PAGE 2-A
`
`Me
`
`DUPLICATE 44
`
`a novel
`
`L15
`AN
`TI
`
`AU
`cs
`so
`
`DT
`LA
`AB
`
`ANSWER 44 OF 51 CA · COPYRIGHT 1996 ACS
`115:105661 CA
`Inhibition of skin graft rejection in mice by rapamycin:
`immunosuppressive macrolide
`Eng, c. P.; Gullo-Brown, J.; Chang, J. Y.; Sehgal, s. N.
`Wyeth-Ayerst Res., Princeton, NJ, 08543, USA
`Transplant. Proc. (1991), 23(1, Bk. 1), 868-9
`CODEN: TRPPA8; ISSN: 0041-1345
`Journal
`English
`Rapamycin had marked potency over cyclosporin A and a combination of
`the 2 drugs had a synergistic effect in prolonging graft survival
`time in the mouse skin allograft model.
`IT 53123-88-9, Rapamycin
`RL: BIOL (Biological study)
`(skin qraft rejection inhibition by)
`53123-88-9 CA
`Rapamycin (9CI)
`
`RN
`CN
`
`(CA INDEX NAME)
`
`Absolute stereochemistry.
`Double bond geometry as shown.
`
`
`
`

`
`PAGE 1-A
`
`Me
`
`s
`
`PAGE 2-A
`
`Me
`
`DUPLICATE 45
`
`ANSWER 45 OF 51 CA COPYRIGHT 1996 ACS
`114 :i.240620 CA
`MetQods~of inhibiting transplant rejection in mammals'using
`·"f.
`rapamycin and derivatives and prodrugs thereof
`G.,~~ne, Roy
`UK
`Eur. Pat. Appl., 9 pp.
`CODEN: EPXXDW
`901212
`EP 401747'° A2
`R: AT, BE, CH, DE, DK, ES, FR, GB, GR, IT, LI, LU, ~L, SE
`EP 90-110'612 900605
`us 89~362354 890606
`Pat~nt
`English
`Qrgan ai;id tissue transplant rejection in mammals is 1nhibited by
`*·
`
`I.;>
`
`•
`
`;.
`
`•
`
`'
`
`L15
`AN
`TI
`
`IN
`p~ so
`PI
`DS
`AI
`PRAI
`DT
`LA
`AB
`
`
`
`

`
`administration of rapamycin or rapamycin in combination with other
`chemotherapeutic agents for inhibiting transplant rejection, e.g.
`azathioprine, corticosteroids, cyclosporin, and FK506. Rapamycin
`was immunosuppressive and not toxic in rats down to 0.5 mg/kg.
`In
`pigs, the drug was tolerated at 1 mg/kg.
`IT 134035-83-9, Azathioprine-rapamycin mixt.
`134061-14-6, Cyclosporin-rapamycin mixt. 134127-87-0
`, FK506-rapamycin mixt.
`RL: BIOL (Biological study)
`(animal transplant rejection inhibition with)
`134035-83-9 CA
`Rapamycin, mixt. with 6-[(1-methyl-4-nitro-lH-imidazol-5-yl)thio]-lH(cid:173)
`purine (9CI)
`(CA INDEX NAME)
`
`RN
`CN
`
`CM
`
`1
`
`CRN 53123-88-9
`CMF C51 H79 N 013
`CDES *
`
`Absolute stereochemistry.
`Double bond geometry as shown.
`
`PAGE 1-A
`
`R
`
`Me a oo
`
`... /
`
`OMe
`
`Me
`
`R
`
`El
`
`Me
`
`OH
`
`Me
`
`IE
`
`..
`hO
`
`~o
`
`Me
`
`IE
`
`~ s
`
`
`
`

`
`PAGE 2-A
`
`Me
`
`CM
`
`2
`
`CRN a46-86-6
`CMF C9 H7 N7 02 S
`
`RN
`CN
`
`134061-14-6 CA
`~apamycin, mixt. with cyclosporin (9CI)
`
`(CA INDEX NAME)
`
`CM
`
`1
`
`fRN 79217-60-0
`CMF Unspecified
`CCI MAN
`*** STRUCTURE DIAGRAM IS NOT AVAILABLE ***
`CM
`
`2
`
`CRN 53123-88-9
`CMF C51 H79 N 013
`CDES *
`Absolute stereochemistry.
`Double bond geometry as shown.
`
`
`
`

`
`PAGE 1-A
`
`l1e
`
`R
`
`R a OH
`
`_,./
`
`OMe
`
`Me
`
`El
`
`Me
`
`OH
`
`Me
`
`Meo·
`
`~o
`
`Me
`
`IE
`
`~ s
`
`PAGE 2-A
`
`Me
`
`RN
`CN
`
`134127-87-0 CA
`Rapamycin, mixt. with [3S-[3R*[E(1S*,3S*,4S*)],4S*,5R*,8S*,9E,12R*,1
`4R*,15S*,16R*,18S*,19S*,26aR*]]-5,6,8,11,12,13,14,15,16,17,18,19,24,
`25,26,26a-hexadecahydro-5,19-dihydroxy-3-(2-(4-hydroxy-3-
`methoxycyclohexyl)-1-methylethenyl]-14,16-dimethoxy-4,10,12,18-
`tetramethyl-8-(2-propenyl)-15,19-epoxy-3H-pyrido[2,l-
`c] (l,4]oxaazacyclotricosine-1,7,20,21(4H,23H)-tetrone (9CI)
`INDEX NAME)
`
`(CA
`
`CM
`
`1
`
`CRN 104987-11-3
`CMF C44 H69 N 012
`CDES *
`
`Absolute stereochemistry.
`
`
`
`

`
`Double bond geometry as shown.
`
`Meo
`
`Me
`
`R
`
`s
`
`Me
`
`MeO
`
`OMe
`
`CM
`
`2
`
`CRN 53123-88-9
`CMF CSl H79 N 013
`CDES *
`
`Absolute stereochemistry.
`double bond geometry as shown.
`
`
`
`

`
`PAGE 1-A
`
`Me
`
`Me
`
`OH
`
`Me
`
`Meo
`
`~o
`
`IE E
`;;;::,
`
`s
`
`Me
`
`PAGE 2-A
`
`Me
`
`IT 53123-88-9, Rapamycin
`RL: BIOL (Biological study)
`(immunosuppressant, animal transplant rejection
`inhibition with)
`53123-88-9 CA
`Rapamycin (9CI)
`
`(CA INDEX NAME)
`
`RN
`CN
`
`Absol~te stereochemistry.
`Double bond geometry as shown.
`
`
`
`

