\
`Cook pct/us00/11129
`
`Page 96
`
`RN
`CN
`
`171488-20-3 CAPLUS
`Pyrazino[1',2':1,6)pyrido[3,4-b]indole-1,4-dione, 6-(1,3-benzodioxol-5-yl)-
`2-cyclohexy1-2,3,6,7,12,12a-hexahydro-, (6R,12aS)-rel-
`(9CI)
`(CA INDEX
`NAME)
`
`Relative stereochemistry.
`
`RN
`CN
`
`171488-21-4 CAPLUS
`Pyrazino[1',2':1,6)pyrido[3,4-b)indole-1,4-dione, 6-(1,3-benzodioxol-5-yl)-
`2,3,6,7,12,12a-hexahydro-2-(phenylmethyl)-, (6R,l2aS)-rel-
`(9CI)
`(CA
`INDEX NAME)
`
`Relative stereochemistry.
`
`Prepared by Toby Port, STIC, Biotech Library 308-3534
`
`INTELGENX 1024, pg. 452
`
`

`
`Cook pct/us00/11129
`
`Page 97
`
`RN
`CN
`
`171488-22-5 CAPLUS
`Pyrazino[l',2' :1,6)pyrido[3,4-b]indole-1,4-dione, 6-(1,3-benzodioxol-5-yl)-
`2-[(4-fluorophenyl)methyl]-2,3,6,7,12,12a-hexahydro-, (6R,12aS)-rel-
`(9CI)
`(CA INDEX NAME)
`
`Relative stereochemistry.
`
`RN
`CN
`
`171488-76-9 CAPLUS
`Pyrazino[1',2':1,6)pyrido[3,4-b]indole-1,4-dione, 6-(1,3-benzodioxol-5-yl)-
`2, 3, 6, 7, 12, 12a-hexahydro-2- ( 2-methylpropyl)-,
`( 6R, 12aR)-
`( 9CI)
`( CA INDEX
`NAME)
`
`Absolute stereochemistry. Rotation (+).
`
`RN
`CN
`
`171488-77-0 CAPLUS
`Pyrazino[l',2' :1,6]pyrido[3,4-b]indo1e-1,4-dione, 6-(1,3-benzodioxol-5-yl)-
`2- ( cyclohexylmethyl) -2, 3, 6, 7, 12, 12a-hexahydro-,
`( 6R, 12aR)-
`( 9CI)
`(CA
`INDEX NAME)
`
`Absolute stereochemistry. Rotation (+).
`
`Prepared by Toby Port, STIC, Biotech Library 308-3534
`
`INTELGENX 1024, pg. 453
`
`

`
`Cook pct/us00/11129
`
`Page 98
`
`RN
`CN
`
`171488-86-1 CAPLUS
`Pyrazino[1',2' :1,6)pyrido[3,4-b)indole-1,4-dione, 6-(1,3-benzodioxol-5-yl)-
`2,3,6,7,12,12a-hexahydro-2,10-dimethyl-, (6R,l2aS)-rel-
`(9CI)
`(CA INDEX
`NAME)
`
`Relative stereochemistry.
`
`Me
`
`RN
`CN
`
`171488-87-2 CAPLUS
`Pyrazino[1',2':1,6)pyrido[3,4-b)indo1e-1,4-dione, 6-(1,3-benzodioxol-5-yl)-
`2-[(3,4-dimethoxyphenyl)methy1)-2,3,6,7, 12,12a-hexahydro-, (6R,l2aR)-
`(9CI)
`(CA INDEX NAME)
`
`Absolute stereochemistry. Rotation (+).
`
`II ~ Y"· ~':Jcl:::/~
`
`I
`
`I
`OMe
`
`MeO
`
`I R
`. N
`I
`lj
`~(N"R/ /~/
`N
`
`J
`
`0~
`0------f. ~
`
`I
`
`·~ /
`0
`
`I
`
`RN
`
`171488-91-8 CAPLUS
`
`Prepared by Toby Port, STIC, Biotech Library 308-3534
`
`INTELGENX 1024, pg. 454
`
`

`
`Cook pct/us00/11129
`
`Page 99
`
`CN
`
`Pyrazino[1',2' :1,6]pyrido[3,4-b]indole-1,4-dione, 6-(1,3-benzodioxol-5-yl)-
`2,3,6,7,12,12a-hexahydro-2-(2-propynyl)-, (6R,12aR)-
`(9CI)
`(CA INDEX
`NAME)
`
`Absolute stereochemistry. Rotation (+).
`
`He=
`
`RN
`CN
`
`171488-92-9 CAPLUS
`Pyrazino[l',2':1,6]pyrido[3,4-b]indole-1,4-dione, 6-(1,3-benzodioxol-5-yl)-
`2-(1,3-benzodioxol-5-ylmethyl)-2,3,6,7,12,12a-hexahydro-, (6R,12aR)-
`(9CI)
`(CA INDEX NAME)
`
`Absolute stereochemistry. Rotation (+).
`
`RN
`CN
`
`171488-94-1 CAPLUS
`Pyrazino[1',2':1,6]pyrido[3,4-b]indole-1,4-dione, 6-(1,3-benzodioxol-5-yl)-
`2-(2-furanylmethyl)-2,3,6,7,12,12a-hexahydro-, (6R,12aR)-
`(9CI)
`(CA INDEX
`NAME)
`
`Absolute stereochemistry. Rotation (+).
`
`Prepared by Toby Port, STIC, Biotech Library 308-3534
`
`INTELGENX 1024, pg. 455
`
`

`
`Cook pct/us00/11129
`
`Page 100
`
`RN
`CN
`
`171488-95-2 CAPLUS
`Pyrazino[1',2':1,6]pyrido[3,4-b]indo1e-1,4-dione, 6-(1,3-benzodioxol-5-yl)-
`2,3,6,7,12,12a-hexahydro-2-(2-thienylmethyl)-, (6R,12aR)-
`(9CI)
`(CA INDEX
`NAME)
`
`Absolute stereochemistry. Rotation (+).
`
`RN
`CN
`
`171489-01-3 CAPLUS
`5H,14H-Pyrrolo[1' ',2' ':4',5']pyrazino[1',2':1,6]pyrido[3,4-b]indole-5,14-
`dione, 12-(1,3-benzodioxol-5-yl)-1,2,3,5a,6,11,12,14a-octahydro-,
`(5aR, 12R, 14aR)-
`(9CI)
`(CA INDEX NAME)
`
`Absolute stereochemistry. Rotation (+).
`
`RN
`
`171489-02-4 CAPLUS
`
`Prepared by Toby Port, STIC, Biotech Library 308-3534
`
`INTELGENX 1024, pg. 456
`
`

