Ketones,” The Journal of Organic Chemistry, 2004, vol. 69 (15), pp. 5082-5086. cited by applicant Aldous D.J., et al. , “A Simple Enantioselective Preparation of (2S,5S)-2,5-diphenylpyrrolidine and Related Diary Amines,” Tetrahedron Asymmetry, 2000, vol. 11, pp. 2455-2462. cited by applicant Alesso E.N., et al., “Synthesis of Diastereoisomeric 1,2,3-Triphenylindans,” Australian Journal of Chemistry, 1997, vol. 50, pp. 149-152. cited by applicant Angiolini M., et al., “Synthesis of Azabicycloalkane Amino Acid Scaffolds as Reverse-Turn Inducer Dipeptide Mimics ,” European Journal Organization Chemistry, 2000, pp. 2571-2581. cited by applicant Boehm T., et al., “Uber Die Bildung Von Gamma-Piperidonderivaten Aus Azetessigester, Aromatischen Aldehyden und Aminen, Eine Modifikation Der Hantzschschen Pyridinsynthese,” Pharmaceutical, 1943, vol. 281, pp. 62-77. cited by applicant Brettle R., et al., “A Highly Efficient Enzymic Route to Novel Chiral Liquid Crystals based on 3-Aryl-2-cycloalken-1 -ones,” Journal of the Chemical Society, Chemical Communications, 1994, pp. 2305-2306. cited by applicant Bundgaard H., “Design of Pro Drugs,” 1985, pp. 1-6. cited by applicant Charifson P.S., et al., “Novel Dual-Targeting Benzimidazole Urea Inhibitors of DNA Gyrase and Topoisomerase IV Possessing Potent Antibacterial Activity: Intelligent Design and Evolution through the Judicious Use of Structure-Guided Design and Stucture-Activity Relationships,” Journal of Medicinal Chemistry, 2008, vol. 51 (17), pp. 5243-5263. cited by applicant Chong J.M., et al. , “Asymmetric Synthesis of trans.2,5-Diphenylpyrrolidine: A C2-Symmetric Chirai Amine,” Tetrahedron Asymmetry, 1995, vol. 6 (2), pp. 409-418. cited by applicant Clark W.M., et al., “A Highly Enantioselective Conjugate Reduction of 3-Arylinden-1-ones Using Bakers' Yeast for the Preparation of (S)-3-Arylindan-1-ones,” Organic Letters, 1999, vol. 1 (11), pp. 1839-1842. cited by applicant Clarke P.A., et al., “Pot, Atom and Step Economic (Pase) Synthesis of Highly Functionalized Piperidines: A Five-Component Condensation,” Tetrahedron Letters , 2007, vol. 48 , pp. 5209-5212. cited by applicant Clarke P.A., et al., “Pot, Atom and Step Economic (PASE) Synthesis of Highly Substituted Piperidines:A Five-Component Condensation,” Synthesis, 2008, No. 28, pp. 3530-3532. cited by applicant Collado I., et al , “Stereoselective Addition of Grignard-Derived Organocopper Reagents to N-Acyliminium Ions: Synthesis of Enantiopure 5- and 4,5-Substituted Prolinates ,” Journal of Organic Chemistry , 1995, vol. 60, pp. 5011-5015. cited by applicant Conte I., et al., “Synthesis and SAR of Piperazinyl-N-Phenylbenzamides as Inhibitors of Hepatitis C Virus RNA Replication in Cell Culture,” Bioorganic and Medicinal Chemistry Letters, 2009, vol. 19 (6), pp. 1779-1783. cited by applicant Dell'Erba C., et al., “Synthetic Exploitation of the Ring-Opening of 3,4-Dinitrothiophene, IX Pyrrolidines, Pyrrolines and Pyrroles from 1,4-Diary1-2,3-Dinitro-1,3-Butadienes Via a 5-Endo-Trig Cyclization,” European Journal of Organic Chemistry, 2000, pp. 903-912. cited by applicant Effenberger F., et al., “Synthesis, Structure, and Spectral Behavior of Donor-Acceptor