`
`PAGE 1-A
`
`Me
`
`0
`
`R
`
`a OH
`
`_,,/
`
`OMe
`
`Me
`
`Me
`
`Meo
`
`s
`
`Me
`
`PAGE 2-A
`
`Me
`
`L15
`AN
`TI
`AU
`cs
`so
`
`DT
`LA
`AB
`
`DUPLICATE 46
`
`ANSWER 46 OF 51 CA COPYRIGHT 1996 ACS
`101:222224 CA
`Activity ot1rapa,mycin (AY-22,9~9) against transplanted tumors
`~pg, C •. P.;.sehgal, S. N.;,Vez1na, Claude
`Dep:"' Microbtiol., Ayerst Res. Lab., Montreal, PQ, H3C 3Jl, Can.
`J. 1\lltibi'et. (1984), 37(10), 1231-1
`CODER: JANTAJ; ISSN: 0021-8820
`Jourr.lal'
`English
`~5312'3-88:-9] exhibits activity against several
`Rapa'-111ycin
`as'cites ·'and~solid transplantable tumors; it is
`.
`sl~ghtly apt:i ve to inactive·.· against leukemias. On a wt. , basis,
`
`rapamycin" was (less active than 5-f luorouracil, cyclophosphamide 1: and·
`adriamycin/'but~lti::apamycin's maximal activity against Colon 3:8
`
`
`
`

`
`tumor was similar to that of 5-fluorouracil
`[51-21-8] and
`cyclophosphamide
`[50-18-0].
`Its activity was such that it
`significantly inhibited tumor growth at any
`stage of development.
`In the active dose range, rapamycin appeared
`In the Colon 38 tumor
`less toxic than the other drugs.
`model, rapamycin at a given dose exhibited the same activity when
`administered i.p., i.v., i.m. and s.c., upon oral administration,
`its activity was reduced but not abolished. Rapamycin was
`compatible with 5-fluorouracil and cyclophosphamide. The sequential
`treatment 5-fluorouracil-rapamycin-cyclophosphamide was
`superior to the sequence 5-fluorouracil-adriamycin
`[23214-92-8]-cyclophosphamide in protecting Colon 38 tumor
`-bearing mice. 29-Demethoxyrapamycin
`[83482-58-0]
`exerted only marginal activity against P388 lymphocytic leukemia; it
`was inactive against B16 melanocarcinoma and Colon 38 solid
`tumor.
`IT 83482-58-0
`RL: BAC {Biological activity or effector, except adverse); THU
`{Therapeutic use); BIOL {Biological study); USES (Uses)
`{neoplasm-inhibiting activity of)
`83482-58-0 CA
`Rapamycin, 32-demethoxy- {9CI)
`
`{CA INDEX NAME)
`
`RN
`CN
`
`Absolute stereochemistry.
`Double bond geometry as shown.
`
`Me
`
`0
`
`PAGE 1-A
`
`R
`
`a oo
`
`,,./
`
`OMe
`
`R
`
`Me
`
`Me
`
`Me
`
`OH
`
`Me
`
`s
`
`
`
`

`
`PAGE 2-A
`
`Me
`
`IT 53123-88-9
`RL: BAC (Biological activity or effector, except adverse); THU
`(Therapeutic use); BIOL (Biological study); USES (Uses)
`(neo.plasm-inhibitinq activity of, drug
`~omblnatl.ons with)
`53123-88-9 ~CA
`·Rapamycin (9CI)
`·'
`Absolute stereochemistry.
`~
`Double bond geo~etry as shown.
`
`RN
`CN
`
`.,t.·t-'[""
`
`(CA INDEX NAME)
`
`PAGE 1-A
`
`Me
`
`R
`
`El
`
`Me
`
`s
`
`Me
`
`Meo·
`
`IE
`
`~ s
`
`OH
`
`Me
`
`
`
`

`
`PAGE 2-A
`
`Me
`
`DUPLICATE 47
`
`L15 ANSWER 47 OF 51 CA COPYRIGHT 1996 ACS
`AN
`101:203757 CA
`results of
`TI
`current NCI preclinical antitumor screening in vivo:
`tumor panel screening, 1976-1982, and future directions
`AU Venditti, John M.; Wesley, Robert A.; Plowman, Jacqueline
`CS Div. Cancer Treat., Natl. Cancer Inst., Bethesda, MD, 20205, USA
`SO
`Adv. Pharmacol. Chemother. (1984), 20, 1-20
`CODEN: AVPCAQ; ISSN: 0065-3144
`Journal
`English
`Experiences in preclin. antitumor agent screening by the Division of
`Cancer Treatment of the NCI are summarized. Efficacies of various
`tumor models in uncovering agents not selected by Ll210 are
`demonstrated.
`IT 53123-88-9
`RL: BAC (Biological activity or effector, except adverse); THU
`(Therapeutic use); BIOL (Biological study); USES (Uses)
`(neoplasm inhibition by)
`53123-88-9 CA
`Rapamycin (9CI)
`
`DT
`LA
`AB
`
`RN
`CN
`
`(CA INDEX NAME)
`
`Absolute stereochemistry.
`Double bond geometry as shown.
`
`
`
`

`
`PAGE 1-A
`
`Me
`
`R
`
`R o:OH
`
`_,,/
`
`OMe
`
`s
`
`Me
`
`OH
`
`Me
`
`Meo
`
`/'o
`
`Me
`
`IE
`
`~ s
`
`PAGE 2-A
`
`Me
`
`DUPLICATE" 48
`
`L15 ANSW,•ER 48 OF 51 CA COPYRIGHT 1996 ACS
`~9:G3770 CA
`AN
`TI
`Human brainitumor xenografts in nude mice as a chemotherapy model
`AU Houchens, David P.; Ovejera, Artemio A.; Riblet, Sylva M.; Slagel,
`Donald E. 1
`CS Battelle Mem. Inst., Columbus, OH, 43201, USA
`SO
`Eur. J. Cancer Clin. Oncol. (1983), 19(6), 799-805
`€ODEN: EJeobs; ISSN: 0277-5379
`Journal '
`English
`Two human brain tumors which were previously established
`in ~ude mice were used to det. antitumor efficacy of various
`tber'p~u·tic r agents. These tumors were a
`meciullobl~stoma (TE-671) and a glioma (U-251) with mass-doubling
`times bf ·3. 5 and 5. 5 days, resp. , as s. c. implants in nude m'i·ce.
`
`DT
`LA
`AB
`
`
`
`