`
`Cook pct/us00/11129
`
`Page 101
`
`CN
`
`Pyrazino[l',2':1,6]pyrido[3,4-b)indole-1,4-dione, 6-(1,3-benzodioxol-5-yl)-
`2,3,6,7,12,12a-hexahydro-2,3-dimethyl-,
`(3R,6R,12aR)-
`(9CI)
`(CA INDEX
`NAME)
`
`Absolute stereochemistry. Rotation (+).
`
`" , ~CO'
`Me !1~ ~{
`I
`I
`)~~N R/ /~
`II
`'
`~ .
`0
`
`N
`
`R
`
`Me
`
`RN
`CN
`
`171596-27-3 CAPLUS
`Pyrazino[l',2' :1,6]pyrido[3,4-b]indole-1,4-dione, 6-(1,3-benzodioxol-5-yl)-
`2,3,6,7,12,12a-hexahydro-2-methyl-, (6R,12aS)-
`(9CI)
`(CA INDEX NAME)
`
`Absolute stereochemistry. Rotation (-).
`
`RN
`CN
`
`171596-28-4 CAPLUS
`Pyrazino[1',2' :1,6)pyrido[3,4-b)indo1e-1,4-dione, 6-(1,3-benzodioxol-5-y1)-
`2,3,6,7,12,12a-hexahydro-2-methyl-, (6S,12aR)-
`(9CI)
`(CA INDEX NAME)
`
`Absolute stereochemistry. Rotation (+).
`
`Prepared by Toby Port, STIC, Biotech Library 308-3534
`
`INTELGENX 1024, pg. 457
`
`

`
`Cook pct/us00/11129
`
`Page 102
`
`RN
`CN
`
`171596-29-5 CAPLUS
`Pyrazino[1',2':1,6]pyrido[3,4-b]indole-1,4-dione, 6-(1,3-benzodioxol-5-yl)-
`2,3,6,7,12,12a-hexahydro-2-methyl-, (6R,12aR)-
`(9CI)
`(CA INDEX NAME)
`
`Absolute stereochemistry. Rotation (+).
`
`RN
`CN
`
`171596-30-8 CAPLUS
`Pyrazino[1',2':1,6]pyrido[3,4-b]indole-1,4-dione, 6-(1,3-benzodioxol-5-yl)-
`2,3,6,7,12,12a-hexahydro-2-(1-methylethyl)-, (6R,12aR)-
`(9CI)
`(CA INDEX
`NAME)
`
`Absolute stereochemistry. Rotation (+).
`
`RN
`CN
`
`171596-31-9 CAPLUS
`Pyrazino[1',2':1,6]pyrido[3,4-b]indole-1,4-dione, 6-(1,3-benzodioxol-5-yl)-
`
`Prepared by Toby Port, STIC, Biotech Library 308-3534
`
`INTELGENX 1024, pg. 458
`
`

`
`2-butyl-2,3,6,7,12,12a-hexahydro-, (6R,l2aR)
`
`(9CI)
`
`(CA INDEX NAME)
`
`Absolute stereochemistry. Rotation (+).
`
`Cook pct/us00/11129
`
`Page 103
`
`RN
`CN
`
`171596-32-0 CAPLUS
`Pyrazino[1',2':1,6)pyrido[3,4-b)indole-1,4-dione, 6-(1,3-benzodioxol-5-yl)-
`( 6R, 12aR)-
`( 9CI)
`( CA INDEX NAME)
`2-cyclopentyl-2, 3 1 6, 7 1 12 1 12a-hexahydro- 1
`
`Absolute stereochemistry. Rotation (+).
`
`RN
`CN
`
`171596-36-4 CAPLUS
`Pyrazino[l',2':1,6]pyrido[3,4-b)indole-1,4-dione, 6-(1,3-benzodioxol-5-yl)-
`2,3,6,7,12,12a-hexahydro-, (6R,l2aR)-
`(9CI)
`(CA INDEX NAME)
`
`Absolute stereochemistry. Rotation (+).
`
`Prepared by Toby Port, STIC, Biotech Library 308-3534
`
`INTELGENX 1024, pg. 459
`
`

`
`Cook pct/us00/11129
`
`Page 104
`
`RN
`CN
`
`171596-39-7 CAPLUS
`5H,l4H-Pyrrolo[l' ',2'':4',5']pyrazino[l',2':1,6]pyrido[3,4-b]indole-5,14-
`dione, 12-(1,3-benzodioxol-5-yl)-1,2,3,5a,6,11,12,14a-octahydro-,
`(5aR,12R,l4aS)-
`(9CI)
`(CA INDEX NAME)
`
`Absolute stereochemistry. Rotation (+).
`
`RN
`CN
`
`171596-40-0 CAPLUS
`Pyrazino[l',2':1,6]pyrido[3,4-b]indole-1,4-dione, 6-(1,3-benzodioxol-5-yl)-
`2,3,6,7,12,12a-hexahydro-2,3-dimethyl-, (3S,6R,12aR)-
`(9CI)
`(CA INDEX
`NAME)
`
`Absolute stereochemistry. Rotation (+).
`
`RN
`CN
`
`187935-15-5 CAPLUS
`Pyrazino[1',2' :1,6]pyrido[3,4-b]indole-1,4-dione, 6-(1,3-benzodioxol-5-yl)-
`2,3,6,7,12,12a-hexahydro-3-methyl-, (3S,6R,12aR)-
`(9CI)
`(CA INDEX NAME)
`
`Absolute stereochemistry.
`
`Prepared by Toby Port, STIC, Biotech Library 308-3534
`
`INTELGENX 1024, pg. 460
`
`