Substituted Biphenyls,” The Journal of Organic Chemistry, 1983, vol. 48, pp. 4649-4658. cited by applicant Fan X., et al., “An Efficient and Practical Synthesis of the HIV Protease Inhibitor Atazanavir via a Highly Diastereoselective Reduction Approach,” Organic Process Research and Development, 2008, vol. 12 (1), pp. 69-75. cited by applicant Fiedler., “Encyclopedia of Excipients for Pharmaceuticals, Cosmetics and related Areas,” 5th Edition, Hoepfner E.M., et al., eds., Editio Cantor Verlag Aulendorf, 2002, Table of Contents. cited by applicant Gordon T.D., et al , “Synthetic Approaches to the Azole Peptide Mimetics,” Tetrahedron Letters, 1993, vol. 34(12), pp. 1901-1904. cited by applicant Greene T.W., et al., “Protection for the Amino group,” Protective Groups in Organic Synthesis, 1999, Third Edition, pp. 494-653. cited by applicant Hartwig J.F., et al., “III.3.2 Palladium-Catalyzed Amination of Aryl Halides and Related Reactions,” Handbook of Organopalladium Chemistry for Organic Synthesis, 2002, pp. 1051-1096. cited by applicant Hoover J.E, Remington's Pharmaceutical Sciences, 15th Edition, 1975, Table of Contents. cited by applicant International Preliminary Report on Patentability and Written Opinion for the Application No. PCT/US2010/031102, mailed on Oct. 18, 2011, 7 pages. cited by applicant International Search Report and Written Opinion for Application No. PCT/US2009/038077, mailed on Jan. 21, 2011, 16 pages. cited by applicant International Search Report and Written Opinion for Application No. PCT/US2009/069177, mailed on Aug. 10, 2010, 17 pages. cited by applicant International Search Report for Application No. PCT/US2009/069188, mailed on Jun. 8, 2010, 4 pages. cited by applicant International Search Report for the Application No. PCT/US2010/031102, mailed on Sep. 1, 2010, 4 pages. cited by applicant Jacques et al., “Enantiomers, Racemates, and Resolutions,” J. Wiley & Sons, Chapter 3, pp. 197-213, 1981. cited by applicant Jeffrey J.L., et al., “Concise Synthesis of Pauciflorol F Using a Larock Annulation,” Organic Letters, 2009, vol. 11 (23), pp. 5450-5453. cited by applicant Jing Q., et al., “Bulky Achiral Triarylphosphines Mimic Binap in Ru(II)—Catalyzed Asymmetric Hydrogenation of Ketones,” Advanced Synthesis & Catalysis, 2005, vol. 347, pp. 1193-1197. cited by applicant Khan A.T., et al., “Effects of Substituents in the -Position of 1,3-Dicarbonyl Compounds in Bromodimethylsulfonium Bromide-Catalyzed Multicomponent Reactions: A Facile Access to Functionalized Piperidines,” Journal of organic chemistry, 2008, vol. 73 , pp. 8398-8402. cited by applicant Kuethe J.T., et al., “Asymmetric Synthesis of 1,2,3-Trisubstituted Cyclopentanes and Cyclohexanes as Key Components of Substance P Antagonists,” The Journal of Organic Chemistry, 2002, vol. 67 (17), pp. 5993-6000. cited by applicant Li Chuan-Ying., et al., “Olefination of Ketenes for the Enantioselective Synthesis of Allenes via an Ylide Route,” Tetrahedron, 2007, vol. 63, pp. 8046-8053. cited by applicant Lieberman L., et al., eds., Pharmaceutical Dosage Forms, vol. 1, Marcel Dekker, Inc., 1980, Table of Contents. cited by applicant Louie J., et al., “Palladium-Catalyzed Amination of