`
`Intracranial tumor challenge was accomplished by
`inoculating tissue culture-grown cells of either tumor
`into the right cerebral hemisphere to a depth of 3 mm. Groups of
`mice which had been inoculated with tumor were
`treated with various doses and schedules of antineoplastic
`compds. by the i.p. route. A new drug (rapamycin
`[
`53123-88-9]) was very effective against the U-251
`tumor. This model system should prove valuable in assessing
`the effects of various chemotherapeutic modalities against brain
`tumors.
`
`DUPLICATE 49
`
`L15 ANSWER 49 OF 51 CA COPYRIGHT 1996 ACS
`AN
`98:22284 CA
`TI Anticancer pharmaceuticals containing rapamycin and picibanil
`PA Ayerst, McKenna and Harrison Inc., Japan
`so
`Jpn. Kokai Tokkyo Koho, 4 pp.
`CODEN: JKXXAF
`821001 Showa
`JP 57159716 A2
`PI
`JP 82-35697 820305
`AI
`PRAI US 81-241867 810309
`DT
`Patent
`LA
`Japanese
`(53123-88-9] and
`AB
`Pharmaceuticals contg. rapamycin (I)
`(39325-01-4] are neoplasm
`picibanil (II)
`inhibitors for treatment of lymphocytic leukemia,
`colon neoplasm, mammary cancer, melanoma, etc.
`Thus, an injection was prepd. contg. I, II, butylated
`hydroxyanisole, anhyd. EtOH, Cremophor EL and H20. Combinations of
`I and II were more effective than I or II alone in
`inhibiting the growth of lymphatic leukemia cells in mice.
`
`L15
`AN
`TI
`
`IN
`PA
`so
`
`PI
`PRAI
`DT
`LA
`AB
`
`DUPLICATE 50
`
`ANSWER 50 OF 51 CA COPYRIGHT 1996 ACS
`93:88940 CA
`Pharmaceutical compositions based on rapamycin for treatment of
`cancerous tumors
`Sehgal, Surendra Nath; Vezina, Claude
`Ayerst, McKenna and Harrison Ltd., Can.
`Belg., 12 pp.
`CODEN: BEXXAL
`BE 877700 800114
`us 78-957626 781103
`Patent
`French
`[53123-88-9] significantly prolonged the
`Rapamycin (I)
`life span of lab. animals bearing tumors and decreased the
`size of the tumors. The ratio of the av. survival in days
`of mice bearing lymphatic leukemia P-388 and treated with
`I
`(9 daily i.p. 12.5-400 mg/kg injections) to that of nontreated
`In rats with mammary tumors,
`leukemic mice was 1.28-1.46.
`the ratio of the av. wt. of tumors at the beginning of
`treatment to that of tumors in nontreated animals
`was .10-.29.
`I may also be combined with presently used
`antineoplastic agents such as alkylating agents, antimetabolites,
`
`
`
`

`
`estrogens, etc.
`IT 53123-88-9
`RL: BAC (Biological activity or effector, except adverse)'; THU
`(Therapeutic use); BIOL (Biological study); USES (Uses)
`(neoplasm inhibition by)
`53123-88-9 CA
`Rapamycin (9CI)
`
`(CA INDEX NAME)
`
`RN
`CN
`
`PAGE 1-A
`
`a.
`
`_,./
`
` OH
`
`OMe
`
`Me
`
`Absolute stereochemistry.
`Double bond geometry as shown.
`
`Me
`
`Me
`
`Meo
`
`Me
`
`IE
`
`IE
`
`s ~
`
`OH
`
`Me
`
`'
`PAGE 2-'A
`
`·Me
`
`L15 ANSWER 51 OF 51 CA COPYRIGHT 1996 ACS
`AN
`90:351 CA
`TI
`Rapamycin (AY-22,989), a new antifungal antibiotic.
`III.
`.and in vivo evaluation
`~4
`Ba~1?r, H.; Sidorowicz, A.; Sehgal, s. N.; Vezina, Cl~;ude
`>'"
`
`AU
`
`DUPLICATE 51
`
`In vitro
`
`
`
`

`
`DT
`LA
`AB
`
`cs Dep. Microbiol., Ayerst Res. Lab., Montreal, Que., Can.
`SO
`J. Antibiot. (1978), 31(6), 539-45
`CODEN: JANTAJ; ISSN: 0021-8820
`Journal
`English
`[53123-88-9], a new
`The activity of rapamycin (I)
`anti-Candida antibiotic, was not affected by pH values between 6 and
`8; at pH 4, however activity was abolished. The min.
`inhibitory concn. of I did not vary drastically with the
`size of inoculum. Serum binding was extensive. Serum levels
`obtained in mice were higher after s.c. injection than after oral
`administration.
`I cured systemic candidosis in mice.
`I and
`amphotericin B, administered at 1, 4 and 24 h after
`infection, gave approx. the same percent survival after 30
`days of observation. When the above treatment was
`extended by an addnl. daily treatment of 6 days, I by the
`s.c. route yielded a higher percentage of survival than either I or
`amphotericin B, administered orally, after a 30-day observation
`period. Vaginal candidosis in female rats was treated
`efficiently (91% cure) by I administered orally. No increase of
`resistance of c. albicans was obsd. during treatment.
`
`FILE 'CAOLD' ENTERED AT 11:54:57 ON 26 APR 96
`USE IS SUBJECT TO THE TERMS OF YOUR CUSTOMER AGREEMENT
`COPYRIGHT (C) 1996 AMERICAN CHEMICAL SOCIETY (ACS)
`
`FILE COVERS 1957-1966
`FILE LAST UPDATED:
`30 OCT 91 (910803/ED)
`
`To help control your online searching costs, consider using the
`HCAOLD File when conducting SmartSELECT searches with large
`numbers of terms.
`
`=> s 12
`L16
`
`0 L2
`
`=> f il casreact
`FILE 'CASREACT' ENTERED AT 11:57:34 ON 26 APR 96
`USE IS SUBJECT TO THE TERMS OF YOUR CUSTOMER AGREEMENT
`COPYRIGHT (C) 1996 AMERICAN CHEMICAL SOCIETY (ACS)
`
`FILE CONTENT:1985-1996 (VOL 102 ISS 1 - VOL 124 ISS 17
`
`>>> Several important enhancements to CASREACT functional group
`<<<
`searching were introduced. Enter HELP FGA or HELP FGC for more <<<
`>>>
`information.
`>>>
`<<<
`
`=> d que stat
`L17
`
`STR
`
`
`
`