`
`Cook pct/us00/11129
`
`Page 105
`
`RN
`CN
`
`303984-32-9 CAPLUS
`Pyrazino[l',2':1,6]pyrido[3,4-b]indole-1,4-dione, 6-(1,3-benzodioxol-5-yl)-
`2-[2-(1,3-benzodioxol-5-yl)ethyl]-2,3,6,7,12,12a-hexahydro-, (6R,l2aR)(cid:173)
`(CA INDEX NAME)
`(9CI)
`
`Absolute stereochemistry.
`
`N~l) N/ ~
`H
`
`~
`l---0------r I
`
`REFERENCE COUNT:
`
`41
`
`THERE ARE 41 CITED REFERENCES AVAILABLE FOR THIS
`RECORD. ALL CITATIONS AVAILABLE IN THE RE FORMAT
`
`L12 ANSWER 27 OF 37
`ACCESSION NUMBER:
`DOCUMENT NUMBER:
`TITLE:
`
`PATENT ASSIGNEE(S):
`SOURCE:
`
`DOCUMENT TYPE:
`LANGUAGE:
`FAMILY ACC. NUM. COUNT:
`PATENT INFORMATION:
`
`CAPLUS COPYRIGHT 2002 ACS
`2000:686171 CAPLUS
`133:271672
`Phosphodiesterase inhibitor preparation for treatment
`of sexual functional disorders
`Lilly !cos Llc, USA
`Ger. Gebrauchsmusterschrift, 47 pp.
`CODEN: GGXXFR
`Patent
`German
`3
`
`PATENT NO.
`---------------
`DE 20007861
`NO 2000002097
`CA 2307101
`FI 2000000976
`
`KIND
`
`Ul
`A
`AA
`A
`
`DATE
`--------
`20000928
`20011026
`20001030
`20001030
`
`APPLICATION NO.
`---------------
`DE 2000-20007861
`NO 2000-2097
`CA 2000-2307101
`FI 2000-976
`
`DATE
`--------
`20000426
`20000425
`20000426
`20000426
`
`Prepared by Toby Port, STIC, Biotech Library 308-3534
`
`INTELGENX 1024, pg. 461
`
`

`
`Cook pct/us00/11129
`
`Page 106
`
`NL 2000-1015027
`
`20000426
`
`SE 2000-1518
`ZA 2000-2058
`WO 2000-US11129
`
`20000426
`20000426
`20000426
`
`AZ,
`EE,
`KG,
`MW,
`TR,
`MD,
`SL,
`IE,
`ML,
`
`BA, BB, BG, BR, BY, CA, CH, CN, CR,
`ES, FI, GB, GD, GE, GH, GM, HR, HU,
`KP, KR, KZ, LC, LK, LR, LS, LT, LU,
`MX, NO, NZ, PL, PT, RO, RU, SD, SE,
`TT, TZ, UA, UG, US, UZ, VN, YU, ZA,
`RU, TJ, TM
`SZ, TZ, UG, ZW, AT, BE, CH, CY, DE,
`IT, LU, MC, NL, PT, SE, BF, BJ, CF,
`MR, NE, SN, TD, TG
`20000426
`DE 2000-10021266
`20000426
`JP 2000-126472
`20000426
`FR 2000-5296
`20000426
`GB 2000-10199
`20000426
`LT 2000-35
`20000426
`LV 2000-56
`20000426
`CN 2000-106987
`BE 2000-295
`20000426
`20000426
`EP 2000-926367
`FR, GB, GR,
`IT, LI, LU, NL, SE, MC, PT,
`
`20000426
`LU 2000-90569
`20011029
`NO 2001-5275
`19990430
`US 1999-132036P P
`20000426
`WO 2000-US11129 W
`A formulation for the treatment of sexual malfunctions (e.g., erectile
`dysfunction in men and decreased libido in women) which contains a
`phosphodiesterase 5 inhibitor with a ICSO of at least 100-fold lower than
`that with phosphodiesterase 6 as active ingredient, and which inhibits
`phosphodiesterase 5 with an ICSO of at least 1000-fold lower than for
`phosphodiesterase lc and a ICSO for PDES of below 1'0 nM.
`171596-29-5
`or effector, except adverse); BSU (Biological
`RL: BAC (Biological
`study, unclassified); PEP (Physical, engineering or chemical process); THU
`(Therapeutic use); BIOL (Biological study); PROC (Process); USES
`(Uses)
`(phosphodiesterase inhibitor prepn. for treatment of sexual functional
`disorders)
`171596-29-5 CAPLUS
`Pyrazino[l',2':1,6)pyrido[3,4-b)indole-1,4-dione, 6-(1,3-benzodioxol-5-yl)-
`2,3,6,7,12,12a-hexahydro-2-methyl-, (6R,l2aR)-
`(9CI)
`(CA INDEX NAME)
`
`NL 1015027
`NL 1015027
`SE 2000001518
`ZA 2000002058
`wo 2000066099
`WO 2000066099
`W: AE, AG,
`CU, CZ,
`ID, IL,
`LV, MA,
`SG, SI,
`ZW, AM,
`RW: GH, GM,
`DK, ES,
`CG, CI,
`DE 10021266
`JP 2000336043
`FR 2795646
`GB 2351663
`LT 4758
`LV 12560
`CN 1292264
`BE 1012957
`EP 1173181
`R: AT, BE,
`IE, SI,
`LU 90569
`NO 2001005275
`PRIORITY APPLN. INFO.:
`
`20001031
`Al
`20010214
`C2
`20001031
`A
`20001102
`A
`20001109
`A2
`20010118
`A3
`AL, AM, AT, AU,
`DE, DK, DM, DZ,
`IN, IS, JP, KE,
`MD, MG, MK, MN,
`SK, SL, TJ, TM,
`AZ, BY, KG, KZ,
`KE, LS, MW, SD,
`FI, FR, GB, GR,
`CM, GA, GN, GW,
`Al
`20001116
`A2
`20001205
`Al
`20010105
`A1
`20010110
`B
`20010226
`B
`20010420
`A
`20010425
`AS
`20010605
`A2
`20020123
`CH, DE, DK, ES,
`LT, LV, FI, RO
`A2
`20020227
`A
`20011206
`
`AB
`
`IT
`
`RN
`CN
`
`Absolute stereochemistry. Rotation (+).
`
`Prepared by Toby Port, STIC, Biotech Library 308-3534
`
`INTELGENX 1024, pg. 462
`
`