Aryl Triflates and Importance of Triflate Addition Rate,” Journal of Organic Chemistry, 1997, vol. 62 (5), pp. 1268-1273. cited by applicant L-selectride, Retrieved from the Internet: Lucas S., et al.,“In Vivo Active Aldosterone Synthase Inhibitors with Improved Aelectivity: Lead Optimization Providing a Series of Pyridine Substituted 3,4-Dihydro-1H-Quinolin-2-one Derivatives,” Journal of Medicinal Chemistry, 2008, vol. 51 (24), pp. 8077-8087. cited by applicant Masters K., “Spray Drying Handbook” 4th Edition, John Wiley & Sons, 1985, Table of Contents. cited by applicant Masui M., et al., “A Practical Method for Asymmetric Borane Reduction of Prochiral Ketones Using Chiral Amino Alcohols and Trimethyl Borate,” Synlett, 1997, pp. 273-274. cited by applicant Matzeit A., et al., “Radical Tandem Cyclizations by Anodic Decarboxylation of Carboxylic Acids,” Synthesis, 1995, pp. 1432-1444. cited by applicant Misra M., et al., “Organocatalyzed Highly Atom Economic One Pot Synthesis of Tetrahydropyridines as Antimalarials,” Bioorganic & Medicinal Chemistry, 2009, vol. 17 , pp. 625-633. cited by applicant Moinet C., et al., “Novel Non-Peptide Ligands for the Somatostatin sst3 Receptor,” Bioorganic & Medicinal Chemistry Letters, 2001, vol. 11 (8), pp. 991-995. cited by applicant Muci A.R., et al., “Practical Palladium Catalysts for C—N. And C—O Bond Formation,” Topics in Current Chemistry, 2002, vol. 219, pp. 131-209. cited by applicant Muri E.M.F., et al., “Pseudo-Peptides Derived From Isomannide as Potential Inhibitors of Serine Proteases,” Amino Acids, 2005, vol. 28 (4), pp. 413-419. cited by applicant Naylor E.M., et al. , “3-Pyridylethanolamines: Potent and Selective Human 63 Adrenergic Receptor Agonists,” Bioorganic & Medicinal Chemistry Letters, 1998, vol. 8 (21), pp. 3087-3092. cited by applicant Nevar N.M., et al., “One Step Preparation of 1,4-Diketones from Methyl Ketones and a-Bromomethyl Ketones in the Presence of ZnCl2·t-BuOH·Et2NR as a Condensation Agent,” Synthesis, 2000, vol. 9, pp. 1259-1262. cited by applicant Pak V.D., et al., “Catalytic Condensation of Schiff's Base With P-Methoxybenzal Acetone,” Catalytic Synthesis of Organic Nitrate Compounds, 1970, vol. 68 (Part 4), pp. 66-71. cited by applicant Peng T., et al., “Construction of a Library of Rhodol Fluorophores for Developing New Fluorescent Probes,” Organic Letters, 2010, vol. 12 (3), pp. 496-499. cited by applicant Penning T.D., et al, “Discovery and SAR of 2-(1-Propylpiperidin-4-yl)-1H-Benzimidazole-4-Carboxamide: A Potent Inhibitor of Poly(ADP-ribose) Polymerase (PARP) for the Treatment of Cancer ,” Bioorganic & Medicinal Chemistry, 2008, vol. 16(14), pp. 6965-6975. cited by applicant Polymer Handbook, Brandrup J., et al., Eds., Interscience Publishers, 1975, Table of Contents. cited by applicant Rosen M.H., et al., “Contraceptive Agents from Cycloaddition Reactions of Diarylcyclopropenones and Diarylthiirene 1, 1-Dioxides,” Journal of Medicinal Chemistry, 1976, vol. 19 (3), pp. 414-419. cited by applicant Sato M., et al., “Efficient Preparation of Optically Pure C2-Symmetrical Cyclic Amines for Chiral Auxiliary,” Synthesis, 2004, vol. 9, pp. 1434-1438. cited by applicant Sawyer J.S., et