`
`NODE ATTRII;mTES:
`DEFAULT MLEVEL IS ATOM
`DEFAULT ECLEVEL IS LIMITED
`
`GRAPH ATTRIBUTES:
`RING(S) ARE ISOLATED OR EMBEDDED
`NVMBER O~·NODES IS 27
`
`STEREO ATTRIBUTES: NONE
`Ll8
`· J::a,:: SEA · FILE=CASREACT SSS FUL Ll 7
`ot
`
`1111"'\4'11'1"'~
`
`74 REACTIONS)
`
`366 VERIFIED
`100.0% DONE
`SEARCH T~ME: 00.00.04
`
`74 HIT RXNS
`
`.11 DOCS
`
`=> d 1-11 bib abs fhit
`
`Ll8 ANSWER 1 OF 11 CASREACT COPYRIGHT 1996 ACS
`f22~314366 CASREACT
`AN
`TI
`c-22 ring stabilized rapamycin derivatives
`
`
`
`

`
`IN Nelson, Frances c.
`PA American Home Products Corp., USA
`SO U.S., 22 pp.
`CODEN: USXXAM
`950207
`US 5387680 A
`US 93-105090 930810
`Patent
`English
`MARPAT 122:314360
`This invention provides C-22 substituted rapamycin derivs. and
`pharmaceutically acceptable salts thereof which are useful for
`inducing immunosuppression.
`
`PI
`AI
`DT
`LA
`OS
`AB
`
`RX(l) OF 20
`
`A + B ===> C •••
`
`* STRUCTURE DIAGRAM TOO LARGE FOR DISPLAY - AVAILABLE VIA OFFLINE PRINT *
`
`PAGE 2-A
`
`Me
`
`A
`
`B
`
`(1) >
`
`* STRUCTURE DIAGRAM TOO LARGE FOR DISPLAY - AVAILABLE VIA OFFLINE PRINT *
`PAGE 2-A
`
`Me
`
`c
`YIELD 27%
`
`RX(l)
`
`RCT A 155435-45-3
`
`STAGE(l)
`
`
`
`

`
`RGT D 4111-54-0 LiN(Pr-i)2
`SOL 109-99-9 THF, 110-82-7 Cyclohexane
`
`STAGE(2)
`RCT B 333-27-7
`PRO C 163389-48-8
`NTE KEY STEP
`
`Ll8
`AN
`TI
`
`AU
`cs
`so
`
`DT
`LA
`~B
`
`RX(12) OF 58
`
`.' .. R + 2 AC ===> AB + AD ...
`
`ANSWER 2 OF 11 CASREACT COPYRIGHT 1996 ACS
`122:105481 CASREACT
`Synth~tic,modifications of ascomycin. I. Chemoselective removal.of
`the cyclohexyl residue of ascomycin
`Zimmer, Reinhold; Grassberger, Maximilian A.; Baumann, Karl; Schulz,
`Gerhard; Haid!, Ewald
`·
`DeP.artment Dermatology, Sandoz Forschungsinstitut, Vienna, A-123·5,
`Afis*'tria
`IA
`retr,anedron,, (1994), 50(48), 13655-70
`CODEN: TETRAB; ISSN: 0040-4020
`Journal
`English
`~n effici~I')t semisynthetic prepn. of des-28-(qyclohexyl)methylene-28-
`dxo-ascomycin derivs. starting from 24,33-0-bis(tert~
`butyld;imetl'}ylsilyl)ascomycin is described. Th~ strategy for prepg.
`2'.8-o,xo!.a~omycin derivs. involves the redn. of c-22 carb<\nyl grpup,
`·'followed by~.5-endo-cyclization of the resulting, c-22~alc. ·with ~the
`F
`,
`·~- •
`~
`C-19/C-20 ·clouble bond using an oxymercuration .reaction; ozonoly.sis
`of the C-2~'1/C-29 double bond and regeneration of the.C-19/C-20
`dotJ.b'*e bond. Further, the 20-mercury-substituted ascomycin derivs.
`could be re'duced in the corresponding metal free cyclic ether's wu.sing
`n-Bu3SnH.
`
`•
`
`•
`
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`
`•
`
`"!!· ..
`
`
`
`

`
`-----~
`
`Me Me
`Ac \I
`/Si"-.__
`0
`H Bu-t
`
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`H
`Hg ..
`
`Cl
`
`........___
`
`0
`
`OMe
`
`H
`
`MeO
`
`R
`
`Me
`
`* STRUCTURE DIAGRAM TOO LARGE FOR DISPLAY -
`
`AVAILABLE VIA OFFLINE PRINT *
`
`PAGE 1-B
`
`OH
`
`AC
`
`Me
`
`* STRUCTURE DIAGRAM TOO LARGE FOR DISPLAY -
`
`AVAILABLE VIA OFFLINE PRINT *
`
`
`
`

`
`OH
`
`AC
`
`(12} >
`
`Me
`
`0
`I
`
`0
`
`H
`
`N
`
`PAGE 1-B
`
`Ac
`
`OH
`
`PAGE 1-A
`
`Me
`
`R
`H
`
`0
`
`OH
`
`0
`
`0
`
`OMe
`
`H
`
`Me
`
`OMe
`
`
`
`

`
`---.
`
`OH
`
`PAGE 1-B
`
`Me
`
`AB
`YIELD 22%
`
`Me
`'-.....0
`
`o
`
`t-Bu
`/
`'-.....
`Si
`/\
`Me Me
`
`Me Me
`\/
`Si
`'-.....
`
`/
`0
`
`Bu-t
`
`Me
`
`AD
`YIELD 42%
`
`RX(12)
`
`RCT
`RGT
`PRO
`SOL
`
`R 160466-87-5, AC 160549-89-3
`Z 7647-01-0 HCl
`AB 160466-90-0, AD 160466-93-3
`7732-18-5 Water, 75-05-8 MeCN
`
`
`
`

`
`L18 ANSWER 3 OF 11 CASREACT COPYRIGHT 1996 ACS
`AN
`122:80964 CASREACT
`TI
`A novel ring contraction of rapamycin
`Ne l,son, Frances c. ; Stachel, Shawn J. ; Mattes, James F.
`AU
`CS
`Chem. Sci.,, Wyeth-Ayerst Res., Princeton, NJ, 08543-8000, USA
`SO
`Tetra:ti'edron Lett. (1994), 35(41), 7557-60
`CODEN: TELEAY; ISSN: 0040-4039
`Journal
`English
`
`OT
`LA
`GI
`
`OMe
`
`Me- ....
`
`Me
`
`OH
`
`0 Me
`
`OH
`
`~o 0
`
`OMe
`
`Meo·
`
`Me
`
`/;/
`
`/;/
`
`/;/
`
`Me
`
`Me
`
`I
`
`AB
`
`The first synthesis of a novel ring contracted analog of rapamycin,
`I, is reported. The synthesis employs a stereoselective and
`regioselective redn. of the C(27) ketone followed by a 1,3-acyl
`migration.
`
`RX(l} OF 13
`
`A + 2 B ===> C .••
`
`* STRUCTURE DIAGRAM TOO LARGE FOR DISPLAY - AVAILABLE VIA OFFLINE PRINT *
`
`
`
`