`
`Cook pct/us00/11129
`
`Page 107
`
`L12 ANSWER 28 OF 37
`ACCESSION NUMBER:
`DOCUMENT NUMBER:
`TITLE:
`
`INVENTOR ( S) :
`PATENT ASSIGNEE(S):
`SOURCE:
`
`DOCUMENT TYPE:
`LANGUAGE:
`FAMILY ACC. NUM. COUNT:
`PATENT INFORMATION:
`
`CAPLUS COPYRIGHT 2002 ACS
`2000:666601 CAPLUS
`133:256811
`Pharmaceutical compositions containing dopamine
`agonists in combination with nitric oxide donors for
`treating and/or preventing sexual dysfunctions
`Garvey, David S.
`Nitromed, Inc., USA
`PCT Int. Appl., 48 pp.
`CODEN: PIXXD2
`Patent
`English
`1
`
`PATENT NO.
`
`KIND DATE
`
`APPLICATION NO.
`
`DATE
`
`20000310
`WO 2000-US3709
`20000921
`Al
`WO 2000054773
`W: AE, AL, AM, AT, AU, AZ, BA, BB, BG, BR, BY, CA, CH, CN, CR, CU,
`CZ, DE, DK, DM, DZ, 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, NO, NZ, PL, PT, RO, RU, SO, 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: GH, GM, KE, LS, MW, SD, SL, SZ, TZ, UG, ZW, AT, BE, CH, CY, DE,
`DK, ES, FI, FR, GB, GR,
`IE, IT, LU, MC, NL, PT, 'SE, BF, BJ, CF,
`CG, CI, CM, GA, GN, GW, ML, MR, NE, SN, TD, TG
`PRIORITY APPLN. INFO.:
`US 1999-123920P P 19990312
`OTHER SOURCE(S):
`MARPAT 133:256811
`AB
`The present invention is directed to novel compns. comprising at least one
`dopamine agonist in combination with at least one nitric oxide donor (i.e.
`compds. that donate, transfer or release nitric oxide, elevate endogenous
`levels of endothelium-derived relaxing factor, stimulate endogenous
`synthesis of nitric oxide or are substrates for nitric oxide synthase).
`The novel compns. may optionally comprise at least one therapeutic agent,
`such as, a vasoactive agent, an antiemetic agent, and mixts. thereof. The
`dopamine agonist is preferably apomorphine. The present invention is also
`directed to methods for treating and/or preventing sexual dysfunctions
`and/or enhancing sexual responses in patients.
`In other embodiments, the
`present invention is directed to methods treating or preventing
`neurodegenerative diseases, mitochondrial diseases, spinal cord injury,
`central or psychostimulant addiction, senile dementia, cir~ulatory
`disorders, cardiovascular disorders, hyperprolactinemia or myopia. The
`compds. and/or compns. of the present invention can also be provided in
`
`Prepared by Toby Port, STIC, Biotech Library 308-3534
`
`INTELGENX 1024, pg. 463
`
`

`
`Cook pct/us00/11129
`
`Page 108
`
`IT
`
`RN
`CN
`
`the form of a pharmaceutical kit (no data).
`171596-29-5, Ic 351
`RL: BAC (Biological activity or effector, except adverse); BSU (Biological
`study, unclassified); THU (Therapeutic use); BIOL (Biological study); USES
`(Uses)
`(pharmaceutical compns. contg. dopamine agonists in combination with
`nitric oxide donors for treating and/or preventing sexual dysfunctions)
`171596-29-5 CAPLUS
`Pyrazino[1',2':1,6)pyrido[3,4-b)indole-1,4-dione, 6-(1,3-benzodioxol-5-yl)-
`2,3,6,7,12,12a-hexahydro·-2-methyl-, (6R,12aR)-
`(9CI)
`(CA INDEX NAME)
`
`Absolute stereochemistry. Rotation (+).
`
`REFERENCE COUNT:
`
`4
`
`THERE ARE 4 CITED REFERENCES AVAILABLE FOR THIS
`RECORD. ALL CITATIONS AVAILABLE IN THE RE FORMAT
`
`L12 ANSWER 29 OF 37
`ACCESSION NUMBER:
`DOCUMENT NUMBER:
`TITLE:
`
`INVENTOR ( S) :
`PATENT ASSIGNEE(S):
`SOURCE:
`
`DOCUMENT TYPE:
`LANGUAGE:
`FAMILY ACC. NUM. COUNT:
`PATENT INFORMATION:
`
`CAPLUS COPYRIGHT 2002 ACS
`2000:645819 CAPLUS
`133:227820
`Pharmaceutical compositions for treating erectile
`dysfunction containing a melanocortin receptor agonist
`and a cyclic-GMP-specific phosphodiesterase inhibitor
`or an .alpha.-adrenergic receptor antagonist
`Stoner, Elizabeth
`Merck & Co., Inc., USA; Waldstreicher, Joanne
`PCT Int. Appl., 25 pp.
`CODEN: PIXXD2
`Patent
`English
`1
`
`APPLICATION NO. DATE
`---------------
`--------
`20000303
`WO 2000-US5711
`
`KIND DATE
`PATENT NO.
`---------------
`--------
`wo 2000053148
`20000914
`A2
`wo 2000053148
`20001214
`A3
`W: AE, AL, AM, AT, AU, AZ, BA, BB, BG, BR, BY, CA, CH, CN, CR, CU,
`ID, IL,
`CZ, DE, DK, DM, EE, ES, FI, GB, GD, GE, GH, GM, HR, HU,
`IN, IS, JP' KE, KG, KR, KZ, LC, LK, LR, LS, LT, LU, LV, MA, MD,
`MG, MK, MN, MW, MX, 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: GH, GM, KE, LS, MW, SD, SL, SZ, TZ, UG, ZW, AT, BE, CH, CY, DE,
`IE, IT, LU, MC, NL, PT, SE, BF, BJ, CF,
`DK, ES, FI, FR, GB, GR,
`CG, CI, CM, GA, GN, GW, ML, MR, NE, SN, TD, TG
`EP 2000-916081
`20011212
`A2
`EP 1161255
`
`20000303
`
`Prepared by Toby Port, STIC, Biotech Library 308-3534
`
`INTELGENX 1024, pg. 464
`
`