al., “Synthetic and Structure/Activity Studies on Acid-Substituted 2-Arylphenols:Discovery of 2-[2-Propyl-3-[3-[2-ethyl-4-(4-fluorophenyl)-5-hydroxyphenoxy]-propoxy]phenoxy] benzoic Acid, a High-Affinity Leukotriene B4 Receptor Antagonist,” Journal of Medicinal Chemistry, 1995, vol. 38 (22), pp. 4411-4432. cited by applicant Smith A.B., et al., “Indole Diterpene Synthetic Studies: Development of a Second-Generation Synthetic Strategy for (+)-Nodulisporic Acids A and B,” Journal of Organic Chemistry, 2007, vol. 72 (13), pp. 4611-4620. cited by applicant Smith D.C., et al., “Reissert Compound Chemistry. XXVI. The Syntheses of Bis-Benzylisoquinolines,” Journal of Heterocyclic Chemistry, 1976, vol. 13, pp. 573-576. cited by applicant Sperling L. H., “Introduction to Physical Polymer Science,” 2nd Edition, John Wiley & Sons, Inc., 1992, Table of Contents. cited by applicant Sugawara M., et al., “Remarkable gamma-Effect of Tin: Acid-Promoted Cyclopropanation Reactions of alpha-((alkoxycarbonyl)oxy)stannanes with Alkenes,” Journal of the American Chemical Society, 1997, vol. 119 (49), pp. 11986-11987. cited by applicant Takagi S., et al., “Antimicrobial Agents From Bletilla Striata,” Phyrochemisrry, 1983, vol. 22 (4), pp. 1011-1015. cited by applicant Tatsumi K., et al., “Enzyme-Mediated Coupling of 3,4-Dichloroaniline and Ferulic Acid: A Model for Pollutant Binding to Humic Materials,” Environmental Science & Technology, 1994, vol. 28 , pp. 210-215. cited by applicant Tellinghuisen T.L., et al., “Structure of the Zinc-Binding Domain of an Essential Component of the Hepatitis C Virus Replicase,” Nature, 2005, vol. 435 (7040), pp. 374-379. cited by applicant Vallee R.J., et al., “Photoannelation Reactions of 3-(Alk-1-ynyl)cyclohept-2-en-1-ones,” Helvetica Chimica Acta, 2010, vol. 93 (1), pp. 17-24. cited by applicant Verboom W., et al., ““tert-Amino effect” in Heterocyclic Synthesis. Formation of N-Heterocycles by Ring Closure Reactions of Substituted 2-vinyl-N,N-dialkylanilines,” Journal of Organic Chemistry, 1984, vol. 49 (2), pp. 269-276. cited by applicant Willis M.C., et al., “Palladium-Catalyzed Tandem Alkenyl and Aryl C—N. Bond Formation: A Cascade N-Annulation Route to 1-Functionalized Indoles,” Angewandte Chemie International Edition, 2005, vol. 44 (3), pp. 403-406. cited by applicant Wolfe J.P., et al., “Palladium-Catalyzed Amination of Aryl Triflates,” Journal of Organic Chemistry, 1997, vol. 62 (5), pp. 1264-1267. cited by applicant Xiao D., et al., “A Practical Synthetic Pathway to Polysubstituted Tetrahydropyridines via Multicomponent Reactions Catalyzed by BF3·OEt2,” Synlett, 2005, vol. 10, pp. 1531-1534. cited by applicant Zhang J., et al., “Stereoselective Bromination-Suzuki Cross-Coupling of Dehydroamino Acids to Form Novel Reverse-Turn Peptidomimetics: Substituted Unsaturated and Saturated Indolizidinone Amino Acids,” Journal of the American Chemical Society , 2002, vol. 4(23), pp. 4029-4032. cited by applicant |
| Primary Examiner: | Lieb, Jeanette |
| Attorney, Agent or Firm: | Zhang, Xu |
| Accession Number: | edspgr.09394279 |
| Database: | USPTO Patent Grants |
| Language: | English |
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