`
`PAGE 2-A
`
`Me
`
`A
`
`Cl Et
`*\I
`_,.......si--........
`Et
`
`Et
`
`2 B
`
`(1) >
`
`* STRUCTURE DIAGRAM TOO LARGE FOR DISPLAY - AVAILABLE VIA OFFLINE PRINT *
`PAGE 2-A
`
`Me
`
`c
`YIELD 84%
`
`RX(l)
`
`RCT
`RGT
`PRO
`SOL
`
`A 53123-88-9, B 994-30-9
`D 288-32-4 lH-Imidazole
`c 155435-45-3
`68-12-2 DMF
`
`AU
`
`Ll8 ANSWER 4 OF 11 CASREACT COPYRIGHT 1996 ACS
`AN
`122:80952 CASREACT
`TI Manipulation of the Rapamycin Effector Domain. Selective
`Nucleophilic Substitution of the C7 Methoxy Group
`Luengo, Juan I.; Konialian-Beck, Arda; Rozamus, Leonard W.; Holt,
`Dennis A.
`CS Department of Medicinal Chemistry, SmithKline Beecham
`Pharmaceuticals, King of Prussia, PA, 19406, USA
`J. Org. Chem. (1994) , 59 (22) , 6512-13
`CODEN: JOCEAH; ISSN: 0022-3263
`Journal
`English
`CJACS-IMAGE; CJACS
`The C7 methoxy group in rapamycin has been found to be labile toward
`acidic reagents. Conditions have been developed to replace this
`group with a no. of different nucleophiles, such as ales., thiols,
`
`SO
`
`OT
`LA
`OS
`AB
`
`
`
`

`
`and electron-rich arom. systems. This novel, efficient
`transformation allows the selective manipulation of the rapamycin
`effector do~ain.
`
`RX(l) OF 16
`
`A ===> B
`
`* STRUCTURE DIAGRAM TOO LARGE FOR DISPLAY -
`
`AVAILABLE VIA OFFLINE PRINT *
`
`PAGE 2-A
`
`Me
`
`A
`
`(1) >
`
`*STRUCTURE DIAGRAM TOO LARGE FOR DISPLAY -
`
`AVAILABLE VIA OFFLINE PRINT *
`
`PAGE 2-A
`
`Me
`
`B
`
`RX(l)
`
`RCT
`PRO
`CAT
`SOL
`NTE
`
`A 53123-88-9
`If 1571S'2-37-1
`1:04-15-4 'fsOH
`67-56-1 MeOH
`(2:1, REACTANT:PRODUCT)
`
`Ll8
`AN
`TI
`AU
`cs
`so
`
`DT
`LA
`AB
`
`ANSWER 5 OF 11 CASREACT COPYRIGHT 1996 ACS
`121:255475 CASREACT
`Acid catalyzed fuhctionalization of rapamycin
`Grinfeld, klexander A.; Caufield, Craig E.; Schiksnis, Robert A.;
`Mattes, Jp.if~s F.; Chan, Ke],vin W.
`Department '~hemfcal Sciences, Wyeth-Ayerst Research, Inc.,
`Princeton, ~J, p8543-8000, USA
`Tetrah"edron Let't. (1994), 35(37), 6835-8
`CODEN: TELEAY; ISSN: 0040-4039
`J'ou~nal
`English
`Rapamycin rapidly undergoes demethoxylation at C-7 in the presence
`
`
`
`

`
`of Lewis acids (BF3.Et20, SnC14 etc.) to give a highly stabilized
`carbocation. This intermediate gives a tetraene or is trapped by
`nucleophiles to give functionalized trienes. Several examples of
`the substitution reaction and elaboration of the reaction scheme are
`reported.
`
`RX(l) OF 8
`
`2 A + 2 B ===> C + D
`
`HO~OyH
`
`OH
`
`2 A
`
`* STRUCTURE DIAGRAM TOO LARGE FOR DISPLAY -
`
`AVAILABLE VIA OFFLINE PRINT *
`PAGE 2-A
`
`B
`
`Me
`
`* STRUCTURE DIAGRAM TOO LARGE FOR DISPLAY -
`
`AVAILABLE VIA OFFLINE PRINT *
`
`PAGE 2-A
`
`Me
`
`B
`
`(1) >
`
`* STRUCTURE DIAGRAM TOO LARGE FOR DISPLAY -
`
`AVAILABLE VIA OFFLINE PRINT *
`
`
`
`

`
`c
`YIELD 40%
`
`Me
`
`* STRUCTURE DIAGRAM TOO LARGE FOR DISPLAY -
`
`AVAILABLE VIA OFFLINE PRINT''*
`PAGE 2~A
`
`',.I
`
`D
`YIELD 40%
`
`RX(l)
`
`RCT
`RGT
`"" PRO
`SOL
`
`A 56-81-5, B 53123-88-9
`E 7646-78-8 SnC14
`c• 158615-16-8, D 158615-19-1
`109-99-9 THF
`
`L18 ANSWER 6 OF 11 CASREACT COPYRIGHT 1996 ACS
`AN
`121:35093 CASREACT
`Lipase meqf~ated hydrolysis of rapamycin 42-hemisuccinate berizyl ;anµ
`TI
`methyl es~ers
`Ada~czky, Maciej; Gehler, John c.; Mattingly, Phillip G.
`AU
`cs Abbott 'Diagn. Div., Abbott Lab., Abbott Park, IL, 60064, USA
`SO
`Tet:r:,~hedron~ Lett. ( 1994) , 35 (7) , 1019-22
`CODEN: TETIEAY; ISSN: 0040-4039
`,Journ~l
`English
`
`DT
`LA
`GI
`
`
`
`

`
`Me
`
`I
`
`AB
`
`Benzyl and Me esters of rapamycin 42-hemisuccinate (I, R = CH2Ph,
`Me) were hydrolyzed under very mild conditions to the rapamycin
`hemisuccinate I
`(R = H) using lipase from Pseudomonas sp. This
`selective deprotection was performed on a
`.gtoreq.100 mg scale for
`both esters resulting in 50% isolated yield from the Me ester and
`29% from the benzyl ester of the desired acid.
`
`RX(l) OF 2
`
`2 A ===> B + C
`
`* STRUCTURE DIAGRAM TOO LARGE FOR DISPLAY -
`
`A
`
`Me
`
`AVAILABLE VIA OFFLINE PRINT *
`PAGE 2-A
`
`* STRUCTURE DIAGRAM TOO LARGE FOR DISPLAY -
`
`AVAILABLE VIA OFFLINE PRINT *
`PAGE 2-A
`
`A
`
`Me
`
`
`
`