`
`Cook pct/us00/11129
`
`Page 109
`
`DE, DK, ES, FR, GB, GR, IT, LI, LU, NL, SE, MC, PT,
`LV, FI, RO
`
`R: AT, BE, CH,
`IE, SI, LT,
`PRIORITY APPLN. INFO.:
`
`19990308
`US 1999-123244P P
`wo 2000-US5711 w
`20000303
`The present invention provides for a method for the treatment of erectile
`dysfunction in a male or female human subject in need of such treatment
`comprising administration of a therapeutically effective amt. of an
`agonist of the melanocortin receptor in combination with a therapeutically
`effective amt. of a cyclic-GMP-specific phosphodiesterase inhibitor or an
`alpha-adrenergic receptor antagonist. Further, the present invention
`provides for pharmaceutical compns. useful in the methods of the present
`invention, as well as a method of manuf. of a medicament useful for
`treating erectile dysfunction. Effect of the combination of 20 mg/kg of
`the invention compds. was tested in rats. A hard gelatin capsule
`contained a melanocortin receptor agonist 5, and a type V
`phosphodiesterase inhibitor 10 mg.
`171596-29-5
`RL: BAC (Biological activity or effector, except adverse); BSU (Biological
`study, unclassified); THO (Therapeutic use); BIOL (Biological study); USES
`(Uses)
`(pharmaceutical compns. for treating erectile dysfunction contg.
`melanocortin receptor agonist and cyclic-GMP-specific phosphodiesterase
`inhibitor or .alpha.-adrenergic receptor antagonist)
`171596-29-5 CAPLUS
`Pyrazino[l',2' :1,6]pyrido[3,4-b]indole-1,4-dione, 6-(1,3-benzodioxol-5-yl)-
`2,3,6,7,12,12a-hexahydro-2-methyl-, (6R,l2aR)-
`(9CI)
`(CA INDEX NAME)
`
`AB
`
`IT
`
`RN
`CN
`
`Absolute stereochemistry. Rotation (+).
`
`""-
`
`N
`
`H
`:
`
`R
`
`,----,--:
`
`Me )OYG
`I Y" R
`
`L12 ANSWER 30 OF 37
`ACCESSION NUMBER:
`DOCUMENT NUMBER:
`TITLE:
`
`INVENTOR ( S) :
`PATENT ASSIGNEE(S):
`SOURCE:
`
`DOCUMENT TYPE:
`LANGUAGE:
`FAMILY ACC. NOM. COUNT:
`PATENT INFORMATION:
`
`CAPLUS COPYRIGHT 2002 ACS
`2000:475525 CAPLUS
`133:109946
`Methylaminodihydroimidazoquinolinones for treating
`sexual disturbances and inducing mating in animals
`Meglasson, Martin Durham; McCall, Robert B.
`Pharmacia & Upjohn Company, USA
`PCT Int. Appl., 48 pp.
`CODEN: PIXXD2
`Patent
`English
`1
`
`PATENT NO.
`
`KIND DATE
`
`APPLICATION NO.
`
`DATE
`
`Prepared by Toby Port, STIC, Biotech Library 308-3534
`
`INTELGENX 1024, pg. 465
`
`

`
`Cook pct/us00/11129
`
`Page 110
`
`wo 1999-US27951 19991220
`
`wo 2000040226
`20000713
`A2
`wo 2000040226
`20010201
`A3
`W: AE, AL, AM, AT, AU, AZ, BA, BB, BG, BR, BY, CA, CH, CN, CR, CU,
`CZ, DE, DK, DM, 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, 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: GH, GM, KE, LS, MW, SD, SL, SZ, TZ, UG, ZW, AT, BE, CH, CY I DE,
`IE, IT, LU, MC, NL, PT, SE, BF, BJ, CF,
`DK, ES, FI, FR, GB, GR,
`CG, CI, CM, GA, GN, GW, ML, MR, NE, SN, TD, TG
`19991220
`BR 9916759
`20010925
`BR 1999-16759
`A
`19991220
`EP 1140092
`20011010
`EP 1999-967142
`A2
`R: AT, BE, CH, DE, DK, ES, FR, GB, GR, IT, LI, LU, NL, SE, MC, PT,
`IE, SI, LT, LV, FI, RO
`PRIORITY APPLN.
`INFO.:
`
`us 1999-114840P p
`19990106
`us 1999-115051P p
`19990108
`us 1999-115922P p
`19990114
`us 1999-120543P p
`19990217
`wo 1999-US27951 w 19991220
`MAR PAT 133:109946
`
`OTHER SOURCE (S):
`GI
`
`AB
`
`IT
`
`RN
`CN
`
`The present invention is a method of treating sexual disturbances in
`humans and inducing mating in non-human mammals using the cornpds. of
`formula (I: Rl,R2,R3 = H, alkyl, alkenyl, cycloalkyl, etc.; X= H, alkyl,
`halogen, OH, etc.; A,B,D
`CH, CH2, CO, N, etc.; n
`0 or 1) in a dosage
`range where the sexually therapeutic amt. is from about 0.2 through 8
`mg/person/dose and where the sexually mating amt. is from about 0.003
`through 0.2 mg/kg/dose.
`171596-29-5, ICOS 351
`RL: BAC (Biological activity or effector, except adverse); BSU (Biological
`study, unclassified); PEP (Physical, engineering or chemical process); THU
`(Therapeutic use); BIOL (Biological study); PROC (Process); USES
`(Uses)
`(treating sexual disturbances and inducing mating in animals)
`171596-29-5 CAPLUS
`Pyrazino[1',2':1,6]pyrido[3,4-b]indole-1,4-dione, 6-(1,3-benzodioxol-
`2,3,6,7,12,12a-hexahydro-2-methyl-, (6R,l2aR)-
`(9CI)
`(CA INDEX NAME)
`
`)-
`
`Absolute stereochemistry. Rotation (+).
`
`Prepared by Toby Port, STIC, Biotech Library 308-3534
`
`INTELGENX 1024, pg. 466
`
`

`
`Cook pct/us00/11129
`
`Page 111
`
`112 ANSWER 31 OF 37
`ACCESSION NUMBER:
`DOCUMENT NUMBER:
`TITLE:
`
`INVENTOR(S):
`PATENT ASSIGNEE(S):
`SOURCE:
`
`DOCUMENT TYPE:
`LANGUAGE:
`FAMILY ACC. NUM. COUNT:
`PATENT INFORMATION:
`
`CAPLUS COPYRIGHT 2002 ACS
`2000:392967 CAPLUS
`133:22405
`Preventives containing 1,6-dihydro-7H-pyrazolo[4,3-
`d]pyrimidin-7-one derivatives and related compounds
`for nitric acid-induced tolerance
`Ellis, Peter
`Pfizer Inc., USA
`Jpn. Kokai Tokkyo Koho, 31 pp.
`CODEN: JKXXAF
`Patent
`Japanese
`1
`
`PATENT NO.
`
`KIND DATE
`
`APPLICATION NO.
`
`DATE
`
`JP 2000159672
`us 6225315
`EP 1022026
`EP 1022026
`R: AT, BE,
`IE, SI,
`AU 9961788
`KR 2000035774
`PRIORITY APPLN. INFO.:
`OTHER SOURCE(S):
`GI
`
`20000613
`A2
`20010501
`B1
`20000726
`A2
`20020410
`A3
`CH, DE, OK, ES,
`LT, LV, FI, RO
`A1
`20000601
`A
`20000626
`
`JP 1999-337606
`us 1999-442821
`EP 1999-309406
`
`19991129
`19991118
`19991125
`
`FR, GB, GR, IT, LI, LU, NL, SE, MC, PT,
`
`AU 1999-61788
`KR 1999-53785
`US 1998-110335P
`MARPAT 133:22405
`
`19991130
`19991130
`19981130
`
`p
`
`Prepared by Toby Port, STIC, Biotech Library 308-3534
`
`INTELGENX 1024, pg. 467
`
`

`
`Cook pct/us00/11129
`
`Page 112
`
`~
`
`rl
`OR3 :(X{N
`
`~
`
`F
`
`, -
`
`'
`
`02S-N
`
`R4
`_\:'R5
`
`R2
`
`I
`
`AB
`
`IT
`
`RN
`CN
`
`H, Cl-3 alkyl, C3-5 cycloalkyl, Cl-3
`The title compds. [I; Rl
`perfluoroalkyl; R2 = H, Cl-3 perfluoroalkyl, Cl-6 alkyl substituted by OH,
`Cl-3 alkoxy, or C3-6 cycloalkyl; R3 = Cl-6 alkyl, C3-6 alkenyl, C3-6
`alkynyl, C3-7 cycloalkyl, Cl-6 perfluoroalkyl, C3-6 cycloalkyl-Cl-6 alkyl;
`R4 together with the R4-bonded N completes 4-N-R6-piperazinyl; R5 = H,
`Cl-4 alkyl, Cl-3 alkoxy, NR7R8, CONR7R8; wherein R6 = H, Cl-6 alkyl,
`hydroxy-C2-6 alkyl, R7RBN-C2-6 alkyl, R7R8NCO-Cl-6 alkyl, CONR7R8,
`CSNR7R8, C(:NH)NR7R8; wherein R7, R8 = H, Cl-4 alkyl, Cl-3 alkoxy-C2-4
`alkyl, hydroxy-C2-4 alkyl], pharmacal. acceptable salts, prodrugs,
`polymorphs, hydrates, solvates, active metabolites, or stereoisomers
`thereof , which are cGMP phosphodiesterase inhibitors and useful for the
`prevention of nitrate tolerance (no data), are prepd. The title compds.
`also include pyrazolo[3,4-d]pyrimidin-4-one, quinazolin-4-one,
`purin-6-one, pyrido[3,2-d]pyrimidin-4-one, and
`pyrazino[l',2':1,6]pyrido[3,4-b]indole derivs.
`171488-10-1P 171488-15-6P 171596-29-5P
`171596-30-8P 171596-32-0P 171596-36-4P
`171596-40-0P 187935-15-SP 273207-76-4P
`RL: SPN (Synthetic preparation); THU (Therapeutic use); BIOL (Biological
`study); PREP (Preparation); USES
`(Uses)
`(preventives contg. 1,6-dihydro-7H-pyrazolo[4,3-d)pyrimidin-7-one
`derivs. and related compds. as cGMP phosphodiesterase inhibitors for
`nitric acid-induced tolerance)
`171488-10-1 CAPLUS
`Pyrazino[1',2':1,6]pyrido[3,4-b)indole-l,4-dione, 6-(1,3-benzodioxol-5-yl)-
`2,3,6,7,12,12a-hexahydro-2-(4-pyridinylmethyl)-, (6R,12aS)-rel-
`(9CI)
`(CA
`INDEX NAME)
`
`Relative stereochemistry.
`
`Prepared by Toby Port, STIC, Biotech Library 308-3534
`
`INTELGENX 1024, pg. 468
`
`

`
`Cook pct/us00/11129
`
`Page 113
`
`RN
`CN
`
`171488-15-6 CAPLUS
`Pyrazino[1',2' :1,6)pyrido[3,4-b)indo1e-1,4-dione, 6-(1,3-benzodioxol-5-yl)-
`2-cyclopropyl-2,3,6,7,12,12a-hexahydro-, (6R,12aS)-rel-
`(9CI)
`(CA INDEX
`NAME)
`
`Relative stereochemistry.
`
`RN
`CN
`
`171596-29-5 CAPLUS
`Pyrazino[1',2':1,6)pyrido[3,4-b]indole-1,4-dione, 6-(1,3-benzodioxol-5-yl)-
`2,3,6,7,12,12a-hexahydro-2-methyl-, (6R,l2aR)-
`(9CI)
`(CA INDEX NAME)
`
`Absolute stereochemistry. Rotation (+).
`
`RN
`CN
`
`171596-30-8 CAPLUS
`Pyrazino[1',2' :1,6)pyrido[3,4-b)~ndole-1,4-dione, 6-(1,3-benzodioxol-5-yl)-
`2,3,6,7,12,12a-hexahydro-2-(l-methylethyl)-, (6R,12aR)-
`(9CI)
`(CA INDEX
`NAME)
`
`Absolute stereochemistry. Rotation (+).
`
`Prepared by Toby Port, STIC, Biotech Library 308-3534
`
`INTELGENX 1024, pg. 469
`
`

`
`Cook pct/us00/11129
`
`Page 114
`
`RN
`CN
`
`171596-32-0 CAPLUS
`Pyrazino[1',2':1,6]pyrido[3,4-b]indole-1,4-dione, 6-(1,3-benzodioxol-5-yl)-
`2-cyc1opentyl-2,3,6,7,12,12a-hexahydro-, (6R,12aR)-
`(9CI)
`(CA INDEX NAME)
`
`Absolute stereochemistry. Rotation (+).
`
`RN
`CN
`
`171596-36-4 CAPLUS
`Pyrazino[1',2':1,6]pyrido[3,4-b]indole-1,4-dione, 6-(1,3-benzodioxol-5-yl)-
`2,3,6,7,12,12a-hexahydro-, (6R,12aR)-
`(9CI)
`(CA INDEX NAME)
`
`Absolute stereochemistry. Rotation (+).
`
`RN
`CN
`
`171596-40-0 CAPLUS
`Pyrazino[1',2':1,6]pyrido[3,4-b]indole-1,4-dione, 6-(1,3-benzodioxol-5-yl)-
`2,3,6,7,12,12a-hexahydro-2,3-dimethyl-, (3S,6R,12aR)-
`(9CI)
`(CA INDEX
`
`Prepared by Toby Port, STIC, Biotech Library 308-3534
`
`INTELGENX 1024, pg. 470
`
`