`
`(1) >
`
`... :.
`* STRUCTURE DIAGRAM TOO LARGE FOR DISPLAY - AVAILABLE VIA OFFLINE PRINT *
`
`, PAGE 2-A
`
`Me
`
`B
`YIELD 68%
`
`* STRUCTURE DIAG'RAM TOO LARGE FOR DISPLAY -
`
`AVAILABLE VIA OFF.Lr:t!E P~INT *
`
`PAGE 2-A
`
`Me
`
`c~
`YIELD-32%
`
`RX(l)
`
`RCT
`RGT
`PRO
`SQL
`
`o"'--',)I
`
`A 155589-15-4
`D 9001~62-1 Lipase
`~ 1ssse9-16-s, c 53123-88-9
`7732-18-5 Water, 75-05-8 MeCN
`
`AV
`cs
`so
`
`L18 ANSWER 7 OF 11 CASREACT COPYRIGHT 1996 ACS
`119; 2497~1 '~ CASREACT
`AN
`TI Total synthesis of rapamycin via a novel titanium-mediated aldol
`mac~o~ycliz~tion reaction
`iniyward, Ch:eryl Mi..; Yohannes, Daniel; Danishefsky, Samuel J.
`Dep~ Cpem~, 'Yafe Univ., New Haven, CT, 06511-8118, USA.
`J~ Am. cn:~m. Soc. (1993), 115 (20), 9345-6
`CODEN: JP(CSAT; ISSN: 0002-7863
`JoJ.Irnal
`·
`Englj.sp
`CJ~CS-IMAGE; CJACS
`
`OT
`LA
`OS
`GI
`
`
`
`

`
`OMe
`
`OT I PS
`
`~e
`
`Me----
`
`I
`0
`
`~o N
`
`0
`
`Me
`
`CHO
`
`Meo
`
`OMe
`
`p
`
`p
`
`~
`
`Me
`
`Me
`
`I
`
`H
`
`AB
`
`A synthesis of rapamycin is described. The key step is the
`formation of the C-27-C-28 bond from the seco precursor I by an
`intramol. aldol condensation.
`
`RX(l} OF 1
`
`2 A ===> B + C
`
`0 Me
`II
`I
`
`Me
`I
`
`PAGE 1-A
`
`Me OMe
`I I
`
`
`
`

`
`'PAGE 1-B
`
`OMe
`
`Me
`
`~O-Si(Pr-i)3
`- c- o- cH-1H- CH2-U
`II
`I
`0
`CH2- C- CH- CH== C- CHO
`II
`I
`I
`o Me
`Me
`
`2 A
`
`(1) >
`
`
`
`

`
`Clio
`
`N
`
`je y
`
`CH-CH2
`
`HO
`
`o
`Me
`
`o-si
`· (Pr-i)3
`
`OMe
`
`OMe
`
`0
`
`Me
`
`MeO Me
`
`~!ELD 11%
`
`I~
`
`Me
`
`je y
`
`CH-CH2
`
`0
`-;:?'Me
`
`0-SJ.
`'(Pr-i)3
`
`OMe
`
`OMe
`
`Me
`
`I~
`
`Me
`
`HO
`Me
`
`c
`
`
`
`

`
`RX(l)
`
`RCT A 151058-36-5
`
`STAGE(l)
`RGT D 3981-83-7 Cl3TiOPr-i
`SOL 75-09-2 CH2Cl2
`
`STAGE(2)
`RGT E 121-44-8 Et3N
`PRO B 151122-98-4, C 151058-34-3
`
`Ll8 ANSWER 8 OF 11 CASREACT COPYRIGHT 1996 ACS
`AN
`1,18: 147403 CASREACT
`TI
`Preparation of rapamycin pyrazoles as immunosuppressants
`failli, Ameieo A.; Steffan, Robert J.
`IN
`PA American ijome Products Corp., USA
`so
`u • s • I ;. 7 pp~.
`CODEN: USXXAM
`921117
`US 5164399 A
`PI
`US 91~793765 911118
`AI
`Patent
`DT
`.
`~~nglish
`LA
`OS MARPAT 118:•147403
`GI
`
`Me
`
`Me
`
`I
`
`.H
`=c··
`.....,OH
`
`AB Title compds. [I; Z = Ql, CO; Rl,R2 = H, alkyl, (substituted)
`phenylaiJ(yl; when Rl is present, R2 is absent, and vice versa;
`doteed lines= double bonds to complete pyrazole structure], were
`grepd. Thus, rapamycin was treated with Dess-Martin periodlnan~ in
`CH2«!12 fo-,:- 2 h at room temp. to give 31-deoxy-31-oxoi:'~par(iycin. Tnis
`.
`
`.
`
`
`
`

`
`was stirred 2 h with N2H4.H20 in MeOH at GO.degree. for 2 h to give
`I
`(Z = Ql, Rl or R2 = H) as a mixt. of tautomers. The latter showed
`IC50 = 205.3 nM in the comitogen-induced lymphocyte proliferation
`test.
`
`RX(l) OF 3
`
`2 A ===> B + C •••
`
`* STRUCTURE DIAGRAM TOO LARGE FOR DISPLAY - AVAILABLE VIA OFFLINE PRINT *
`PAGE 2-A
`
`A
`
`Me
`
`* STRUCTURE DIAGRAM TOO LARGE FOR DISPLAY -
`
`AVAILABLE VIA OFFLINE PRINT *
`PAGE 2-A
`
`Me
`
`A
`
`(1) >
`
`
`
`

`
`. '
`
`B
`
`HO
`Me
`
`c
`
`M~-CH2-(I
`
`0
`Me
`
`TOH
`OMe
`
`OMe
`
`0
`
`Me
`
`Me
`
`l:-CH2~
`
`0
`
`0
`~Me
`
`OMe
`
`OMe
`
`Me
`
`I~
`
`Me
`
`- RX(l}
`
`RCT A
`
`53123-88-9
`
`
`
`