`
`Cook pct/us00/11129
`
`Page 115
`
`NAME)
`
`Absolute stereochemistry. Rotation (+).
`
`M•~~
`--~ /N R
`lr
`
`Me
`
`RN
`CN
`
`187935-15-5 CAPLUS
`Pyrazino[l',2':1,6]pyrido[3,4-b]indole-1,4-dione, 6-(1,3-benzodioxol-5-yl)-
`2,3,6,7,12,12a-hexahydro-3-methyl-, (3S,6R,l2aR)-
`(9CI)
`(CA INDEX NAME)
`
`Absolute stereochemistry.
`
`RN
`CN
`
`273207-76-4 CAPLUS
`5H,l4H-1,2,4-Triazolo[4' ',3' ':4',5']pyrazino[l',2':1,6]pyrido[3,4-b]indole-
`5,14-dione, 12-(1,3-benzodioxol-5-yl)-1,2,3,5a,6,11,12,14a-octahydro-,
`(5aR,12R,14aS)-
`(9CI)
`(CA INDEX NAME)
`
`Absolute stereochemistry.
`
`Prepared by Toby Port, STIC, Biotech Library 308-3534
`
`INTELGENX 1024, pg. 471
`
`

`
`Cook pct/us00/11129
`
`Page 116
`
`L12 ANSWER 32 OF 37
`ACCESSION NUMBER:
`DOCUMENT NUMBER:
`TITLE:
`INVENTOR(S):
`
`PATENT ASSIGNEE(S):
`SOURCE:
`
`DOCUMENT TYPE:
`LANGUAGE:
`FAMILY ACC. NUM. COUNT:
`PATENT INFORMATION:
`
`CAPLUS COPYRIGHT 2002 ACS
`2000:240994 CAPLUS
`132:270098
`Tablets immediately disintegrating in the oral cavity
`Furitsu, Hisao; Kato, Akira; Ohwaki, Takayuki; Yasui,
`Masanori
`Eisai Co., Ltd., Japan
`PCT Int. Appl., 39 pp.
`CODEN: PIXXD2
`Patent·
`Japanese
`1
`
`KIND DATE
`
`APPLICATION NO.
`
`DATE
`
`A1
`
`20000413
`
`WO 1999-JP5298
`
`19990928
`
`IE, IT, LU, MC, NL,
`
`PATENT NO.
`wo 2000020033
`W:
`CA, US
`RW: AT, BE, CH, CY, DE, DK, ES, FI, FR, GB, GR,
`PT, SE
`19990928
`EP 1999-944874
`20010801
`A1
`EP 1120120
`R: AT, BE, CH, DE, DK, ES, FR, GB, GR,
`IT, LI, LU, NL, SE, MC, PT,
`IE, FI
`JP 2000178204
`JP 2000191518
`PRIORITY APPLN. INFO.:
`
`JP
`JP
`wo
`MARPAT 132:270098
`OTHER SOURCE(S):
`AB
`The invention relates to tablets immediately disintegrating in the oral
`cavity which contain a phosphodiesterase inhibitor having an effect of
`ameliorating erectile dysfunction and a process for producing the same;
`and tablets immediately disintegrating in the oral cavity which contain a
`hardly sol. drug and show an improved soly.; and a process for producing
`the same. Namely, tablets immediately disintegrating in the oral cavity
`which contain a cyclic GMP phosphodiesterase inhibitor [e.g. sildenafil]
`and saccharides and process for producing the same; and a process for
`producing tablets immediately disintegrating in the oral cavity which
`comprises dissolving the hardly sol. drug together with a surfactant
`and/or a water-sol. polymer in an org. solvent or an aq. org. solvent,
`mixing saccharides with a molded matter obtained by coating a filler or
`granulating together with a filler, adding an org. solvent, water or an
`aq. org. solvent thereto, kneading the resultant mixt. and then
`compression molding the same.
`263392-02-5 263392-03-6
`(Uses)
`RL: THU (Therapeutic use); BIOL (Biological study); USES
`(tablets immediately disintegrating in the oral cavity)
`263392-02-5 CAPLUS
`Pyrazino[l',2' :1,6]pyrido[3,4-b]indole-1,4-dione, 6-(1,3-benzodioxol-5-yl)-
`2,3,6,7,12,12a-hexahydro-2-methyl-, (6S)-
`(9CI)
`(CA INDEX NAME)
`
`A2
`A2
`
`20000627
`20000711
`
`JP 1999-276133
`JP 1999-276134
`1998-282378
`A
`1998-295947
`A
`1999-JP5298 W
`
`19990929
`19990929
`19981005
`19981019
`19990928
`
`IT
`
`RN
`CN
`
`Absolute stereochemistry.
`
`Prepared by Toby Port, STIC, Biotech Library 308-3534
`
`INTELGENX 1024, pg. 472
`
`

`
`Cook pct/us00/11129
`
`Page 117
`
`Me 1
`, N/ ~~~~--r~~,)
`l (N~j" .. A/
`/~.: Ol)
`
`,
`:
`:
`
`I
`0
`
`N
`H
`
`0
`
`0
`
`RN
`CN
`
`263392-03-6 CAPLUS
`Pyrazino[l',2':1,6]pyrido[3,4-b]indole-1,4-dione, 6-(1,3-benzodioxol-5-yl)-
`2,3,6,7,12,12a-hexahydro-2,3-dimethyl-, (3S,6S)-
`(9CI)
`(CA INDEX NAME)
`
`Absolute stereochemistry.
`
`REFERENCE COUNT:
`
`28
`
`THERE ARE 28 CITED REFERENCES AVAILABLE FOR THIS
`RECORD. ALL CITATIONS AVAILABLE IN THE RE FORMAT
`
`L12 ANSWER 33 OF 37
`ACCESSION NUMBER:
`DOCUMENT NUMBER:
`TITLE:
`
`INVENTOR ( S) :
`PATENT ASSIGNEE(S):
`SOURCE:
`
`DOCUMENT TYPE:
`LANGUAGE:
`FAMILY ACC. NUM. COUNT:
`PATENT INFORMATION:
`
`CAPLUS COPYRIGHT 2002 ACS
`1999:753072 CAPLUS
`131:346565
`Combination of phentolamine and cyclic GMP
`phosphodiesterase inhibitors for the treatment of
`sexual dysfunction
`Estok, Thomas Mark
`Schering Corporation, USA
`PCT Int. Appl., 104 pp.
`CODEN: PIXXD2
`Patent
`English
`1
`
`DATE
`APPLICATION NO.
`KIND DATE
`PATENT NO.
`---------------
`--------
`---------------
`--------
`wo 1999-US7046
`wo 9959584
`19990517
`Al
`19991125
`W: AE, AL, AM, AT, AU, AZ, BA, BB, BG, BR, BY, CA, CH, CN, cz, DE,
`OK, EE, ES, FI, GB, GD, GE, HR, HU,
`ID, IL, IN, IS, JP, KG, KR,
`KZ, LC, LK, LR, LT, LU, LV, MD, MG, MK, MN, MX, NO, NZ, PL, PT,
`
`Prepared by Toby Port, STIC, Biotech Library 308-3534
`
`INTELGENX 1024, pg. 473
`
`

`
`Cook pct/us00/11129
`
`Page 118
`
`RO, RU, SE, SG, SI, SK, SL, TJ, TM, TR, TT, UA, US, UZ, VN, YU,
`ZA, AM, AZ, BY, KG, KZ, RU, TJ, TM
`RW: GH, GM, KE, LS, MW, SD, SL, SZ, UG, ZW, AT, BE, CH, CY, DE, DK,
`ES, FI, FR, GB, GR, IE, IT, LU, MC, NL, PT, SE, BF, BJ, CF, CG,
`CI, CM, GA, GN, GW, ML, MR, NE, SN, TD, TG
`19990517
`A1
`19991206
`AU 1999-40685
`AU 9940685
`us 1998-81640
`PRIORITY APPLN. INFO.:
`A 19980520
`us 1998-82977
`A2 19980521
`us 1998-106517
`A 19980629
`WO 1999-US7046 w 19990517
`A method of treating sexual dysfunction comprising administering a
`therapeutically effective amt. of a combination of phentolamine and cGMP
`PDE inhibitor (e.g. sildenafil), as well as pharmaceutical compns. and
`kits useful in those methods, are disclosed.
`171596-29-5 171596-40-0
`RL: BAC (Bio1ogic~l activity or effector, except adverse); BSU (Biological
`study, unclassified); THU (Therapeutic use); BIOL (Biological study); USES
`(Uses)
`(phentolamine and cyclic GMP phosphodiesterase inhibitors for the
`treatment of sexual dysfunction)
`171596-29-5 CAPLUS
`Pyrazino[1',2':1,6)pyrido[3,4-b)indole-1,4-dione, 6-(1,3-benzodioxol-5-yl)-
`2,3,6,7,12,12a-hexahydro-2-methyl-, (6R,12aR)-
`(9CI)
`(CA INDEX NAME)
`
`AB
`
`IT
`
`RN
`CN
`
`Absolute stereochemistry. Rotation (+).
`
`RN
`CN
`
`171596-40-0 CAPLUS
`Pyrazino[1',2':1,6)pyrido[3,4-b]indole-1,4-dione, 6-(1,3-benzodio~ol-5-yl)-
`2,3,6,7,12,12a-hexahydro-2,3-dimethyl-, (3S,6R,12aR)-
`(9CI)
`(CA INDEX
`NAME)
`
`Absolute stereochemistry. Rotation (+).
`
`Prepared by Toby Port, STIC, Biotech Library 308-3534
`
`INTELGENX 1024, pg. 474
`
`

`
`Cook pct/us00/11129
`
`Page 119
`
`REFERENCE COUNT:
`
`9
`
`THERE ARE 9 CITED REFERENCES AVAILABLE FOR THIS
`RECORD. ALL CITATIONS AVAILABLE IN THE RE FORMAT
`
`L12 ANSWER 34 OF
`ACCESSION NUMBER:
`DOCUMENT NUMBER:
`TITLE:
`AUTHOR($):
`CORPORATE SOURCE:
`SOURCE:
`
`37 CAPLUS COPYRIGHT 2002 ACS
`1999:393867 CAPLUS
`131:193591
`IC-351 ICOS Corp
`Norman, Peter
`Norman Consulting, Bucks, SL1 8JW, UK
`Current Opinion in Central & Peripheral Nervous System
`Investigational Drugs (1999), 1(2), 268-271
`CODEN: COCDFA;
`ISSN: 1464-844X
`Current Drugs Ltd.
`PUBLISHER:
`Journal; General Review
`DOCUMENT TYPE:
`English
`LANGUAGE:
`AB
`A review with 35 refs.
`IC-351 (GF-196960), an inhibitor of
`phosphodiesterase 5
`(PDE5) from ICOS Corp, is in phase II trials for the
`treatment of mild to moderate erectile dysfunction (ED)
`[274568],
`[296831]. A randomized, placebo-controlled, crossover study assessed the
`safety and physiol. effects of IC-351 in patients with ED [274568].
`Enrollment was completed in Apr. 1998 [284935]. Results from the trial
`showed that IC-351 demonstrated significant benefit over placebo [311566].
`In Oct. 1998, ICOS entered into a joint venture agreement with Eli Lilly
`for the development and commercialization of IC-351 for the treatment of
`sexual dysfunction [300118],
`[310951].
`IC-351 is also in development for
`the treatment of female sexual dysfunction [321995].
`In Mar. 1998, the
`company announced that the compd. was in preclin. evaluation for the
`treatment of hypertension [284638]. A collaboration with Glaxo Wellcome
`(GW) was terminated in Mar. 1997 [240438] and intellectual property rights
`were assigned to ICOS. This left ICOS to develop the compds. with
`royalties payable to GW. Although GW reserved the right to pursue its own
`program, it does not appear to be doing so.
`In Feb. 1999 Deutsche Bank
`predicted sales of $200 million in 2002 rising to $400 million in 2003 for
`IC-351 [316821].
`171596-29-5
`RL: ADV (Adverse effect, including toxicity); BAC (Biological activity or
`effector, except adverse); BPR (Biological process); BSU (Biological
`study, unclassified); THU (Therapeutic use); BIOL (Biological study); PROC
`(Process); USES
`(Uses)
`(effect of IC-351 for treatment of mild to moderate erectile
`dysfunction)
`171596-29-5 CAPLUS
`Pyrazino[1',2':1,6)pyrido[3,4-b]indole-1,4-dione, 6-(1,3-benzodioxol-5-yl)-
`2,3,6,7,12,12a-hexahydro-2-methyl-, (6R,12aR)-
`(9CI)
`(CA INDEX NAME)
`
`IT
`
`RN
`CN
`
`Prepared by Toby Port, STIC, Biotech Library 308-3534
`
`INTELGENX 1024, pg. 475
`
`

`
`Absolute stereochemistry. Rotation (+).
`
`Cook pct/us00/11129
`
`Page 120
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