`
`RGT D 87413-09-0 Martin's reagent
`PRO B 146352-12-7, C 146352-14-9
`SOL 75-09-2 CH2Cl2
`NTE Room tern., 2 h
`
`L18 ANSWER 9 OF 11 CASREACT COPYRIGHT 1996 ACS
`AN
`118:80729 CASREACT
`TI
`(carbamoyl)rapamycin derivatives, a method for their preparation and
`their use as immunosuppressants
`IN Kao, Wenling; Vogel, Robert Lewis; Musser, John Henry
`PA American Home Products Corp., USA
`so
`Eur. Pat. Appl., 16 pp.
`CODEN: EPXXDW
`921021
`EP 509795 A2
`PI
`R: AT, BE, CH, DE, DK, ES, FR, GB, GR, IT, LI, LU, NL, PT, SE
`DS
`EP 92-303401 920415
`AI
`PRAI US 91-686728 910417
`us 92-837048 920218
`Patent
`English
`MARPAT 118:80729
`Some rapamycin carbamate derivs. are claimed. Pharmaceuticals
`contg. said compds. are claimed. A mixt. of rapamycin, pyridine,
`and 4-fluorophenyl isocyanate was stirred at O.degree. for 5 h to
`give rapamycin 42-[(4-fluorophenyl)carbamate] (I). The
`immunosuppressant activity of I was demonstrated in a thymocyte
`proliferation test, mixed lymphocyte reaction and in the survival of
`a pinch skin graft on mice.
`
`DT
`LA
`OS
`AB
`
`RX(l) OF 6
`
`A + B ===> C •••
`
`* STRUCTURE DIAGRAM TOO LARGE FOR DISPLAY - AVAILABLE VIA OFFLINE PRINT *
`
`PAGE 2-A
`
`Me
`
`A
`
`Cl Me
`'*'-I
`/s~
`Me
`Bu-t
`
`B
`
`(1) >
`
`
`
`

`
`, '
`
`HO
`Me
`
`c
`
`RX(l)
`
`~o 0 N
`Me
`I
`CH-CH2~ Me
`o-di- Bu-t
`0
`?"'
`I
`Me
`Me
`
`OMe
`
`I Me
`
`OMe
`
`lh
`
`Me
`
`Me
`
`RCT A 53123-88-9, B 18162-48-6
`RGT D 288-32-4 lH-Imidazole
`PRO C 143030-02-8
`SOL 68-12-2 DMF
`
`Ll8
`AN
`TI
`
`IN
`
`PA so
`
`PI
`AI
`OT
`LA
`OS
`AB
`
`ANSWER 10 OF 11 CASREACT COPYRIGHT 1996 ACS
`117:150807 CASREACT
`[(carbamoylalkyl)acyl]rapamycin derivatives, a method for~their
`,preparation and their use as immunosppressants
`Caufield, Craig E.
`Jllneric;:an Home Products Corp., USA
`u. s., 7 pp.
`.
`CODEN: USXXAM
`920602
`US 5118677 A
`us 91~703240 910520
`Patent
`:English
`MARPAT 117:150807
`Certain rapamycin esters are claimed. Pharmaqeuticals contg. said
`co~pds. a~ immunosuppressive agents are claim~q. Acylrapamyc~n'
`deriv~. aJ_so have antifungal activity (no'data)~ Acylation of
`rppamycin with N,N-dimethylsuccinamic acid gave''''42-(4-
`(dim'ethylamino)-4-oxobutanoyl)rapamycin (I).
`I showed
`immuno5suppressant activity in a mixed lymphocyte reaction and in a
`pinch skin graft survival test.
`
`~I
`
`
`
`

`
`,.
`
`RX(l) OF 2
`
`A + B ===> C
`
`0
`
`A
`
`OH
`*
`
`0
`
`* STRUCTURE DIAGRAM TOO LARGE FOR DISPLAY -
`
`AVAILABLE VIA OFFLINE PRINT *
`PAGE 2-A
`
`Me
`
`B
`
`( 1) >
`
`. .
`
`
`
`

`
`..
`
`Oto
`
`0
`o~
`
`HO
`Me
`
`I /;:
`
`Me
`
`Me
`
`c
`YIELD 10%
`
`RX(l)
`
`RCT
`RGT
`~RO
`SOL
`
`A 2564-95-6, B 53123-88-9
`D.,1892-57-5 EtN:C:N(CH2)3NMe2, E 1122-58-3 4-DMAP
`c 143029-88-3
`75-09-2 CH2Cl2
`
`L18 ANSWER 11 OF 11 CASREACT COPYRIGHT 1996 ACS
`117:111387 CASREACT
`AN
`TI
`carbamoylrapamycin derivatives, a method for their preparati9n and
`their use as immunosuppressants
`IN Kao, W~nling; Vogel, Robert L.; Musser, John H.
`PA American Home Products Corp., USA
`so
`u.s~, 1 pp~
`CODEN: USX>fAM
`920602
`US 5118678 A
`PI
`ys 91-686728 910417
`~I
`Patent
`DT
`En.glish
`LA
`OS MARPAT 117:111387
`AB Certain derivs. of rapamycin, i.e., carbamoylrapamycin derivs., are
`claim~d. Pharmaceuticals contg. said compds. as immunos.µppress1ve
`agents· are claimed. Rapamycin derivs. are also pote:r:itia1 neoplasm
`inhibitors and antifungal agents. Treatment of rapamycin with
`··
`4-fluorophenyl isocyanate gave 42-[(4-fluorophenyl)cqrbamoyl]rapamyc
`in (I) and 31,42-bis((4-fluorophenyl)carbamoyl]rapam¥cin.~ I sh~wed
`,immunosupgressant activity in a mixed lymphocyte reaction an.d iri ·a:·
`pinch sRin·graft survival test .
`•
`
`•
`
`;>~-
`
`•
`
`•
`
`~ •
`
`r fl •
`
`
`
`

`
`RX(l) OF 4
`
`A + B ===> C
`
`* STRUCTURE DIAGRAM TOO LARGE FOR DISPLAY -
`
`AVAILABLE VIA OFFLINE PRINT *
`PAGE 2-A
`
`Me
`
`(1) >
`
`A
`
`B
`
`HO
`Me
`
`c
`
`...
`
`je -y_ o
`
`cH-cH 2
`~o
`Me
`
`II
`o-C-NH~
`~
`F
`
`I
`
`OMe
`
`OMe
`
`Meo
`
`Me
`
`I~
`
`Me
`
`
`
`

`
`... . . ...
`
`RX(l)
`
`RCT
`RGT
`PRO
`
`A 53123-88-9, B 1195-45-5
`D 110-86-1 Pyridine
`c 143029-91-8
`
`=> fil marpat; d que stat 119; fil marpatprev
`FILE 'MARPAT' ENTERED AT 12:03:18 ON 26 APR 96.
`USE IS SUBJECT TO THE TERMS OF YOUR CUSTOMER AGREEMENT
`COPYRIGHT CC) 1996 American Chemical Society (ACS)
`
`FILE CONTENT: 1988-1996 (VOL 108 ISS 14 - VOL 124 ISS 17) (960~19 ED)
`
`MOST ~ECENT CITATIONS FOR PATENTS FROM FIVE MAJOR ISSUING AGENC~ES
`
`(COVERAGE mo THESE DATES IS NOT COMPLETE):
`
`5492544 20 Feb 1996
`US
`DE 195~5777 08 Feb 1996
`EP
`28 Feb 1996
`698933
`JP 0~024363 30 Jan 1996
`..
`WO
`86016Z4 25 Jan 1996
`NOTICE:
`
`~
`1996 patents have started appearing in MARPAT.
`
`Ll
`
`STR
`
`
`
`

`
`1C// \\C3
`
`6 C
`
`c
`\c/4:17
`5
`2o ‘?rC£3
`24
`23 //C\\ 25
`¢
`F
`F
`°12
`C
`27 C
`/fig
`28 ‘xq/§g%&\fi29
`
`C8
`
`Tc
`
`;z
`
`3%y€yC3l
`34%
`33 ,/C\\ 35
`T
`‘F
`38C\\C//C35
`37
`
`NODE ATTRIBUTES:
`NODE ATTRIBUTES:
`DEFAULT MLEVEL IS ATOM
`DEFAULT MLEVEL IS ATOM
`DEFAULT ECLEVEL IS LIMITED
`DEFAULT ECLEVEL IS LIMITED
`
`GRAPH ATTRIBUTES:
`GRAPH ATTRIBUTES:
`RING(S) ARE ISOLATED OR EMBEDDED
`RING(S) ARE ISOLATED OR EMBEDDED
`NUMBER OF NODES IS 27
`NUMBER OF NODES IS 27
`
`STEREO ATTRIBUTES: NONE
`STEREO ATTRIBUTES: NONE
`
`ATTRIBUTES SPECIFIED AT SEARCH-TIME:
`ATTRIBUTES SPECIFIED AT SEARCH-TIME:
`ECLEVEL IS LIM ON ALL NODES
`ECLEVEL IS LIM ON ALL NODES
`ALL RING(S) ARE ISOLATED
`ALL RING(S) ARE ISOLATED
`
`L19
`L19
`
`0 SEA FILE=MARPAT SSS FUL Ll (MODIFIED ATTRIBUTES)
`0 SEA FILE=MARPAT SSS FUL L1 (MODIFIED ATTRIBUTES)
`
`190 ITERATIONS
`100.0% PROCESSED
`190 ITERATIONS
`100.0% PROCESSED
`SEARCH TIME: 00.00.15
`SEARCH TIME: 00.00.15
`
`0 ANSWERS
`0 ANSWERS
`
`•...
`
`··--
`
`
`
`

`
`FILE '~PATPREV' ENTERED AT 12:03:20 ON 26 APR 96
`USE IS SUBJECT TO THE TERMS OF YOUR CUSTOMER AGREEMENT
`COPYRIGHT (C) 1996 American Chemical Society (ACS)
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`FILE COVERS CURRENT RECORDS AND IS UPDATED DAILY
`FILE LAST UPDATED: 26 Apr 1996 (960426)
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`MOST RECENT CITATIONS FOR PATENTS FROM FIVE MAJOR ISSUING AGENCIES
`THESE DATES IS
`NOT COMPLETE) :
`(COVERAGE TO
`us
`05,Mar 1996
`549'6810
`DE
`4432888
`21 Mar 1996
`EP
`702073
`20, Mar 1996
`JP 08050312
`20~- Feb 1996
`25 Jan 1996
`WO
`9602003
`
`0
`30
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`J2czc31
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`349
`33 /c~ 35
`c
`0
`I
`I
`c
`c
`38 ~c/ 36
`37
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`NODE ATTRIBUTES:
`DEFA~T MLEWEL IS ATOM
`DEFAULT ECLEVEL IS LIMITED
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`GRAPH ATTRIBUTES:
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`RING(S) ARE ISOLATED OR EMBEDDED
`RING(S) ARE ISOLATED OR EMBEDDED
`NUMBER OF NODES IS 27
`NUMBER OF NODES IS 27
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`STEREO ATTRIBUTES: NONE
`STEREO ATTRIBUTES: NONE
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`ATTRIBUTES SPECIFIED AT SEARCH-TIME:
`ATTRIBUTES SPECIFIED AT SEARCH-TIME:
`ECLEVEL IS LIM ON ALL NODES
`ECLEVEL IS LIM ON ALL NODES
`ALL RING(S) ARE ISOLATED
`ALL RING(S) ARE ISOLATED
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`L20
`L20
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`0 SEA FILE=MARPATPREV SSS FUL Ll (MODIFIED ATTRIBUTES)
`0 SEA FILE=MARPATPREV SSS FUL Ll
`(MODIFIED ATTRIBUTES)
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`UNITED STATE:.,; DEPARTMENT OF COMMERCE
`Patent and Trademark Office
`Address: COMMISSIONER OF PATENTS AND TRADEMARKS
`Washington. D.C. 20231
`[SEfl!Al_!:!!IM[;H; r-·fll!~l(,!lhT~-~T~===-1i··-~''.ilA"'.!:0~wror_=~.:.~. --.::_ .. -,,-::"ri!, ..
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`COMMISSIQ;o;£ H OF Pf\ Tf:f';l h AND TB !\DE M/iJ1f~ S
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`0 Respons!ve to communication filed on ______ _
`IKI Thls application has been examined
`0 This action is made final
`/tJ((l;-f,"
`A shortened statutory period for response to this action is set to expire _u}_ month(s). ___ days from the date of ttiis letter.
`Failure to respond within the period for response wm cause the application to become abandoned. 35 U.S.C. 133
`
`Part I THE FOLLOWING ATTACHMENTjS) ARE PART OF THIS ACTION:
`
`1. ~ Notice of References Cited by Examiner, PT0-892.
`3. 0 Notice of Art Ciled by Applicant PT0-1449.
`5. 0 lnformatlonon How to Effect Drawing Changes, PT0·1474.
`
`2. 0 NoU<".e o! Draftsman's Paten1 Orawtng Review PT0-948.
`4. 0 Notice of Informal Patent Appticnlion, PTQ. H;2.
`6. o _______ _
`
`Part 11
`
`SUMMARY OF ACTION
`
`1. l1J Claims. __ 1_-·-~~;J-----------·---------
`
`m~ pending in tt1e app!icallon.
`
`Of the above, cla!ms ______________________ are wiltidrawn from consideration.
`
`2.0 C la im s - - - - - - - - - - - - - - - - - - - - - - - - -
`3. 0 Claims ______________________________ arca!Jowc:d.
`
`have heon cancelled.
`
`meretacted.
`
`4. Ei!J Claims __ /_-~$~~--------------------
`s.D Clalms _______________________